tbuckley/cabot-search huggingface dataset:
The Principles of Anatomic Illustration Before Vesalius: An Inquiry into the Rationale of Artistic Anatomy.
Journal: JAMA (1926)

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Covid-19: Government will consider call to allow GPs to vaccinate in their own surgeries
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The health secretary Matt Hancock has said he will examine a call to allow GPs to administer covid-19 vaccinations in their own surgeries in the next phase of the national programme.The promise came after the matter was raised in parliament 1 last week amid reports that some primary care networks (PCNs)-which have been coordinating local vaccination efforts by pooling staff and resources-have withdrawn from the second phase of the national vaccination programme (to vaccinate adults aged 18-49) because of workforce and workload pressures.
Low-burden <i>TP53</i> mutations in CLL: clinical impact and clonal evolution within the context of different treatment options
Authors: Jitka Malcikova, Sarka Pavlova, Barbara Kunt Vonkova, Lenka Radova, Karla Plevova, Jana Kotaskova, Karol Pal, Barbara Dvorackova, Marcela Zenatova, Jakub Hynst, Eva Ondrouskova, Anna Panovska, Yvona Brychtova, Kristyna Zavacka, Boris Tichy, Nikola Tom, Jiri Mayer, Michael Doubek, Sarka Pospisilova
Journal: Blood (2021)

Patients with chronic lymphocytic leukemia (CLL) bearing TP53 mutations experience chemorefractory disease and are therefore candidates for targeted therapy. However, the significance of low-burden TP53 mutations with <10% variant allele frequency (VAF) remains a matter for debate. Herein, we describe clonal evolution scenarios of low-burden TP53 mutations, the clinical impact of which we analyzed in a "real-world" CLL cohort. TP53 status was assessed by targeted next-generation sequencing (NGS) in 511 patients entering first-line treatment with chemo- and/or immunotherapy and 159 patients in relapse before treatment with targeted agents. Within the pretherapy cohort, 16% of patients carried low-burden TP53 mutations (0.1% to 10% VAF). Although their presence did not significantly shorten event-free survival after first-line therapy, it affected overall survival (OS). In a subgroup with TP53 mutations of 1% to 10% VAF, the impact on OS was observed only in patients with unmutated IGHV who had not received targeted therapy, as patients benefited from switching to targeted agents, regardless of initial TP53 mutational status. Analysis of the clonal evolution of low-burden TP53 mutations showed that the highest expansion rates were associated with fludarabine, cyclophosphamide, and rituximab regimen in both first- and second-line treatments (median VAF increase, 14.8× and 11.8×, respectively) in contrast to treatment with less intense treatment regimens (1.6×) and no treatment (0.8×). In the relapse cohort, 33% of patients carried low-burden TP53 mutations, which did not expand significantly upon targeted treatment (median VAF change, 1×). Sporadic cases of TP53 mutations' clonal shifts were connected with the development of resistance-associated mutations. Altogether, our data support the incorporation of low-burden TP53 variants in clinical decision making.
HEMODYNAMIC PREDICTORS OF SURVIVAL IN PATIENTS UNDERGOING TRANSSEPTAL CATHETERIZATION FOR ASSESSMENT OF MITRAL STENOSIS SECONDARY TO MITRAL ANNULAR CALCIFICATION
Authors: Abdallah El Sabbagh, Rick Nishimura, Mackram Eleid, Sorin Pislaru, Patricia Pellikka, Charanjit Rihal, Mayra Guerrero, David Hodge, William Miranda
Journal: Journal of the American College of Cardiology (2021)
THE EFFECTS OF ALIROCUMAB VERSUS EZETIMIBE ON TOP OF STATINS ON VASCULAR INFLAMMATION AND FUNCTION
Authors: Paul J. Cacciottolo, Michalis Kostapanos, Annette Hubsch, Evangelia Vamvaka, Fotini Kaloyirou, Joanna Helmy, Elena H. Sancho, Holly Pavey, Kaisa Maki-Petaja, Ian Wilkinson, Joseph Cheriyan
Journal: Journal of the American College of Cardiology (2021)
ECHOCARDIOGRAPHIC ABNORMALITIES ARE COMMON AMONG PATIENTS WITH COVID-19 INFECTION AND INDEPENDENTLY CONFER INCREASED RISK OF IN-HOSPITAL MORTALITY
Authors: Edwin A. Homan, Alexander Volodarskiy, Hannah W. Mitlak, David T. Zhang, Romina Tafreshi, Meridith Pollie, Jerry Lee, Rohini Kopparam, Kumudha Ramasubbu, Evelyn Horn, Parag Goyal, Monika M. Safford, Richard Devereux, Jonathan Weinsaft, Jiwon Kim
Journal: Journal of the American College of Cardiology (2021)
Molecular surveillance of HIV-1 newly diagnosed infections in Shenzhen, China from 2011 to 2018
Authors: Dong Zhang, Chenli Zheng, Hanping Li, Hao Li, Yongjian Liu, Xiaolin Wang, Lei Jia, Lin Chen, Zhengrong Yang, Yongxia Gan, Yifan Zhong, Jingwan Han, Tianyi Li, Jingyun Li, Jin Zhao, Lin Li
Journal: Journal of Infection (2021)

