Physical Sciences and Mathematics Commons^™

Ultrasoft Platelet-Like Particles Stop Bleeding In Rodent And Porcine Models Of Trauma, Kimberly Nellenbach, Emily Mihalko, Seema Nandi, Drew W. Koch, Jagathpala Shetty, Leandra Moretti, Jennifer Sollinger, Nina Moiseiwitsch, Ana Sheridan, Sanika Pandit, Maureane Hoffman, Lauren V. Schnabel, L. Andrew Lyon, Thomas H. Barker, Ashley C. Brown

Engineering Faculty Articles and Research

Uncontrolled bleeding after trauma represents a substantial clinical problem. The current standard of care to treat bleeding after trauma is transfusion of blood products including platelets; however, donated platelets have a short shelf life, are in limited supply, and carry immunogenicity and contamination risks. Consequently, there is a critical need to develop hemostatic platelet alternatives. To this end, we developed synthetic platelet-like particles (PLPs), formulated by functionalizing highly deformable microgel particles composed of ultralow cross-linked poly (N-isopropylacrylamide) with fibrin-binding ligands. The fibrin-binding ligand was designed to target to wound sites, and the cross-linking of fibrin polymers was designed …

De Novo Drug Design Using Transformer-Based Machine Translation And Reinforcement Learning Of An Adaptive Monte Carlo Tree Search, Dony Ang, Cyril Rakovski, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researchers to explore innovative methods that harness the power of deep learning and reinforcement learning techniques. Here, we introduce a novel drug design approach called drugAI that leverages the Encoder–Decoder Transformer architecture in tandem with Reinforcement Learning via a Monte Carlo Tree Search (RL-MCTS) to expedite the process of drug discovery while ensuring the production of valid small molecules with drug-like characteristics and strong binding affinities towards …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Assessing The Reidentification Risks Posed By Deep Learning Algorithms Applied To Ecg Data, Arin Ghazarian, Jianwei Zheng, Daniele Struppa, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

ECG (Electrocardiogram) data analysis is one of the most widely used and important tools in cardiology diagnostics. In recent years the development of advanced deep learning techniques and GPU hardware have made it possible to train neural network models that attain exceptionally high levels of accuracy in complex tasks such as heart disease diagnoses and treatments. We investigate the use of ECGs as biometrics in human identification systems by implementing state-of-the-art deep learning models. We train convolutional neural network models on approximately 81k patients from the US, Germany and China. Currently, this is the largest research project on ECG identification. …

A High Precision Machine Learning-Enabled System For Predicting Idiopathic Ventricular Arrhythmia Origins, Jianwei Zheng, Guohua Fu, Daniele Struppa, Islam Abudayyeh, Tahmeed Contractor, Kyle Anderson, Huimin Chu, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background: Radiofrequency catheter ablation (CA) is an efficient antiarrhythmic treatment with a class I indication for idiopathic ventricular arrhythmia (IVA), only when drugs are ineffective or have unacceptable side effects. The accurate prediction of the origins of IVA can significantly increase the operation success rate, reduce operation duration and decrease the risk of complications. The present work proposes an artificial intelligence-enabled ECG analysis algorithm to estimate possible origins of idiopathic ventricular arrhythmia at a clinical-grade level accuracy.

Method: A total of 18,612 ECG recordings extracted from 545 patients who underwent successful CA to treat IVA were proportionally sampled into training, …

Applications Of Unsupervised Machine Learning In Autism Spectrum Disorder Research: A Review, Chelsea Parlett-Pelleriti, Elizabeth Stevens, Dennis R. Dixon, Erik J. Linstead

Engineering Faculty Articles and Research

Large amounts of autism spectrum disorder (ASD) data is created through hospitals, therapy centers, and mobile applications; however, much of this rich data does not have pre-existing classes or labels. Large amounts of data—both genetic and behavioral—that are collected as part of scientific studies or a part of treatment can provide a deeper, more nuanced insight into both diagnosis and treatment of ASD. This paper reviews 43 papers using unsupervised machine learning in ASD, including k-means clustering, hierarchical clustering, model-based clustering, and self-organizing maps. The aim of this review is to provide a survey of the current uses of …

