tbuckley/cabot-search huggingface dataset:
Abstract 19: Ultra-Fast Cooling Induced by Total Liquid Ventilation Provides Neuroprotection Through a Delay in the Acute Systemic Inflammatory Response After Cardiac Arrest in Rabbits
Authors: Emilie Boissady, Matthias Kohlhauer, Fanny Lidouren, Bijan Ghaleh, Renaud Tissier
Journal: Circulation (2019)

Introduction: Ultra-fast cooling with total liquid ventilation (TLV) is potently protective in animal models of cardiac arrest. Hypothesis: Here, we hypothesized that this protection involves a mitigation of the acute phase of the inflammatory syndrome after cardiac arrest. Methods: Rabbits were anesthetized and submitted to 10 min of ventricular fibrillation. After resuscitation, animals underwent normothermic follow-up (Control, n=6) or ultra-fast cooling by TLV started after resuscitation (TLV, n=6). TLV was used for induction of cooling during 20 min and hypothermia was further maintained during 3 h using external techniques before rewarming. A third group was submitted to a Sham procedure (n=5). Survival and neurological dysfunction were assessed during 3 days. Results: TLV improved the clinical neurological recovery as compared to Control group after cardiac arrest. It was corroborated by histological examination showing an attenuation of neuronal degeneration in parasagittal cortex and hippocampus in TLV vs Control groups. After resuscitation, TLV delayed the elevation of interleukin-6 blood levels as compared to Control after cardiac arrest (e.g., 298±63 vs 991±471 pg/ml at 180 min after cardiac arrest in TLV vs Control, respectively). Blood cytometry analyses showed a massive recruitment of neutrophils and leukocytes (including T4, T8 and B-lymphocytes) in both groups. The early lymphocytosis was attenuated in TLV vs Control groups, despite not achieving statistical significance. Blood levels of high-mobility group box 1 increased rapidly and similarly in both groups after cardiac arrest. This suggests that TLV does not mitigate the early release of danger-associated molecular patterns after resuscitation, which is closely related to the immediate cell death after resuscitation. Altogether, these results show an attenuation of the early inflammatory response during hypothermia, suggesting a role of early but not delayed inflammation in the mechanism of ultra-fast cooling after cardiac arrest. Conclusion: Beneficial effect of hypothermic TLV could be explained by a delay in immune peripheral cells activation and cytokine release, rather than sustained inhibition of inflammation after cardiac arrest.
Mildly Abnormal Lipid Levels, but Not High Lipid Variability, Are Associated With Increased Risk of Myocardial Infarction and Stroke in “Statin-Naive” Young Population A Nationwide Cohort Study
Authors: Jun-Bean Park, Da Hye Kim, Heesun Lee, In-Chang Hwang, Yeonyee E. Yoon, Hyo Eun Park, Su-Yeon Choi, Yong-Jin Kim, Goo-Yeong Cho, Kyungdo Han, Hyung-Kwan Kim
Journal: Circulation Research (2020)

