tbuckley/cabot-search huggingface dataset:
Abstract 16304: Readiness for Physical Activity in Patients With Heart Failure
Authors: Elena Marques-Sule, Luis Almenar, Pallav Deka, Dola Pathak, Raquel López-Vilella, Leonie Klompstra
Journal: Circulation (2020)

Introduction: Little attention has been given to assessing the physical readiness and psychological readiness (motivation &amp; self-efficacy) in patients with heart failure (HF). The aim of this study is to explore the readiness for PA (physical and psychological) in patients with HF and factors related. Method: A cross-sectional study with 163 patients included (mean age 66±16, 50% female, 63% NYHA I, 37% NYHA II) assessing background and clinical data, physical activity (IPAQ-s), depression and anxiety (HADs), quality of life (SF36). Readiness for PA was assessed with physical readiness based on the PA Readiness Questionnaire (PAR-Q) and psychological readiness was measured with the Exercise Self-efficacy Scale (ESES) and motivation with the Motivation for PA and Exercise/ Working Out questionnaire (RM 4-FM). Correlational analyses were done to explore the relationship between physical readiness and psychological readiness and factors related. A multivariate analysis of covariance was done to test the effect of categorical variables on readiness for PA. Results: Of the patients, 64% were not physically ready in becoming more physically active (n=105), 80% of the patients reported low self-efficacy (n=129), 45% (n=74) were extrinsically motivated for change and 55% (n=89) had primarily internal factors that motivated. Physical readiness and psychological readiness were highly correlated with each other. There was a statistically significant higher readiness for PA based on lower age (p &lt; 0.01), male gender (p &lt; 0.01), lower time since diagnose (p &lt; 0.01), being married (p &lt; 0.01), higher educational level (p &lt; 0.01), lower NYHA-class (p = 0.04), lower BMI (p &lt; 0.01), not having COPD (p &lt; 0.01), higher quality of life (p &lt; 0.01) and lower experience of anxiety symptoms (p = 0.03). Conclusions: A prudent first step in fitness assessments and exercise prescription process is the determination of readiness for PA. Along with screening for any physical limitations, it is also important to screen for psychological readiness for engaging in PA. Our findings may assist healthcare providers who are dealing with patients with HF to modify current and develop new practices related to risk reduction as screening readiness for PA before entering PA programs.
Therapeutic targeting of FLT3 and associated drug resistance in acute myeloid leukemia
Authors: Melat T. Gebru, Hong-Gang Wang
Journal: Journal of Hematology & Oncology (2020)

Acute myeloid leukemia (AML) is a heterogeneous disease caused by several gene mutations and cytogenetic abnormalities affecting differentiation and proliferation of myeloid lineage cells. FLT3 is a receptor tyrosine kinase commonly overexpressed or mutated, and its mutations are associated with poor prognosis in AML. Although aggressive chemotherapy often followed by hematopoietic stem cell transplant is the current standard of care, the recent approval of FLT3-targeted drugs is revolutionizing AML treatment that had remained unchanged since the 1970s. However, despite the dramatic clinical response to targeted agents, such as FLT3 inhibitors, remission is almost invariably short-lived and ensued by relapse and drug resistance. Hence, there is an urgent need to understand the molecular mechanisms driving drug resistance in order to prevent relapse. In this review, we discuss FLT3 as a target and highlight current understanding of FLT3 inhibitor resistance.
Abstract 17131: Myocardial Fibrosis Measured by Magnetic Resonance Imaging in People Living With Human Immunodeficiency Virus and Ethnic Differences: Myocardial and Coronary Abnormalities in HIV Infection (MACHIN) Study
Authors: Pavan Reddy, Arazin Minasian, Ahsan Javed, April Banayan, Samuel Valencerina, Krishna Nayak, Michael P Dube, Hossein Bahrami
Journal: Circulation (2020)

