Publications by authors named "Marcus Badgeley"

Article Synopsis
  • Pharmacogenomic testing is increasingly important for psychiatric care, but more research is needed to understand its practical benefits in real-world settings.
  • A study involving 15,000 patients revealed that 65% had potentially actionable genetic traits related to drug metabolism, particularly for the genes CYP2C19 and CYP2D6, with 87% showing some potential for actionable insights.
  • The use of advanced genetic sequencing helped identify significant genetic variations that could affect treatment decisions, suggesting that early pharmacogenomic testing might improve medication prescribing and patient outcomes in psychiatric care.
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Purpose: Anesthesiologists simultaneously manage several aspects of patient care during general anesthesia. Automating administration of hypnotic agents could enable more precise control of a patient's level of unconsciousness and enable anesthesiologists to focus on the most critical aspects of patient care. Reinforcement learning (RL) algorithms can be used to fit a mapping from patient state to a medication regimen.

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Objectives: This study sought to develop DL models capable of comprehensively quantifying left and right ventricular dysfunction from ECG data in a large, diverse population.

Background: Rapid evaluation of left and right ventricular function using deep learning (DL) on electrocardiograms (ECGs) can assist diagnostic workflow. However, DL tools to estimate right ventricular (RV) function do not exist, whereas those to estimate left ventricular (LV) function are restricted to quantification of very low LV function only.

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Deep learning models in healthcare may fail to generalize on data from unseen corpora. Additionally, no quantitative metric exists to tell how existing models will perform on new data. Previous studies demonstrated that NLP models of medical notes generalize variably between institutions, but ignored other levels of healthcare organization.

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Background: In recent years, the fibroblast growth factor receptor (FGFR) pathway has been proven to be an important therapeutic target in bladder cancer. FGFR-targeted therapies are effective for patients with FGFR mutation, which can be discovered through genetic sequencing. However, genetic sequencing is not commonly performed at diagnosis, whereas a histologic assessment of the tumor is.

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In current anesthesiology practice, anesthesiologists infer the state of unconsciousness without directly monitoring the brain. Drug- and patient-specific electroencephalographic (EEG) signatures of anesthesia-induced unconsciousness have been identified previously. We applied machine learning approaches to construct classification models for real-time tracking of unconscious state during anesthesia-induced unconsciousness.

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Here, we report a nanoparticle-based probe that affords facile cell labeling with cholesterol in cholesterol efflux (CE) assays. This probe, called ezFlux, was optimized through a screening of multiple nanoformulations engineered with a Förster resonance energy transfer (FRET) reporter. The physicochemical- and bio-similarity of ezFlux to standard semi-synthetic acetylated low-density lipoprotein (acLDL) was confirmed by testing uptake in macrophages, the intracellular route of degradation, and performance in CE assays.

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Significant effort toward the automation of general anesthesia has been made in the past decade. One open challenge is in the development of control-ready patient models for closed-loop anesthesia delivery. Standard depth-of-anesthesia tracking does not readily capture inter-individual differences in response to anesthetics, especially those due to age, and does not aim to predict a relationship between a control input (infused anesthetic dose) and system state (commonly, a function of electroencephalography (EEG) signal).

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Background: Genetic loss-of-function variants (LoFs) associated with disease traits are increasingly recognized as critical evidence for the selection of therapeutic targets. We integrated the analysis of genetic and clinical data from 10,511 individuals in the Mount Sinai BioMe Biobank to identify genes with loss-of-function variants (LoFs) significantly associated with cardiovascular disease (CVD) traits, and used RNA-sequence data of seven metabolic and vascular tissues isolated from 600 CVD patients in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study for validation. We also carried out in vitro functional studies of several candidate genes, and in vivo studies of one gene.

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Article Synopsis
  • Hip fractures are very serious for older people and can lead to death or long-term problems.
  • A study used advanced computer programs to help detect these fractures by looking at X-ray images and other patient and hospital information.
  • The best results came when combining X-ray images with patient information, showing that understanding what the computer sees can be tricky and more research is needed for better explanations.
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Article Synopsis
  • Electronic health records (EHRs) are widely used in healthcare, but issues with interoperability and technical requirements hinder their application in research, prompting the need for more accessible tools for researchers.
  • PatientExploreR is a user-friendly application built on the R/Shiny framework that allows researchers to interact with EHR data, creating dynamic reports and visualizations without needing programming skills.
  • The software is open-source and can be downloaded from GitHub, providing researchers with easy access to EHR data and a synthesized data sandbox for those without direct EHR access.
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Background: There is interest in using convolutional neural networks (CNNs) to analyze medical imaging to provide computer-aided diagnosis (CAD). Recent work has suggested that image classification CNNs may not generalize to new data as well as previously believed. We assessed how well CNNs generalized across three hospital systems for a simulated pneumonia screening task.

