tbuckley/cabot-search huggingface dataset:
Abstract 11113: Telemedicine Services Are Acceptable to Neurologists for the Delivery of Outpatient Specialty Neurology Care During the Covid-19 Pandemic, but Require Improvement
Authors: Alyssa Chao, Steven R Zeiler, Martha Abshire Saylor, Mona N Bahouth
Journal: Circulation (2021)

Introduction: The COVID-19 pandemic accelerated the adoption of telemedicine services for the delivery of outpatient neurological care. To date, teleneurology has been primarily used in the hospital setting related to both billing restrictions and the need for hands-on maneuvers to complete the neurological assessment. We sought to understand perceptions of neurology specialists during rapid proliferation of telemedicine services into their outpatient practices and the acceptance of this technology. Hypothesis: Neurologists may report profound challenges acclimating to the telemedicine platform, completing visits, and making clinical decisions via telemedicine. We also expected that neurology sub-specialties would differ in their attitudes. Methods: Adapted from the Telehealth Usability Questionnaire (TUQ), our 29 item questionnaire evaluated the teleneurology system in three domains: quality of the telemedicine platform, ability to conduct a sufficient neurological examination, and areas for improvement. The survey was distributed to 88 clinical Neurology faculty in the Johns Hopkins Health System. Seven-point Likert scale responses were collapsed into “Favorable”, “Neutral”, and “Unfavorable.” Within each domain, responses to individual questions were analyzed by neurology sub-specialty using descriptive statistics. Results: We received completed surveys from 46/88 (52%) neurology faculty. Of those, most reported comfort with the current platform (98%) and favorably regarded the system’s ease of use (73%) and quality (80%). However, responses indicated only average ability to troubleshoot telemedicine platform issues when they occurred (55%) and to complete a neurological exam (52%). Sub-specialty comparisons revealed differences in diagnostic confidence; only 30% of neuromuscular faculty indicated they could make accurate neurological diagnoses through a tele-exam as opposed to 84% or greater for other specialties. Conclusions: Teleneurology appears to be feasible and acceptable to a majority of academic neurologists, though diagnostic confidence may differ by sub-specialty. Improvements in technological infrastructure and care models are needed to advance telemedicine neurological care delivery.
A movement for common care
Authors: Victor Montori
Journal: BMJ (2021)

Fuelled by the medicalisation of life and an ever-expanding remit, healthcare has become industrialised and unsustainable. Sustainable healthcare requires a shift from industrial healthcare to careful and kind care as well as addressing the social and environmental determinants of health. Caring for, about, and with each other is a social determinant of health, writes Victor Montori
Abstract 9707: Validation of Japanese High Bleeding Risk Criteria in Patients Undergoing Percutaneous Coronary Intervention and Comparisons With Contemporary Bleeding Risk Scores
Authors: Takeshi Shimizu, Yusuke Kimishima, Tomofumi Misaka, Akiomi Yoshihisa, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2021)