ObjectivesShenzhen is suffering severe HIV epidemic. No systematic surveillance on high risk populations, HIV genetic diversity, transmitted drug resistance (TDR) and molecular transmission clusters (MTCs) have been reported yet. In this study, we described them based on newly diagnosed HIV positive cases from 2011 to 2018 in Shenzhen city, China.MethodsPlasma samples of newly reported HIV positive cases in Shenzhen, China were collected from 2011 to 2018. The HIV pol gene was amplified and sequenced for subtyping, genetic characterization, TDR and phylogenetic analysis. Demographic and risk characteristics associated with transmitted drug resistance-associated mutations (TDRAMs) and MTCs were explored by using logistic regression analyses.Results10,378 HIV pol sequences were successfully obtained from newly diagnosed patients with available background information. The most prevalent HIV-1 subtype was CRF07_BC (40.92%). CRF07_BC, CRF55_01B and URFs increased across years. Total TDR was 6.02% during 2011 to 2018. CRF01_AE, CRF08_BC, CRF55_01B and subtype B were more likely to be associated with TDRAMs than CRF07_BC. 4460 (42.98%) patients were infected with strains included in MTCs. Patients younger than 30 and over 50 years were more likely to cluster.ConclusionsThe prevalence of HIV-1 drug resistance and molecular transmission clusters in Shenzhen should raise a high alert. Interventions targeting on patients with strains locating in MTCs should be considered to improve prevention effect in Shenzhen.
Abstract 16199: Trend of Hypertensive Emergencies in Atrial Fibrillation Hospitalization; National Estimate
Authors: Mae'n Al-Dabbas, Jay Shah, devina adalja, Archana Gundabolu, Ashish Kumar, Mariam Shariff, Samarthkumar J Thakkar, Haresh Gandhi, Harsh P Patel, Nageshwara Gullapalli, Rajkumar P Doshi
Journal: Circulation (2020)

Introduction: Hypertension has been reported as one of the most common risk factor causing atrial fibrillation (AF). Also, hypertension is associated with more persistent AF. However the epidemiology for incidence of hypertensive emergency in AF hospitalization is not well documented. Hypothesis: We hypothesize that frequency of hypertensive emergency has been increasingly associated with Atrial fibrillation. Methods: National inpatient sample from 2005 -2015 was used for the present analysis. Patients over 18 years, with AF as the primary diagnosis were identified using International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9-CM) code, 427.31. Patients with hypertensive emergency were identified using ICD-9-CM code. 401.0, 402.0, 403.0, 404.0, 405.0. Results: A total of 4,988,269 AF patients over 18 years of age were included in the present analysis. Of these hospitalization 49,423 had hypertensive emergency during hospitalizations and the rest 4,938,846 had no hypertensive emergency. There was a monotonic increase in the trend of rates of hypertensive emergency per 1000 AF hospitalizations, from 2005 - 2015. (P value &lt;0.001) [Figure 1]. Conclusion: There has been a significant increase in the rates of hypertensive emergency among AF hospitalization, over the past decade. Further research is needed to investigate the reason for this increased trend.
WHEN OCCAM'S RAZOR FAILS TO EXPLAIN! A CASE OF HYPERTROPHIC CARDIOMYOPATHY, NON-COMPACTION, MYOCARDIAL INFARCTION AND SEVERE MITRAL REGURGITATION ON CARDIAC MRI
Authors: Saikrishna Patibandla, George Sokos, Yasmin Hamirani, Madhavi Kadiyala
Journal: Journal of the American College of Cardiology (2021)
MMP9‐Responsive Peptides: Matrix Metalloproteinase‐9‐Responsive Surface Charge‐Reversible Nanocarrier to Enhance Endocytosis as Efficient Targeted Delivery System for Cancer Diagnosis and Therapy (Adv. Healthcare Mater. 9/2021)
Authors: Qiu‐Ju Han, Xiao‐Tong Lan, Ying Wen, Chuan‐Zeng Zhang, Michael Cleary, Yasra Sayyed, Guangdong Huang, Xiaoling Tuo, Long Yi, Zhen Xi, Lu‐Yuan Li, Qiang‐Zhe Zhang
Journal: Advanced Healthcare Materials (2021)

