Digital Commons Network^™

Fc Gamma Receptors Promote Antibody-Induced Lilrb4 Internalization And Immune Regulation Of Monocytic Aml, Joshua W Morse, Xun Gui, Mi Deng, Ryan Huang, Xiaohua Ye, Xuejun Fan, Chengcheng Zhang, Ningyan Zhang, Zhiqiang An

Faculty, Staff and Student Publications

The immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4) is found specifically on the cell surface of acute monocytic leukemia (monocytic AML), an aggressive and common subtype of AML. We have developed a humanized monoclonal IgG1 LILRB4-blocking antibody (h128-3), which improved immune regulation but reduced cell surface expression of LILRB4 in monocytic AML models by 40–60%. Interestingly, most of this effect was neutralized by mutation of the Fc region of the antibody (h128-3/N297A), which prevents interaction with Fc gamma receptors (FcγRs). This suggested that there is FcγR-dependent antigenic modulation underlying h128-3’s effects, a mechanism known to alter the function of antibodies …

A Novel Assessment Of Whole-Mount Gleason Grading In Prostate Cancer To Identify Candidates For Radical Prostatectomy: A Machine Learning-Based Multiomics Study, Jing Ning, Clemens P Spielvogel, David Haberl, Karolina Trachtova, Stefan Stoiber, Vojtech Bystry, Pascal Baltzer, Elisabeth Gurnhofer, Gerald Timelthaler, Michaela Schlederer, Laszlo Papp, Helga Schachner, Thomas Helbich, Markus Hartenbach, Bernhard Grubmüller, Shahrokh F Shariat, Marcus Hacker, Alexander Haug, Lukas Kenner

Faculty, Staff and Student Publications

Purpose: This study aims to assess whole-mount Gleason grading (GG) in prostate cancer (PCa) accurately using a multiomics machine learning (ML) model and to compare its performance with biopsy-proven GG (bxGG) assessment.

Materials and Methods: A total of 146 patients with PCa recruited in a pilot study of a prospective clinical trial (NCT02659527) were retrospectively included in the side study, all of whom underwent ⁶⁸Ga-PSMA-11 integrated positron emission tomography (PET) / magnetic resonance (MR) before radical prostatectomy (RP) between May 2014 and April 2020. To establish a multiomics ML model, we quantified PET radiomics features, pathway-level genomics …

Non-Homologous End-Joining Genotype, Mrna Expression, And Dna Repair Capacity In Childhood Acute Lymphocytic Leukemia, Chao-Chun Chen, Wen-Shin Chang, Jen-Sheng Pei, Chien-Chung Kuo, Chung-Hsing Wang, Pei-Chen Hsu, Jian Gu, Da-Tian Bau, Chia-Wen Tsai

Faculty, Staff and Student Publications

Background/aim: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL.

Materials and methods: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation …

Fa4sans-Gan: A Novel Machine Learning Generative Adversarial Network To Further Understand Ophthalmic Changes In Spaceflight Associated Neuro-Ocular Syndrome (Sans), Sharif Amit Kamran, Khondker Fariha Hossain, Joshua Ong, Ethan Waisberg, Nasif Zaman, Andrew G Lee

Faculty, Staff and Student Publications

PURPOSE: To provide an automated system for synthesizing fluorescein angiography (FA) images from color fundus photographs for averting risks associated with fluorescein dye and extend its future application to spaceflight associated neuro-ocular syndrome (SANS) detection in spaceflight where resources are limited.

DESIGN: Development and validation of a novel conditional generative adversarial network (GAN) trained on limited amount of FA and color fundus images with diabetic retinopathy and control cases.

PARTICIPANTS: Color fundus and FA paired images for unique patients were collected from a publicly available study.

METHODS: FA4SANS-GAN was trained to generate FA images from color fundus photographs using 2 …

Incorporating Variable Rbe In Impt Optimization For Ependymoma, Hadis Moazami Goudarzi, Gino Lim, David Grosshans, Radhe Mohan, Wenhua Cao

Faculty, Staff and Student Publications

PURPOSE: To study the dosimetric impact of incorporating variable relative biological effectiveness (RBE) of protons in optimizing intensity-modulated proton therapy (IMPT) treatment plans and to compare it with conventional constant RBE optimization and linear energy transfer (LET)-based optimization.

