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2023

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The Development Of Novel Radioscandium And Hydroxypyridinonate Based Radiopharmaceuticals, Michael Phipps Sep 2023

The Development Of Novel Radioscandium And Hydroxypyridinonate Based Radiopharmaceuticals, Michael Phipps

Dissertations, Theses, and Capstone Projects

The use of radiometals in radiopharmaceutical development has drastically increased over the last decade, owed in part to the diverse chemistry and emission characteristics of the radiometals, which allow chemists to create a toolbox of agents to better tailor patient care. Challenges with the use of radiometals include the selection of the metal and the development of optimized chelators to cover the diverse chemistry of the metals which make up the majority of the periodic table. Scandium is the first transition metal and has multiple radioisotopes whose emission characteristics have potential application in medicine. 3,4,3-LI(1,2-HOPO) is a chelator whose denticity, …


Visualizing Dopamine Activity In Deletion Of D2 Receptors In Medium Spiny Neurons, Kunhee Lee Sep 2023

Visualizing Dopamine Activity In Deletion Of D2 Receptors In Medium Spiny Neurons, Kunhee Lee

Dissertations, Theses, and Capstone Projects

Dopamine has been implicated in motivated behaviors and reinforcement learning. In this study, we are looking at the role of dopamine in allocating efforts when obtaining reward. Using Cre recombinase genetic tool, D2 receptors in striatal indirect pathway neurons were selectively deleted, and dopamine signal was recorded in ventral striatum using fiber photometry. Behaviorally, D2 receptor deletion resulted in less effort in a Progressive Ratio (PR) paradigm shown by decreased breakpoint, number of presses, and reward pellets earned. Due to the previous evidence that dopamine positively modulates effort, we hypothesized that there would be less dopamine release in D2 deleted …


Characterization Of The Conformational Binding Of N-Methyl Mesoporphyrin Ix With Dna Model Telomeric G-Quadruplex Forming Sequences, Jessica Desamero Sep 2023

Characterization Of The Conformational Binding Of N-Methyl Mesoporphyrin Ix With Dna Model Telomeric G-Quadruplex Forming Sequences, Jessica Desamero

Dissertations, Theses, and Capstone Projects

DNA G-quadruplexes are alternative secondary structures formed from guanine rich DNA sequences. G-quadruplexes are found most abundantly at the ends of chromosomes called telomeres, where they can ultimately prevent further tumor growth and progression. Thus, quadruplex interactive agents, or ligands that can bind to and stabilize DNA G-quadruplex structures, are of high interest for their potential chemotherapeutic abilities. One quadruplex interactive agent is the porphyrin N-methyl mesoporphyrin IX (NMM), which has high binding selectivity for quadruplex structures. While the NMM-quadruplex complex in crystallized form has been greatly studied, this complex in solution form is not as well studied. Through circular …


Isatin-Pyrimidine Hybrid Derivatives As Enoyl Acyl Carrier Protein Reductase (Inha) Inhibitors Against Mycobacterium Tuberculosis, Amira Khalil, Samy Mohamady, Amgad Albohy, Marwa M. Abdel-Aziz, Abdalrahman Khalifa Sep 2023

Isatin-Pyrimidine Hybrid Derivatives As Enoyl Acyl Carrier Protein Reductase (Inha) Inhibitors Against Mycobacterium Tuberculosis, Amira Khalil, Samy Mohamady, Amgad Albohy, Marwa M. Abdel-Aziz, Abdalrahman Khalifa

Pharmacy

Tuberculosis is a worldwide problem that impose a burden on the economy due to continuous development of resistant strains. The development of new antitubercular drugs is a need and can be achieved through inhibition of druggable targets. Mycobacterium tuberculosis enoyl acyl carrier protein (ACP) reductase (InhA) is an important enzyme for Mycobacterium tuberculosis survival. In this study, we report the synthesis of isatin derivatives that could treat TB through inhibition of this enzyme. Compound 4l showed IC50 value (0.6 ± 0.94 µM) similar to isoniazid but is also effective against MDR and XDR Mycobacterium tuberculosis strains (MIC of 0.48 and …


An End-To-End Cnn Approach For Enhancing Underwater Images Using Spatial And Frequency Domain Techniques, Dr Khaled Nagaty, Ayah Hesham Abo El Rejal, The British University In Egypt Sep 2023