In article number 2002143 by Qiang-Zhe Zhang, Lu-Yuan Li, and co-workers, a novel MMP9-catalyzed charge reversal nanoparticle (O-NP) is developed for theranostic agents in cancer diagnosis and therapy. The O-NP nanohybrid successfully performs preferential accumulation and enhances the endocytosis in MMP9-expressing xenografted tumors by charge reversal from negative to positive in mouse models, which improves the sensitivity of diagnosis agents and the anti-tumor effects of drugs in vivo by overcoming their low solubility and/or nonspecific enrichment.
Abstract 16231: Machine Learning of Remodeled Ventricular Action Potentials and Long-Term Follow-Up of Ventricular Arrhythmias
Authors: Albert J Rogers, Mahmood Alhusseini, Anojan Selvalingam, David E Krummen, Firas Abuzaid, Junaid A Zaman, Tina Baykaner, Paul Clopton, Peter Bailis, Matei Zaharia, Sanjiv M Narayan
Journal: Circulation (2019)

Introduction: Ventricular monophasic action potentials (MAPs) reflect electrical remodeling in patients with ischemic cardiomyopathy. It is unclear if machine learning of such signals can predict s...
RISK FACTORS AND OUTCOMES ASSOCIATED WITH LV THROMBUS IN PATIENTS WITH PERIPARTUM CARDIOMYOPATHY
Authors: Bhanu Harshita Settipalle, Kritika Luthra, Raju Murugesan, Sindhu Avula, Rajiv Doddamani, Karthik Gangu, Zainulabedin Waqar, Jay Shah, Hemindermeet Singh, Syed Ali
Journal: Journal of the American College of Cardiology (2021)
COVID-19 Outbreak Among Farmworkers — Okanogan County, Washington, May–August 2020
Authors: James S. Miller, Michelle Holshue, Tia K.H. Dostal, Laura P. Newman, Scott Lindquist
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Okanogan County, Washington, experienced increased community transmission of SARS-CoV-2, the virus that causes COVID-19, during summer 2020 (1).Multiple COVID-19 outbreaks occurred in agricultural settings, including a large outbreak among employees of a fruit grower during May-August.Because of this outbreak, Okanogan County Public Health and the Washington State Department of Health initiated one-time, on-site screening testing (2) of all orchard and warehouse employees in August 2020 and assessed risk factors for SARS-CoV-2 infection.Among 3,708 known orchard employees, a valid SARS-CoV-2 test result or information on COVID-19-like symptoms in the absence of a test was available for 3,013 (81%).Cumulative incidence of SARS-CoV-2 infection during approximately 3 months among tested orchard employees was 6%.Cumulative incidence was 12% in employees residing in the community, compared with 4% in employees residing in farmworker housing (p<0.001);point prevalence during the single screening testing event was 1% in both groups.Among 1,247 known warehouse employees, a valid result was available for 726 (58%).Cumulative incidence over approximately 3 months among tested warehouse employees was 23%, with substantial variation across job roles.Positive test results were received by 28% of employees who worked packing and sorting fruit, 24% of those in other roles in the packing and sorting area, 10% of forklift operators, 7% of employees in other warehouse roles, and 6% of office employees.Point prevalence among all warehouse workers was 1% at the screening testing event.Collaboration among employers, community groups, and public health authorities can reveal risk factors and help decrease farmworkers' risk for SARS-CoV-2 infection in the community and the workplace.Creation of a COVID-19 assessment and control plan by agricultural employers, with particular focus on indoor workers whose jobs limit physical distancing, could reduce workplace transmission.The Okanogan County fruit grower began referring symptomatic employees for SARS-CoV-2 testing in late May 2020.One-time SARS-CoV-2 screening testing of all employees was conducted on-site in late August.*Before then, asymptomatic * Employees who previously received a positive test result were not retested during the screening testing.Although 16 tests had a reported test date of September 1, 2020, these tests were likely collected in late August at the screening testing event and occurred, or were reported to the fruit grower, on September 1.
Abstract 4016: Impact of Gender and Age in Patients Undergoing Percutaneous Coronary Intervention: Insights from the DEScover Registry
Authors: Amar D Patel, Marcus L Williams, Helen Vlachos, Habib Samady, Kevin Kip, David O Williams, Alice K Jacobs, Amy Orlick, Henry A Liberman
Journal: Circulation (2006)

