tbuckley/cabot-search huggingface dataset:
Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System
Authors: Mahmoud Gheblawi, Kaiming Wang, Anissa Viveiros, Quynh Nguyen, Jiu-Chang Zhong, Anthony J. Turner, Mohan K. Raizada, Maria B. Grant, Gavin Y. Oudit
Journal: Circulation Research (2020)

ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1-7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.
Assessment and management of tinnitus: summary of NICE guidance
Authors: Sedina Lewis, Emtiyaz Chowdhury, David Stockdale, Veronica Kennedy
Journal: BMJ (2020)

### What you need to know

Tinnitus is a common condition in children, young people, and adults. It is the perception of sounds in the ears or head that do not come from an outside source.1 Ten per cent of the population will have tinnitus at some point.2 It can be associated with difficulty in concentrating and listening, and for some people it can be extremely distressing and have a substantial impact on their mental wellbeing, family, work, and social life.2

This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) guideline on tinnitus: assessment and management (https://www.nice.org.uk/guidance/ng155). The guideline does not cover the full clinical pathway but focuses on areas raised at the stakeholder consultations.

NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the guideline development committee (GC)’s experience and opinion of what constitutes good practice. The levels of evidence supporting the recommendations are given in italics in square brackets.

### Tinnitus support

Tinnitus support (sometimes known as tinnitus counselling) should provide people with tinnitus and their family members or carers with the opportunity to discuss their experience of tinnitus with a healthcare professional (including …
Americans are told to wear cloth masks
Authors: Janice Hopkins Tanne
Journal: BMJ (2020)

The US Centers for Disease Control and Prevention (CDC) has told Americans to wear cloth masks to prevent coronavirus transmission. President Donald Trump said at a press briefing last week that the advice was voluntary, and he was choosing not to wear one.

Trump said that the next week or two would be bad and there would be many deaths. The pandemic is expected to peak in the next week or two in New York.

In a television interview, Surgeon General Jerome Adams said the next week or two would be a 911 or Pearl Harbour moment for Americans. White House coordinator Deborah Birx told Americans to stay home, not to go to the grocery store or pharmacy, and do everything to protect …
Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19
Authors: Yan Zhang, Meng Xiao, Shulan Zhang, Peng Xia, Wei Cao, Wei Jiang, Huan Chen, Xin Ding, Hua Zhao, Hongmin Zhang, Chunyao Wang, Jing Zhao, Xuefeng Sun, Ran Tian, Wei Wu, Dong Wu, Jie Ma, Yu Chen, Dong Zhang, Jing Xie, Xiaowei Yan, Xiang Zhou, Zhengyin Liu, Jinglan Wang, Bin Du, Yan Qin, Peng Gao, Xuzhen Qin, Yingchun Xu, Wen Zhang, Taisheng Li, Fengchun Zhang, Yongqiang Zhao, Yongzhe Li, Shuyang Zhang
Journal: New England Journal of Medicine (2020)

Coagulopathy in Critical Illness with Covid-19 The authors describe a 69-year-old man with Covid-19 diagnosed in January 2020 in Wuhan, China, along with two other critically ill patients with Covi...
The Role of Metabolic Lipases in the Pathogenesis and Management of Liver Disease
Authors: Matteo Tardelli, Francesca Virginia Bruschi, Michael Trauner
Journal: Hepatology (2020)

Intracellular lipolysis is an enzymatic pathway responsible for the catabolism of triglycerides (TGs) that is complemented by lipophagy as the autophagic breakdown of lipid droplets. The hydrolytic cleavage of TGs generates free fatty acids (FFAs), which can serve as energy substrates, precursors for lipid synthesis, and mediators in cell signaling. Despite the fundamental and physiological importance of FFAs, an oversupply can trigger lipotoxicity with impaired membrane function, endoplasmic reticulum stress, mitochondrial dysfunction, cell death, and inflammation. Conversely, impaired release of FFAs and other lipid mediators can also disrupt key cellular signaling functions that regulate metabolism and inflammatory processes. This review will focus on specific functions of intracellular lipases in lipid partitioning, covering basic and translational findings in the context of liver disease. In addition, the clinical relevance of genetic mutations in human disease and potential therapeutic opportunities will be discussed.
Mucoadhesive nanoparticles based on ROS activated gambogic acid prodrug for safe and efficient intravesical instillation chemotherapy of bladder cancer
Authors: Xin Xu, Kunpeng Liu, Binbin Jiao, Kejun Luo, Jian Ren, Guan Zhang, Qingsong Yu, Zhihua Gan
Journal: Journal of Controlled Release (2020)
Abstract 17111: Genetic Influences on Human Plasma Metabolites That Determine Mortality in Heart Failure Patients
Authors: David E Lanfear, Hongsheng Gui, Jia Li, Ruicong She, Edward Peterson, L. K Williams, Hani N Sabbah
Journal: Circulation (2018)

