tbuckley/cabot-search huggingface dataset:
TCT-300 Combining baseline distal-to-aortic pressure ratio and fractional flow reserve in the assessment of coronary stenosis severity
Authors: Mauro Echavarria-Pinto, Tim P. van de Hoef, Martijn A. van Lavieren, Sukhjinder S. Nijjer, Borja Ibañez, Stuart J. Pocock, Alicia Quirós, Justin E. Davies, M. Meuwissen, Patrick W. Serruys, Carlos Macaya, Jan Piek, Javier Escaned
Journal: Journal of the American College of Cardiology (2015)
Targeting REV-ERBα for therapeutic purposes: promises and challenges
Authors: Shuai Wang, Feng Li, Yanke Lin, Baojian Wu
Journal: Theranostics (2020)

REV-ERBα (NR1D1) is a circadian clock component that functions as a transcriptional repressor.Due to its role in direct modulation of metabolic genes, REV-ERBα is regarded as an integrator of cell metabolism with circadian clock.Accordingly, REV-ERBα is first proposed as a drug target for treating sleep disorders and metabolic syndromes (e.g., dyslipidaemia, hyperglycaemia and obesity).Recent years of studies uncover a rather broad role of REV-ERBα in pathological conditions including local inflammatory diseases, heart failure and cancers.Moreover, REV-ERBα is involved in regulation of circadian drug metabolism that has implications in chronopharmacology.In the meantime, recent years have witnessed discovery of an array of new REV-ERBα ligands most of which have pharmacological activities in vivo.In this article, we review the regulatory role of REV-ERBα in various types of diseases and discuss the underlying mechanisms.We also describe the newly discovered ligands and the old ones together with their targeting potential.Despite well-established pharmacological effects of REV-ERBα ligands in animals (preclinical studies), no progress has been made regarding their translation to clinical trials.This implies certain challenges associated with drug development of REV-ERBα ligands.In particular, we discuss the potential challenges related to drug safety (or adverse effects) and bioavailability.For new drug development, it is advocated that REV-ERBα should be targeted to treat local diseases and a targeting drug should be locally distributed, avoiding the adverse effects on other tissues.
IN VITRO PHARMACODYNAMIC EFFECTS OF CANGRELOR ON PLATELET P2Y12 RECEPTOR MEDIATED SIGNALING IN TICAGRELOR TREATED PATIENTS
Authors: Fabiana Rollini, Francesco Franchi, Estela Thano, Gabriel Faz, Yongwhi Park, Jenny Hu, Megha Kureti, Niti Aggarwal, Ashwin Durairaj, Jung Rae Cho, Latonya Been, Zeina Alobaidi, Martin Zenni, Theodore Bass, Dominick Angiolillo
Journal: Journal of the American College of Cardiology (2016)
NIR-II fluorescence microscopic imaging of cortical vasculature in non-human primates
Authors: Zhaochong Cai, Liang Zhu, Mengqi Wang, Anna Wang Roe, Wang Xi, Jun Qian
Journal: Theranostics (2020)

Vasculature architecture of the brain can provide revealing information about mental and neurological function and disease.Fluorescence imaging in the second near-infrared (NIR-II) regime with less light scattering is a more promising method for detecting cortical vessels than traditional visible and NIR-I modes.Methods: Clinically approved dye indocyanine green (ICG) was used for NIR-II fluorescence imaging.Here, for the first time, we developed two NIR-II fluorescence microscopy systems for brain vasculature imaging in macaque monkeys.The first is a wide-field microscope with high temporal resolution for measuring blood flow velocity and cardiac impulse period, while the second is a high spatial resolution confocal microscope producing three-dimensional maps of the cortical microvascular network.Both were designed with flexibility to image various cortical locations on the head.Results: Here, ICG was proved to have high brightness in NIR-II region and an 8-fold QY increase in serum than in water.We achieved cerebrovascular functional imaging of monkey with high temporal resolution (25 frames/second) with wide-field microscope.The blood flow velocity of capillaries can be precisely calculated and the cardiac impulse period can be monitored as well.In vivo structural imaging of cerebrovasculature was accomplished with both high spatial lateral resolution (~8 µm) and high signal to background ratio (SBR).Vivid 3D reconstructed NIR-II fluorescence confocal microscopic images up to depth of 470 μm were also realized. Conclusion:This work comprises an important advance towards studies of neurovascular coupling, stroke, and other diseases relevant to neurovascular health in humans.