Background: The impact of gender and age on percutaneous coronary intervention (PCI) outcomes has yielded conflicting results; however, these studies focused on in-hospital outcomes only, small coh...
RE-APPRAISAL OF THE CAVOTRICUSPID REGION AS A FUNCTIONAL ISTHMUS DURING ATRIAL FLUTTER: A HIGH RESOLUTION ACTIVATION MAPPING STUDY
Authors: Swati Rao, Agatha Kwasnik, Hemal Nayak, Zaid Aziz, Gaurav Upadhyay, Andrew Beaser, Roderick Tung
Journal: Journal of the American College of Cardiology (2021)
A mathematical model to identify optimal combinations of drug targets for dupilumab poor responders in atopic dermatitis
Authors: Takuya Miyano, Alan D. Irvine, Reiko J. Tanaka
Journal: Allergy (2021)

Several biologics for atopic dermatitis (AD) have demonstrated good efficacy in clinical trials, but with a substantial proportion of patients being identified as poor responders. This study aims to understand the pathophysiological backgrounds of patient variability in drug response, especially for dupilumab, and to identify promising drug targets in dupilumab poor responders.We conducted model-based meta-analysis of recent clinical trials of AD biologics and developed a mathematical model that reproduces reported clinical efficacies for nine biological drugs (dupilumab, lebrikizumab, tralokinumab, secukinumab, fezakinumab, nemolizumab, tezepelumab, GBR 830, and recombinant interferon-gamma) by describing system-level AD pathogenesis. Using this model, we simulated the clinical efficacy of hypothetical therapies on virtual patients.Our model reproduced reported time courses of %improved EASI and EASI-75 of the nine drugs. The global sensitivity analysis and model simulation indicated the baseline level of IL-13 could stratify dupilumab good responders. Model simulation on the efficacies of hypothetical therapies revealed that simultaneous inhibition of IL-13 and IL-22 was effective, whereas application of the nine biologic drugs was ineffective, for dupilumab poor responders (EASI-75 at 24 weeks: 21.6% vs. max. 1.9%).Our model identified IL-13 as a potential predictive biomarker to stratify dupilumab good responders, and simultaneous inhibition of IL-13 and IL-22 as a promising drug therapy for dupilumab poor responders. This model will serve as a computational platform for model-informed drug development for precision medicine, as it allows evaluation of the effects of new potential drug targets and the mechanisms behind patient variability in drug response.
BIOMARKERS OF INFLAMMATION AND OUTCOMES OF PATIENTS HOSPITALIZED FOR COVID-19: THE INTERNATIONAL STUDY OF INFLAMMATION IN COVID-19
Authors: Chelsea Meloche, Tariq Azam, Elizabeth Anderson, Husam Shadid, Hanna Berlin, Michael Pan, Rafey Feroze, Patrick O’Hayer, Abbas Bitar, Kishan Padalia, Erinleigh Michaud, Christopher Launius, Penelope Blakely, Venkatesh Murthy, Frederick Korley, Frank Tacke, Athanasios Chalkias, Sven Loosen, Jochen Reiser, Evangelos J. Giamarellos-Bourboulis, Jesper Eugen-Olsen, Salim Hayek
Journal: Journal of the American College of Cardiology (2021)
COMPARISON OF SELF-EXPANDING EVOLUT PRO+ AND EVOLUT R IN THE 34MM TAVR, A SINGLE-CENTER EXPERIENCE
Authors: Matthew McDiarmid, Stacie Kroboth, Ana Cristina Perez Moreno, Bijoy Khandheria, Suhail Allaqaband, John Crouch, Eric Weiss, Charnai Sherry, Renuka Jain, Tanvir Bajwa
Journal: Journal of the American College of Cardiology (2021)
Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial
Authors: Anna Molto, Clementina López-Medina, Filip E Van den Bosch, Annelies Boonen, Casper Webers, Emanuelle Dernis, Floris A van Gaalen, Martin Soubrier, Pascal Claudepierre, Athan Baillet, Mirian Starmans-Kool, Anneke Spoorenberg, Peggy Jacques, Philippe Carron, Rik Joos, Jan Lenaerts, Laure Gossec, Sophie Pouplin, Adeline Ruyssen-Witrand, Laetitia Sparsa, Astrid van Tubergen, Désirée van der Heijde, Maxime Dougados
Journal: Annals of the Rheumatic Diseases (2021)