In young adults, the role of mildly abnormal lipid levels and lipid variability in the risk of atherosclerotic cardiovascular diseases remains uncertain.To investigate the association of these abnormalities in lipid profiles with the risk of myocardial infarction (MI) and stroke in young population.From the Korean National Health Insurance Service, a nationwide population-based cohort of 1 934 324 statin-naive adults aged 20 to 39 years, with ≥3 lipid profile measurements and without a history of MI and stroke, were followed-up until the date of MI or stroke, or December 31, 2017. The primary measure of lipid variability was variability independent of the mean. Higher baseline total cholesterol, LDL-C (low-density lipoprotein-cholesterol), and triglycerides and lower HDL-C (high-density lipoprotein-cholesterol) levels were significantly associated with increased MI risk; respective adjusted hazard ratios and 95% CIs comparing the highest versus lowest quartiles were 1.35 (1.20-1.53) for total cholesterol, 1.41 (1.25-1.60) for LDL-C, 1.28 (1.11-1.47) for triglycerides, and 0.82 (0.72-0.94) for HDL-C. Adjusted analyses for deciles of lipid profiles showed that MI risk was significantly elevated among participants with total cholesterol ≥223.4 mg/dL, LDL-C ≥139.5 mg/dL, HDL-C ≤41.8 mg/dL, and triglycerides ≥200.1 mg/dL. The associations between lipid levels and stroke risk were less prominent. Multivariable-adjusted restricted cubic spline analysis demonstrated that the increase in MI risk was not exclusively driven by extreme values of lipid profiles. Similar results were obtained on sensitivity analyses of baseline lipid levels. However, associations between lipid variability and the risk of MI and stroke varied depending on the measure of lipid variability used.Mildly abnormal baseline lipid levels were associated with an increased future risk of atherosclerotic cardiovascular disease events, particularly MI, whereas measures of lipid variability were not. Therefore, in young adults, achieving optimal lipid levels could be valuable in the prevention of atherosclerotic cardiovascular disease.
Value of Minimal Residual Disease (MRD) Monitoring Using Real-Time Quantitative PCR in Patients with Acute Promyelocytic Leukemia (APL) Treated with ATRA, ATO, +/- GO
Authors: Jorge Cortes, Hagop M. Kantarjian, Tapan M. Kadia, Guillermo Garcia-Manero, Elias Jabbour, Gautam M. Borthakur, Kiran Naqvi, Nicholas J. Short, Yesid Alvarado, Musa E. Yilmaz, Naval G. Daver, David McCue, Sherry A. Pierce, Jorge E. Cortes, Farhad Ravandi
Journal: Blood (2019)
GNPAT Variant Associated With Severe Iron Overload in HFE Hemochromatosis Reply
Authors: Christine E McLaren, Mary J Emond, V Nathan Subramaniam, Pradyumna D Phatak, James C Barton, Paul C Adams, Lawrie W Powell, Lyle C Gurrin, Grant A Ramm, Gregory J Anderson, Gordon D McLaren
Journal: Hepatology (2015)
Response to: ‘The cost of arthralgia ‘pretreatment’ to prevent rheumatoid arthritis’ by Rothschild
Authors: Annette van der Helm-van Mil, Robert BM Landewé
Journal: Annals of the Rheumatic Diseases (2020)

Achieving evidence for the management of arthralgia at risk for RA.Response to: 'The cost of arthralgia 'pretreatment' to prevent rheumatoid arthritis' by RothschildWe read the letter from Rothschild with interest. 1 We agree that we need more data and better evidence on: (1) how to determine the risk of patients with arthralgia progressing to 'true RA' and on (2) whether or not Disease Modifying AntiRheumatic Drug (DMARD) treatment is better than placebo in this phase.Both points were discussed in our Viewpoint. 2Cost-benefit analyses can only be performed afterwards.Rothschild seems to agree with us not to condone treating patients presenting with arthralgia with DMARDs, pending further evidence.Still, there are different opinions in the field.This is illustrated by a recent study from the UK, in which rheumatologists were asked about their management in clinical practice of arthralgia patients with positive anti-cyclic citrullinated peptide antibodies antibodies and signs of synovitis on power Doppler in at least one joint, but in the absence of clinically apparent arthritis.Seventy-one per cent of consultants said to start DMARD treatment, 16% would treat with glucocorticoids only, 8% considered inclusion in a clinical trial and only 3% replied to wait and see without immediate initiation of DMARD treatment. 3 We believe it may be harmful if the rheumatic field gets too comfortable with initiating DMARD treatment already in arthralgia patients with a certain risk of developing true rheumatoid arthritis (RA) without solid proof.Such a behaviour hampers the course of observational studies to properly determine the risk of RA in individual patients.Hindering the natural course of patients in observational studies with DMARD treatment means that we will never be able to know which patients are being overtreated.Importantly, the regular use of DMARDs in this setting may also hinder the inclusion of arthralgia patients in ongoing and future placebo-controlled trials, as this will then be considered increasingly counterintuitive or unethical because physicians in daily clinical practice may increasingly consider DMARD treatment standard of therapy.
TSLP and IL‐33 reciprocally promote each other's lung protein expression and ILC2 receptor expression to enhance innate type‐2 airway inflammation
Authors: Shinji Toki, Kasia Goleniewska, Jian Zhang, Weisong Zhou, Dawn C. Newcomb, Baohua Zhou, Hirohito Kita, Kelli L. Boyd, Ray S. Peebles
Journal: Allergy (2020)