An End-To-End Cnn Approach For Enhancing Underwater Images Using Spatial And Frequency Domain Techniques, Dr Khaled Nagaty, Ayah Hesham Abo El Rejal, The British University In Egypt

Computer Science

Underwater image processing area has been a central point of interest to many people in many fields such as control of underwater vehicles, archaeology, marine biology research, etc. Underwater exploration is becoming a big part of our life such as underwater marine and creatures research, pipeline and communication logistics, military use, touristic and entertainment use. Underwater images are subject to poor visibility, distortion, poor quality, etc., due to several reasons such as light propagation. The real problem occurs when these images have to be taken at a depth which is more than 500 feet where artificial light needs to be …


Mineral Licks As A Potential Nidus For Parasite Transmission, William J. Severud, Todd M. Kautz, Jerrold L. Belant, Seth A. Moore Sep 2023

Mineral Licks As A Potential Nidus For Parasite Transmission, William J. Severud, Todd M. Kautz, Jerrold L. Belant, Seth A. Moore

Natural Resource Management Faculty Publications

Discrete landscape features can concentrate animals in time and space, leading to non-random interspecific encounters. These encounters have implications for predator-prey interactions, habitat selection, intraspecific competition, and transmission of parasites and other pathogens. The lifecycle of the parasitic nematode Parelaphostrongylus tenuis requires an intermediate host of a terrestrial gastropod. Natural hosts of P. tenuis are whitetailed deer, and an aberrant host of conservation concern is moose, which are susceptible to high levels of mortality as a naive host to the parasite. Intermediate hosts become infected when P. tenuis larvae are shed in deer feces, then consumed or enter the gastropod …


If You Don’T Live By The Sea, You Won’T Talk About Sailing: An Interpretative Phenomenological Approach Of The Polish Immigrant Experience In Chicago And The Acculturation Of Racial Beliefs, Monica Zabinski Sep 2023

If You Don’T Live By The Sea, You Won’T Talk About Sailing: An Interpretative Phenomenological Approach Of The Polish Immigrant Experience In Chicago And The Acculturation Of Racial Beliefs, Monica Zabinski

Dissertations

There has been a steady increase in research and focus on defining and understanding racism and the role it plays in the ongoing inequality and inequity between individuals of White descent and individuals who are Black, indigenous, or people of color (BIPOC). However, little research has focused on what changes with racial beliefs when individuals immigrate between various countries where racism, discrimination, and racial beliefs may appear differently. Our objective was to increase our understanding of how the acculturation process may impact or change racial beliefs over time. Our research sought participants of Polish descent in the Chicagoland area and …


Going Circular: History, Present, And Future Of Circrnas In Cancer, Giuseppina Pisignano, David C Michael, Tanvi H Visal, Radu Pirlog, Michael Ladomery, George A Calin Sep 2023

Going Circular: History, Present, And Future Of Circrnas In Cancer, Giuseppina Pisignano, David C Michael, Tanvi H Visal, Radu Pirlog, Michael Ladomery, George A Calin

Faculty, Staff and Student Publications

To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and post-transcriptionally and exhibit distinct tissue- and development-specific expression patterns associated with a variety of normal and disease conditions, including cancer pathogenesis. Over the past years, due to their intrinsic stability and resistance to ribonucleases, particular attention has been drawn to their use as reliable diagnostic and prognostic biomarkers in cancer diagnosis, treatment, and prevention. However, there are some critical caveats to their utility in the clinic. Their …


Design Of A Phase Iii, Double-Blind, Randomised, Placebo-Controlled Trial Of Bi 1015550 In Patients With Progressive Pulmonary Fibrosis (Fibroneer-Ild), Toby M Maher, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Michael Kreuter, Justin M Oldham, Luca Richeldi, Claudia Valenzuela, Marlies S Wijsenbeek, Carl Coeck, Christina Schlecker, Florian Voss, Daniel Wachtlin, Fernando J Martinez Sep 2023

Design Of A Phase Iii, Double-Blind, Randomised, Placebo-Controlled Trial Of Bi 1015550 In Patients With Progressive Pulmonary Fibrosis (Fibroneer-Ild), Toby M Maher, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Michael Kreuter, Justin M Oldham, Luca Richeldi, Claudia Valenzuela, Marlies S Wijsenbeek, Carl Coeck, Christina Schlecker, Florian Voss, Daniel Wachtlin, Fernando J Martinez

Faculty, Staff and Student Publications

INTRODUCTION: Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). However, disease progression appears comparable between PPF and IPF, suggesting a similar underlying pathology relating to pulmonary fibrosis. Following positive results in a phase II study in IPF, this phase III study will investigate the efficacy and safety of BI 1015550 in patients with PPF (FIBRONEER-ILD).

