Digital Commons Network^™

Myeloid Lineage Switch In Kmt2a- Rearranged Acute Lymphoblastic Leukemia Treated With Lymphoid Lineagedirected Therapies, Alex Bataller, Tareq Abuasab, David Mccall, Wei Wang, Branko Cuglievan, Ghayas C Issa, Elias Jabbour, Nicholas Short, Courtney D Dinardo, Guilin Tang, Guillermo Garcia-Manero, Hagop M Kantarjian, Koji Sasaki

Faculty, Staff and Student Publications

No abstract provided.

Editorial: Mathematical Modeling And Computational Predictions In Oncoimmunology, Vladimir A Kuznetsov, Heiko Enderling, Mark Chaplain

Faculty, Staff and Student Publications

No abstract provided.

Spatial Multiplexing And Omics, Julienne L Carstens, Santhoshi N Krishnan, Arvind Rao, Anna G Sorace, Erin H Seeley, Sammy Ferri-Borgogno, Jared K Burks

Faculty, Staff and Student Publications

Much like solving a game of Clue, understanding physiological mysteries involves answering who, what, when, and where. Multi-omics approaches delve into cellular and molecular identities (the who and what), while longitudinal data collection addresses the when. Spatial dimensions address the where. This Primer discusses current technologies enabling quantification across biological scales, emphasizing the importance of retaining the spatial dimension of that data. We outline experimental design considerations, including targeted versus untargeted approaches, sample types, biological scale, and four main classes of molecule detection. Spatial analytics are explored, covering questioning approaches, analytical platforms, image segmentation and sampling. Example applications, reproducibility considerations, …

Fueling Cardiac Myocyte Proliferation, Manisha Deogharia, Priyatansh Gurha

Faculty, Staff and Student Publications

No abstract provided.

Editorial: Chronobiology In Cardiometabolic Health And Disease, Cristina Manuela Dragoi, Zhihong Yang, Baharan Fekry, Andrea Brenna

Faculty, Staff and Student Publications

No abstract provided.

The Potential Of Suspended Chitosan Nanoparticles As A Surgical Irrigation Fluid, Miles D Holmes, Analisa J Narro, Hugh L Jones, Philip C Noble, Catherine G Ambrose

Faculty, Staff and Student Publications

In this study, we sought to synthesize chitosan nanoparticles (CS-NPs) and characterize their morphology, efficacy in inhibiting bacterial attachment, and efficacy in eradicating bacteria established on implantable hardware. CS-NPs possess desirable properties, including antibacterial properties in biofilm-mediated infections. CS-NPs were produced using ionic gelation and characterized via scanning electron microscope imaging. Staphylococcus aureus was incubated with CS-NPs at various concentrations and compared to a 1% povidone-iodine with 1% H2 O2 control in 24-well plates. Stainless steel bone screws were placed in six-well plates and inoculated with S. aureus. After 24 h, the screws were transferred to one of three solutions …

Precision Needle-Punch Tumor Enrichment From Paraffin Blocks Improves The Detection Of Clinically Actionable Genomic Alterations And Biomarkers, Douglas I Lin, Richard S P Huang, Ioannis Ladas, Rachel B Keller, Nimesh R Patel, Sotirios Lakis, Brennan Decker, Tyler Janovitz, Douglas A Mata, Jeffrey S Ross, Jo-Anne Vergilio, Julia A Elvin, Roy S Herbst, Philip C Mack, Jonathan K Killian

Faculty, Staff and Student Publications

BACKGROUND: While many molecular assays can detect mutations at low tumor purity and variant allele frequencies, complex biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) require higher tumor purity for accurate measurement. Scalable, quality-controlled, tissue-conserving methods to increase tumor nuclei percentage (TN%) from tumor specimens are needed for complex biomarkers and hence necessary to maximize patient matching to approved therapies or clinical trial enrollment. We evaluated the clinical utility and performance of precision needle-punch enrichment (NPE) compared with traditional razor blade macroenrichment of tumor specimens on molecular testing success.

METHODS: Pathologist-directed NPE …

Association Between Serum Vitamin D Status And Uterine Leiomyomas: A Case-Control Study, Chukwuemeka Chukwubuikem Okoro, Okechukwu Christian Ikpeze, George Uchenna Eleje, Gerald Okanandu Udigwe, Chukwuemeka Okwudili Ezeama, Joseph Odirichukwu Ugboaja, Chukwunonso Isaiah Enechukwu, Osita Samuel Umeononihu, Chukwudi Anthony Ogabido, Charlotte Blanche Oguejiofor, Tobechi Kingsley Njoku, Richard Obinwanne Egeonu, Chigozie Geoffrey Okafor, Hillary Ikechukwu Obiagwu, Chukwudubem Chinagorom Onyejiaka, Afam Ben Obidike, Christian Ejike Onah, Ifeanyi Uzukwu, Amarachukwu Doris Okoro, Evaristus Chino Ezema, Adaobi Maryann Ibekwe, Joseph Ifeanyichukwu Ikechebelu

Faculty, Staff and Student Publications

OBJECTIVE: Uterine leiomyoma is a common gynecological condition that negatively affects women's quality of life. Vitamin D plays an important role in tumor development and progression. However, clinical studies comparing serum vitamin D levels between women with and without uterine leiomyomas are limited and inconclusive. This study aimed to compare serum vitamin D levels in women with and without uterine leiomyomas.

METHODS: This hospital-based case-control study included 150 women who visited a gynecological clinic. The cases included 75 women with uterine leiomyoma, whereas the controls included 75 age-and parity-matched participants without uterine leiomyoma. Serum vitamin D levels were measured in …

Metformin In Conjunction With Stereotactic Radiotherapy For Early-Stage Non-Small Cell Lung Cancer: Long-Term Results Of A Prospective Phase Ii Clinical Trial, Molly K Tate, Mike Hernandez, Joe Y Chang, Steven H Lin, Zhongxing Liao, Suja M Koshy, Heath D Skinner, Stephen G Chun

Faculty, Staff and Student Publications

Background/aim: Non-small cell lung cancer (NSCLC) is increasingly detected in early stages and there is interest in improving outcomes with stereotactic body radiotherapy (SBRT). As metformin affects NSCLC signaling pathways, it might alter the metabolism of NSCLC treated with SBRT. This study investigated the long-term outcomes of a phase II clinical trial evaluating metformin in conjunction with SBRT for early-stage NSCLC.

Patients and methods: The trial evaluated patients with American Joint Commission on Cancer (AJCC) 7th edition Stage I-II, cT1-T2N0M0 NSCLC who were randomized 6:1 to receive metformin versus placebo in conjunction with SBRT. The outcomes analyzed included local failure …

Predicting Suicidality In Late-Life Depression By 3d Convolutional Neural Network And Cross-Sample Entropy Analysis Of Resting-State Fmri, Chemin Lin, Chih-Mao Huang, Wei Chang, You-Xun Chang, Ho-Ling Liu, Shu-Hang Ng, Huang-Li Lin, Tatia Mei-Chun Lee, Shwu-Hua Lee, Shun-Chi Wu

Faculty, Staff and Student Publications

Background: Predicting suicide is a pressing issue among older adults; however, predicting its risk is difficult. Capitalizing on the recent development of machine learning, considerable progress has been made in predicting complex behavior such as suicide. As depression remained the strongest risk for suicide, we aimed to apply deep learning algorithms to identify suicidality in a group with late-life depression (LLD).

Methods: We enrolled 83 patients with LLD, 35 of which were non-suicidal and 48 were suicidal, including 26 with only suicidal ideation and 22 with past suicide attempts, for resting-state functional magnetic resonance imaging (MRI). Cross-sample entropy (CSE) analysis …

The Kidney In Heart Failure: The Role Of Venous Congestion, Oluwaseun Adebayo Bamodu, Chen-Chih Chung, Thomas R Pisanic, Alexander T H Wu

Faculty, Staff and Student Publications

BACKGROUND: Cancer stem cells (CSCs) have emerged as pivotal players in tumorigenesis, disease progression, and resistance to therapies.

OBJECTIVE: This comprehensive review delves into the intricate relationship between CSCs and the cell-of-origin in diverse cancer types.

DESIGN: Comprehensive review of thematically-relevant literature.

METHODS: We explore the underlying molecular mechanisms that drive the conversion of normal cells into CSCs and the impact of the cell-of-origin on CSC properties, tumor initiation, and therapeutic responses. Moreover, we discuss potential therapeutic interventions targeting CSCs based on their distinct cell-of-origin characteristics.

RESULTS: Accruing evidence suggest that the cell-of-origin, the cell type from which the tumor …

A Milestone In Epithelial-Mesenchymal Transition, Yutong Sun, Li Ma

Faculty, Staff and Student Publications

No abstract provided.

Differential Regulation Of Tissue-Resident And Blood-Derived Macrophages In Models Of Autoimmune And Traumatic Peripheral Nerve Injury, Alina Sprenger-Svačina, Martin K R Svačina, Tong Gao, Rodney M Ritzel, Louise D Mccullough, Kazim A Sheikh, Gang Zhang

Faculty, Staff and Student Publications

Introduction: The current study focuses on understanding the functional role of different subsets of endoneurial macrophages in autoimmune polyneuropathies (AP) and traumatic peripheral nerve injury (TPNI), which holds potential for clinical application. Recent studies have advanced our understanding of the diverse origins of macrophages within peripheral nerves. However, there remains a gap in our knowledge regarding how endoneurial macrophages from different origins affect disease progression in AP versus TPNI.

Methods: Flow cytometry was utilized to analyze macrophage phenotypes, including polarization states, cytokine production, and myelin phagocytosis in animal models of AP and TPNI. This study focuses on two distinct origins …

High Wall Shear Stress-Dependent Podosome Formation In A Novel Murine Model Of Intracranial Aneurysm, Jiayi Lu, Mengjun Dai, Yuanqing Yan, Louise D Mccullough, Yan-Ning Rui, Zhen Xu

Faculty, Staff and Student Publications

High wall shear stress (HWSS) contributes to intracranial aneurysm (IA) development. However, the underlying molecular mechanisms remain unclear, in part due to the lack of robust animal models that develop IAs in a HWSS-dependent manner. The current study established a new experimental IA model in mice that was utilized to determine HWSS-triggered downstream mechanisms. By a strategic combination of HWSS and low dose elastase, IAs were induced with a high penetrance in hypertensive mice. In contrast, no IAs were observed in control groups where HWSS was absent, suggesting that our new IA model is HWSS-dependent. IA outcomes were assessed by …

Optimizing Medication Querying Using Ontology-Driven Approach With Omop: With An Application To A Large-Scale Covid-19 Ehr Dataset, Xiaojin Li, Yan Huang, Licong Cui, Shiqiang Tao, 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 …

Characterizing Treatment Non-Responders And Responders In Completed Alzheimer's Disease Clinical Trials, Dulin Wang, Yaobin Ling, Kristofer Harris, Paul E Schulz, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Characterizing differential responses to Alzheimer's disease (AD) drugs will provide better insights into personalized treatment strategies. Our study aims to identify heterogeneous treatment effects and pre-treatment features that moderate the treatment effect of Galantamine, Bapineuzumab, and Semagacestat from completed trial data. The causal forest method can capture heterogeneity in treatment responses. We applied causal forest modeling to estimate the treatment effect and identify efficacy moderators in each trial. We found several patient's pretreatment conditions that determined treatment efficacy. For example, in Galantamine trials, whole brain volume (1092.54 vs. 1060.67 ml, P < .001) and right hippocampal volume (2.43e-3 vs. 2.79e-3, P < .001) are significantly different between responsive and non-responsive subgroups. Overall, our implementation of causal forests in AD clinical trials reveals the heterogeneous treatment effects and different moderators for AD drug responses, highlighting promising personalized treatment based on patient-specific characteristics in AD research and drug development.

Grief On Pain And Quality Of Life In Combat Veterans With Ptsd, Melba A Hernandez-Tejada, Madeleine Desrochers, Ron Acierno

Faculty, Staff and Student Publications

Background: Persistent Complex Bereavement Disorder (PCBD) comprises a set of grief symptoms that are often linked to other psychological conditions such as PTSD and depression, may be prevalent in Veterans with combat experience, and may also impact general health.

Objective: This study investigated the association between grief and sleep, pain, PTSD, and depression, among Veterans participating in a clinical trial for PCBD treatment.

Method: Data from 155 Veterans receiving treatments for PCBD were analysed to explore the association between PCBD and symptoms of sleep pain, PTSD, and depression. Veterans experiencing grief reported symptoms related to physical health, emotional problems, energy, …

Acute Exposure To Diisopropylfluorophosphate In Mice Results In Persistent Cognitive Deficits And Alterations In Senescence Markers In The Brain, Alvin V Terry, Wayne D Beck, Victoria Zona, Yutaka Itokazu, Ashutosh Tripathi, Amit Kumar Madeshiya, Anilkumar Pillai

Faculty, Staff and Student Publications

Organophosphates (OPs) are found in hundreds of important products used worldwide; however, they have been associated with adverse long-term health consequences ranging from neurodevelopmental deficits to age-related neurological diseases. OP exposure has also been implicated in Gulf War Illness; a cluster of medically unexplained chronic symptoms estimated to affect 25-32% of veterans of the Persian Gulf war in 1991. The development of multiple types of chronic illnesses in these veterans at an early age compared to the general population has led to the suggestion that they are experiencing signs of premature or accelerated aging. The process of cellular senescence and …

Novel Oppositional Defiant Disorder Or Conduct Disorder 24 Months After Traumatic Brain Injury In Children And Adolescents, Daniel S Lowet, Florin Vaida, John R Hesselink, Linda Ewing-Cobbs, Russell J Schachar, Sandra B Chapman, Erin D Bigler, Elisabeth A Wilde, Ann E Saunders, Tony T Yang, Olga Tymofiyeva, Mingxiong Huang, Jeffrey E Max

Faculty, Staff and Student Publications

Objective: The authors sought to identify predictive factors of new-onset or novel oppositional defiant disorder or conduct disorder assessed 24 months after traumatic brain injury (TBI).

Methods: Children ages 5 to 14 years who had experienced TBI were recruited from consecutive hospital admissions. Soon after injury, participants were assessed for preinjury characteristics, including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, and family function, and the presence and location of lesions were documented by MRI. Psychiatric outcomes, including novel oppositional defiant disorder or conduct disorder, were assessed 24 months after injury.

Results: Of the children without preinjury oppositional defiant disorder, conduct …

Large T Antigen Mediated Target Gene Replication Improves Site-Specific Recombination Efficiency, Zening Wang, Chuan Chen, Xin Ge

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, Ki Baek Lee, Xin Ge

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).

One-Step Production Of Fully Biotinylated And Glycosylated Human Fc Gamma Receptors, Minhyo Kang, Zening Wang, Xin Ge

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 …

Atypical Presentation Of Psoriasis On The Breast Of An Elderly Woman: A Case Report, Susuana Adjei, Mohamad R Taha, Anisha B Patel, Stephen K Tyring

Faculty, Staff and Student Publications

Psoriasis is a chronic, inflammatory skin disease that affects over 60 million adults and children globally. It is classically characterized by pink plaques covered with silver scales on the extensor surfaces, trunk, or scalp. In this report, we describe the case of a woman in her late 60s with psoriasis presenting as a painful plaque on her left breast. This case highlights the importance of considering psoriasis as a differential diagnosis in patients with unilateral breast plaques, even in the absence of typical psoriasis scaling elsewhere on the body.

Intra-Decadal Increase In Globally-Spread Magallana Gigas In Southern California Estuaries, Marah L Wolfe, Chelsea M Bowers-Doerning, Anabell Espinosa, Ty Frantz, William J Hoese, Joann G Lam, Kailee R Lamp, Rachael A Lyons, Justin K Nguyen, Bryce D Keyes, Jada Smith, Holly L Suther, Meaghan Swintek, Juliann C Vannordstrand, Danielle C Zacherl

Faculty, Staff and Student Publications

Introduction and establishment of non-indigenous species (NIS) has been accelerated on a global scale by climate change. NIS Magallana gigas' (formerly Crassostrea gigas') global spread over the past several decades has been linked to warming waters, specifically during summer months, raising the specter of more spread due to predicted warming. We tracked changes in density and size distribution of M. gigas in two southern California, USA bays over the decade spanning 2010-2020 using randomly placed quadrats across multiple intertidal habitats (e.g., cobble, seawalls, riprap) and documented density increases by 2.2 to 32.8 times at 7 of the 8 sites surveyed …

Association Of Risk Factors And Comorbidities With Chronic Pain In The Elderly Population, Neil Mookerjee, Nicole Schmalbach, Gianna Antinori, Subhadra Thampi, Dylan Windle-Puente, Amy Gilligan, Ha Huy, Megha Andrews, Angela Sun, Roshni Gandhi, William Benedict, Austin Chang, Ben Sanders, Justin Nguyen, Maanika Reddy Keesara, Janet Aliev, Aneri Patel, Isaiah Hughes, Ian Millstein, Krystal Hunter, Satyajeet Roy

Faculty, Staff and Student Publications

INTRODUCTION/OBJECTIVE: Chronic pain disorders affect about 20% of adults in the United States, and it disproportionately affects individuals living in the neighborhoods of extreme socioeconomic disadvantage. In many instances, chronic pain has been noted to arise from an aggregation of multiple risk factors and events. Therefore, it is of importance to recognize the modifiable risk factors. The aim of this study was to investigate the comorbid medical conditions and risk factors associated with chronic pain disorders in patients aged 65 years and older.

METHODS: Our team retrospectively reviewed medical records of elderly patients (65 years and older) who were evaluated …

Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Megan Palmisano, Jeaneen Kulp, Susan Bender, Darko Stefanovski, Mary Robinson, Amy Johnson

Faculty, Staff and Student Publications

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses.

HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses.

ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November …

Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Megan Palmisano, Jeaneen Kulp, Susan Bender, Darko Stefanovski, Mary Robinson, Amy Johnson

Faculty, Staff and Student Publications

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses.

HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses.

ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November …

International Ocean Discovery Program Expedition 399 Preliminary Report: Building Blocks Of Life, Atlantis Massif, Andrew M. Mccaig, S.Q. Lang, Peter Blum, Expedition 399 Scientists, Andrew Parsons

School of Geography, Earth and Environmental Sciences

No abstract provided.

Addressing Digital Exclusion Via The Inter-Generational Codesign Of Extended Reality, Underwater Telepresence, Social Games, And Voice Ai Technologies, Ray Jones, Rory Baxter, Marius Varga, Oksana Hagen, Amir Aly, Dena Bazazian, Alejandro Veliz Reyes, Swen Gaudl

School of Nursing and Midwifery

Addressing Digital Exclusion via the Inter-Generational Codesign of Extended Reality, Underwater Telepresence, Social Games, and Voice AI Technologies

The Effect Of Mindfulness-Based Interventions On Anxiety Disorders Through Intolerance Of Uncertainty And Resilience, Aysun Parlar Yazici

School of Psychology Theses

Anxiety is one of the most complicated and widespread mental health conditions, and effective treatment of anxiety disorders is vital to public health. Investigating the mechanisms that are linked to and contribute to anxiety disorders, such as intolerance of uncertainty (IU), a transdiagnostic factor of all anxiety disorders, may be an appropriate approach for a better understanding of anxiety disorders. Furthermore, examining the role of resilience, which has a protective function in mental health conditions, could contribute to improving our understanding of anxiety and treatment. This thesis investigates the impact of mindfulness-based interventions (MBI), on anxiety, IU, and resilience. The …