METHODS: This study included 10 pediatric ependymoma patients with challenging anatomical features for treatment planning. Four plans were generated for each patient according to different optimization strategies: (1) constant RBE optimization (ConstRBEopt) considering standard-of-care dose requirements; (2) LET optimization (LETopt) using a composite cost function simultaneously optimizing dose-averaged LET (LET

RESULTS: We found that the LETopt plans consistently achieved increased LET in …

Hypoxia-Adenosine Axis As Therapeutic Targets For Acute Respiratory Distress Syndrome, Holger Klaus Eltzschig

Faculty, Staff and Student Publications

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially …

Optimizing Medication Querying Using Ontology-Driven Approach With Omop: With An Application To A Large-Scale Covid-19 Ehr Dataset, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Efficient querying for medication information in Electronic Health Record (EHR) datasets is crucial for effective patient care and clinical research. To address the complexity and data volume challenges involved in efficient medication information retrieval, we propose an ontology-driven medication query (ODMQ) optimization approach, leveraging the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). Integrating semantic ontology structures from the OMOP CDM can help enhance query accuracy and efficiency by broadening the scope of relevant medication terms like drug names, National Drug Codes, and generics, resulting in more comprehensive query outcomes than traditional methods. ODMQ significantly reduces manual search time …

Shift In Algal Blooms From Micro‐ To Macroalgae Around China With Increasing Eutrophication And Climate Change, Yuan Feng, Yonglong Xiong, Jm Hall‐Spencer, Kailin Liu, John Beardall, K Gao, Jingke Ge, Juntian Xu, G Gao

School of Biological and Marine Sciences

Blooms of microalgal red tides and macroalgae (e.g., green and golden tides caused by Ulva and Sargassum) have caused widespread problems around China in recent years, but there is uncertainty around what triggers these blooms and how they interact. Here, we use 30 years of monitoring data to help answer these questions, focusing on the four main species of microalgae Prorocentrum donghaiense, Karenia mikimotoi, Noctiluca scintillans, and Skeletonema costatum) associated with red tides in the region. The frequency of red tides increased from 1991 to 2003 and then decreased until 2020, with S. costatum red tides exhibiting the highest rate …

Selective Fast Fiber Damage After Leg Press Exercise Leading To Failure: A Pole Vaulter Case Report, Gerard Carmona, Gerard Moras, Raúl Bescós, Adrián García-Fresneda, Joan A. Cadefau

School of Health Professions

The aim of this study was to investigate, in a trained pole vaulter (PV) and in an endurance-trained physical education student (PE), the effect of a leg press exercise leading to failure (LPF) on changes in serum activity of muscle enzymes and serum concentration of fast (FM) and slow (SM) myosin isoforms, while simultaneously examining mechanical output components as indicators of performance and fatigue developed throughout exercise. A case report study design based on an observational comparison of response between two dichotomous participants, PV and PE, was used. Differences between the participants’ exercise outputs were examined by unpaired t-test or …

Enhancing Pitch Stability In Floating Wind Platforms: The Hydrodynamic Effects Of Thin Plates, Ignacio Pregnan Johannesen

School of Engineering, Computing and Mathematics Theses

The Floating Offshore Wind Turbines (FOWT) technology is still at an early stage looking for ways to make it competitive. In the case of semi-submersible FOWT the large structure has been pointed as an option to tackle the final energy price and therefore, smaller/cheaper platforms are desired. However, this would have implications on the platform hydrodynamic performance. This thesis discusses the use of thin disks as pitch motion suppression surfaces for FOWT platforms, employing three methodologies; potential flow, Computational Fluid Dynamics (CFD) and Experiments. With NEMOH a boundary element method code, the added mass and excitation forces/moments were calculated for …

Early-Stage Codesign Of A Material Passport For Volumetric Timber Building Components, Alejandro Veliz Reyes, Duhan Olmez, Alexandra Carr

School of Art, Design and Architecture

No abstract provided.

Digital Seascapes: Can We Use Digital Technologies To Engage Coastal Communities In Building Marine Citizenship?: Resilience And Adaptation: Parallel Workshop (6), Ashita Gupta, Katharine Willis

School of Art, Design and Architecture

No abstract provided.

Clinical Coding Of Long Covid In Primary Care 2020–2023 In A Cohort Of 19 Million Adults: An Opensafely Analysis, Alasdair D. Henderson, Ben Fc Butler-Cole, John Tazare, Laurie A. Tomlinson, Michael Marks, Mark Jit, Andrew Briggs, Liang Yu Lin, Oliver Carlile, Chris Bates, John Parry, Sebastian Cj Bacon, Iain Dillingham, William A. Dennison, Ruth E. Costello, Yinghui Wei, Alex Walker, William Hulme, Ben Goldacre, Amir Mehrkar, Brian Mackenna, The Opensafely Collaborative, Emily Herrett, Rosalind M. Eggo