A Prospective, Phase 1 Trial of Nivolumab, Ipilimumab, and Radiotherapy in Patients with Advanced Melanoma
Authors: Michael A. Postow, Susan J. Knox, Debra A. Goldman, Yuval Elhanati, Vikram Mavinkurve, Phillip Wong, Darragh Halpenny, Sunil K. Reddy, Kenya Vado, Danielle McCabe, Kristen Aufiero Ramirez, Mary Macri, Paul Schwarzenberger, Toni Ricciardi, Aileen Ryan, Ralph Venhaus, Parisa Momtaz, Alexander N. Shoushtari, Margaret K. Callahan, Paul B. Chapman, Jedd D. Wolchok, Priyanka B. Subrahmanyam, Holden T. Maecker, Katherine S. Panageas, Christopher A. Barker
Journal: Clinical Cancer Research (2020)

Preclinical data suggest that radiotherapy (RT) is beneficial in combination with immune checkpoint blockade. Clinical trials have explored RT with single-agent immune checkpoint blockade, but no trials have reported RT with the combination of nivolumab and ipilimumab.We conducted a phase 1 study of patients with stage IV melanoma receiving nivolumab and ipilimumab with two different dose-fractionation schemes of RT. Patients had at least one melanoma metastasis that would benefit from palliative RT and one metastasis that would not be irradiated. Nivolumab 1 mg/kg + ipilimumab 3 mg/kg and extracranial RT with a dose of 30 Gy in 10 fractions was administered in Cohort A, and then 27 Gy in 3 fractions was administered in Cohort B. The primary outcome was safety.Twenty patients were treated (10 in each cohort). The rates of treatment-related grade 3-4 adverse events in Cohort A and B were 40% and 30%, respectively. There were no grade ≥3 adverse events attributed to RT. Patients responded to treatment outside of the irradiated volume (Cohort A 5/10; Cohort B 1/9). No evaluable patients had progression of irradiated metastases. Immunologic changes were seen in the peripheral blood with increases in T-cell receptor diversity in some responding patients.RT with nivolumab and ipilimumab was safe compared with historical data of nivolumab and ipilimumab alone. Immunologic effects were observed in the peripheral blood. Randomized studies are ongoing to assess whether RT increases the efficacy of nivolumab and ipilimumab.
TCT-722 Temporal Trends of 30-Day Readmission for Patients Undergoing Transcatheter or Surgical Aortic Valve Replacement: A Nationwide Cohort Study
Authors: Yasser Al-Khadra, Fahed Darmoch, Homam Moussa Pacha, Mohamad Soud, Amir Kaki, Samir Kapadia, M. Chadi Alraies
Journal: Journal of the American College of Cardiology (2019)
HEART FAILURE RISK ACROSS THE SPECTRUM OF ANKLE–BRACHIAL INDEX: THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY
Authors: Deepak K. Gupta, Hicham Skali, Brian Claggett, Rumen Kasabov, Amil M. Shah, Laura Loehr, Gerardo Heiss, Vijay Nambi, David Aguilar, Lisa Wruck, Aaron Folsom, Wayne Rosamond, Scott Solomon
Journal: Journal of the American College of Cardiology (2013)
Association of the Meaningful Use Electronic Health Record Incentive Program With Health Information Technology Venture Capital Funding
Authors: Samuel Lite, William Joseph Gordon, Ariel Dora Stern
Journal: JAMA Network Open (2020)

Although the Health Information Technology for Economic and Clinical Health (HITECH) Act has accelerated electronic health record (EHR) adoption since its passage, clinician satisfaction with EHRs remains low, and the association of HITECH with health care information technology (IT) entrepreneurship has remained largely unstudied.