Introduction: Recent studies have suggested that increased risk of cardiovascular disease (CVD) in people living with HIV (PLWH) extends beyond coronary artery disease to involve myocardial fibrosis. Cardiac MRI can accurately detect overt scar and diffuse fibrosis in this population. Hypothesis: Compared to controls, virologically-suppressed PLWH without known clinical CVD have increased risk of myocardial fibrosis and scar, as demonstrated by T1/ECV (extracellular volume) mapping and late gadolinium enhancement (LGE) respectively. Methods: Myocardial structure and function were assessed using CMR (GE 3.0T; acquisition: RT-Hawk, Heart Vista Inc; analysis: cvi42, Circle Inc, v5.10). Our protocol included cine, pre-contrast images, LGE and post contrast T1 mapping 12 minutes after infusion of 0.1mmol/kg of gadolinium (Multihance). 12-minute ECV maps were generated and ECV&gt;32% was considered increased extracellular volume indicating diffuse fibrosis. Results: We studied 92 participants (54 PLWH and 38 HIV- controls, mean age 47±14 years, 28% female). There was no difference in LV systolic function and mass between groups. Clinically detectable LGE was observed in 5 PLWH (10%) and no controls (p :0.04). While there was no significant difference in pre-contrast T1 values in cases vs controls (1044±14 vs 1023±15 ms, p: 0.30), PLWH were more likely to have 12mECV values above the median of 25.5% (57% vs 41%, p: 0.23). In regression models, PLWH had higher ECV values (coefficient: 3.4%, p:0.04) and higher odds of increased ECV (OR: 3.9, 95%CI: 1.0-15.6, p:0.05) adjusted for age, gender, and ethnicity. In multivariable models, women had significantly lower ECV values (p: 0.04). African Americans (AAs) had significantly higher chance of having LGE (OR:12.6, p: 0.03). However, while non-black PLWH had a significantly higher odds of increased ECV (adjusted OR:6.0, p: 0.03), this association was not significant in AAs (p:0.9). Conclusion: Virologically suppressed PLWH are at higher risk of clinically detectable LGE in myocardium and diffuse myocardial fibrosis, independent of their demographics and cardiac function. HIV infection is associated with higher risk of LGE in AAs, while subclinical increased ECV is the more common finding in other ethnicities.
Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons
Authors: Nils Rother, Cansu Yanginlar, Rik G.H. Lindeboom, Siroon Bekkering, Mandy M.T. van Leent, Baranca Buijsers, Inge Jonkman, Mark de Graaf, Marijke Baltissen, Lieke A. Lamers, Niels P. Riksen, Zahi A. Fayad, Willem J.M. Mulder, Luuk B. Hilbrands, Leo A.B. Joosten, Mihai G. Netea, Michiel Vermeulen, Johan van der Vlag, Raphaël Duivenvoorden
Journal: Cell Reports Medicine (2020)

Hydroxychloroquine is being investigated for a potential prophylactic effect in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its mechanism of action is poorly understood. Circulating leukocytes from the blood of coronavirus disease 2019 (COVID-19) patients show increased responses to Toll-like receptor ligands, suggestive of trained immunity. By analyzing interferon responses of peripheral blood mononuclear cells from healthy donors conditioned with heat-killed Candida, trained innate immunity can be modeled in vitro. In this model, hydroxychloroquine inhibits the responsiveness of these innate immune cells to virus-like stimuli and interferons. This is associated with a suppression of histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation of inflammation-related genes, changes in the cellular lipidome, and decreased expression of interferon-stimulated genes. Our findings indicate that hydroxychloroquine inhibits trained immunity in vitro, which may not be beneficial for the antiviral innate immune response to SARS-CoV-2 infection in patients.
SINGLE CENTER ASSESSMENT OF LIVER INJURY AND MORTALITY BASED ON RACE AND ETHNICITY IN INDIVIDUALS WITH COVID-19
Authors: E. S. Aby, H. Rodin, J. D. Debes
Journal: Hepatology (2020)

