Epigenetic Profiling of Mutant JMML Hematopoietic Stem and Progenitor Cells Reveals an Aberrant Histone Landscape.

Juvenile myelomonocytic leukemia (JMML) is a deadly pediatric leukemia driven by pathway mutations, of which >35% are gain-of-function in . Although DNA hypermethylation portends severe clinical phenotypes, the landscape of histone modifications and chromatin profiles in JMML patient cells have not been explored. Using global mass cytometry, Epigenetic Time of Flight (EpiTOF), we analyzed hematopoietic stem and progenitor cells (HSPCs) from five JMML patients with mutations.

Ancestry-based differences in the immune phenotype are associated with lupus activity.

Systemic lupus erythematosus (SLE) affects 1 in 537 Black women, which is >2-fold more than White women. Black patients develop the disease at a younger age, have more severe symptoms, and have a greater chance of early mortality. We used a multiomics approach to uncover ancestry-associated immune alterations in patients with SLE and healthy controls that may contribute biologically to disease disparities.

Mass-Cytometry-Based Quantification of Global Histone Post-Translational Modifications at Single-Cell Resolution Across Peripheral Immune Cells in IBD.

Background And Aims: Current understanding of histone post-translational modifications [histone modifications] across immune cell types in patients with inflammatory bowel disease [IBD] during remission and flare is limited. The present study aimed to quantify histone modifications at a single-cell resolution in IBD patients during remission and flare and how they differ compared to healthy controls.

Methods: We performed a case-control study of 94 subjects [83 IBD patients and 11 healthy controls].

Repurposing Halicin as a potent covalent inhibitor for the SARS-CoV-2 main protease.

The rapid spread of COVID-19 has caused a worldwide public health crisis. For prompt and effective development of antivirals for SARS-CoV-2, the pathogen of COVID-19, drug repurposing has been broadly conducted by targeting the main protease (M), a key enzyme responsible for the replication of virus inside the host. In this study, we evaluate the inhibition potency of a nitrothiazole-containing drug, halicin, and reveal its reaction and interaction mechanism with M.

New-onset IgG autoantibodies in hospitalized patients with COVID-19.

COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls.

The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination.

Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza induced persistently diminished H3K27ac in monocytes and myeloid dendritic cells (mDCs), which was associated with impaired cytokine responses to Toll-like receptor stimulation.

Repression of CTSG, ELANE and PRTN3-mediated histone H3 proteolytic cleavage promotes monocyte-to-macrophage differentiation.

Chromatin undergoes extensive reprogramming during immune cell differentiation. Here we report the repression of controlled histone H3 amino terminus proteolytic cleavage (H3ΔN) during monocyte-to-macrophage development. This abundant histone mark in human peripheral blood monocytes is catalyzed by neutrophil serine proteases (NSPs) cathepsin G, neutrophil elastase and proteinase 3.

New-Onset IgG Autoantibodies in Hospitalized Patients with COVID-19.

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. We developed three different protein arrays to measure hallmark IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 patients in three different centers. Autoantibodies were identified in approximately 50% of patients, but in <15% of healthy controls.

Using Long Short-Term Memory (LSTM) Neural Networks to Predict Emergency Department Wait Time.

Emergency Department (ED) overcrowding is a major global healthcare issue. Many research studies have been conducted to predict ED wait time using various machine learning prediction models to enhance patient experience and improve care efficiency and resource allocation. In this paper, we used Long Short-Term Memory (LSTM) recurrent neural networks to build a model to predict ED wait time in the next 2 hours using a randomly generated patient timestamp dataset of a typical patient hospital journey.

Using Long Short-Term Memory (LSTM) Neural Networks to Predict Emergency Department Wait Time.

Emergency Department (ED) overcrowding is a major global healthcare issue. In this paper, we used Long Short-Term Memory (LSTM) recurrent neural networks to build a model to predict ED wait time in the next 2 hours using a randomly generated patient timestamp dataset of a typical patient hospital journey. Compared with Linear Regression model, the average mean absolute error for the LSTM model is decreased by 15% (3 minutes) (p<0.

Monitoring Physical Activity Levels Using Twitter Data: Infodemiology Study.

Background: Social media technology such as Twitter allows users to share their thoughts, feelings, and opinions online. The growing body of social media data is becoming a central part of infodemiology research as these data can be combined with other public health datasets (eg, physical activity levels) to provide real-time monitoring of psychological and behavior outcomes that inform health behaviors. Currently, it is unclear whether Twitter data can be used to monitor physical activity levels.

Single-cell technologies - studying rheumatic diseases one cell at a time.