School of Engineering, Computing and Mathematics

Background: Long COVID is the patient-coined term for the persistent symptoms of COVID-19 illness for weeks, months or years following the acute infection. There is a large burden of long COVID globally from self-reported data, but the epidemiology, causes and treatments remain poorly understood. Primary care is used to help identify and treat patients with long COVID and therefore Electronic Health Records (EHRs) of past COVID-19 patients could be used to help fill these knowledge gaps. We aimed to describe the incidence and differences in demographic and clinical characteristics in recorded long COVID in primary care records in England. Methods: …

Shipwrecks Act As De Facto Marine Protected Areas In Areas Of Heavy Fishing Pressure, Jenny Hickman, Joe Richards, Adam Rees, Emma V. Sheehan

School of Biological and Marine Sciences

Ubiquitous, industrial use of bottom‐towed fishing gear since the 1800s has altered marine communities and ecosystem services. Outside of legal protection, only areas inaccessible to trawlers are offered any protection. Shipwrecks present hazards to fishing gear and are rarely subject to trawling pressure. As many have been in situ for >100 years, they offer a baseline of ecological potential when trawling pressure is reduced or removed. Five shipwrecks were surveyed off the Berwickshire coast, some within the Static Gear Reserve and others outside. Video transects were collected of shipwrecks, the surrounding 50 m radius and control locations >150 m from …

Co-Making And Prototyping Community Housing Futures, Alejandro Veliz Reyes, Alexandra Carr, Timothy Crabtree

School of Art, Design and Architecture

An emerging area of research on automated futures is that of digital equity- how to innovate and develop digital products, services, and experiences which promote equality of access, and align with the lived experiences of communities they are expected to benefit. In this chapter, we outline a research project focused on the adoption of digital fabrication technologies by a rural community in Bridport, United Kingdom. Their challenge is that of housing futures not only in terms of stock demand, but more broadly in terms of sustainable forms of housing construction (i.e., modern methods of construction) using local materials and skills. …

Botulinum Toxin Treatment May Improve Myoelectric Pattern Recognition In Robot-Assisted Stroke Rehabilitation, Zhiyuan Lu, Yingchun Zhang, Sheng Li, Ping Zhou

Faculty, Staff and Student Publications

No abstract provided.

Taking Action To Achieve Health Equity And Eliminate Healthcare Disparities Within Acute Care Surgery, Lillian S Kao

Faculty, Staff and Student Publications

Addressing disparities is crucial for enhancing population health, ensuring health security, and fostering resilient health systems. Disparities in acute care surgery (trauma, emergency general surgery, and surgical critical care) have been well documented and the magnitude of inequities demand an intentional, organized, and effective response. As part of its commitment to achieve high-quality, equitable care in all aspects of acute care surgery, the American Association for the Surgery of Trauma convened an expert panel at its eigty-second annual meeting in September 2023 to discuss how to take action to work towards health equity in acute care surgery practice. The panel …

Large T Antigen Mediated Target Gene Replication Improves Site-Specific Recombination Efficiency

Faculty, Staff and Student Publications

With advantages of high-fidelity, monoclonality and large cargo capacity, site-specific recombination (SSR) holds great promises for precise genomic modifications. However, broad applications of SSR have been hurdled by low integration efficiency, and the amount of donor DNA available in nucleus for SSR presents as a limiting factor. Inspired by the DNA replication mechanisms observed in double-stranded DNA virus SV40, we hypothesized that expression of SV40 large T antigen (TAg) can increase the copy number of the donor plasmid bearing an SV40 origin, and in consequence promote recombination events. This hypothesis was tested with dual recombinase-mediated cassette exchange (RMCE) in suspension …

Generation Of Protease Inhibitory Antibodies By Functional In Vivo Selection

Faculty, Staff and Student Publications

Targeting dysregulated protease expression and/or abnormal substrate proteolysis, highly selective inhibition of pathogenic proteases by monoclonal antibodies (mAbs) presents an attractive therapeutic approach for the treatment of diseases including cancer. Herein, we report a functional selection method for protease inhibitory mAbs by periplasmic co-expression of three recombinant proteins-a protease of interest, an antibody Fab library, and a modified β-lactamase TEM-1. We validate this approach by isolation of highly selective and potent mAbs inhibiting human matrix metalloproteinase 9 (MMP9).