METHODS AND ANALYSIS: In this phase III, double-blind, placebo-controlled trial, patients are being randomised 1:1:1 to receive BI 1015550 (9 mg or 18 mg) or placebo twice daily over at least 52 weeks, …


Carm1 Arginine Methyltransferase As A Therapeutic Target For Cancer, Margarida Santos, Jee Won Hwang, Mark T Bedford Sep 2023

Carm1 Arginine Methyltransferase As A Therapeutic Target For Cancer, Margarida Santos, Jee Won Hwang, Mark T Bedford

Faculty, Staff and Student Publications

Coactivator-associated arginine methyltransferase 1 (CARM1) is an arginine methyltransferase that posttranslationally modifies proteins that regulate multiple levels of RNA production and processing. Its substrates include histones, transcription factors, coregulators of transcription, and splicing factors. CARM1 is overexpressed in many different cancer types, and often promotes transcription factor programs that are co-opted as drivers of the transformed cell state, a process known as transcription factor addiction. Targeting these oncogenic transcription factor pathways is difficult but could be addressed by removing the activity of the key coactivators on which they rely. CARM1 is ubiquitously expressed, and its KO is less detrimental in …


Aerobic Exercise Alters The Melanoma Microenvironment And Modulates Erk5 S496 Phosphorylation, Hannah Savage, Sumedha Pareek, Jonghae Lee, Riccardo Ballarò, Darlan Conterno Minussi, Karma Hayek, Mumina Sadullozoda, Brooke S Lochmann, Jennifer L Mcquade, Emily C Lavoy, Enrica Marmonti, Hetal Patel, Guangyu Wang, Masaki Imanishi, Sivareddy Kotla, Jun-Ichi Abe, Keri Schadler Sep 2023

Aerobic Exercise Alters The Melanoma Microenvironment And Modulates Erk5 S496 Phosphorylation, Hannah Savage, Sumedha Pareek, Jonghae Lee, Riccardo Ballarò, Darlan Conterno Minussi, Karma Hayek, Mumina Sadullozoda, Brooke S Lochmann, Jennifer L Mcquade, Emily C Lavoy, Enrica Marmonti, Hetal Patel, Guangyu Wang, Masaki Imanishi, Sivareddy Kotla, Jun-Ichi Abe, Keri Schadler

Faculty, Staff and Student Publications

Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a …


Cytoreductive Nephrectomy For Patients With Metastatic Sarcomatoid And/Or Rhabdoid Renal Cell Carcinoma Treated With Immune Checkpoint Therapy, Andrew W Hahn, Ritesh R Kotecha, Paul V Viscuse, Alberto C Pieretti, Andrew J Wiele, Eric Jonasch, Chung-Han Lee, Jianjun Gao, Amado J Zurita, Amishi Y Shah, Matthew T Campbell, Padmanee Sharma, Robert J Motzer, Paul Russo, Christopher G Wood, Nizar M Tannir, Martin H Voss, Jose A Karam, A Ari Hakimi, Pavlos Msaouel Sep 2023

Cytoreductive Nephrectomy For Patients With Metastatic Sarcomatoid And/Or Rhabdoid Renal Cell Carcinoma Treated With Immune Checkpoint Therapy, Andrew W Hahn, Ritesh R Kotecha, Paul V Viscuse, Alberto C Pieretti, Andrew J Wiele, Eric Jonasch, Chung-Han Lee, Jianjun Gao, Amado J Zurita, Amishi Y Shah, Matthew T Campbell, Padmanee Sharma, Robert J Motzer, Paul Russo, Christopher G Wood, Nizar M Tannir, Martin H Voss, Jose A Karam, A Ari Hakimi, Pavlos Msaouel

Faculty, Staff and Student Publications

BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is a highly aggressive tumor with a poor prognosis. Immune checkpoint therapy (ICT) has shown significant treatment efficacy in this subtype. There remains uncertainly regarding the role of cytoreductive nephrectomy (CN) for patients with metastatic RCC (mRCC) with S/R who received ICT.