Branched-Chain Amino Acid Catabolism Promotes Thrombosis Risk by Enhancing Tropomodulin-3 Propionylation in Platelets
Authors: Yanyan Xu, Haojie Jiang, Li Li, Fengwu Chen, Yunxia Liu, Meiyi Zhou, Ji Wang, Jingjing Jiang, Xiaoying Li, Xuemei Fan, Lin Zhang, Junfeng Zhang, Junqiang Qiu, Yi Wu, Chao Fang, Haipeng Sun, Junling Liu
Journal: Circulation (2020)

Branched-chain amino acids (BCAAs), essential nutrients including leucine, isoleucine, and valine, serve as a resource for energy production and the regulator of important nutrient and metabolic signals. Recent studies have suggested that dysfunction of BCAA catabolism is associated with the risk of cardiovascular disease. Platelets play an important role in cardiovascular disease, but the functions of BCAA catabolism in platelets remain unknown.The activity of human platelets from healthy subjects before and after ingestion of BCAAs was measured. Protein phosphatase 2Cm specifically dephosphorylates branched-chain α-keto acid dehydrogenase and thereby activates BCAA catabolism. Protein phosphatase 2Cm-deficient mice were used to elucidate the impacts of BCAA catabolism on platelet activation and thrombus formation.We found that ingestion of BCAAs significantly promoted human platelet activity (n=5; P<0.001) and arterial thrombosis formation in mice (n=9; P<0.05). We also found that the valine catabolite α-ketoisovaleric acid and the ultimate oxidation product propionyl-coenzyme A showed the strongest promotion effects on platelet activation, suggesting that the valine/α-ketoisovaleric acid catabolic pathway plays a major role in BCAA-facilitated platelet activation. Protein phosphatase 2Cm deficiency significantly suppresses the activity of platelets in response to agonists (n=5; P<0.05). Our results also suggested that BCAA metabolic pathways may be involved in the integrin αIIbβ3-mediated bidirectional signaling pathway that regulates platelet activation. Mass spectrometry identification and immunoblotting revealed that BCAAs enhanced propionylation of tropomodulin-3 at K255 in platelets or Chinese hamster ovary cells expressing integrin αIIbβ3. The tropomodulin-3 K255A mutation abolished propionylation and attenuated the promotion effects of BCAAs on integrin-mediated cell spreading, suggesting that K255 propionylation of tropomodulin-3 is an important mechanism underlying integrin αIIbβ3-mediated BCAA-facilitated platelet activation and thrombosis formation. In addition, the increased levels of BCAAs and the expression of positive regulators of BCAA catabolism in platelets from patients with type 2 diabetes mellitus are significantly correlated with platelet hyperreactivity. Lowering dietary BCAA intake significantly reduced platelet activity in ob/ob mice (n=4; P<0.05).BCAA catabolism is an important regulator of platelet activation and is associated with arterial thrombosis risk. Targeting the BCAA catabolism pathway or lowering dietary BCAA intake may serve as a novel therapeutic strategy for metabolic syndrome-associated thrombophilia.
PARADOXICAL ARTERIAL REMODELING OF THE PROXIMAL SEGMENT OF THE LEFT ANTERIOR DESCENDING ARTERY PREDICTS LONG-TERM MORTALITY AFTER HEART TRANSPLANTATION
Authors: Kozo Okada, Hideki Kitahara, Hyoung-Mo Yang, Shigemitsu Tanaka, Yuhei Kobayashi, Helen Luikart, Paul Yock, Alan Yeung, Peter Fitzgerald, Kiran Khush, Yasuhiro Honda, William Fearon
Journal: Journal of the American College of Cardiology (2015)
Clinical spectrum, prognosis and estimated prevalence of DNAJB11-kidney disease
Authors: Vinh T. Huynh, Marie-Pierre Audrézet, John A. Sayer, Albert C. Ong, Siriane Lefevre, Valoris Le Brun, Aurore Després, Sarah R. Senum, Fouad T. Chebib, Miguel Barroso-Gil, Chirag Patel, Andrew J. Mallett, Himanshu Goel, Amali C. Mallawaarachchi, Albertien M. Van Eerde, Eléonore Ponlot, Marc Kribs, Yannick Le Meur, Peter C. Harris, Emilie Cornec-Le Gall
Journal: Kidney International (2020)
Classification System for <i>International Classification of Diseases, Ninth Revision, Clinical Modification</i> and <i>Tenth Revision</i> Pediatric Mental Health Disorders
Authors: Bonnie T. Zima, James C. Gay, Jonathan Rodean, Stephanie K. Doupnik, Carol Rockhill, Amber Davidson, Matt Hall
Journal: JAMA Pediatrics (2020)

This study examines how much the Child and Adolescent Mental Health Disorders Classification System of diagnosis overlaps with diagnoses in the Clinical Classification Software and the ICD-9-CM and ICD-10-CM.