Cyclic Peptide-Gadolinium Nanocomplexes As Sirna Delivery Tools, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Dindyal Mandal, David Stickley, Stephanie Nagasawa, Joshua Long, Sandeep Lohan, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

We have recently reported that a cyclic peptide containing five tryptophan, five arginine, and one cysteine amino acids [(WR)₅C], was able to produce peptide-capped gadolinium nanoparticles, [(WR)₅C]-GdNPs, in the range of 240 to 260 nm upon mixing with an aqueous solution of GdCl₃. Herein, we report [(WR)₅C]-GdNPs as an efficient siRNA delivery system. The peptide-based gadolinium nanoparticles (50 µM) did not exhibit significant cytotoxicity (~93% cell viability at 50 µM) in human leukemia T lymphoblast cells (CCRF-CEM) and triple-negative breast cancer cells (MDA-MB-231) after 48 h. Fluorescence-activated cell sorting (FACS) analysis indicated …

Optimal Analytical Methods For High Accuracy Cardiac Disease Classification And Treatment Based On Ecg Data, Jianwei Zheng

Computational and Data Sciences (PhD) Dissertations

This work constitutes six projects. In the first project, a newly inaugurated research database for 12-lead electrocardiogram signals was created under the auspices of Chapman University and Shaoxing People's Hospital (Shaoxing Hospital Zhejiang University School of Medicine). This database aims to enable the scientific community in conducting new studies on arrhythmia and other cardiovascular conditions. In the second project, we created a new 12-lead ECG database under the auspices of Chapman University and Ningbo First Hospital of Zhejiang University that aims to provide high quality data enabling detection of the distinctions between idiopathic ventricular arrhythmia from right ventricular outflow tract …

A High-Precision Machine Learning Algorithm To Classify Left And Right Outflow Tract Ventricular Tachycardia, Jianwei Zhang, Guohua Fu, Islam Abudayyeh, Magdi Yacoub, Anthony Chang, William Feaster, Louis Ehwerhemuepha, Hesham El-Askary, Xianfeng Du, Bin He, Mingjun Feng, Yibo Yu, Binhao Wang, Jing Liu, Hai Yao, Hulmin Chu, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Introduction: Multiple algorithms based on 12-lead ECG measurements have been proposed to identify the right ventricular outflow tract (RVOT) and left ventricular outflow tract (LVOT) locations from which ventricular tachycardia (VT) and frequent premature ventricular complex (PVC) originate. However, a clinical-grade machine learning algorithm that automatically analyzes characteristics of 12-lead ECGs and predicts RVOT or LVOT origins of VT and PVC is not currently available. The effective ablation sites of RVOT and LVOT, confirmed by a successful ablation procedure, provide evidence to create RVOT and LVOT labels for the machine learning model.

Methods: We randomly sampled training, validation, and testing …

Optimal Multi-Stage Arrhythmia Classification Approach, Jianwei Zhang, Huimin Chu, Daniele Struppa, Jianming Zhang, Sir Magdi Yacoub, Hesham El-Askary, Anthony Chang, Louis Ehwerhemuepha, Islam Abudayyeh, Alexander Barrett, Guohua Fu, Hai Yao, Dongbo Li, Hangyuan Guo, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Arrhythmia constitutes a problem with the rate or rhythm of the heartbeat, and an early diagnosis is essential for the timely inception of successful treatment. We have jointly optimized the entire multi-stage arrhythmia classification scheme based on 12-lead surface ECGs that attains the accuracy performance level of professional cardiologists. The new approach is comprised of a three-step noise reduction stage, a novel feature extraction method and an optimal classification model with finely tuned hyperparameters. We carried out an exhaustive study comparing thousands of competing classification algorithms that were trained on our proprietary, large and expertly labeled dataset consisting of 12-lead …

Image Restoration Using Automatic Damaged Regions Detection And Machine Learning-Based Inpainting Technique, Chloe Martin-King