Background: Heart failure with reduced ejection fraction (HFrEF) continues to be a global health burden. We recently reported a strong association of plasma metabolite profile (thirteen different metabolites) with survival among patients with HFrEF but the mechanism of this association is unclear. We studied the genetic associations of plasma metabolite to try to illuminate the disease mechanisms at work. Methods: A prospective genetic registry including 1032 HFrEF with genome-wide genotyping and imputation of single nucleotide polymorphisms (SNP; ~7 millions) and targeted metabolomics profiling. Genome-wide (GW) association analyses were performed to investigate the genetic impact of each SNP on the 13 metabolites of interest. Analyses were performed using linear models stratified by race (European Americans [N=516] and African Americans [N=516] and including the top five principal components (PC) for each population to avoid spurious associations due to population stratification. A fixed-effect meta-analysis was then used to combine results from the two populations. Threshold for GW significance was p&lt;5E-8. As a second step, Cox proportional hazard regression models of overall survival were tested for each SNP that met GW significance. Results: We found at least one SNP reaching GW significance for 6 metabolites metabolites (a-KG, C5.Isovaleryl, Fumarate, Leucine, Succinate and X3.HBA). The most significant SNP (rs77836784, an intronic variant within PACRG) was associated with X3.HBA in African American HF patients (Beta estimate=22.82, P-value=7.14E-14). A cross-checking of SNP associations on both metabolites and HF survival identified 13 independent SNPs that may partially explain the contribution of the metabolites on HF mortality (Table 1) and seem to have biologic plausibility including for example a G-protein coupled receptor (GPR68) and protein kinase C (PRKC1). Conclusion: Genetic variants are associated with predictive plasma metabolites and survival. This may be useful to understand the underlying pathways connecting metabolites to HF progression. A complete investigation of genomic and metabolomics determinants including causal mediation and pathway analyses are on-going.
KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma
Authors: Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie-Jose Kersten, Noel Milpied, Henry Fung, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Lianqing Zheng, John M. Rossi, Rajul K. Jain, Arati V. Rao, Patrick M. Reagan
Journal: New England Journal of Medicine (2020)

Patients with relapsed or refractory mantle-cell lymphoma who have disease progression during or after the receipt of Bruton's tyrosine kinase (BTK) inhibitor therapy have a poor prognosis. KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, may have benefit in patients with relapsed or refractory mantle-cell lymphoma.
Computational Image Analysis of T-Cell Infiltrates in Resectable Gastric Cancer: Association with Survival and Molecular Subtypes
Authors: Benjamin R Challoner, Katharina von Loga, Andrew Woolston, Beatrice Griffiths, Nanna Sivamanoharan, Maria Semiannikova, Alice Newey, Louise J Barber, David Mansfield, Lindsay C Hewitt, Yuichi Saito, Naser Davarzani, Naureen Starling, Alan Melcher, Heike I Grabsch, Marco Gerlinger
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background Gastric and gastro-esophageal junction cancers (GCs) frequently recur after resection, but markers to predict recurrence risk are missing. T-cell infiltrates have been validated as prognostic markers in other cancer types, but not in GC because of methodological limitations of past studies. We aimed to define and validate the prognostic role of major T-cell subtypes in GC by objective computational quantification. Methods Surgically resected chemotherapy-naïve GCs were split into discovery (n = 327) and validation (n = 147) cohorts. CD8 (cytotoxic), CD45RO (memory), and FOXP3 (regulatory) T-cell densities were measured through multicolor immunofluorescence and computational image analysis. Cancer-specific survival (CSS) was assessed. All statistical tests were two-sided. Results CD45RO-cell and FOXP3-cell densities statistically significantly predicted CSS in both cohorts. Stage, CD45RO-cell, and FOXP3-cell densities were independent predictors of CSS in multivariable analysis; mismatch repair (MMR) and Epstein–Barr virus (EBV) status were not statistically significant. Combining CD45RO-cell and FOXP3-cell densities into the Stomach Cancer Immune Score showed highly statistically significant (all P ≤ .002) CSS differences (0.9 years median CSS to not reached). T-cell infiltrates were highest in EBV-positive GCs and similar in MMR-deficient and MMR-proficient GCs. Conclusion The validation of CD45RO-cell and FOXP3-cell densities as prognostic markers in GC may guide personalized follow-up or (neo)adjuvant treatment strategies. Only those 20% of GCs with the highest T-cell infiltrates showed particularly good CSS, suggesting that a small subgroup of GCs is highly immunogenic. The potential for T-cell densities to predict immunotherapy responses should be assessed. The association of high FOXP3-cell densities with longer CSS warrants studies into the biology of regulatory T cells in GC.
Annals Graphic Medicine - Alone in a Crowded Workroom
Authors: Kyan Lynch, Elizabeth Cusick
Journal: Annals of Internal Medicine (2020)