Unified Resource Browser: An Interactive And Reconfigurable Web Framework For Biomedical Metadata Exploration, Visualization, And Management, Shiwei Lin, Ling Tong, Kimberly A Smith, Lydia Ng, Tyler Mollenkopf, Yan Huang, Rashmie Abeysinghe, Wei-Chun Chou, Antarr T Byrd, Licong Cui, Guo-Qiang Zhang, Xiaojin Li, Shiqiang Tao

Faculty, Staff and Student Publications

We present Unified Resource Browser, a web-based framework designed to optimize the configuration, exploration, visualization, and dissemination of complex biomedical metadata. As a core component of Neuroanatomy-Anchored Information Management Platform (NIMP), Unified Resource Browser enables researchers to efficiently access donor information, brain tissue samples, and sequencing data through structured resource tables and advanced search and filtering capabilities. The platform allows users to customize data views, share configurations via direct links, and seamlessly export data for further analysis. Integrated visualization tools offer immediate insights through customizable charts, enhancing data interpretation. By improving the accessibility and usability of biomedical data resources, Unified …

Relational Database-Based Resource-Provenance Visualization Engine: With An Application To Bican Data, Xiaojin Li, Yan Huang, Lydia Ng, Kimberly A Smith, Wei-Chun Chou, Rashmie Abeysinghe, Ling Tong, Shiwe Lin, Licong Cui, Shiqiang Tao, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Provenance tracking ensures data integrity, security, and accountability in healthcare and biomedical research. As biomedical data grows in complexity, comprehensive tracking mechanisms are needed to maintain reproducibility, transparency, and compliance with regulatory standards, such as GDPR. Traditional log-based and ontology-based approaches capture and standardize data lineage, while cryptographic and blockchain-based methods enhance security and verifiability. However, challenges remain in scalability, security, and usability. To address these, we introduce the Resource-Provenance Visualization Engine (RPVE), an advanced system integrating data lineage tracking and interactive visualization. RPVE employs the Randomized N-gram Hashing Identifier (NHash ID) to establish precise data links within the BRAIN …

An Interactive Information Visualization System For Temporal Queries In A Large-Scale Covid-19 Ehr Dataset (Covid-Sphere): Development And Qualitative Evaluation, Yan Huang, Shiqiang Tao, Wei-Chun Chou, Licong Cui, Guo-Qiang Zhang, Xiaojin Li

Faculty, Staff and Student Publications

COVID-SPHERE is a self-service web application designed to advance clinical research informatics by facilitating secondary use of Electronic Health Records (EHR) for COVID-19 research. The system employs a flexible EHR concept framework that defines hierarchical concepts and ontologies, enabling clinical researchers to build complex temporal queries through an intuitive, single-click interface without requiring database expertise. Our method dynamically generates MongoDB queries in real-time and offers interactive, faceted visualizations to analyze longitudinal patient activities and integrated health records, supporting both individual patient analysis and population-level research. Hosted on a server managing over 5 TB of data encompassing 30 billion health records …

Endoscopic Innovations In Diagnosis And Management Of Pancreatic Cancer: A Narrative Review And Future Directions, Prateek Suresh Harne, Vaishali Harne, Curtis Wray, Nirav Thosani

Faculty, Staff and Student Publications

Background: Noncompressible torso hemorrhage is a leading cause of preventable death. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to control hemorrhage but full aortic occlusion is limited by distal ischemia. Partial REBOA (pREBOA) allows some distal perfusion to prolong occlusion, but precise balloon titration is difficult with standard devices. The COBRA-OS 4 French (Fr) aortic occlusion catheter was evaluated in vitro and in vivo for partial REBOA.

Methods: Bench-top (in vitro) and porcine (in vivo) models were used. The titration window of the device was evaluated in a non-hemorrhage porcine model and in a pulsatile aortic model. …

Re-Evaluating The Gender Gap: A Cross-Sectional Analysis Of Accepted American Academy Of Neurology Annual Meeting Abstracts In 2020 And 2021

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Prior studies reveal that invited speaker panels, editorial boards, authors of practice guidelines, and senior authors of published articles are disproportionately male in the neurology field. We aimed to analyze a gender gap in authorship of accepted abstracts to the American Academy of Neurology annual meetings in 2020 and 2021.

DESIGN/METHODS: This is a cross-sectional study evaluating the proportions of female first and senior abstract authors in 2020 and 2021. Abstracts were reviewed manually (

RESULTS: Accepted abstracts with female first and senior authors comprised 46%, 34% in 2020, and the same in 2021, without change. Female …

Safety And Feasibility Of Paired Vagus Nerve Stimulation With Rehabilitation For Improving Upper Extremity Function In People With Cervical Spinal Cord Injury: Study Protocol For A Pilot Randomized Controlled Trial

Faculty, Staff and Student Publications

Introduction: Pairing vagus nerve stimulation with traditional rehabilitation therapies results in improved motor recovery in people with stroke. However, this approach has not yet been studied in people with spinal cord injury (SCI). Motor recovery continues to be challenging after SCI, and there is a need for innovative research strategies to enhance motor recovery after SCI. Hence, this pilot randomized controlled trial aims to evaluate the safety, feasibility, and potential efficacy of pairing vagus nerve stimulation (VNS) with rehabilitation therapy to restore the motor function of the paretic upper limbs in people with cervical SCI.

