Digital Commons Network^™

Foxo Factors’ Ability In Binding To And Inducing Tcf7 In Glioblastoma Cells, Stephanie Oyervides

Theses and Dissertations

Glioblastoma Multiforme (GBM) is an aggressive astrocytoma tumor type with a poor prognosis and limited immunotherapeutic options for those inflicted. Stem gene expression of this cancer indicates a direct relationship with the transcription factors, Forkhead box subfamily O (FOXO-1, -3 and - 4). These transcription factors are evolutionarily conserved, partially redundant. They are involved in diverse and fundamental biological processes such as cell survival, stem cell homeostasis, cell fate determination, cell cycle maintenance, metabolism, and apoptosis. Increasing evidence suggests interconnectivity between the WNT Pathway and FOXO transcription factors; however, the mechanism and full extent to which these interactions play a …

Contributions Of Citizen Science Data To Butterflies Of The Lower Rio Grande Valley, Akane Jazmyn Benitez

Theses and Dissertations

Citizen science-provided insect data inherently exhibits variability in accuracy. In the Lower Rio Grande Valley (LRGV), butterfly occurrence reporting is predominantly reliant on citizen science contributions. My research compared fieldwork conducted monthly over a year to occurrence records submitted by visitors at the National Butterfly Center and in Mission, Hidalgo County, Texas. I hypothesized that butterfly occurrences at the Center would be maximized during the fall and minimized during winter and summer months. My research findings revealed that butterfly taxa richness is contingent upon the following factors: 1) the impact of citizen science submitting reports, and 2) monthly butterfly activity …

Oxytocin As A Possible Vegf Inhibitor For Treatment Of Diabetic Retinopathy, Daira Yepez

Theses and Dissertations

Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of vision loss largely driven by the overexpression of vascular endothelial growth factor (VEGF), which promotes neovascularization and vascular permeability in the retina. Current treatments, primarily anti-VEGF injections, inhibit the effects of VEGF once it has been secreted but can be ineffective in a certain subset of patients. Recent studies suggest that oxytocin (OXT), a neuropeptide mainly known for its roles in reproduction and social bonding, may downregulate VEGF expression. This study aimed to investigate whether OXT influences VEGF secretion in the human retinal pigment epithelial (RPE) …

Microbial Biosensor For Sensing And Treatment Of Intestinal Inflammation, Duolong Zhu, Jeffrey Galley, Jason Pizzini, Elena Musteata, Martin V Douglas, Walter J Chazin, Eric P Skaar, Jeffrey J Tabor, Robert A Britton

Faculty, Staff and Students Publications

Synthetic biology has enabled the development of biosensors to detect intestinal inflammation, yet few target the clinically validated biomarker of intestinal inflammation calprotectin with both diagnostic and therapeutic capabilities. Here, an optimized calprotectin biosensor is presented that leverages a zinc uptake regulator (Zur) controlled promoter coupled with a memory circuit to detect and record intestinal inflammation in vivo. The level of biosensor activation strongly correlates with calprotectin levels in the colon of two independent mouse models of colitis. Coupling of the biosensor with the production of the anti-inflammatory cytokine IL10 allowed for the resolution of chemically induced colitis, demonstrating the …

Association Of Statin Use On Survival Outcomes Of Patients With Early-Stage Her2-Positive Breast Cancer In The Aphinity Trial, Christian Maurer, Elisa Agostinetto, Lieveke Ameye, Matteo Lambertini, Samuel Martel, Noam Ponde, Mariana Brandão, Francesca Poggio, Arlindo Ferreira, Rachel Schiff, Carmine De Angelis, Richard D Gelber, Susan Dent, Christoph Thomssen, Martine Piccart, Evandro De Azambuja

Faculty, Staff and Students Publications

Purpose: There is evidence that statins might improve the outcome of patients with breast cancer. The role of statins in patients with early HER2-positive breast cancer is unknown. Therefore, we explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial (adjuvant pertuzumab/trastuzumab).