OBJECTIVE: Here, we report the outcomes with ICT for patients with mRCC and S/R dedifferentiation by CN status.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was conducted of 157 patients with sarcomatoid, rhabdoid, or sarcomatoid plus rhabdoid dedifferentiation who received an ICT-based regimen at two cancer centers. …


Impact Of Serial Intralesional Steroid Injections On Idiopathic Subglottic Stenosis, Matthew R Hoffman, Ankita Patro, Li-Ching Huang, Sheau-Chiann Chen, Lynn D Berry, Alexander Gelbard, David O Francis Sep 2023

Impact Of Serial Intralesional Steroid Injections On Idiopathic Subglottic Stenosis, Matthew R Hoffman, Ankita Patro, Li-Ching Huang, Sheau-Chiann Chen, Lynn D Berry, Alexander Gelbard, David O Francis

Faculty, Staff and Student Publications

OBJECTIVES: Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi-institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea.

METHODS: Post-hoc secondary analysis of the North American Airway Collaborative data were performed to evaluate the outcomes of iSGS patients undergoing and not undergoing SILSI. The primary outcome was time to recurrent operation, evaluated using Kaplan-Meier curves and Cox regression analysis. Secondary outcomes were change in PEF and clinical chronic obstructive pulmonary disease questionnaire (CCQ) …


Lineage Plasticity And Stemness Phenotypes In Prostate Cancer: Harnessing The Power Of Integrated "Omics" Approaches To Explore Measurable Metrics, Souzana Logotheti, Eugenia Papadaki, Vasiliki Zolota, Christopher Logothetis, Aristidis G Vrahatis, Rama Soundararajan, Vasiliki Tzelepi Sep 2023

Lineage Plasticity And Stemness Phenotypes In Prostate Cancer: Harnessing The Power Of Integrated "Omics" Approaches To Explore Measurable Metrics, Souzana Logotheti, Eugenia Papadaki, Vasiliki Zolota, Christopher Logothetis, Aristidis G Vrahatis, Rama Soundararajan, Vasiliki Tzelepi

Faculty, Staff and Student Publications

Prostate cancer (PCa), the most frequent and second most lethal cancer type in men in developed countries, is a highly heterogeneous disease. PCa heterogeneity, therapy resistance, stemness, and lethal progression have been attributed to lineage plasticity, which refers to the ability of neoplastic cells to undergo phenotypic changes under microenvironmental pressures by switching between developmental cell states. What remains to be elucidated is how to identify measurements of lineage plasticity, how to implement them to inform preclinical and clinical research, and, further, how to classify patients and inform therapeutic strategies in the clinic. Recent research has highlighted the crucial role …


Quantitative Longitudinal Mapping Of Radiation-Treated Prostate Cancer Using Mr Fingerprinting With Radial Acquisition And Subspace Reconstruction, Victoria Y Yu, Ricardo Otazo, Can Wu, Ergys Subashi, Manuel Baumann, Peter Koken, Mariya Doneva, Peter Mazurkewitz, Daniel Shasha, Michael Zelefsky, Laura Cervino, Ouri Cohen Sep 2023

Quantitative Longitudinal Mapping Of Radiation-Treated Prostate Cancer Using Mr Fingerprinting With Radial Acquisition And Subspace Reconstruction, Victoria Y Yu, Ricardo Otazo, Can Wu, Ergys Subashi, Manuel Baumann, Peter Koken, Mariya Doneva, Peter Mazurkewitz, Daniel Shasha, Michael Zelefsky, Laura Cervino, Ouri Cohen

Faculty, Staff and Student Publications

MR fingerprinting (MRF) enables fast multiparametric quantitative imaging with a single acquisition and has been shown to improve diagnosis of prostate cancer. However, most prostate MRF studies were performed with spiral acquisitions that are sensitive to B0 inhomogeneities and consequent blurring. In this work, a radial MRF acquisition with a novel subspace reconstruction technique was developed to enable fast T1/T2 mapping in the prostate in under 4 min. The subspace reconstruction exploits the extensive temporal correlations in the MRF dictionary to pre-compute a low dimensional space for the solution and thus reduce the number of radial spokes to accelerate the …


Fibronectin Contributes To A Braf Inhibitor-Driven Invasive Phenotype In Thyroid Cancer Through Egr1, Which Can Be Blocked By Inhibition Of Erk1/2, Hannah M Hicks, Nikita Pozdeyev, Sharon B Sams, Umarani Pugazhenthi, Elise S Bales, Marie-Claude Hofmann, Logan R Mckenna, Rebecca E Schweppe Sep 2023

Fibronectin Contributes To A Braf Inhibitor-Driven Invasive Phenotype In Thyroid Cancer Through Egr1, Which Can Be Blocked By Inhibition Of Erk1/2, Hannah M Hicks, Nikita Pozdeyev, Sharon B Sams, Umarani Pugazhenthi, Elise S Bales, Marie-Claude Hofmann, Logan R Mckenna, Rebecca E Schweppe

Faculty, Staff and Student Publications

Mutations in BRAF are common in advanced papillary and anaplastic thyroid cancer (PTC and ATC). However, patients with BRAF-mutant PTC currently lack therapies targeting this pathway. Despite the approved combination of BRAF and MEK1/2 inhibition for patients with BRAF-mutant ATC, these patients often progress. Thus, we screened a panel of BRAF-mutant thyroid cancer cell lines to identify new therapeutic strategies. We showed that thyroid cancer cells resistant to BRAF inhibition (BRAFi) exhibit an increase in invasion and a proinvasive secretome in response to BRAFi. Using reverse-phase protein array (RPPA), we identified a nearly 2-fold increase in expression of the extracellular …


Gut Oncomicrobiome Signatures (Goms) As Next-Generation Biomarkers For Cancer Immunotherapy, Andrew Maltez Thomas, Marine Fidelle, Bertrand Routy, Guido Kroemer, Jennifer A Wargo, Nicola Segata, Laurence Zitvogel Sep 2023

Gut Oncomicrobiome Signatures (Goms) As Next-Generation Biomarkers For Cancer Immunotherapy, Andrew Maltez Thomas, Marine Fidelle, Bertrand Routy, Guido Kroemer, Jennifer A Wargo, Nicola Segata, Laurence Zitvogel

Faculty, Staff and Student Publications

Oncogenesis is associated with intestinal dysbiosis, and stool shotgun metagenomic sequencing in individuals with this condition might constitute a non-invasive approach for the early diagnosis of several cancer types. The prognostic relevance of antibiotic intake and gut microbiota composition urged investigators to develop tools for the detection of intestinal dysbiosis to enable patient stratification and microbiota-centred clinical interventions. Moreover, since the advent of immune-checkpoint inhibitors (ICIs) in oncology, the identification of biomarkers for predicting their efficacy before starting treatment has been an unmet medical need. Many previous studies addressing this question, including a meta-analysis described herein, have led to the …


Efficacy Of Immune Checkpoint Inhibitors For The Treatment Of Advanced Melanoma In Patients With Concomitant Chronic Lymphocytic Leukemia, S H Cass, J W D Tobin, Y D Seo, G Gener-Ricos, E Z Keung, E M Burton, M A Davies, J L Mcquade, A J Lazar, R Mason, M Millward, S Sandhu, C Khoo, L Warburton, V Guerra, A Haydon, H Dearden, A M Menzies, M S Carlino, J L Smith, P Mollee, M Burgess, S Mapp, C Keane, V Atkinson, S A Parikh, S N Markovic, W Ding, T G Call, P J Hampel, G V Long, J A Wargo, A Ferrajoli Sep 2023

Efficacy Of Immune Checkpoint Inhibitors For The Treatment Of Advanced Melanoma In Patients With Concomitant Chronic Lymphocytic Leukemia, S H Cass, J W D Tobin, Y D Seo, G Gener-Ricos, E Z Keung, E M Burton, M A Davies, J L Mcquade, A J Lazar, R Mason, M Millward, S Sandhu, C Khoo, L Warburton, V Guerra, A Haydon, H Dearden, A M Menzies, M S Carlino, J L Smith, P Mollee, M Burgess, S Mapp, C Keane, V Atkinson, S A Parikh, S N Markovic, W Ding, T G Call, P J Hampel, G V Long, J A Wargo, A Ferrajoli

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses.

PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients …


Cell Entry And Release Of Quasi-Enveloped Human Hepatitis Viruses, Anshuman Das, Efraín E Rivera-Serrano, Xin Yin, Christopher M Walker, Zongdi Feng, Stanley M Lemon Sep 2023

Cell Entry And Release Of Quasi-Enveloped Human Hepatitis Viruses, Anshuman Das, Efraín E Rivera-Serrano, Xin Yin, Christopher M Walker, Zongdi Feng, Stanley M Lemon

Faculty, Staff and Student Publications

Infectious hepatitis type A and type E are caused by phylogenetically distinct single-stranded, positive-sense RNA viruses that were once considered to be non-enveloped. However, studies show that both are released nonlytically from hepatocytes as 'quasi-enveloped' virions cloaked in host membranes. These virion types predominate in the blood of infected individuals and mediate virus spread within the liver. They lack virally encoded proteins on their surface and are resistant to neutralizing anti-capsid antibodies induced by infection, yet they efficiently enter cells and initiate new rounds of virus replication. In this Review, we discuss the mechanisms by which specific peptide sequences in …


Time For Bugs: The Immune Microenvironment And Microbes In Precancer, Mikayla Borthwick Bowen, Beth A Helmink, Jennifer A Wargo, Melinda S Yates Sep 2023

Time For Bugs: The Immune Microenvironment And Microbes In Precancer, Mikayla Borthwick Bowen, Beth A Helmink, Jennifer A Wargo, Melinda S Yates

Faculty, Staff and Student Publications

Major advances in our understanding of the tumor immune microenvironment (TIME) in established cancer have been made, including the influence of host-intrinsic (host genomics) and -extrinsic factors (such as diet and the microbiome) on treatment response. Nonetheless, the immune and microbiome milieu across the spectrum of precancerous tissue and early neoplasia is a growing area of interest. There are emerging data describing the contribution of the immune microenvironment and microbiota on benign and premalignant tissues, with opportunities to target these factors in cancer prevention and interception. Throughout this review, we provide rationale for not only the critical need to further …


Bayesian Hierarchical Quantile Regression With Application To Characterizing The Immune Architecture Of Lung Cancer, Priyam Das, Christine B Peterson, Yang Ni, Alexandre Reuben, Jiexin Zhang, Jianjun Zhang, Kim-Anh Do, Veerabhadran Baladandayuthapani Sep 2023

Bayesian Hierarchical Quantile Regression With Application To Characterizing The Immune Architecture Of Lung Cancer, Priyam Das, Christine B Peterson, Yang Ni, Alexandre Reuben, Jiexin Zhang, Jianjun Zhang, Kim-Anh Do, Veerabhadran Baladandayuthapani

Faculty, Staff and Student Publications

The successful development and implementation of precision immuno-oncology therapies requires a deeper understanding of the immune architecture at a patient level. T-cell receptor (TCR) repertoire sequencing is a relatively new technology that enables monitoring of T-cells, a subset of immune cells that play a central role in modulating immune response. These immunologic relationships are complex and are governed by various distributional aspects of an individual patient's tumor profile. We propose Bayesian QUANTIle regression for hierarchical COvariates (QUANTICO) that allows simultaneous modeling of hierarchical relationships between multilevel covariates, conducts explicit variable selection, estimates quantile and patient-specific coefficient effects, to induce individualized …


Spatially-Aware Clustering Improves Ajcc-8 Risk Stratification Performance In Oropharyngeal Carcinomas, Guadalupe Canahuate, Andrew Wentzel, Abdallah S R Mohamed, Lisanne V Van Dijk, David M Vock, Baher Elgohari, Hesham Elhalawani, Clifton D Fuller, G Elisabeta Marai Sep 2023

Spatially-Aware Clustering Improves Ajcc-8 Risk Stratification Performance In Oropharyngeal Carcinomas, Guadalupe Canahuate, Andrew Wentzel, Abdallah S R Mohamed, Lisanne V Van Dijk, David M Vock, Baher Elgohari, Hesham Elhalawani, Clifton D Fuller, G Elisabeta Marai

Faculty, Staff and Student Publications

OBJECTIVE: Evaluate the effectiveness of machine learning tools that incorporate spatial information such as disease location and lymph node metastatic patterns-of-spread, for prediction of survival and toxicity in HPV+ oropharyngeal cancer (OPC).

MATERIALS & METHODS: 675 HPV+ OPC patients that were treated at MD Anderson Cancer Center between 2005 and 2013 with curative intent IMRT were retrospectively collected under IRB approval. Risk stratifications incorporating patient radiometric data and lymph node metastasis patterns via an anatomically-adjacent representation with hierarchical clustering were identified. These clusterings were combined into a 3-level patient stratification and included along with other known clinical features in a …


Interleukin-10 In Cancer Immunotherapy: From Bench To Bedside, Mohamad Adham Salkeni, Aung Naing Sep 2023

Interleukin-10 In Cancer Immunotherapy: From Bench To Bedside, Mohamad Adham Salkeni, Aung Naing

Faculty, Staff and Student Publications

Interleukin (IL)-10 was one of the first cytokines to be recognized. However, its functionality in promoting antitumor immunity was described more recently. Context- and concentration-dependent biological effects are the hallmarks of the pleiotropic role of IL-10. Despite reducing tumor-promoting inflammation, IL-10 may have a role in rejuvenating exhausted tumor-resident T cells. Contrary to the assumption that IL-10 produces an immunosuppressive tumor microenvironment (TME), it promotes activation of tumor-resident CD8+ T cells, which aids tumor rejection. Emerging data from published early-Phase trials have shown mixed results in different tumor types. In this review, we summarize the biological effects of IL-10 and …


Numerical Investigation Of Stress Concentrations At The Attachment Of Tendon To Bone, Panwei Yuan Sep 2023

Numerical Investigation Of Stress Concentrations At The Attachment Of Tendon To Bone, Panwei Yuan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Attachment of dissimilar materials can result in high levels of localized stress at their interfaces, which can predispose a structure to failure. The stress concentrations at such interfaces are well characterized for linear elasticity. However, extending this understanding to nonlinear materials is not straightforward. In biological materials, local stiffness may increase in response to elevated stress, and in metals, local stiffness may decrease; however, the effect of this is not well characterized for free edge singularities. The main goal of this research was therefore to investigate the effect of nonlinearity using numerical analysis, then to describe stress concentrations that arise …


Advances And Perspectives Of Using Stable Isotope Probing (Sip)-Based Technologies In Contaminant Biodegradation, Jinha Kim, Myung Hwangbo, Chih-Hsuan Shih, Kung-Hui Chu Sep 2023

Advances And Perspectives Of Using Stable Isotope Probing (Sip)-Based Technologies In Contaminant Biodegradation, Jinha Kim, Myung Hwangbo, Chih-Hsuan Shih, Kung-Hui Chu

School of Earth, Environmental, & Marine Sciences Faculty Publications

Stable isotope probing (SIP) is a powerful tool to study microbial community structure and function in both nature and engineered environments. Coupling with advanced genomics and other techniques, SIP studies have generated substantial information to allow researchers to draw a clearer picture of what is occurring in complex microbial ecosystems. This review provides an overview of the advances of SIP-based technologies over time, summarizes the status of SIP applications to contaminant biodegradation, provides critical perspectives on ecological interactions within the community, and important factors (controllable and non-controllable) to be considered in SIP experimental designs and data interpretation. Current trend and …


Protective Factors In The Relationship Between Perceived Discrimination And Risky Drinking Among American Indian Adolescent, Ying Guo, Randall C. Swaim, W. Alex Mason Sep 2023

Protective Factors In The Relationship Between Perceived Discrimination And Risky Drinking Among American Indian Adolescent, Ying Guo, Randall C. Swaim, W. Alex Mason

Department of Child, Youth, and Family Studies: Faculty Publications

Introduction: The relationship between perceived discrimination and risky drinking among American Indian (AI) youth is understudied, and the potential protective factors that may buffer this association are unknown. Therefore, the objective of this study was to examine protective factors across individual, family, school, peer, and cultural domains of the social ecology that might attenuate the relationship between perceived discrimination and risky drinking among AI adolescents.

Method: Data were from the Substance Use Among American Indian Youth Study (Swaim and Stanley, 2018, 2021). AI youth who have used alcohol in their lifetime (n = 2516 within 62 schools) …


Associations Between Birth Weight And Adult Sleep Characteristics: A Cross-Sectional Analysis From The Uaehfs, Nirmin F. Juber, Abdishakur Abdulle, Amar Ahmad, Andrea Leinberger-Jabari, Ayesha S.Al Dhaheri, Fatma Al-Maskari, Fatme Alanouti, Mohammad Al-Houqani, Mohammed Hag Ali, Omar El-Shahawy, Scott Sherman, Syed M. Shah, Tom Loney, Youssef Idaghdour, Raghib Ali Sep 2023

Associations Between Birth Weight And Adult Sleep Characteristics: A Cross-Sectional Analysis From The Uaehfs, Nirmin F. Juber, Abdishakur Abdulle, Amar Ahmad, Andrea Leinberger-Jabari, Ayesha S.Al Dhaheri, Fatma Al-Maskari, Fatme Alanouti, Mohammad Al-Houqani, Mohammed Hag Ali, Omar El-Shahawy, Scott Sherman, Syed M. Shah, Tom Loney, Youssef Idaghdour, Raghib Ali

All Works

Abnormal birth weight, particularly low birth weight (LBW), is known to have long-term adverse health consequences in adulthood, with disrupted sleep being suggested as a mediator or modifier of this link. We thus aimed to assess the associations between birth weight and self-reported adult sleep characteristics: sleep duration, difficulty waking up in the morning, daily nap frequency, sleep problems at night, snoring, daytime tiredness or sleepiness, and ever-stop breathing during sleep. This cross-sectional analysis used the United Arab Emirates Healthy Future Study data collected from February 2016 to March 2023 involving 2124 Emiratis aged 18–61 years. We performed a Poisson …


Investigating The Differences Between Neuropsychological And Physiological Markers In A Ptsd-Only Group Among Vietnam Veterans, Ashtan Madsen Sep 2023

Investigating The Differences Between Neuropsychological And Physiological Markers In A Ptsd-Only Group Among Vietnam Veterans, Ashtan Madsen

Dissertations

Individuals diagnosed with posttraumatic stress disorder (PTSD) have demonstrated extinction-resistant symptoms and long-lasting impacts on the brain’s functional activity (Krystal et al., 2017; Stark et al., 2015). PTSD illustrates a strong relationship with cognitive functioning, and research has found lower parietal and hippocampal volume and deterioration in brain function and structure, resulting in executive dysfunction, attentional deficits, mood dysregulation, and memory difficulties (Krystal et al., 2017; Stark et al., 2015; Weiner et al. 2017). Sleep has been investigated to better understand its contribution to AD pathologies as well as its impact on PTSD treatment and prognosis. Although sleep’s functions are …


Characterization Of P75ntr Interactors In Midbrain Dopaminergic Neurons, Lorelei Darzi Sep 2023

Characterization Of P75ntr Interactors In Midbrain Dopaminergic Neurons, Lorelei Darzi

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by the deterioration of neurons that communicate via dopamine. These dopaminergic neurons undergo a phenomenon known as oxidative stress, which obstructs neuronal functioning and results in cell death. There is no treatment for PD that is highly effective in preventing neurodegeneration, so it is imperative to research its mechanisms at the molecular level. The p75 neurotrophin receptor (p75NTR) is a poorly understood protein that is involved in neurodegeneration. Oxidative stress has been shown to induce p75NTR signaling by triggering regulated proteolysis of the receptor. In the present study, we evaluated …


Describing The Effects Of Antibiotic-Resistance Ribosomes On Gene Expression In Bacteria, Kieffer Haehnlein Sep 2023

Describing The Effects Of Antibiotic-Resistance Ribosomes On Gene Expression In Bacteria, Kieffer Haehnlein

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

The ribosome is the cellular structure responsible for protein synthesis and is the target of certain antibiotics in bacteria. All peptides leave the ribosome through a region called the exit tunnel, which is composed of proteins and rRNA. Interactions between peptides exiting the ribosome and the component of the exit tunnel called the constriction site can be a determining factor in whether gene expression will continue. Previous research efforts have found that SVS1144 Escherichia Coli (E. coli) experience a decrease in expression of the lysine-dependent acid-resistance gene CadB when the cells possessed the K90D mutation, in which the 90th residue …