Introduction: The Japanese version of high bleeding risk (J-HBR) criteria have been established by modifying the Academic Research Consortium criteria for high bleeding risk (ARC-HBR), since East-Asian people have several distinct risk factors that were not included in ARC-HBR. We aimed to validate the J-HBR criteria for bleeding outcomes and compare with contemporary risk scores. Methods: Consecutive 1643 patients with coronary artery disease who underwent percutaneous coronary intervention were enrolled. We followed-up bleeding events of Bleeding Academic Research Consortium (BARC) 3 or 5. Results: Among 1643 patients, 1143 (69.6%) who met J-HBR criteria had a higher accumulated bleeding rate than those who did not (P &lt; 0.001, left figure). BARC 3 or 5 bleeding event rates at 1 year were 4.8% in patients who met J-HBR criteria and 0.6% in those who did not (P &lt; 0.01). The J-HBR criteria had higher sensitivity than ARC-HBR, PRECISE-DAPT and PARIS bleeding risk score (94.8%, 81.0%, 75.9% and 87.9%, respectively) and lower specificity than those (31.4%, 52.6%, 54.1% and 51.0%, respectively). J-HBR score was calculated by adding 1 point for major criterion and 0.5 point for minor criterion in J-HBR criteria. The bleeding event rate increased with advancing J-HBR score (right figure). The c-statistics of J-HBR score for predicting BARC 3 or 5 bleeding at 1 year was 0.74 (95% CI, 0.67 - 0.80) that was comparable to ARC-HBR score, PRECISE-DAPT score and PARIS bleeding risk score (0.73, 0.73 and 0.72, respectively). In the multivariate analysis, chronic kidney disease, anemia and heart failure were associated with BARC 3 or 5 bleeding (HR 6.39, P &lt; 0.01; HR 3.38, P &lt; 0.01; and HR 2.95, P &lt; 0.01; respectively) among factors included in J-HBR criteria. Conclusions: The J-HBR criteria successfully identified patients at high bleeding risk, with high sensitivity and low specificity. The bleeding risk was closely related to J-HBR score and its individual component.
Abstract 13348: Single Nuclear RNA-seq of Human Thoracic Aortic Dissection Identifies Expansion of Vascular Smooth Muscle Cells With a Distinct Transcriptional Phenotype
Authors: Shamsudheen Vellarikkal, Deepak Atri, Vivian Lee-Kim, Ankith Reddy, Tsuyoshi Kaneko, Hari R MALLIDI, Rakhshinda Rehman, Prem S Shekar, Laura E Fredenburgh, Oscar Sias-Garcia, J Daniel D Muehlschlegel, Rajat Gupta
Journal: Circulation (2021)

Introduction: Phenotypic switching of vascular cells is a complex process associated with vascular disorders, including thoracic aortic aneurysm (TAA). Vascular smooth muscle cells (VSMCs) appear to switch from a contractile to synthetic phenotype in TAA. Single nuclear RNA-seq (snRNA-seq) of normal human and TAA aortas may be used to characterize cell heterogeneity of normal aortas, population shifts in disease, and the transcriptional profile of VSMC phenotypic switching. Hypothesis: snRNA-seq of normal and TAA aortas will identify the cell heterogeneity and transcriptional profiles of TAA. Methods: We performed snRNA-seq of 5 aortas from 2 normal and 3 TAA patients. We used a 10X-CellBender pipeline for profiling and analysis. Results: snRNA-seq identified 6 major cell types. The majority were VSMCs, exhibiting 4 sub-populations in all specimens (a). Cell distribution comparisons showed VSMC1 (ELN, PKD1, FLNA high) and VSMC2 (PRKG1, PDE3A, PCDH7 high) to be differentially-enriched in controls and TAA samples, respectively (b,c). Gene set and trajectory analyses confirmed prior observations of phenotypic switching (d,e). Genes associated with switching in VSMCs included TAA genes (PRKG1, PKD1, FLNA) with concordance of expression and putative function of Mendelian variants (i-k). Cell junction and regulation of muscle contraction pathways drove trajectory. We further assessed cell-type heritability of vascular GWAS variants (h). These gene sets were differentially-regulated between control and TAA. The strongest association was between VSMC2 and ascending aortic size (h). Conclusions: In this study, we demonstrated a dissociation bias-free method for snRNA-Seq of human vasculature. We confirmed enrichment of synthetic VSMCs in TAA and implicate phenotypic switching as a pathologic mechanism. Our study identifies a cell type-specific transcriptional profile of aortopathy genes, which may drive TAA and represent therapeutic targets.
Abstract 9916: Relationship Between Blood Pressure Categorization and Subclinical Left Ventricular Dysfunction in Antihypertensive Medication-Naive Individuals
Authors: Koki Nakanishi, Masao Daimon, Yuriko Yoshida, Jumpei Ishiwata, Naoko Sawada, Megumi Hirokawa, Hidehiro Kaneko, Tomoko Nakao, Yoshiko Mizuno, Hiroyuki Morita, Marco Di Tullio, Shunichi Homma, Issei Komuro
Journal: Circulation (2021)