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Motivation: Radiologists have used algorithms for Computer-Aided Diagnosis (CAD) for decades. These algorithms use machine learning with engineered features, and there have been mixed findings on whether they improve radiologists' interpretations. Deep learning offers superior performance but requires more training data and has not been evaluated in joint algorithm-radiologist decision systems.

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Rapid diagnosis and treatment of acute neurological illnesses such as stroke, hemorrhage, and hydrocephalus are critical to achieving positive outcomes and preserving neurologic function-'time is brain'. Although these disorders are often recognizable by their symptoms, the critical means of their diagnosis is rapid imaging. Computer-aided surveillance of acute neurologic events in cranial imaging has the potential to triage radiology workflow, thus decreasing time to treatment and improving outcomes.

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Purpose To compare different methods for generating features from radiology reports and to develop a method to automatically identify findings in these reports. Materials and Methods In this study, 96 303 head computed tomography (CT) reports were obtained. The linguistic complexity of these reports was compared with that of alternative corpora.

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Article Synopsis
  • Stroke is a major cause of long-term disability, and timely intervention can greatly impact patient outcomes, though not all patients benefit from rapid treatment.
  • Neuroimaging helps identify potentially salvageable brain areas, with new techniques like deep learning improving the assessment of stroke severity and prognosis.
  • Machine learning, particularly through deep neural networks and convolutional neural networks, is revolutionizing stroke management by enhancing image analysis and enabling personalized treatment strategies.
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The feasibility of using mobile health applications to conduct observational clinical studies requires rigorous validation. Here, we report initial findings from the Asthma Mobile Health Study, a research study, including recruitment, consent, and enrollment, conducted entirely remotely by smartphone. We achieved secure bidirectional data flow between investigators and 7,593 participants from across the United States, including many with severe asthma.

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Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) and chronic diseases (arterial hypertension) necessitate effective therapies to improve health outcomes. However, the rapid increase in drug development cost demands innovative and sustainable drug discovery approaches. Drug repositioning, the discovery of new or improved therapies by reevaluation of approved or investigational compounds, solves a significant gap in the public health setting and improves the productivity of drug development.

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Motivation: Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries.

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Objective: To design, develop and prototype clinical dashboards to integrate high-frequency health and wellness data streams using interactive and real-time data visualisation and analytics modalities.

Materials And Methods: We developed a clinical dashboard development framework called electronic healthcare data visualization (EHDViz) toolkit for generating web-based, real-time clinical dashboards for visualising heterogeneous biomedical, healthcare and wellness data. The EHDViz is an extensible toolkit that uses R packages for data management, normalisation and producing high-quality visualisations over the web using R/Shiny web server architecture.

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Monitoring and modeling biomedical, health care and wellness data from individuals and converging data on a population scale have tremendous potential to improve understanding of the transition to the healthy state of human physiology to disease setting. Wellness monitoring devices and companion software applications capable of generating alerts and sharing data with health care providers or social networks are now available. The accessibility and clinical utility of such data for disease or wellness research are currently limited.

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Article Synopsis
  • Macrophages are versatile immune cells involved in various physiological processes, such as defending against pathogens and repairing tissue.
  • The study presents a novel method of targeting M1 inflammatory macrophages using hybrid lipid-latex nanoparticles (LiLa), which can be customized for drug delivery and imaging.
  • The optimized LiLa nanoparticles show promising results in selectively delivering anti-inflammatory treatments and enhancing MRI imaging, suggesting potential clinical applications for diagnosing and treating conditions like atherosclerosis and obesity.
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Motivation: Modern molecular technologies allow the collection of large amounts of high-throughput data on the functional attributes of genes. Often multiple technologies and study designs are used to address the same biological question such as which genes are overexpressed in a specific disease state. Consequently, there is considerable interest in methods that can integrate across datasets to present a unified set of predictions.

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Context: High-density lipoprotein (HDL) particles perform numerous vascular-protective functions. Animal studies demonstrate that exposure to fine or ultrafine particulate matter (PM) can promote HDL dysfunction. However, the impact of PM on humans remains unknown.

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