Association of Medicaid Expansion With Insurance Coverage Among Children With Cancer
Authors: Justin M. Barnes, Abigail R. Barker, Allison A. King, Kimberly J. Johnson
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> Despite evidence of improved insurance coverage under the Affordable Care Act and Medicaid expansion among adults with cancer, little is known regarding the association of these policies with coverage among children with cancer. <h3>Objective</h3> To assess the association of early Medicaid expansion with rates of Medicaid coverage, private coverage, and no uninsurance among children with cancer. <h3>Design, Setting, and Participants</h3> This cross-sectional study used data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2007, to December 31, 2015, to identify children diagnosed with cancer at ages 0 to 14 years in the United States. Data were analyzed from July 27, 2017, to October 7, 2019. <h3>Exposures</h3> Changes in insurance status at diagnosis after early Medicaid expansion in California, Connecticut, Washington, and New Jersey (EXP states) were compared with changes in nonexpansion (NEXP) states (Arkansas, Georgia, Hawaii, Iowa, Kentucky, Louisiana, Michigan, New Mexico, and Utah). <h3>Main Outcomes and Measures</h3> Difference-in-differences (DID) analyses were used to compare absolute changes in insurance status (uninsured, Medicaid, private/other) at diagnosis before (2007 to 2009) and after (2011 to 2015) expansion in EXP relative to NEXP states. <h3>Results</h3> A total of 21 069 children (11 265 [53.5%] male; mean [SD] age, 6.18 [4.57] years) were included. A 5.25% increase (95% CI, 2.61%-7.89%;<i>P</i> &lt; .001) in Medicaid coverage in children with cancer was observed in EXP vs NEXP states, with larger increases among children of counties with middle to high (adjusted DID estimates, 10.18%; 95% CI, 4.22%-16.14%;<i>P</i> = .005) and high (adjusted DID estimates, 6.13%; 95% CI, 1.10%-11.15%;<i>P</i> = .05) poverty levels (<i>P</i> = .04 for interaction). Expansion-associated reductions of children reported as uninsured (−0.73%; 95% CI, −1.49% to 0.03%;<i>P</i> = .06) and with private or other insurance (−4.52%; 95% CI, −7.16% to −1.88%;<i>P</i> &lt; .001) were observed. For the latter, the decrease was greater for children from counties with middle to high poverty (−9.00%; 95% CI, −14.98% to −3.02%) and high poverty (−6.38%; 95% CI, −11.36% to −1.40%) (<i>P</i> = .04 for interaction). <h3>Conclusions and Relevance</h3> In this study, state Medicaid expansions were associated with increased Medicaid coverage in children with cancer overall and in some subgroups primarily owing to switching from private coverage, particularly in counties with higher levels of poverty but also through reductions in the uninsured.
Covid-19: most patients require mechanical ventilation in first 24 hours of critical care
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: most patients require mechanical ventilation in first 24 hours of critical care Elisabeth MahaseThe BMJ Two thirds (132) of covid-19 patients who required critical care in the UK had mechanical ventilation within 24 hours of admission, an audit of patients from England, Wales, and Northern Ireland has found.The report from the Intensive Care National Audit and Research Centre summarised all the confirmed cases of covid-19 in critical care (199 admissions for 196 patients) up to midnight on 19 March from participating critical care units. 1 Of these, 29% (57) were female and 71% (139) were male; their median age was 64.Of the 196 patients, 16 died, 17 patients were discharged alive from critical care, and 163 patients were last reported as still being in critical care.Most of these patients (106) were being managed by the three London Operational Delivery Networks.