Background: The impact of blood pressure (BP) levels on subclinical left ventricular (LV) dysfunction and possible sex-specific difference remains unclarified. This study aimed to investigate the relationship between BP categories given in the new 2017 ACC/AHA hypertension guideline and subclinical LV dysfunction in subjects free of cardiac disease. Methods: We examined antihypertensive medication-naive 858 individuals who underwent extensive cardiovascular health check-up. LV global longitudinal (GLS) and circumferential strain (GCS) were assessed by 2-dimensional speckle-tracking echocardiography. Participants were categorized into 4 groups according to the BP levels: normal BP, elevated BP, isolated diastolic hypertension (IDH) and systolic hypertension (SH). Results: Among the 858 participants (61±11 years, 459 men), 422 individuals had normal BP, 113 had elevated BP, 160 had IDH, and 163 had SH. Prevalence of abnormal LVGLS (&gt;-18.6%) was greatest in SH group (19.0%), followed by IDH (17.5%), elevated BP (14.2%) and normal BP (7.1%, p&lt;0.001; Figure); no significant differences were observed for LVGCS (p=0.671). In the multivariable analyses, IDH and SH were associated with impaired LVGLS (adjusted odds ratio [OR] 2.69 and 2.66, p&lt;0.001) and borderline significance was observed for elevated BP (adjusted OR 1.90, p=0.060); there was no significant association between any of the BP groups and LVGCS. In sex-stratified analysis, IDH and SH carried the significant risk of abnormal LVGLS in both sexes, while elevated BP was associated with LVGLS only in women. Conclusion: IDH and SH redefined by ACC/AHA guideline carried a significant risk for LVGLS, but not LVGCS. Elevated BP was associated with LVGLS only in women. Our findings provide information on cardiac correlates of the newly established BP categories.
Abstract 12120: Cost-Effectiveness of Earlier Initiation of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With a History of Heart Failure
Authors: Robert Miller, Derek Chew, Lei Qin, Nowell Fine, John JV McMurray, Jonathan G Howlett, Phil McEwan
Journal: Circulation (2021)

Background: Patients with heart failure (HF) are at increased risk after hospitalisations for HF (HHF). Timely initiation of medical therapy may reduce morbidity and mortality in these patients. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial demonstrated that dapagliflozin reduced the risk of worsening HF and mortality when added to guideline-directed medical therapy (GDMT). Whilst previous economic evaluations have demonstrated that dapagliflozin is cost-effective; timing of initiation has not been considered. Objective: This study assessed whether early addition of dapagliflozin (D+GDMT) was cost-effective compared to a 12-month delay. Methods: A published lifetime Markov model was utilised with health states defined by Kansas City Cardiomyopathy (KCCQ) score, type 2 diabetes status and incidence of HF events. We analysed the DAPA-HF trial to estimate the incidence of HF events using a negative binomial regression model, and parametric survival analysis for all-cause death. Direct healthcare costs (2019 GBP) and utility values were sourced from the published literature and DAPA-HF, respectively. We estimated lifetime costs and quality adjusted life years (QALYs) for early initiation of D+GDMT compared to a 12-month delay. Results: Standard therapy was associated with lifetime costs of £12,641 and 4.11 QALYs. Treatment with D+GDMT with 12 months delay was associated with total discounted lifetime costs and QALYs of £15,966 and 4.71 respectively. Early initiation was associated with lifetime cost and QALYS; £16,518 and 4.78 respectively. Consequently, early initiation was associated with an additional cost of £552 and QALY gains of 0.08 resulting in an incremental cost effectiveness ratio of £8,515. Conclusion: Early or late initiation of D+GDMT is cost-effective. However, earlier initiation is associated with rapid improvement in patient symptoms leading to 10% greater QALY gains at a very attractive ICER.
Abstract 11662: Extracellular Vesicle (EV)-Derived PiRNA, ImEX-Pi, is Protective in a Rat Model of Ischemia/Reperfusion Injury
Authors: Alessandra Ciullo, Liang Li, Chang Li, Eduardo Marban, Ahmed G Ibrahim
Journal: Circulation (2021)