Web Exclusives7 April 2020Annals Graphic Medicine - Alone in a Crowded WorkroomFREEKyan Lynch, MD, MA and Elizabeth Cusick, MDKyan Lynch, MD, MAUniversity of Rochester Medical Center, Rochester, New York (K.L., E.C.)Search for more papers by this author and Elizabeth Cusick, MDUniversity of Rochester Medical Center, Rochester, New York (K.L., E.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0059 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Rochester Medical Center, Rochester, New York (K.L., E.C.)Disclosures: The authors have disclosed no conflicts of interest. The forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0059.Author/Illustrator Information: Kyan Lynch, MD, MA, is an OB/GYN Department Education Specialist at the University of Rochester Medical Center (e-mail, [email protected]rochester.edu). Elizabeth Cusick, MD, is a resident in the Department of Dermatology at the University of Rochester Medical Center (e-mail, [email protected]Rochester.edu). PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 April 2020Volume 172, Issue 7Page: W89-W90KeywordsConflicts of interestDermatologyDisclosureHealth careMedical educationObstetrics and gynecology ePublished: 7 April 2020 Issue Published: 7 April 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Risk of invasive fungal infections in patients with <scp>high‐risk MDS</scp> and <scp>AML</scp> receiving hypomethylating agents
Authors: Gee Youn (Geeny) Kim, Jonathan Burns, Craig W. Freyer, Keith W. Hamilton, Noelle V. Frey, Saar I. Gill, Elizabeth O. Hexner, Selina M. Luger, James K. Mangan, Mary E. Martin, Shannon R. McCurdy, Alexander E. Perl, David L. Porter, Mindy G. Schuster, Edward A. Stadtmauer, Alison W. Loren
Journal: American Journal of Hematology (2020)

Abstract Invasive fungal infections (IFI) are a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Given the heterogeneity of the population receiving hypomethylating agents (HMA), it is difficult for clinicians to accurately assess their patients' risk of infection. Literature on the incidence of IFI following HMA is limited to several studies of azacitidine. The primary objective of this retrospective study was to establish the incidence of IFI in HMA treated AML/MDS patients at a large U.S. comprehensive cancer center. Secondary objectives included comparing incidence of IFI among pre‐specified subgroups to identify potential risk factors for IFI. Two hundred three patients with AML, intermediate to very high risk MDS or chronic myelomonocytic leukemia who received at least two cycles of HMA were included. The incidence of IFI, as defined by the European Organization for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group criteria, was 9.6%, with 20 IFI diagnosed following HMA (three proven, four probable, 13 possible). Among the proven cases of IFI, molds included Scedosporium and Fusarium spp. Eleven patients who developed IFIs were neutropenic upon initiating HMA. The majority (17/20) of infections occurred during the first four cycles. Given this incidence, mold‐active prophylaxis can be considered in patients who are neutropenic at the start of therapy.
Stroke: “striking reductions” are seen in number of people with symptoms seeking help
Authors: Jacqui Thornton
Journal: BMJ (2020)

People are ignoring stroke symptoms and failing to ring 999 because they fear being a burden on the NHS in England during the covid-19 pandemic, the national clinical director for stroke has warned.