Copy Number Amplification of DNA Damage Repair Pathways Potentiates Therapeutic Resistance in Cancer
Authors: Zhiyuan Wu, Sihan Li, Xuemei Tang, Yue Wang, Weiwei Guo, Guojun Cao, Kun Chen, Min Zhang, Ming Guan, Da Yang
Journal: Theranostics (2020)

Rationale: Loss of DNA damage repair (DDR) in the tumor is an established hallmark of sensitivity to DNA damaging agents such as chemotherapy. However, there has been scant investigation into gain-of-function alterations of DDR genes in cancer. This study aims to investigate to what extent copy number amplification of DDR genes occurs in cancer, and what are their impacts on tumor genome instability, patient prognosis and therapy outcome. Methods: Retrospective analysis was performed on the clinical, genomics, and pharmacogenomics data from 10,489 tumors, matched peripheral blood samples, and 1,005 cancer cell lines. The key discoveries were verified by an independent patient cohort and experimental validations. Results: This study revealed that 13 of the 80 core DDR genes were significantly amplified and overexpressed across the pan-cancer scale. Tumors harboring DDR gene amplification exhibited decreased global mutation load and mechanism-specific mutation signature scores, suggesting an increased DDR proficiency in the DDR amplified tumors. Clinically, patients with DDR gene amplification showed poor prognosis in multiple cancer types. The most frequent Nibrin (NBN) gene amplification in ovarian cancer tumors was observed in 15 out of 31 independent ovarian cancer patients. NBN overexpression in breast and ovarian cancer cells leads to BRCA1-dependent olaparib resistance by promoting the phosphorylation of ATM-S1981 and homology-dependent recombination efficiency. Finally, integration of the cancer pharmacogenomics database of 37 genome-instability targeting drugs across 505 cancer cell lines revealed significant correlations between DDR gene copy number amplification and DDR drug resistance, suggesting candidate targets for increasing patient treatment response. Principal Conclusions: DDR gene amplification can lead to chemotherapy resistance and poor overall survival by augmenting DDR. These amplified DDR genes may serve as actionable clinical biomarkers for cancer management.
TCT-126 First Experience with the Coronary Sinus Reducer System for the Management of Refractory Angina in Patients Without Obstructive Coronary Artery Disease
Authors: Francesco Giannini, Luca Baldetti, Alfonso Ielasi, Neil Ruparelia, Francesco Ponticelli, Azeem Latib, Satoru Mitomo, Antonio Esposito, Anna Palmisano, Alaide Chieffo, Antonio Colombo
Journal: Journal of the American College of Cardiology (2017)
CHARACTERISTICS, TREATMENTS, AND OUTCOMES OF HOSPITALIZED HEART FAILURE PATIENTS STRATIFIED BY ETIOLOGIES OF NON-ISCHEMIC CARDIOMYOPATHY
Authors: Supriya Shore, Maria Grau-Sepulveda, Deepak Bhatt, Paul Heidenreich, Zubin Eapen, Adrian Hernandez, Clyde Yancy, Gregg Fonarow
Journal: Journal of the American College of Cardiology (2014)
PET Imaging of Liposomal Glucocorticoids using <sup>89</sup>Zr-oxine: Theranostic Applications in Inflammatory Arthritis
Authors: Peter J. Gawne, Fiona Clarke, Keren Turjeman, Andrew P. Cope, Nicholas J. Long, Yechezkel Barenholz, Samantha Y. A. Terry, Rafael T. M. de Rosales
Journal: Theranostics (2020)