Methods: All patients (intent-to-treat population, n = 4804) were included (6.2 years median follow-up database). The primary objective was to investigate the association of statin use on invasive disease-free survival (IDFS), distant relapse-free interval (DRFI), and overall survival (OS). Patients who received statins at baseline, or started …

Activation Of Toll-Like Receptor 2 Promotes The Expression Of Inflammatory Mediators And Cell Proliferation Of Human Polycystic Kidney Disease Cells, Yang Zhang, Matthew Plansinis, Sophia Peak, Elisabeth Weber, Aiping Wei, Yu Xu, Madelyn Ross, Abigail Leagjeld, Darren P. Wallace, Yan Zhang

Michigan Tech Publications

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive enlargement of fluid-filled cysts, leading to a decline in renal function. Toll-like receptors (TLR)-2 and TLR4 are pattern recognition receptors and components of the innate immune response. We found that mRNA levels for TLR2 and TLR4, an adaptor protein MyD88, and the transcription factor NF-κB were elevated in the kidneys of ADPKD patients and PKD mice. There was decreased expression of IκBα, an inhibitory protein sequestering NF-κB in the cytosol, and increased NF-κB nuclear translocation in human ADPKD kidneys compared with normal human kidneys (NHK). Pam3CSK4, a synthetic TLR2 …

A Brief Guide To Statistical Analysis Of Grouped Data In Preclinical Research, Colby J Vorland, Lilian Golzarri-Arroyo, David B Allison

Children’s Nutrition Research Center Staff Publications

Clustering and nesting (C&N) arise in many preclinical studies such as when animals are group-housed, share litters, or in cell culture. Ignoring C&N undermines the validity of analyses. We explain how C&N arise and valid designs and analyses.

Lianas Reduce Tree Height With Negative Consequences For Carbon Storage And Growth Estimates, Xingyan Cao, Frieke Van Coillie, Sruthi M. Krishna Moorthy, Kasper Coppieters, Barbara D'Hont, Stefan A. Schnitzer, Geertje M. F. Van Der Heijden, Hans Verbeeck, Félicien Meunier

Biological Sciences Faculty Research and Publications

1. Current evidence suggests that liana (woody vine) competition with trees could be threatening the carbon sink by reducing carbon uptake and storage in tropical forests. Previous studies investigating forest demography in liana removal experiments have, however, assumed similar allometries for trees, regardless of the amount of lianas they support. Yet, recent observations suggest that liana load may alter tree shape and structure, including height, which could result in an underestimation of the liana effects on forest carbon stocks and tree growth.
2. In this study, we used terrestrial laser scanning (TLS) in a liana removal experiment in Gigante Peninsula, Panama, collected …

L-Quebrachitol Modulates The Anti-Convulsant Effects Of Carbamazepine Possibly Through Voltage-Gated Sodium Channel Blocking Mechanism In Chicks: In Vivo And In Silico Studies, Asifa Asrafi, Mohammad Aslam, Ali G. Alkhathami, Md. Sakib Hossain, Imam Hossen Rakib, Md. Sakib Al Hasan, Feroz Khan Nun, Md. Faisal Amin, Muhammad Torequl Islam

School of Integrative Biological & Chemical Sciences Faculty Publications

Introduction: L-Quebrachitol (LQB), a naturally occurring bioactive compound, exhibits anti-inflammatory, anti-oxidant, anti-cancer, and anti-diabetic properties. However, its therapeutic potential in convulsant management remains largely unexplored. The objective of this study was to investigate the anticonvulsant effects of LQB in an In Vivo model and to examine its molecular interactions via In Silico docking simulations.

Methods: In the In Vivo study, pentylenetetrazol (PTZ) was administered intraperitoneally (i.p.) at 80 mg/kg to induce convulsions, and the test animals were treated orally with three doses of LQB (1, 5, and 10 mg/kg), with carbamazepine (CBZ) at 80 mg/kg as a standard drug.