Background: A significant number of those infected with COVID-19 present with gastrointestinal-related manifestations, particularly acute liver injury Most data originate from China, and it is unclear that similar patterns hold in different ethno-social contexts Methods: We performed a retrospective assessment of all individuals diagnosed with COVID-19 in an ethnically diverse county hospital in Minnesota Individuals with a positive COVID-19 test between March 1 and May 25, 2020 were included We evaluated the role of race, ethnicity, and co-morbidities on the pattern of liver injury, hospital admission, and mortality Logistic regressions were performed using SAS 9 4  Statistical significance was reported at a 05 level Results: 2164 individuals diagnosed with COVID-19 were identified  Median age was 39 years (IQR 28-51) and 52 4% were males  12 5% were classified as white, 38 6% as African American, 34 6% as Hispanic, and 14 2% as other/unknown Of those admitted to the hospital (N=323), median values for liver markers were as follow: ALT 26 IU/L (IQR 18-45), AST 40 IU/L (IQR 27-63), total bilirubin 0 5mg/dl (IQR 0 3-0 6) and alkaline phosphatase 74 IU/L (IQR 59-100, Table) Only 2 6% and 3 7% of individuals without chronic liver disease presented with elevated ALT or AST, respectively, whereas 9 9% and 14 1% of those with chronic liver disease presented with elevated ALT or AST, respectively Men were more likely to have abnormal ALT and AST (p=0 002 and p=0 005 respectively) Hispanic ethnicity was associated with an elevated ALT on admission, OR 2 5 (95% CI 1 2-5 1) An elevated AST, but not ALT, on admission was associated with an increased OR of mortality, OR 4 2 (95% CI 1 4-12 1), this effect was present after adjusting for race Conclusion: Our findings suggest that elevated AST on admission, but not ALT, was associated with increased risk of mortality related to COVID-19 Overall, minimal hepatic injury was inflicted by COVID-19 in those without concurrent liver disease, regardless of race or ethnicity
Should drugs be decriminalised? Yes
Authors: Kailash Chand
Journal: BMJ (2007)

Recent government figures suggest that the UK drug treatment programmes have had limited success in rehabilitating drug users, leading to calls for decriminalisation from some parties. <b>Kailash Chand</b> believes that this is the best way to reduce the harm drugs cause, but <b>Joseph Califano</b> thinks not
European Association of Urology Position Paper on the Prevention of Infectious Complications Following Prostate Biopsy
Authors: Adrian Pilatz, Rajan Veeratterapillay, Konstantinos Dimitropoulos, Muhammad Imran Omar, Benjamin Pradere, Yuhong Yuan, Tommaso Cai, Tunde Mezei, Wout Devlies, Franck Bruyère, Riccardo Bartoletti, Bela Köves, Suzanne Geerlings, Sören Schubert, Jeremy Grummet, Nicolas Mottet, Florian Wagenlehner, Gernot Bonkat
Journal: European Urology (2020)
Gradient of Risk and Associations With Cardiovascular Efficacy of Ertugliflozin by Measures of Kidney Function
Authors: David Z.I. Cherney, Darren K. McGuire, Bernard Charbonnel, Francesco Cosentino, Richard Pratley, Samuel Dagogo-Jack, Robert Frederich, Mario Maldonado, Jie Liu, Annpey Pong, Chih-Chin Liu, Christopher P. Cannon
Journal: Circulation (2020)
Aetiology and incidence of sudden cardiac arrest and death in young competitive athletes in the USA: a 4-year prospective study
Authors: Danielle F Peterson, Kristen Kucera, Leah Cox Thomas, Joseph Maleszewski, David Siebert, Martha Lopez-Anderson, Monica Zigman, Jared Schattenkerk, Kimberly G Harmon, Jonathan A Drezner
Journal: British Journal of Sports Medicine (2020)

To investigate the aetiology and incidence of sudden cardiac arrest and death (SCA/D) in US competitive athletes.Prospective surveillance was conducted from 1 July 2014 to 30 June 2018 through the National Center for Catastrophic Sports Injury Research in collaboration with national sports organisations. Autopsy reports, death certificates, and medical records were reviewed by an expert panel to determine aetiology. Athlete participation statistics from the National Federation of State High School Associations and the National Collegiate Athletic Association (NCAA) were used to calculate incidence rates per athlete-years (AY). Comparisons of incidence rates were calculated using incidence rate ratios (IRR) with 95% CIs.331 cases of confirmed SCA/D (158 survivors; 173 fatalities) were identified; 15.4% in middle school, 61.6% in high school and 16.6% in college and professional athletes. Average age was 16.7 (11-29) years, and the majority were in male (83.7%), basketball (28.7%) or American football (25.4%) athletes. Common causes included hypertrophic cardiomyopathy (20.6%), idiopathic left ventricular hypertrophy (13.4%), coronary artery anomalies (12.0%) and autopsy-negative sudden unexplained death (9.6%). Coronary anomalies were more common in middle school athletes (28%), while cardiomyopathies (hypertrophic, arrhythmogenic, dilated, non-compaction or restricted) accounted for 47% of cases in college and professional athletes. Incidence was higher in male versus female athletes at the high school (1:43 932 AY (95% CI 1:38 101 to 1:50 907) vs 1:203 786 AY (95% CI 1:145 251 to 1:293 794); IRR 4.6 (95% CI 3.1 to 7.2)) and NCAA (1:34 906 AY (95% CI 1:25 385 to 1:49 173) vs 1:123 278 AY (95% CI 1:66 078 to 1:249 853); IRR 3.5 (95% CI 1.5 to 9.5)) levels. African American male NCAA Division I basketball players had the highest annual incidence rate of SCA/D (1:2087 AY (95% CI 1:1073 to 1:4 450)).Cardiomyopathies account for nearly half of SCA/D cases in college and professional athletes, while coronary artery anomalies play a more prominent role than expected in middle school athletes. Over half of SCA cases in athletes result in sudden death, calling for improved prevention strategies.
Abstract 13957: Inpatient Outcomes of Infective Endocarditis in Patients With HIV: Analysis From the National Inpatient Sample
Authors: Mohamed Khayata, Nour Tashtish, Sadeer Al-Kindi, Antoine Addoumieh, Saqer Alkharabsheh, Beni R Verma, Muhammad M Furqan, Nishant P Shah, Guilherme H Oliveira, Allan L Klein
Journal: Circulation (2019)

Introduction: Infective endocarditis (IE) is a common cause of hospitalization, with high morbidity and mortality rates. HIV infection increases the risk of IE, especially among injecting drug user...
Widespread Repression of Gene Expression in Cancer by a Wnt/β-Catenin/MAPK Pathway
Authors: Nathan Harmston, Jun Yi Stanley Lim, Oriol Arqués, Héctor G. Palmer, Enrico Petretto, David M. Virshup, Babita Madan
Journal: Cancer Research (2020)

Aberrant Wnt signaling drives a number of cancers through regulation of diverse downstream pathways. Wnt/β-catenin signaling achieves this in part by increasing the expression of proto-oncogenes such as MYC and cyclins. However, global assessment of the Wnt-regulated transcriptome in vivo in genetically distinct cancers demonstrates that Wnt signaling suppresses the expression of as many genes as it activates. In this study, we examined the set of genes that are upregulated upon inhibition of Wnt signaling in Wnt-addicted pancreatic and colorectal cancer models. Decreasing Wnt signaling led to a marked increase in gene expression by activating ERK and JNK; these changes in gene expression could be mitigated in part by concurrent inhibition of MEK. These findings demonstrate that increased Wnt signaling in cancer represses MAPK activity, preventing RAS-mediated senescence while allowing cancer cells to proliferate. These results shift the paradigm from Wnt/β-catenin primarily as an activator of transcription to a more nuanced view where Wnt/β-catenin signaling drives both widespread gene repression and activation. SIGNIFICANCE: These findings show that Wnt/β-catenin signaling causes widespread gene repression via inhibition of MAPK signaling, thus fine tuning the RAS-MAPK pathway to optimize proliferation in cancer.
Abstract 16626: Endothelial Zinc Transporter Zip8 Regulates Ventricular Trabeculation and Compaction
Authors: Jihyun Jang, Deqiang Li
Journal: Circulation (2020)

Trabeculation and subsequent compaction of the ventricular wall are essential for normal heart morphogenesis. In human, excessive trabeculation and impaired myocardial compaction during earlyheart development lead to left ventricular non compaction (LVNC), a third most common cardiomyopathies after dilated and hypertrophic cardiomyopathies. LVNC is also associated with cardiac arrhythmia and sudden cardiac death. The etiology of LVNC is poorly understood. Recently our group identified that Zip8, a Zinc transporter, implicated in ventricular trabeculation and compaction (JCI, 2018,PMID: 29337306). However, it remains elusive how Zip8 regulates these processes through cellular and molecular mechanisms. We conditionally ablated Zip8 in the endothelial cells, epicardial cells and cardiomyocytes in the developing heart respectively. Strikingly, deletion of Zip8 in the endothelial cellsgave rise to LVNC phenotypes, identical to cardiac phenotypes from the global Zip8 knockouts. Incontrast, hearts with deletions of Zip8 in either epicardium or myocardium developed normally. Further,we found only conditional deletion of Zip8 in the endothelium in the early developing hearts (at E8.5)generated LVNC but not in the late gestation stage (E13.5), suggesting that Zip8 plays critical roles during the initial trabeculation stage. Interestingly, we found that endocardial Zip8 deficiency resulted inthe upregulation of Notch signaling, as evidenced by the increase of intracellular domain of notch protein(NICD) and its downstream target gene, bone morphogenetic protein 10 (BMP10). When the notch signaling is inhibited in the endothelial Zip8 knockout hearts either by DAPI, a γ secretase inhibitor, or by genetic deletion of Rbpj, the LVNC cardiac phenotypes are partially rescued. These results suggest thatZip8 orchestrates myocardial trabeculation and compaction by regulating notch signaling.Collectively, our study provides novel insights into the mechanisms of LVNC, suggesting that genetic mutations in Zip8 or zinc deficiency may contribute to LNVC in humans.
Testing Clinical Prediction Models
Authors: Junfeng Wang, Yue Li
Journal: JAMA (2020)

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Risk Assessment and Management of COVID-19 Among Travelers Arriving at Designated U.S. Airports, January 17–September 13, 2020
Authors: Philip Dollard, Isabel Griffin, Andre Berro, Nicole J. Cohen, Kimberly Singler, Yoni Haber, Chris de la Motte Hurst, Amber Stolp, Sukhshant Atti, Leslie Hausman, Caitlin E. Shockey, Shahrokh Roohi, Clive M. Brown, Lisa D. Rotz, Martin S. Cetron, Francisco Alvarado-Ramy
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In January 2020, with support from the U.S. Department of Homeland Security (DHS), CDC instituted an enhanced entry risk assessment and management (screening) program for air passengers arriving from certain countries with widespread, sustained transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). The objectives of the screening program were to reduce the importation of COVID-19 cases into the United States and slow subsequent spread within states. Screening aimed to identify travelers with COVID-19-like illness or who had a known exposure to a person with COVID-19 and separate them from others. Screening also aimed to inform all screened travelers about self-monitoring and other recommendations to prevent disease spread and obtain their contact information to share with public health authorities in destination states. CDC delegated postarrival management of crew members to airline occupational health programs by issuing joint guidance with the Federal Aviation Administration.* During January 17-September 13, 2020, a total of 766,044 travelers were screened, 298 (0.04%) of whom met criteria for public health assessment; 35 (0.005%) were tested for SARS-CoV-2, and nine (0.001%) had a positive test result. CDC shared contact information with states for approximately 68% of screened travelers because of data collection challenges and some states' opting out of receiving data. The low case detection rate of this resource-intensive program highlighted the need for fundamental change in the U.S. border health strategy. Because SARS-CoV-2 infection and transmission can occur in the absence of symptoms and because the symptoms of COVID-19 are nonspecific, symptom-based screening programs are ineffective for case detection. Since the screening program ended on September 14, 2020, efforts to reduce COVID-19 importation have focused on enhancing communications with travelers to promote recommended preventive measures, reinforcing mechanisms to refer overtly ill travelers to CDC, and enhancing public health response capacity at ports of entry. More efficient collection of contact information for international air passengers before arrival and real-time transfer of data to U.S. health departments would facilitate timely postarrival public health management, including contact tracing, when indicated. Incorporating health attestations, predeparture and postarrival testing, and a period of limited movement after higher-risk travel, might reduce risk for transmission during travel and translocation of SARS-CoV-2 between geographic areas and help guide more individualized postarrival recommendations.
Reconfigurable nanophotonic silicon probes for sub-millisecond deep-brain optical stimulation
Authors: Aseema Mohanty, Qian Li, Mohammad Amin Tadayon, Samantha P. Roberts, Gaurang R. Bhatt, Euijae Shim, Xingchen Ji, Jaime Cardenas, Steven A. Miller, Adam Kepecs, Michal Lipson
Journal: Nature Biomedical Engineering (2020)