Cells, the basic units of life, have striking differences at transcriptomic, proteomic and epigenomic levels across tissues, organs, organ systems and organisms. The coordination of individual immune cells is essential for the generation of effective immune responses to pathogens while immune tolerance is maintained to protect the host. In rheumatic diseases, when immune responses are dysregulated, pathologically important cells might represent only a small fraction of the immune system.

Design and Usability Evaluation of Mobile Cloud Healthcare System for Diabetes Prevention.

In this study, a mobile cloud healthcare system was implemented to assist middle- and old-aged people with diabetes preventive healthcare. First of all, a prototype system was developed. It was a system relying on data mining computing technology and big data analytics.

System Dynamics in Remote Monitoring Service for Cardiovascular Implantable Electronic Devices.

This methodological paper describes how system dynamics was applied in evaluating the effect of remote monitoring (RM) of cardiovascular implantable electronic device (CIED) workload on clinical resource utilization. The development of a causal loop diagram and a stock and flow diagram and the construction of the simulation model for comparison of an in-person clinic group and RM clinic group are described.

A Hadoop/MapReduce Based Platform for Supporting Health Big Data Analytics.

In this paper, we report our practical experience in designing and implementing a platform with Hadoop/MapReduce framework for supporting health Big Data Analytics. Three billion of emulated health raw data was constructed and cross-referenced with data profiles and metadata based on existing health data at the Island Health Authority, BC, Canada. The patient data was stored over a Hadoop Distributed File System to simulate a presentation of an entire health authority's information system.

Single-cell epigenetics - Chromatin modification atlas unveiled by mass cytometry.

Modifications of histone proteins are fundamental to the regulation of epigenetic phenotypes. Dysregulations of histone modifications have been linked to the pathogenesis of diverse human diseases. However, identifying differential histone modifications in patients with immune-mediated diseases has been challenging, in part due to the lack of a powerful analytic platform to study histone modifications in the complex human immune system.

Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging.

Post-translational modifications of histone proteins and exchanges of histone variants of chromatin are central to the regulation of nearly all DNA-templated biological processes. However, the degree and variability of chromatin modifications in specific human immune cells remain largely unknown. Here, we employ a highly multiplexed mass cytometry analysis to profile the global levels of a broad array of chromatin modifications in primary human immune cells at the single-cell level.

Implementation of clinical practice changes by experienced anesthesiologists after simulation-based ultrasound-guided regional anesthesia training.

Background: Anesthesiologists who have finished formal training and want to learn ultrasound-guided regional anesthesia (UGRA) commonly attend 1 day workshops. However, it is unclear whether participation actually changes clinical practice. We assessed change implementation after completion of a 1 day simulation-based UGRA workshop.

Registry Data-Valuable Lessons But Beware the Confounders.

A mature national joint registry with widespread adoption and audit can successfully demonstrate trends and influence future orthopedic practice. Correlations can be identified; however, this should not be misinterpreted as causality. It is essential to consider confounding when analyzing observational datasets.

Design and Development of a Web-Based Self-Monitoring System to Support Wellness Coaching.

We analyzed, designed and deployed a web-based, self-monitoring system to support wellness coaching. A wellness coach can plan for clients' exercise and diet through the system and is able to monitor the changes in body dimensions and body composition that the client reports. The system can also visualize the client's data in form of graphs for both the client and the coach.

Integration of Health Information Systems Using HL7: A Case Study.

Interoperability is a prerequisite for health information systems (HIS) that will reduce waste of unnecessary costs, errors, delays, and futile repetition. Many previous studies had proposed different approaches in the attempt to solve interoperability challenges. In this paper, we report our experiences in using Health Level 7 (HL7) standard and adopting the Common Gateway Model for exchanging heath data.

Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity.

Systemic sclerosis (SSc) is a rare autoimmune disease with the highest case-fatality rate of all connective tissue diseases. Current efforts to determine patient response to a given treatment using the modified Rodnan skin score (mRSS) are complicated by interclinician variability, confounding, and the time required between sequential mRSS measurements to observe meaningful change. There is an unmet critical need for an objective metric of SSc disease severity.

How are electronic medical records used by nurse practitioners?

In this paper we describe how nurse practitioners (NPs) use electronic medical records (EMR) features and functions at: (1) an individual and (2) a clinic level to support patient wellness and chronic disease management activities. Fifteen NPs from British Columbia (BC), Canada participated in a qualitative, semi-structured interview study. NPs used EMRs with individual patients and at a clinic level to support wellness and chronic disease management activities.

A molecular threading mechanism underlies Jumonji lysine demethylase KDM2A regulation of methylated H3K36.

The dynamic reversible methylation of lysine residues on histone proteins is central to chromatin biology. Key components are demethylase enzymes, which remove methyl moieties from lysine residues. KDM2A, a member of the Jumonji C domain-containing histone lysine demethylase family, specifically targets lower methylation states of H3K36.