Computational and Data Sciences (PhD) Dissertations

In this dissertation we propose two novel image restoration schemes. The first pertains to automatic detection of damaged regions in old photographs and digital images of cracked paintings. In cases when inpainting mask generation cannot be completely automatic, our detection algorithm facilitates precise mask creation, particularly useful for images containing damage that is tedious to annotate or difficult to geometrically define. The main contribution of this dissertation is the development and utilization of a new inpainting technique, region hiding, to repair a single image by training a convolutional neural network on various transformations of that image. Region hiding is also …

Identifying Depression In The National Health And Nutrition Examination Survey Data Using A Deep Learning Algorithm, Jihoon Oh, Kyongsik Yun, Uri Maoz, Tae-Suk Kim, Jeong-Ho Chae

Psychology Faculty Articles and Research

Background

As depression is the leading cause of disability worldwide, large-scale surveys have been conducted to establish the occurrence and risk factors of depression. However, accurately estimating epidemiological factors leading up to depression has remained challenging. Deep-learning algorithms can be applied to assess the factors leading up to prevalence and clinical manifestations of depression.

Methods

Customized deep-neural-network and machine-learning classifiers were assessed using survey data from 19,725 participants from the NHANES database (from 1999 through 2014) and 4949 from the South Korea NHANES (K-NHANES) database in 2014.

Results

A deep-learning algorithm showed area under the receiver operating characteristic curve (AUCs) …

Applications Of Supervised Machine Learning In Autism Spectrum Disorder Research: A Review, Kayleigh K. Hyde, Marlena N. Novack, Nicholas Lahaye, Chelsea Parlett-Pelleriti, Raymond Anden, Dennis R. Dixon, Erik Linstead

Engineering Faculty Articles and Research

Autism spectrum disorder (ASD) research has yet to leverage "big data" on the same scale as other fields; however, advancements in easy, affordable data collection and analysis may soon make this a reality. Indeed, there has been a notable increase in research literature evaluating the effectiveness of machine learning for diagnosing ASD, exploring its genetic underpinnings, and designing effective interventions. This paper provides a comprehensive review of 45 papers utilizing supervised machine learning in ASD, including algorithms for classification and text analysis. The goal of the paper is to identify and describe supervised machine learning trends in ASD literature as …

The Chapman Bone Algorithm: A Diagnostic Alternative For The Evaluation Of Osteoporosis, Elise Levesque, Anton Ketterer, Wajiha Memon, Cameron James, Noah Barrett, Cyril Rakovski, Frank Frisch

Mathematics, Physics, and Computer Science Faculty Articles and Research

Osteoporosis is the most common metabolic bone disease and goes largely undiagnosed throughout the world, due to the inaccessibility of DXA machines. Multivariate analyses of serum bone turnover markers were evaluated in 226 Orange County, California, residents with the intent to determine if serum osteocalcin and serum pyridinoline cross-links could be used to detect the onset of osteoporosis as effectively as a DXA scan. Descriptive analyses of the demographic and lab characteristics of the participants were performed through frequency, means and standard deviation estimations. We implemented logistic regression modeling to find the best classification algorithm for osteoporosis. All calculations and …

Reduced Acute Inflammatory Responses To Microgel Conformal Coatings, Amanda W. Bridges, Neetu Singh, Kellie L. Burns, Julia E. Babensee, L. Andrew Lyon, Andrés J. García

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Implantation of synthetic materials into the body elicits inflammatory host responses that limit medical device integration and biological performance. This inflammatory cascade involves protein adsorption, leukocyte recruitment and activation, cytokine release, and fibrous encapsulation of the implant. We present a coating strategy based on thin films of poly(N-isopropylacrylamide) hydrogel microparticles (i.e. microgels) cross-linked with poly(ethylene glycol) diacrylate. These particles were grafted onto a clinically relevant polymeric material to generate conformal coatings that significantly reduced in vitro fibrinogen adsorption and primary human monocyte/macrophage adhesion and spreading. These microgel coatings also reduced leukocyte adhesion and expression of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, …