To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC).Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive.(1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion.Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed.Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC.160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC.TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective.NCT03043846.
OFF-LABEL USE OF DRUG COATED BALLOONS AND STENTS IN PATIENTS WITH FEMOROPOPLITEAL AND ADVANCED CHRONIC KIDNEY DISEASE. INSIGHTS FROM THE VASCULAR QUALITY INITIATIVE
Authors: Yulanka Castro Dominguez, Matthew Pichert, Olamide Alabi, Jiaming Huang, Jelani Qurat-Ul-Ain, Ahmad Arham, Aaron Brice, Zain Ahmed, Cassius Ochoa Chaar, Mitchel Stacy, Jeffrey Turner, Kim Smolderen, Carlos Mena Hurtado
Journal: Journal of the American College of Cardiology (2021)
B-cell receptor signaling and genetic lesions in TP53 and CDKN2A/CDKN2B cooperate in Richter transformation
Authors: Supriya Chakraborty, Claudio Martines, Fabiola Porro, Ilaria Fortunati, Alice Bonato, Marija Dimishkovska, Silvano Piazza, Brijesh S. Yadav, Idanna Innocenti, Rosa Fazio, Tiziana Vaisitti, Silvia Deaglio, Alberto Zamò, Aleksandar J. Dimovski, Luca Laurenti, Dimitar G. Efremov
Journal: Blood (2021)
THORACOTOMY VERSUS STERNOTOMY? THE EFFECT OF SURGICAL APPROACH ON OUTCOMES AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION: A REVIEW OF THE LITERATURE AND META-ANALYSIS
Authors: Berhane M. Worku, Ivan Gambardella, Eric Zimmerman, Mohamed Rahouma, Michelle Demetres, Mario Gaudino, Leonard Girardi
Journal: Journal of the American College of Cardiology (2021)
Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution
Authors: Subramanian Venkatesan, Mihaela Angelova, Clare Puttick, Haoran Zhai, Deborah R. Caswell, Wei-Ting Lu, Michelle Dietzen, Panagiotis Galanos, Konstantinos Evangelou, Roberto Bellelli, Emilia L. Lim, Thomas B.K. Watkins, Andrew Rowan, Vitor H. Teixeira, Yue Zhao, Haiquan Chen, Bryan Ngo, Lykourgos-Panagiotis Zalmas, Maise Al Bakir, Sebastijan Hobor, Eva Grönroos, Adam Pennycuick, Ersilia Nigro, Brittany B. Campbell, William L. Brown, Ayse U. Akarca, Teresa Marafioti, Mary Y. Wu, Michael Howell, Simon J. Boulton, Cosetta Bertoli, Tim R. Fenton, Robertus A.M. de Bruin, Apolinar Maya-Mendoza, Eric Santoni-Rugiu, Robert E. Hynds, Vassilis G. Gorgoulis, Mariam Jamal-Hanjani, Nicholas McGranahan, Reuben S. Harris, Sam M. Janes, Jirina Bartkova, Samuel F. Bakhoum, Jiri Bartek, Nnennaya Kanu, Charles Swanton
Journal: Cancer Discovery (2021)

Abstract APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast ductal carcinoma in situ, and in preinvasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx preinvasive to invasive non–small cell lung cancer (NSCLC) lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early in cancer evolution. Significance: This study reveals the dynamics and drivers of APOBEC3 gene expression in preinvasive disease and the exacerbation of cellular diversity by APOBEC3B through DNA replication stress to promote chromosomal instability early in cancer evolution. This article is highlighted in the In This Issue feature, p. 2355