Introduction: Cardiosphere-derived cells (CDCs ) are a population of heart-derived progenitors with demonstrated therapeutic efficacy in preclinical and clinical settings. CDCs exert their effect through the secretion of EVs, lipid-bilayer nanoparticles laden with bioactive molecules. Among the bioactive cargo identified in these immortalized CDC (imCDC)-derived EVs (imCDC-EV) are piwi RNAs (PiRNAs). PiRNAs bind Piwi proteins (members of the argonaute family) and regulate both the epigenome and transcriptome. The role of piRNAs (in particular EV-derived piRNAs) in modulating gene expression remains undescribed. Here we describe the role of a PiRNA highly enriched in imCDC-EVs (imEX-Pi). Methods: EVs were prepared by 24 hours hypoxic conditioning followed by normoxic recovery for three cycles. EVs were isolated from conditioned media using ultrafiltration. Fractions were analyzed for particle size, concentration and piRNA content. In vitro, bone marrow derived-macrophages (BMDM) were exposed to imCDC-EV, imEX-Pi and vehicle for transcriptomic analysis. In vivo, myocardial ischemia-reperfusion (I/R) injury was induced in 8-10-week-old Wistar-Kyoto female rats by LAD coronary ligation for 45 minutes followed by reperfusion. Twenty minutes later, imCDC-EV, imEX-Pi, scramble or vehicle were injected into the left ventricle with an aortic cross-clamp. Cardiac Troponin I levels, infarct size and circulating monocytes were assessed at 24 and 48 hrs post I/R. Results: RNA sequencing showed that piRNAs are enriched in both CDC-EV and imCDC-EV. ImEX-Pi was one of the most highly-expressed non-coding RNAs. In vitro , imEX-Pi altered the transcriptome of BMDMs compared to vehicle. This included upregulation of inflammatory and cell death pathways. In a rat model of I/R injury, imEX-Pi reduced infarct size and cardiac troponin levels compared to vehicle- and scrambled- treated animals. ImEX-Pi also significantly decreased circulating monocytes at 24 hours followed by a significant increase at 48hrs. Conclusions: We show that imEX-Pi is a key mediator of imCDC-EV therapeutic efficacy and that the principle target cells may be macrophages. This is further rationalized by the critical role that macrophages play in the injury and resolution response.
Abstract 14248: Obesity-Induced Abnormal Epigenetic Response in Macrophages Deteriorates Wound Healing
Authors: Kentaro Takahashi, Jinghua Liu, Norifumi Urao
Journal: Circulation (2021)

Background: Macrophages play key roles in the normal wound healing process, and their dysregulation is linked with impaired wound healing in disease conditions such as diabetes and obesity. Epigenetic mechanism such as histone modification involves in macrophage dysregulation. Epigenetic response to hypoxic environment has implications in macrophage functions in inflammation. Whether obesity influences histone modification under hypoxia is unknown. Methods and Results: Wild-type mice were fed normal diet (ND) or high-fat diet (HFD) for 4-5 months to induce obesity. Bone marrow-derived macrophages (BMDMs) were obtained from both groups. BMDMs were treated in hypoxic condition (1% O 2 ) for 1 hour, and the enrichment of histone 3 lysine 4 tri-methylation (H3K4me3) in BMDMs was assessed with western blotting and high-content imaging analysis. We found that hypoxia increases total H3K4me3 levels in BMDMs from ND, whereas this hypoxia-induced H3K4me3 upregulation was abolished in BMDMs from HFD. ChIP-seq was performed to investigate detailed H3K4me3 landscape and revealed hypoxia-induced H3K4me4 enrichment in promoter regions targeted by a H3K4 demethylase Kdm5a, including Hoxb9 and Sart3 in BMDMs from ND but not from HFD. This is aligned with the role of Kdm5a as a rapid hypoxia sensor and indicates impaired pro-healing activity of macrophages in HFD. Mechanistically, paralleled western blot of phospho-Akt showed a linear correlation with H3K4me3 levels, supporting the previous finding that p-Akt negatively regulates nuclear translocation of Kdm5a. Conclusion: Obesity impairs the wound healing response of macrophages by modifying epigenetics via p-Akt/Kdm5a axis.
Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
Authors: Hayley Holt, Mohammad Talaei, Matthew Greenig, Dominik Zenner, Jane Symons, Clare Relton, Katherine S Young, Molly R Davies, Katherine N Thompson, Jed Ashman, Sultan Saeed Rajpoot, Ahmed Ali Kayyale, Sarah El Rifai, Philippa J Lloyd, David Jolliffe, Olivia Timmis, Sarah Finer, Stamatina Iliodromiti, Alec Miners, Nicholas S Hopkinson, Bodrul Alam, Graham Lloyd-Jones, Thomas Dietrich, Iain Chapple, Paul E Pfeffer, David McCoy, Gwyneth Davies, Ronan A Lyons, Christopher Griffiths, Frank Kee, Aziz Sheikh, Gerome Breen, Seif O Shaheen, Adrian R Martineau
Journal: Thorax (2021)