Abstract Background The epithelial cell‐derived danger signal mediators thymic stromal lymphopoietin (TSLP) and IL‐33 are consistently associated with adaptive Th2 immune responses in asthma. In addition, TSLP and IL‐33 synergistically promoted group 2 innate lymphoid cell (ILC2) activation to induce innate allergic inflammation. However, the mechanism of this synergistic ILC2 activation is unknown. Methods BALB/c WT and TSLP receptor‐deficient (TSLPR −/− ) mice were challenged intranasally with Alternaria extract (Alt‐Ext) or PBS for 4 consecutive days to evaluate innate airway allergic inflammation. WT mice pre‐administered with rTSLP or vehicle, TSLPR −/− mice, and IL‐33 receptor‐deficient (ST2 −/− ) mice were challenged intranasally with Alt‐Ext or vehicle once or twice to evaluate IL‐33 release and TSLP expression in the lung. TSLPR and ST2 expression on lung ILC2 were measured by flow cytometry after treatment of rTSLP, rIL‐33, rTSLP + rIL‐33, or vehicle. Results Thymic stromal lymphopoietin receptor deficient mice had significantly decreased the number of lung ILC2 expressing IL‐5 and IL‐13 following Alt‐Ext‐challenge compared to WT mice. Further, eosinophilia, protein level of lung IL‐4, IL‐5, and IL‐13, and airway mucus score were also significantly decreased in TSLPR −/− mice compared to WT mice. Endogenous and exogenous TSLP increased Alt‐Ext‐induced IL‐33 release into BALF, and ST2 deficiency decreased Alt‐Ext‐induced TSLP expression in the lung. Further, rTSLP and rIL‐33 treatment reciprocally increased each other's receptor expression on lung ILC2 in vivo and in vitro. Conclusion Thymic stromal lymphopoietin and IL‐33 signaling reciprocally enhanced each other's protein release and expression in the lung following Alt‐Ext‐challenge and each other's receptor expression on lung ILC2 to enhance ILC2 activation.
Consultant is struck off for dishonesty over case of girl who died from meningococcal septicaemia
Authors: Clare Dyer
Journal: BMJ (2020)

A consultant in emergency medicine has been struck off the UK medical register after a tribunal found he lied repeatedly to cover up his failure to recognise and treat meningococcal septicaemia in a 6 year old girl who later died.

Harsha Rajanna was an specialty trainee year 6 registrar in emergency medicine in February 2017 when he failed to examine Layla-Rose Ermenekli properly. Layla’s mother had brought her to the Royal Oldham Hospital’s emergency department, feeling ill and with a high temperature. Rajanna did not notice a rash on her hip, the tribunal found.

After a brief test of tolerance for liquids, he ordered her discharged, but a concerned paediatric sister called in a junior doctor who noticed a non-blanching rash on the child’s hip, which she recognised as a classic sign …
Coronavirus Infections—More Than Just the Common Cold
Authors: Catharine I. Paules, Hilary D. Marston, Anthony S. Fauci
Journal: JAMA (2020)

In this Viewpoint Anthony Fauci and colleagues review the emergence of pathogenic human coronaviruses (SARS-Cov and MERS-CoV) as background for discussing a rapidly spreading novel coronavirus (2019-nCoV) identified in 2019 in China and the public health strategies necessary to contain the threat.
Screening ToxCast™ for Chemicals That Affect Cholesterol Biosynthesis: Studies in Cell Culture and Human Induced Pluripotent Stem Cell–Derived Neuroprogenitors
Authors: Phillip A. Wages, Piyush Joshi, Keri A. Tallman, Hye-Young H. Kim, Aaron B. Bowman, Ned A. Porter
Journal: Environmental Health Perspectives (2020)