Results: …

Bibliometric Analysis Of Congenital Toxoplasmosis: A Ten-Year (2013-2023) Review Of Research Publications, Festus Mulakoli, Horatius Musembi, Ann Kimani

School of Nursing & Midwifery, East Africa

Background:Toxoplasma gondii, an obligate intracellular protozoan, infects more than one-third of the global population and causes toxoplasmosis, which can lead to severe fetal complications in pregnant women. The global prevalence of latent toxoplasmosis in pregnant women is 33.8%, with regional variations and risk factors, including the consumption of undercooked meat, exposure to cat feces, and consumption of contaminated water. Pregnant women lack sufficient awareness of these risk factors, necessitating enhanced education, regular screening, and counseling during antenatal care for early detection and management.

Aim: This study performed a comprehensive bibliometric analysis of research on congenital toxoplasmosis published between 2013 …

Teratogenic Effects Of Serotonin Receptor 2b Disruption On The Migration And Cardiac Derivatives Of The Cardiac Neural Crest, Brian K. Wells, Gwyneth K. Garramone, Amira Mahomed, Max Ezin

Biology Faculty Works

Background: Cardiac neural crest cells (cNCCs) are critical for heart development, and their disruption can result in congenital heart defects. Serotonin (5-HT) signaling, specifically via 5-HT2B and 5-HT2C receptors, regulates diverse physiological processes, including neural crest migration. This study investigates how modulation of 5-HT2B and 5-HT2C receptor activity impacts cNCC migration and the development of their derivatives, with relevance to serotonergic drug safety during pregnancy.

Methods

Chicken embryos at HH8 were treated with 50 μL of 20 μM 1-Methylpsilocin (1-MP), an inverse agonist of 5-HT2B and agonist of 5-HT2C, and collected at HH14 to assess cNCC migration. Embryos were pre-treated …

Reaction Control Mechanism In Deoxyuridine 5'-Triphosphate Nucleotidohydrolase, Aaron Delay

School of Biological Sciences: Dissertations, Theses, and Student Research

Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is an enzyme involved in the pyrimidine biosynthesis pathway, a key component of cellular DNA metabolism. It regulates intracellular uracil carrying triphosphate levels by hydrolyzing dUTP, thereby providing a substrate for thymidylate synthase (TS). The effective inhibition of dUTPase is expected to enhance TS-targeted chemotherapy by promoting thymine-less apoptosis.

Although the reaction mechanism of dUTPase has been studied, the human nuclear homotrimeric form remains complex, as all three subunits cooperatively form a single active site. As a result, the detailed molecular dynamics of its catalysis are still not fully understood. In this study, I investigated the …

Mammals Of Malheur National Wildlife Refuge And Surrounding Harney County, Oregon, John E. Cornely, Leslie N. Carraway

Monographs of the Western North American Naturalist

Malheur National Wildlife Refuge (NWR), located in southeastern Oregon, is part of the National Wildlife Refuge System (NWRS) of the United States. Currently, NWRS includes more than 568 NWRs, 38 Wetland Management Districts, and 5 Marine National Monuments. Malheur NWR, like a majority of the refuges in the NWRS, was established for the conservation of migratory birds. Many of these NWRs also provide significant habitat for mammals. Malheur NWR, one of the oldest (established 1908) and largest refuges in the system, is one of those with significant habitat for mammals. In addition to the refuge, we have included Harney County, …

Renal G Protein-Coupled Estrogen Receptor 1 Regulates The Epithelial Sodium Channel Promoting Natriuresis To A Greater Extent In Females, Victoria L Nasci, Jean C Bopassa, Elena Mironova, Megan Rhoads, Ravneet Singh, Dennis P Buehler, David M Pollock, Oleh M Pochynyuk, James D Stockand, Eman Y Gohar

Faculty, Staff and Student Publications

Hypertension prevalence is lower in women than men. Enhanced renal sodium (Na+) handling in females has been implicated in sex-differences in hypertension. Epithelial Na+ channel (ENaC) is a key contributor to Na+ homeostasis and is regulated by estrogen. Recent evidence suggests G protein-coupled estrogen receptor 1 (GPER1) evokes a female-specific natriuresis that involves endothelin-1 (ET-1). ET-1 has been shown to downregulate ENaC activity, but whether GPER1 regulates ENaC to modulate natriuresis is unknown. We tested the hypothesis that renal GPER1 functionally interacts with ENaC to promote natriuresis in a sex-specific manner. RNAscope confirmed co-expression of GPER1 and ENaC in rat …

Functional Regulation Of Macrophages By Ces1d-Mediated Lipid Signaling In Immunometabolism, Long J Shao, Fathima Elizondo, Feng Gao, Rabie Habib, Xin Li, Katherine Pham, Jazmin Ysaguirre, Maryam Elizondo, Shirindokht Shirazi, Kristin L Eckel-Mahan, Sean Hartig, Huaizhu Wu, Kai Sun

Faculty, Staff and Student Publications

Objective: Macrophage accumulation in metabolically active tissues during obesity is common in both animals and humans, but the lipid signaling mechanisms that trigger macrophage inflammation remain unclear. This study investigates the role of Ces1d, an unconventional lipase, in regulating macrophage inflammation under nutritional stress.

Methods: A myeloid-specific Ces1d knockout (LysM-Cre-Ces1d floxed/floxed, KO) mouse model was used for the studies. For in vitro tests, bone marrow-derived macrophages (BMDMs) from control (Ces1d floxed/floxed, WT) and KO mice were assessed for migration, polarization, and activation. For in vivo experiments, WT and KO mice were induced to obesity via a high-fat diet (HFD) and …

Coordinated Regulation By Lncrnas Results In Tight Lncrna-Target Couplings, Hua-Sheng Chiu, Sonal Somvanshi, Chung-Te Chang, Eric James De Bony De Lavergne, Zhaowen Wei, Chih-Hung Hsieh, Wim Trypsteen, Kathleen A Scorsone, Ektaben Patel, Tien T Tang, David B Flint, Mohammad Javad Najaf Panah, Hyunjae Ryan Kim, Purva Rathi, Yan-Hwa Wu Lee, Sarah E Woodfield, Sanjeev A Vasudevan, Andras Attila Heczey, M Waleed Gaber, Gabriel O Sawakuchi, Ting-Wen Chen, Pieter Mestdagh, Xuerui Yang, Pavel Sumazin

Faculty, Staff and Student Publications

The determination of long non-coding RNA (lncRNA) function is a major challenge in RNA biology with applications to basic, translational, and medical research. We developed BigHorn to computationally infer lncRNA-DNA interactions that mediate transcription and chromatin-remodeling factor activity. Its accurate inference enabled the identification of lncRNAs that coordinately regulate both the transcriptional and post-transcriptional processing of their targets. These lncRNAs may act as molecular chaperones, regulating the stability and translation of mRNAs they helped transcribe, leading to tightly coupled expression profiles. Our analysis suggests that lncRNAs regulate cancer genes across tumor contexts, thus propagating the effects of non-coding alterations to …

The Long-Term Effects Of Chemotherapy On Normal Blood Cells, Emily Mitchell, My H Pham, Anna Clay, Rashesh Sanghvi, Nicholas Williams, Sandra Pietsch, Joanne I Hsu, Nina Friesgaard Øbro, Hyunchul Jung, Aditi Vedi, Sarah Moody, Jingwei Wang, Daniel Leonganmornlert, Michael Spencer Chapman, Ellie Dunstone, Anna Santarsieri, Alex Cagan, Heather E Machado, E Joanna Baxter, George Follows, Daniel J Hodson, Ultan Mcdermott, Gary J Doherty, Inigo Martincorena, Laura Humphreys, Krishnaa Mahbubani, Kourosh Saeb Parsy, Koichi Takahashi, Margaret A Goodell, David Kent, Elisa Laurenti, Peter J Campbell, Raheleh Rahbari, Jyoti Nangalia, Michael R Stratton

Faculty, Staff and Student Publications

Several chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage in normal tissues. To investigate the impact of chemotherapy on mutation burdens and the cell population structure of normal tissue, we sequenced blood cell genomes from 23 individuals aged 3-80 years who were treated with a range of chemotherapy regimens. Substantial additional somatic mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but the effects were dependent on the drug and blood cell types. Chemotherapy induced premature changes …

Pollination And Essential Oil Production Of Lavandula Angustifolia Mill. (Lamiaceae), Riley B. Jackson, Tyler M. Wilson, Joseph S. Wilson, Zabrina Ruggles, