tbuckley/cabot-search huggingface dataset:
Sex‐based differences in biomarkers, health status, and reverse cardiac remodelling in patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan
Authors: Nasrien E. Ibrahim, Ileana L. Piña, Alexander Camacho, Devavrat Bapat, G. Michael Felker, Alan S. Maisel, Javed Butler, Margaret F. Prescott, Cheryl A. Abbas, Scott D. Solomon, James L. Januzzi
Journal: European Journal of Heart Failure (2020)

We sought to determine sex-based differences in biomarkers, self-reported health status, and magnitude of longitudinal changes in measures of reverse cardiac remodelling among patients with heart failure with reduced ejection fraction (HFrEF, left ventricular ejection fraction ≤40%) treated with sacubitril/valsartan (S/V).This was a subgroup analysis of patients initiated on S/V in the Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure (PROVE-HF) study. There were 226 (28.5%) women in the study. Though women had lower baseline N-terminal pro B-type natriuretic peptide (NT-proBNP), they had more rapid early reduction in the biomarker after initiation of S/V. Compared to men, women had lower average baseline Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 Total Symptom score (67.6 vs. 71.9; P = 0.003) but showed greater linear improvement (7.4 vs. 5.5 points; P < 0.001) and faster pace of KCCQ change (P < 0.001) over the course of the trial. Women and men demonstrated similar degrees of reverse left ventricular remodelling following S/V initiation; however, women did so earlier than men with more consistent changes. These results remained unchanged with adjustment for relevant covariates. Reduction in NT-proBNP was associated with reverse cardiac remodelling in both women and men. Treatment with S/V was well tolerated in all.In women with HFrEF, treatment with S/V was associated with significant NT-proBNP reduction, health status improvement and reverse cardiac remodelling.
The Fragility Index and Trial Significance
Authors: Alexander Chaitoff, Alexander Zheutlin, Joshua D. Niforatos
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
A Decision-Making Algorithm for Children With Suspected Coronavirus Disease 2019
Authors: Gavriela Maria Feketea, Vasiliki Vlacha
Journal: JAMA Pediatrics (2020)

weight across the life span certainly warrant exploration.However, the focus of our study was specifically to investigate the role of energy-balance behaviors in mediating the association between video game use and BMI in childhood.Inclusion of aggression, or other emotional drivers of weight, was therefore beyond the scope of the study.Additionally, while we agree that previous research suggests there is an association between aggression and BMI, 2 we also note that the evidence for an association between aggression and video game use in childhood is more mixed.For example, a meta-analysis of 101 video game studies in children found minimal associations between video game use and childhood aggression. 3Furthermore, a previous longitudinal study using the same data set as our study (the UK-based Millenium Cohort) found no association between video game use at age 5 years and conduct problems at age 7 years (the only measure of aggression available in this data set). 4This suggests it is unlikely that conduct problems (as an indicator of aggression) would have been considered for inclusion as a mediator within our final model had we explored this association.It is also important to highlight that in the United Kingdom, children are restricted in their ability to buy violent video games by the Pan-European Game Information age rating system. 5This means video game use in our sample of 5-year-old children is unlikely to have included violent games, which are of particular concern in relation to aggressive behaviors. 6 We therefore feel that the inclusion of aggression as a potential mediator was not appropriate for this study.However, this is certainly an interesting area of research and future studies could consider exploring these associations further in cohorts of older teenagers and young adults, using appropriate measures of aggression and stress.
Integrating Mathematical Modeling with High-Throughput Imaging Explains How Polyploid Populations Behave in Nutrient-Sparse Environments
Authors: Gregory J. Kimmel, Mark Dane, Laura M. Heiser, Philipp M. Altrock, Noemi Andor
Journal: Cancer Research (2020)

Breast cancer progresses in a multistep process from primary tumor growth and stroma invasion to metastasis. Nutrient-limiting environments promote chemotaxis with aggressive morphologies characteristic of invasion. It is unknown how coexisting cells differ in their response to nutrient limitations and how this impacts invasion of the metapopulation as a whole. In this study, we integrate mathematical modeling with microenvironmental perturbation data to investigate invasion in nutrient-limiting environments inhabited by one or two cancer cell subpopulations. Subpopulations were defined by their energy efficiency and chemotactic ability. Invasion distance traveled by a homogeneous population was estimated. For heterogeneous populations, results suggest that an imbalance between nutrient efficacy and chemotactic superiority accelerates invasion. Such imbalance will spatially segregate the two populations and only one type will dominate at the invasion front. Only if these two phenotypes are balanced, the two subpopulations compete for the same space, which decelerates invasion. We investigate ploidy as a candidate biomarker of this phenotypic heterogeneity and discuss its potential to inform the dose of mTOR inhibitors (mTOR-I) that can inhibit chemotaxis just enough to facilitate such competition. SIGNIFICANCE: This study identifies the double-edged sword of high ploidy as a prerequisite to personalize combination therapies with cytotoxic drugs and inhibitors of signal transduction pathways such as mTOR-Is. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/22/5109/F1.large.jpg.
Aspirin reduces cardiovascular events in patients with pneumonia: a prior event rate ratio analysis in a large primary care database
Authors: Fergus Hamilton, David Arnold, William Henley, Rupert A. Payne
Journal: European Respiratory Journal (2020)

Ischaemic stroke and myocardial infarction (MI) are common after pneumonia and are associated with long-term mortality. Aspirin may attenuate this risk and should be explored as a therapeutic option.We extracted all patients with pneumonia (aged over 50 years) from the Clinical Practice Research Datalink (CPRD), a large UK primary care database, from inception until January 2019. We then performed a prior event rate ratio (PERR) analysis with propensity score matching (PSM), an approach that allows for control of measured and unmeasured confounding, with aspirin usage as the exposure and ischaemic events as the outcome. The primary outcome was the combined outcome of ischaemic stroke and MI. Secondary outcomes were ischaemic stroke and MI individually. Relevant confounders (smoking, comorbidities, age and gender) were included in the analysis.48 743 patients were eligible for matching. Of these, 9864 were aspirin users who were matched to 9864 non-users. Aspirin users had a reduced risk of the primary outcome (adjusted hazard ratio 0.64, 95% CI 0.52-0.79) in the PERR analysis. For both secondary outcomes, aspirin use was also associated with a reduced risk for MI (hazard ratio 0.46, 95% CI 0.30-0.72) and stroke (hazard ratio 0.70, 95% CI 0.55-0.91), respectively.This study provides supporting evidence that aspirin use is associated with reduced ischaemic events after pneumonia in a primary care setting. This drug may have a future clinical role in preventing this important complication.
Ethical Convergence and Ethical Possibilities: The Implications of New Materialism for Understanding the Molecular Turn in HIV, the Response to COVID-19, and the Future of Bioethics
Authors: Adrian Guta, Marilou Gagnon, Morgan M. Philbin
Journal: The American Journal of Bioethics (2020)

Click to increase image sizeClick to decrease image sizeThis article refers to:Reassessing the Ethics of Molecular HIV Surveillance in the Era of Cluster Detection and Response: Toward HIV Data Justice ACKNOWLEDGEMENTSAdrian Guta is a University of Windsor, Faculty of Arts, Humanities, and Social Sciences, Humanities Research Group Fellow.Additional informationFundingThis work was supported by grants from the Canadian Institutes of Health Research and the Social Science and Humanities Research Council. Morgan M. Philbin was supported by a US National Institute on Drug Abuse funded grant (K01DA039804A).
Mechanism of allosteric activation of SIRT6 revealed by the action of rationally designed activators
Authors: Shaoyong Lu, Yingyi Chen, Jiacheng Wei, Mingzhu Zhao, Duan Ni, Xinheng He, Jian Zhang
Journal: Acta Pharmaceutica Sinica B (2020)

The recent discovery of activator compounds binding to an allosteric site on the NAD+-dependent protein lysine deacetylase, sirtuin 6 (SIRT6) has attracted interest and presents a pharmaceutical target for aging-related and cancer diseases. However, the mechanism underlying allosteric activation of SIRT6 by the activator MDL-801 remains largely elusive because no major conformational changes are observed upon activator binding. By combining molecular dynamics simulations with biochemical and kinetic analyses of wild-type SIRT6 and its variant M136A, we show that conformational rotation of 2-methyl-4-fluoro-5-bromo substituent on the right phenyl ring (R-ring) of MDL-801, which uncovers previously unseen hydrophobic interactions, contributes to increased activating deacetylation activity of SIRT6. This hypothesis is further supported by the two newly synthesized MDL-801 derivatives through the removal of the 5-Br atom on the R-ring (MDL-801-D1) or the restraint of the rotation of the R-ring (MDL-801-D2). We further propose that the 5-Br atom serves as an allosteric driver that controls the ligand allosteric efficacy. Our study highlights the effect of allosteric enzyme catalytic activity by activator binding and provides a rational approach for enhancing deacetylation activity.
Abstract 215: New Mannequin Made by Recyclable Plastic Bottles for Training Thoracic Compressions at Schools
Authors: Agnaldo Piscopo, Isabella C Piscopo, Alvaro AVEZUM, Ibrain M Pinto, Francisco K Saraiva
Journal: Circulation (2018)

Introduction: The teaching of Cardiopulmonary Resuscitation (CPR) in schools is already established by the "Kids Save Lives".A low-cost mannequin with the possibility of using recycled material may be a new means of training for children and young people in low-income areas. Objectives: To develop a low-cost mannequin derived from recycled material and evaluate its ability to demonstrate simulations of chest compressions for children and young people. Methods: Development of the model of a low fidelity mannequin made by children in a standard platform based on a plastic bottle (PET) inserted in a T-shirt with other recycled materials such as paper and Styrofoam. The compression simulation test was conducted by a randomized, single-blind study with the inclusion of volunteers at a high school. The children, without previous training in CPR, were randomized to one of the training arms of Laerdal’s Litle Anne mannequin (L) or plastic bottle mannequin (PB). The compression test was performed on a multi-sport court, during 60 minutes, through a video demonstration of CPR with emphasis on chest compressions. The two groups were balanced in age and gender. After the training, all students underwent a test on the Anne Quality Laedal mannequin with two minutes of chest compressions supervised by an instructor (blind to the previous training), that evaluate the frequency of the compressions, correct position of the hands, mean time without compression, total number of compressions and mean depth of compressions. Results: A total of 88 children and young people with a mean age of 14 years of both genders were included. Forty children trained with the L mannequin and 48 with the PB. The variable depth of compression showed differences between the trained groups, where the PB model was 4.1 points higher than the L model (p=0.012) without being able to affirm that there was an effect on the item depth sufficient (p=0.077). Others variables did not present differences between groups. Conclusion: The PB mannequins have very low cost and can be a new model for CPR training in schools. On the compressions ability, only the depth variable was superior in the PB model, perhaps due to the greater similarity of the mannequin to human chest strength.
Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with Alzheimer’s disease
Authors: Jin Xu, Giulia Bankov, Min Kim, Asger Wretlind, Jodie Lord, Rebecca Green, Angela Hodges, Abdul Hye, Dag Aarsland, Latha Velayudhan, Richard J. B. Dobson, Petroula Proitsi, Cristina Legido-Quigley
Journal: Translational Neurodegeneration (2020)

Abstract Background There is an urgent need to understand the pathways and processes underlying Alzheimer’s disease (AD) for early diagnosis and development of effective treatments. This study was aimed to investigate Alzheimer’s dementia using an unsupervised lipid, protein and gene multi-omics integrative approach. Methods A lipidomics dataset comprising 185 AD patients, 40 mild cognitive impairment (MCI) individuals and 185 controls, and two proteomics datasets (295 AD, 159 MCI and 197 controls) were used for weighted gene co-expression network analyses (WGCNA). Correlations of modules created within each modality with clinical AD diagnosis, brain atrophy measures and disease progression, as well as their correlations with each other, were analyzed. Gene ontology enrichment analysis was employed to examine the biological processes and molecular and cellular functions of protein modules associated with AD phenotypes. Lipid species were annotated in the lipid modules associated with AD phenotypes. The associations between established AD risk loci and the lipid/protein modules that showed high correlation with AD phenotypes were also explored. Results Five of the 20 identified lipid modules and five of the 17 identified protein modules were correlated with clinical AD diagnosis, brain atrophy measures and disease progression. The lipid modules comprising phospholipids, triglycerides, sphingolipids and cholesterol esters were correlated with AD risk loci involved in immune response and lipid metabolism. The five protein modules involved in positive regulation of cytokine production, neutrophil-mediated immunity, and humoral immune responses were correlated with AD risk loci involved in immune and complement systems and in lipid metabolism (the APOE ε4 genotype). Conclusions Modules of tightly regulated lipids and proteins, drivers in lipid homeostasis and innate immunity, are strongly associated with AD phenotypes.
COVID-19 among people experiencing homelessness in England: a modelling study
Authors: Dan Lewer, Isobel Braithwaite, Miriam Bullock, Max T Eyre, Peter J White, Robert W Aldridge, Alistair Story, Andrew C Hayward
Journal: The Lancet Respiratory Medicine (2020)

People experiencing homelessness are vulnerable to COVID-19 due to the risk of transmission in shared accommodation and the high prevalence of comorbidities. In England, as in some other countries, preventive policies have been implemented to protect this population. We aimed to estimate the avoided deaths and health-care use among people experiencing homelessness during the so-called first wave of COVID-19 in England-ie, the peak of infections occurring between February and May, 2020-and the potential impact of COVID-19 on this population in the future.
SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes
Authors: Denisa Bojkova, Julian U G Wagner, Mariana Shumliakivska, Galip S Aslan, Umber Saleem, Arne Hansen, Guillermo Luxán, Stefan Günther, Minh Duc Pham, Jaya Krishnan, Patrick N Harter, Utz H Ermel, Achilleas S Frangakis, Hendrik Milting, Andreas M Zeiher, Karin Klingel, Jindrich Cinatl, Andreas Dendorfer, Thomas Eschenhagen, Carsten Tschöpe, Sandra Ciesek, Stefanie Dimmeler
Journal: Cardiovascular Research (2020)

Abstract Aims Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality. It is unclear whether cardiac injury is caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation. Here, we investigate whether cardiomyocytes are permissive for SARS-CoV-2 infection. Methods and results Two strains of SARS-CoV-2 infected human induced pluripotent stem cell-derived cardiomyocytes as demonstrated by detection of intracellular double-stranded viral RNA and viral spike glycoprotein expression. Increasing concentrations of viral RNA are detected in supernatants of infected cardiomyocytes, which induced infections in Caco-2 cell lines, documenting productive infections. SARS-CoV-2 infection and induced cytotoxic and proapoptotic effects associated with it abolished cardiomyocyte beating. RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signalling, apoptosis, and reactive oxygen stress. SARS-CoV-2 infection and cardiotoxicity was confirmed in a 3D cardiosphere tissue model. Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2. Coronavirus particles were further observed in cardiomyocytes of a patient with coronavirus disease 2019. Infection of induced pluripotent stem cell-derived cardiomyocytes was dependent on cathepsins and angiotensin-converting enzyme 2, and was blocked by remdesivir. Conclusion This study demonstrates that SARS-CoV-2 infects cardiomyocytes in vitro in an angiotensin-converting enzyme 2- and cathepsin-dependent manner. SARS-CoV-2 infection of cardiomyocytes is inhibited by the antiviral drug remdesivir.
Lung mesenchymal cells elicit lipid storage in neutrophils that fuel breast cancer lung metastasis
Authors: Peishan Li, Ming Lu, Jiayuan Shi, Zheng Gong, Li Hua, Qing Li, Bora Lim, Xiang H.-F. Zhang, Xiaowen Chen, Sheng Li, Leonard D. Shultz, Guangwen Ren
Journal: Nature Immunology (2020)
Baseline Predictors of Longitudinal Changes in Symptom Severity and Quality of Life in Patients With Suspected Gastroparesis
Authors: Allen A. Lee, Krishna Rao, Henry P. Parkman, Richard W. McCallum, Irene Sarosiek, Linda A. Nguyen, John M. Wo, Michael I. Schulman, Baharak Moshiree, Satish Rao, Braden Kuo, William L. Hasler
Journal: Clinical Gastroenterology and Hepatology (2020)
Hybrid Indocyanine Green–99mTc-nanocolloid for Single-photon Emission Computed Tomography and Combined Radio- and Fluorescence-guided Sentinel Node Biopsy in Penile Cancer: Results of 740 Inguinal Basins Assessed at a Single Institution
Authors: Paolo Dell’Oglio, Hielke M. de Vries, Elio Mazzone, Gijs H. KleinJan, Maarten L. Donswijk, Henk G. van der Poel, Simon Horenblas, Fijs W.B. van Leeuwen, Oscar R. Brouwer
Journal: European Urology (2020)
Comment on Cai et al. Obesity and COVID-19 Severity in a Designated Hospital in Shenzhen, China. Diabetes Care 2020;43:1392–1398
Authors: Zebao He, Jie Li
Journal: Diabetes Care (2020)

In this issue of Diabetes Care , a comment letter by He and Li showed that obesity was consistently a significant risk factor for coronavirus disease 2019 (COVID-19) severity (1). Furthermore, they also reported 17 risk factors affecting the disease severity in 98 patients with COVID-19. Beyond the study findings themselves, this study is of interest in its use of four machine learning classification algorithms, although most of the predictors of COVID-19 severity have been reported recently (2). Similar predictors from different patient series identified by using different statistical methods might strengthen causal inference and shed light on …
Efficacy of corticosteroid treatment for hospitalized patients with severe COVID-19: a multicentre study
Authors: Michele Bartoletti, Lorenzo Marconi, Luigia Scudeller, Livia Pancaldi, Sara Tedeschi, Maddalena Giannella, Matteo Rinaldi, Linda Bussini, Ilaria Valentini, Anna Filomena Ferravante, Antonella Potalivo, Elisa Marchionni, Giacomo Fornaro, Renato Pascale, Zeno Pasquini, Massimo Puoti, Marco Merli, Francesco Barchiesi, Francesca Volpato, Arianna Rubin, Annalisa Saracino, Tommaso Tonetti, Paolo Gaibani, Vito Marco Ranieri, Pierluigi Viale, Francesco Cristini
Journal: Clinical Microbiology and Infection (2020)
A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target
Authors: Andrea Ghelli Luserna di Rorà, Claudio Cerchione, Giovanni Martinelli, Giorgia Simonetti
Journal: Journal of Hematology & Oncology (2020)

Abstract The inhibition of the DNA damage response (DDR) pathway in the treatment of cancer has recently gained interest, and different DDR inhibitors have been developed. Among them, the most promising ones target the WEE1 kinase family, which has a crucial role in cell cycle regulation and DNA damage identification and repair in both nonmalignant and cancer cells. This review recapitulates and discusses the most recent findings on the biological function of WEE1/PKMYT1 during the cell cycle and in the DNA damage repair, with a focus on their dual role as tumor suppressors in nonmalignant cells and pseudo-oncogenes in cancer cells. We here report the available data on the molecular and functional alterations of WEE1/PKMYT1 kinases in both hematological and solid tumors. Moreover, we summarize the preclinical information on 36 chemo/radiotherapy agents, and in particular their effect on cell cycle checkpoints and on the cellular WEE1/PKMYT1-dependent response. Finally, this review outlines the most important pre-clinical and clinical data available on the efficacy of WEE1/PKMYT1 inhibitors in monotherapy and in combination with chemo/radiotherapy agents or with other selective inhibitors currently used or under evaluation for the treatment of cancer patients.