Changes in cholesterol metabolism are common hallmarks of neurodevelopmental pathologies. A diverse array of genetic disorders of cholesterol metabolism support this claim as do multiple lines of research that demonstrate chemical inhibition of cholesterol biosynthesis compromises neurodevelopment. Recent work has revealed that a number of commonly used pharmaceuticals induce changes in cholesterol metabolism that are similar to changes induced by genetic disorders with devastating neurodevelopmental deficiencies.We tested the hypothesis that common environmental toxicants may also impair cholesterol metabolism and thereby possibly contribute to neurodevelopmental toxicity.Using high-throughput screening with a targeted lipidomic analysis and the mouse neuroblastoma cell line, Neuro-2a, the ToxCast™ chemical library was screened for compounds that impact sterol metabolism. Validation of chemical effects was conducted by assessing cholesterol biosynthesis in human induced pluripotent stem cell (hiPSC)-derived neuroprogenitors using an isotopically labeled cholesterol precursor and by monitoring product formation with UPLC-MS/MS.Twenty-nine compounds were identified as validated lead-hits, and four were prioritized for further study (endosulfan sulfate, tributyltin chloride, fenpropimorph, and spiroxamine). All four compounds were validated to cause hypocholesterolemia in Neuro-2a cells. The morpholine-like fungicides, fenpropimorph and spiroxamine, mirrored their Neuro-2a activity in four immortalized human cell lines and in a human neuroprogenitor model derived from hiPSCs, but endosulfan sulfate and tributyltin chloride did not.These data reveal the existence of environmental compounds that interrupt cholesterol biosynthesis and that methodologically hiPSC neuroprogenitor cells provide a particularly sensitive system to monitor the effect of small molecules on de novo cholesterol formation. https://doi.org/10.1289/EHP5053.
Primary Hepatocellular Carcinoma With Intense 68Ga-PSMA Uptake But Slight 18F-FDG Uptake on PET/CT Imaging
Authors: Seval Erhamamci, Nesrin Aslan
Journal: Clinical Nuclear Medicine (2019)

Abstract 68 Ga-PSMA PET/CT imaging is an emerging imaging modality in prostate cancer. PSMA expression is also reported for nonprostate malignancies, including primary hepatocellular carcinoma. Herein, we present a case of a 74-year-ald man with recently diagnosed hepatocellular carcinoma who was referred for 18 F-FDG PET/CT imaging for initial staging. The patient underwent 18 F-FDG PET/CT as part of staging procedure; he also underwent 68 Ga-PSMA PET/CT. PET/CT images revealed only slight 18 F-FDG uptake in the liver lesion, but intense 68 Ga-PSMA uptake, without any metastatic lesion seen elsewhere in the body.
Cast in stone: university honours female pioneers
Authors: Tom Moberly
Journal: BMJ (2020)

Stonewest

The names of Florence Nightingale, Alice Augusta Ball, and Marie Sklodowska-Curie have been added to the facade of the London School of Hygiene and Tropical Medicine’s Keppel Street building.

The names join those of 23 other health innovators inscribed in the 1920s facade, all …
Chronic myelogenous leukemia cells remodel the bone marrow niche via exosome-mediated transfer of miR-320
Authors: Xiaotong Gao, Zhuo Wan, Mengying Wei, Yan Dong, Yingxin Zhao, Xutao Chen, Zhelong Li, Weiwei Qin, Guodong Yang, Li Liu
Journal: Theranostics (2019)

Rationale:Reciprocal interactions between leukemic cells and bone marrow mesenchymal stromal cells (BMMSC) remodel the normal niche into a malignant niche, leading to leukemia progression.Exosomes have emerged as an essential mediator of cell-cell communication.Whether leukemic exosomes involved in bone marrow niche remodeling remains unknown.Methods: We investigated the role of leukemic exosomes in molecular and functional changes of BMMSC in vitro and in vivo.RNA sequencing and bioinformatics were employed to screen for miRNAs that are selectively sorted into leukemic exosomes and the corresponding RNA binding proteins.Results: We demonstrated that leukemia cells significantly inhibited osteogenesis by BMMSC both in vivo and in vitro.Some tumor suppressive miRNAs, especially miR-320, were enriched in exosomes and thus secreted by leukemic cells, resulting in increased proliferation of the donor cells.In turn, the secreted exosomes were significantly endocytosed by adjacent BMMSC and thus inhibited osteogenesis at least partially via β-catenin inhibition.Mechanistically, miR-320 and some other miRNAs were sorted out into the exosomes by RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), as these miRNAs harbor the recognition site for HNRNPA1.Conclusion: HNRNPA1-mediated exosomal transfer of miR-320 from leukemia cells to BMMSC is an important mediator of leukemia progression and is a potential therapeutic target for CML.
When Deploying Predictive Algorithms, Are Summary Performance Measures Sufficient?
Authors: Dan W. Joyce, John Geddes
Journal: JAMA Psychiatry (2020)