Risk factors for severe COVID-19 include older age, male sex, obesity, black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain.We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 May 2020 to 5 February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted ORs (aORs) for associations between potential risk factors and odds of COVID-19.We recorded 446 incident cases of COVID-19 in 15 227 participants (2.9%). Increased odds of developing COVID-19 were independently associated with Asian/Asian British versus white ethnicity (aOR 2.28, 95% CI 1.33 to 3.91), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11 to 1.43), any versus no visits to/from other households in previous week (aOR 1.31, 1.06 to 1.62), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.02 to 1.09), frontline occupation excluding health/social care versus no frontline occupation (aOR 1.49, 1.12 to 1.98) and raised body mass index (BMI) (aOR 1.50 (1.19 to 1.89) for BMI 25.0-30.0 kg/m2 and 1.39 (1.06 to 1.84) for BMI >30.0 kg/m2 versus BMI <25.0 kg/m2). Atopic disease was independently associated with decreased odds (aOR 0.75, 0.59 to 0.97). No independent associations were seen for age, sex, other medical conditions, diet or micronutrient supplement use.After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased odds of developing COVID-19, while atopic disease was associated with decreased odds.ClinicalTrials.gov Registry (NCT04330599).
Improving support for children with autism and their families using a 100 day challenge framework
Authors: Lauren Wallace-Thompson, Jason Rose
Journal: BMJ (2021)

Community-based support for autistic children and their families can prevent individuals from reaching crisis point and reduce inpatient admissions.1 Lauren Wallace-Thompson and Jason Rose describe how they set up a joint initiative with Bromley Council and the parents and carers of children and young people with autism, and what changes this has introduced.
Perspectives on scaling production of adipose tissue for food applications
Authors: John S.K. Yuen Jr, Andrew J. Stout, N. Stephanie Kawecki, Sophia M. Letcher, Sophia K. Theodossiou, Julian M. Cohen, Brigid M. Barrick, Michael K. Saad, Natalie R. Rubio, Jaymie A. Pietropinto, Hailey DiCindio, Sabrina W. Zhang, Amy C. Rowat, David L. Kaplan
Journal: Biomaterials (2021)
Abstract 9897: Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults
Authors: Daniel H Katz
Journal: Circulation (2021)

Introduction: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Hypothesis: Whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry will increase power to identify novel genetic determinants. Methods: Proteomic profiling of 1,301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan®). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥ 5. Results were validated using an alternative, antibody-based, proteomic platform (Olink®) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study. Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8 х 10 -11 . These associations include 134 novel locus-protein relationships and an additional 205 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β = 0.61±0.05, p-value = 3.27 х 10 -30 ) and MMP-3 (β = -0.60±0.05, p = 1.67 х 10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with nine proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1 associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β = 0.34±0.04, p = 1.34 х 10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community dwelling individuals without heart failure. Discussion: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation and myocardial function.