Deb Lowe, consultant stroke physician at Wirral University Teaching Hospital, said that doctors across the country were seeing “quite striking reductions” in the number of people coming into hospital with symptoms of stroke. She said, “It appears that people aren’t seeking emergency help or going to hospital when they suspect a stroke, possibly due to fear of the virus or not wanting to …
Novel Use of GLP-1 Receptor Agonist Therapy in HNF4A-MODY
Authors: David T. Broome, Zehra Tekin, Kevin M. Pantalone, Adi E. Mehta
Journal: Diabetes Care (2020)

Maturity-onset diabetes of the young (MODY) is an inherited form of diabetes caused by a mutation in a single gene. The frequency of mutation carriers for HNF4A-MODY has been reported to be 1.2% (1). Our group has previously published on the successful use of glucagon-like peptide 1 receptor agonist (GLP-1 RA) therapy in three consecutive generations of a family with an HNF1A-MODY (2). Although GLP-1 RA therapy has been studied in patients with HNF1A-MODY (3), it has not been studied in patients with HNF4A-MODY. In this father-son cohort, we demonstrate successful use of GLP-1 RA therapy in two patients with c.790:1 bp deletion of G; codon:264 mutations of HNF4A.

The son first presented with neonatal hypoglycemia, then later developed diabetes and …
Activation of a Subset of Evolutionarily Young Transposable Elements and Innate Immunity Are Linked to Clinical Responses to 5-Azacytidine
Authors: Hitoshi Ohtani, Andreas D. Ørskov, Alexandra S. Helbo, Linn Gillberg, Minmin Liu, Wanding Zhou, Johanna Ungerstedt, Eva Hellström-Lindberg, Weili Sun, Gangning Liang, Peter A. Jones, Kirsten Grønbæk
Journal: Cancer Research (2020)

The DNA methyltransferase inhibitors (DNMTi) 5-azacytidine and 5-aza-2-deoxycytidine have been approved for the treatment of different types of hematologic malignancies. However, only about 50% of patients respond to treatment. Therefore, a more comprehensive understanding of the molecular changes in patients treated with DNMTi is needed. Here, we examined gene expression profiles in a total of 150 RNA samples from two adult cohorts and one pediatric cohort with hematologic cancers taken before, during, and after treatment with 5-azacytidine (40 patients; 15 nonresponders, 25 responders). Using each patient as their own control, malignant cells showed preferential activation of a subset of evolutionarily young transposable elements (TE), including endogenous retroviral long terminal repeats (LTR), short and long interspersed nuclear elements (SINE and LINE), and the type I IFN pathway in responders, all independent of disease classification. Transfection of eight upregulated LTRs into recipient human cells in culture showed robust and heterogenous activation of six genes in the type I IFN pathway. These results, obtained in diverse hematologic disease entities, show that common targets (TE) activated by the same drug (5-azacytidine) elicit an immune response, which may be important for patient's responses to DNMTi. SIGNIFICANCE: Activation of specific classes of evolutionarily young transposable elements can lead to activation of the innate immune system.
Preparedness among Ophthalmologists: During and Beyond the COVID-19 Pandemic
Authors: Ji-Peng Olivia Li, Jessica Shantha, Tien Y. Wong, Edmund Y. Wong, Jod Mehta, Haotian Lin, Xiaofeng Lin, Nicholas G. Strouthidis, Ki Ho Park, Adrian T. Fung, Stephen D. McLeod, Massimo Busin, David W. Parke, Gary N. Holland, James Chodosh, Steven Yeh, Daniel S.W. Ting
Journal: Ophthalmology (2020)
Neoantigen responses, immune correlates, and favorable outcomes after ipilimumab treatment of patients with prostate cancer
Authors: Sumit K. Subudhi, Luis Vence, Hao Zhao, Jorge Blando, Shalini S. Yadav, Qing Xiong, Alexandre Reuben, Ana Aparicio, Paul G. Corn, Brian F. Chapin, Louis L. Pisters, Patricia Troncoso, Rebecca Slack Tidwell, Peter Thall, Chang-Jiun Wu, Jianhua Zhang, Christopher L. Logothetis, Andrew Futreal, James P. Allison, Padmanee Sharma
Journal: Science Translational Medicine (2020)

Low–tumor mutational burden prostate tumors express neoantigens that elicit T cell responses associated with favorable clinical outcomes to ipilimumab.
Abstract 13742: Utility of Pre-Treatment Non-Cholesterol Sterols in the Prediction of LDL-C Lowering Response to Statins and Ezetimibe
Authors: Paul T Williams, Michael L Dansinger, H. R Superko, Ernst J Schaefer
Journal: Circulation (2019)

Hypothesis: Statins inhibit cholesterol synthesis, while ezetimibe inhibits cholesterol absorption. Our hypothesis was that plasma markers of cholesterol synthesis (lathosterol) and absorption (cam...
Implications of Postoperative Infections on Long-term Outcomes—Reply
Authors: William J. O’Brien, Kalpana Gupta, Kamal M. F. Itani
Journal: JAMA Surgery (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 Surgery 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 Surgery journal