Methods and analysis: In this …

Proportional Sway-Based Electrotactile Feedback Improves Lateral Standing Balance, Hangue Park

Faculty, Staff and Student Publications

INTRODUCTION: Plantar cutaneous augmentation is a promising approach in balance rehabilitation by enhancing motion-dependent sensory feedback. The effect of plantar cutaneous augmentation on balance has been mainly investigated in its passive form (e.g., textured insole) or on lower-limb amputees. In this study, we tested the effect of plantar cutaneous augmentation on balance in its active form (i.e., electrical stimulation) for individuals with intact limbs.

METHODS: Ten healthy subjects participated in the study and were instructed to maintain their balance as long as possible on the balance board, with or without electrotactile feedback evoked on the medial side of the heel, …

A Web-Based Interface For Visualizing And Documenting Seeg Strategic Planning (Wisp): Development And Qualitative Evaluation, Guo-Qiang Zhang

Faculty, Staff and Student Publications

WISP stands as an efficacious solution to the challenges associated with Stereoelectroencephalography (SEEG) strategic planning, offering lightweight and interactive web interfaces for rendering multiple brain views. These interfaces facilitate collaborative engagement among care team members across various disciplines during patient case conferences and SEEG strategic planning sessions. Moreover, WISP incorporates a collaborative electrode and electrode group library, serving as a standardized repository of knowledge. The application enables seamless conversion of case conference outcomes and SEEG plans into images and PDF files, with transmission to Electronic Health Record (EHR) systems through a customized HL7 engine. The initial assessment findings demonstrate WISP …

Advancements In Varicose Vein Treatment: Anatomy, Pathophysiology, Minimally Invasive Techniques, Sclerotherapy, Patient Satisfaction, And Future Directions, Rashed A Alsubari, Hareem Arif, Sophia B Bellegarde, Pakeezah Bisharat, Muhayya Faizullah

Faculty, Staff and Student Publications

Varicose veins are a common vascular condition known for causing discomfort and cosmetic concerns. This comprehensive narrative review delves into their anatomy, pathophysiology, and modern treatment options, with a focus on endovenous techniques and sclerotherapy. The review starts by emphasizing the intricate anatomy of lower extremity venous circulation, underlining the significance of both superficial and deep venous networks in venous return. It also addresses how changes in the venous wall, including valvular insufficiency, contribute to the development of varicose veins. Endovenous techniques like endovenous laser ablation (EVLA), radiofrequency ablation (RFA), and mechanochemical endovenous ablation (MOCA) are explored in detail. These …

Exploring Uniform, Dual, And Dynamic Topologies Of Membrane Proteins By Substituted Cysteine Accessibility Method (Scam™)

Faculty, Staff and Student Publications

A described simple and advanced protocol for Substituted Cysteine Accessibility Method as applied to transmembrane (TM) orientation (SCAM™) permits a topology analysis of proteins in their native state and can be universally adapted to any membrane system to either systematically map an uniform or identify and quantify the degree of mixed topology or establish transmembrane assembly dynamics from relatively static experimental data such as endpoint topologies of membrane proteins. In this approach, noncritical individual amino acids that are thought to reside in the putative extracellular or intracellular loops of a membrane protein are replaced one at the time by cysteine …

One-Step Production Of Fully Biotinylated And Glycosylated Human Fc Gamma Receptors

Faculty, Staff and Student Publications

Initiating and regulating humoral immunity, Fc gamma receptors (FcγRs) have been identified both as therapeutics and as drug targets, and thus production of biologically active FcγRs is highly demanded for biopharmaceutical development. Focusing on low-affinity FcγRs IIA (131H/R allotypes), IIB, and IIIA (176F/V), this study used human 293-F cells to achieve correct post-translational modifications (PTMs) including biotinylation, N-glycosylation, and disulfides. Approaches involving co-expression of FcγR-AviTag and Escherichia coli biotin ligase BirA, endoplasmic reticulum retention, stable and transient transfections, and optimization of transgene ratio were investigated. Protein electrophoresis under reducing and non-reducing conditions, enzymatic deglycosylation, streptavidin pull-down assays, and binding kinetic …