The encapsulation of Glucocorticoids (GCs) into long-circulating liposomes (LCLs) is a proven strategy to reduce the side effects of glucocorticoids and improve the treatment of inflammatory diseases, such as rheumatoid arthritis (RA).With the aim of supporting the development of GC-loaded LCLs, and potentially predict patient response to therapy clinically, we evaluated a direct PET imaging radiolabelling approach for preformed GC-LCLs in an animal model of human inflammatory arthritis.Methods: A preformed PEGylated liposomal methylprednisolone hemisuccinate (NSSL-MPS) nanomedicine was radiolabelled using [ 89 Zr]Zr(oxinate)4 ( 89 Zr-oxine), characterised and tracked in vivo using PET imaging in a K/BxN serum-transfer arthritis (STA) mouse model of inflammatory arthritis and non-inflamed controls.Histology and joint size measurements were used to confirm inflammation.The biodistribution of 89 Zr-NSSL-MPS was compared to that of free 89 Zr in the same model.A therapeutic study using NSSL-MPS using the same time points as the PET/CT imaging was carried out.Results: The radiolabelling efficiency of NSSL-MPS with [ 89 Zr]Zr(oxinate)4 was 69 ± 8 %.PET/CT imaging of 89 Zr-NSSL-MPS showed high uptake (3.6 ± 1.5 % ID; 17.4 ± 9.3 % ID/mL) at inflamed joints, with low activity present in non-inflamed joints (0.5 ± 0.1 % ID; 2.7 ± 1.1 % ID/mL).Importantly, a clear correlation between joint swelling and high 89 Zr-NSSL-MPS uptake was observed, which was not observed with free 89 Zr.STA mice receiving a therapeutic dose of NSSL-MPS showed a reduction in inflammation at the time points used for the PET/CT imaging compared with the control group.Conclusions: PET imaging was used for the first time to track a liposomal glucocorticoid, showing high uptake at visible and occult inflamed sites and a good correlation with the degree of inflammation.A subsequent therapeutic response matching imaging time points in the same model demonstrated the potential of this radiolabeling method as a theranostic tool for the prediction of therapeutic responsewith NSSL-MPS and similar nanomedicines -in the treatment of inflammatory diseases
TCTAP A-058 Favorable Outcomes for Systemic Pharmacokinetic Study of Sirolimus-eluting Bioresorbable Vascular Scaffold System in Treating De Novo Native Coronary Artery Lesion: A Sub Study of MeRes-1 Trial
Authors: Ashok Seth, Praveen Chandra, Ajaykumar Umakant Mahajan, Manjunath Cholenahally Nanjappa, Viveka Kumar, Parvin Kumar Goel, G.S. Wander, Vinay K. Bahl, Mathew Samuel Kalarickal, Ajitkumar Velaparambil Kumaran, Upendra Kaul, P.C. Rath, Anil Mishra, Vijay Kumar Trehan, Gaurav Ganeshwala, A George Koshy
Journal: Journal of the American College of Cardiology (2017)
Fair Allocation of Scarce Medical Resources in the Time of Covid-19
Authors: Ezekiel J. Emanuel, Govind Persad, Ross Upshur, Beatriz Thome, Michael Parker, Aaron Glickman, Cathy Zhang, Connor Boyle, Maxwell Smith, James P. Phillips
Journal: New England Journal of Medicine (2020)

Allocating Scarce Medical Resources for Covid-19 The Covid-19 pandemic has already stressed health care systems throughout the world, requiring rationing of medical equipment and care. The authors ...
Loss of Ceacam1 promotes prostate cancer progression in Pten haploinsufficient male mice
Authors: Jehnan Liu, Harrison T. Muturi, Saja S. Khuder, Raghd Abu Helal, Hilda E. Ghadieh, Sadeesh K. Ramakrishnan, Meenakshi K. Kaw, Sumona Ghosh Lester, Ahmed Al-Khudhair, Philip B. Conran, Khew-Voon Chin, Cara Gatto-Weis, Sonia M. Najjar
Journal: Metabolism (2020)
Covid-19: Don’t forget the impact on US family physicians
Authors: Douglas Kamerow
Journal: BMJ (2020)

As covid-19 continues its exponential growth in parts of the United States, we have heard a great deal in the media about brave, exhausted emergency room doctors and staff.1 2 Very little that I have seen, however, has focused on a much larger group of doctors who are also on the front lines of the war against covid-19: those who deliver primary care. In the US there are more than twice as many family doctors as ER doctors and almost three times as many pediatricians, most of whom work exclusively in primary care.3 Altogether there are more than five times more primary care doctors than ER doctors, and that is not counting general internists, many of whom in the US are …