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Abstract 471: Barriers to Performing CPR in a Community With a Low Prevalence of Bystander CPR
Authors: Parth Patel, Christina Smith, Barry Knapp, Joseph Lang, Julie Stoner
Journal: Circulation (2019)

Introduction: Sudden cardiac arrest is a leading cause of mortality in the United States, with over 475,000 people dying annually. Bystander CPR significantly improves the odds of neurologically intact survival, yet nationally is performed in only 46% of out of hospital cardiac arrests. Significant regional variation exists in the performance of bystander CPR, with our community performing lower than national norms (26%). We sought to assess our community’s awareness of current American Heart Association (AHA) recommendations and the perceived barriers to performing bystander CPR. Methods: Adult study volunteers were recruited within the community (Norfolk, VA; pop. 244,703) and completed a 15-question anonymous survey that assessed knowledge of AHA recommendations, willingness to perform, and perceived barriers to performing CPR. Results: A total of 1,017 respondents completed all or part of the survey (40% male; 60% female). Knowledge of the importance of CPR was high. Of the respondents, 78% (n=708) indicated they would know if CPR was required, 84% (n=756) recognized the importance of performing CPR on a person who is unconscious and not breathing, and 89% (n=733) agreed CPR should not be delayed until the arrival of an ambulance. Though 70% (n=597) of respondents indicated they had been previously trained to perform CPR, only 44% (n=397) had been trained to perform “hands-only” CPR. Several barriers to performing CPR were identified. Forty-nine percent of respondents (n=402) believed they must perform “mouth to mouth” during CPR while 32% (n=284) were concerned they could catch a disease. Fear of doing something wrong while performing CPR was a concern for 28% (n=257). Twenty-six percent (n=237) reported concerns about the legal consequences of performing CPR. Conclusions: Though the importance of bystander CPR is well recognized in our community, misunderstandings regarding requirements and risks continue to exist. Education efforts should focus on increasing community awareness of current AHA recommendations.
Regulatory RNAs in Heart Failure
Authors: Clarissa Pedrosa da Costa Gomes, Blanche Schroen, Gabriela M. Kuster, Emma L. Robinson, Kerrie Ford, Iain B. Squire, Stephane Heymans, Fabio Martelli, Costanza Emanueli, Yvan Devaux
Journal: Circulation (2020)

Cardiovascular disease is an enormous socioeconomic burden worldwide and remains a leading cause of mortality and disability despite significant efforts to improve treatments and personalize healthcare. Heart failure is the main manifestation of cardiovascular disease and has reached epidemic proportions. Heart failure follows a loss of cardiac homeostasis, which relies on a tight regulation of gene expression. This regulation is under the control of multiple types of RNA molecules, some encoding proteins (the so-called messenger RNAs) and others lacking protein-coding potential, named noncoding RNAs. In this review article, we aim to revisit the notion of regulatory RNA, which has been thus far mainly confined to noncoding RNA. Regulatory RNA, which we propose to abbreviate as regRNA, can include both protein-coding RNAs and noncoding RNAs, as long as they contribute, directly or indirectly, to the regulation of gene expression. We will address the regulation and functional role of messenger RNAs, microRNAs, long noncoding RNAs, and circular RNAs (ie, regRNAs) in heart failure. We will debate the utility of regRNAs to diagnose, prognosticate, and treat heart failure, and we will provide directions for future work.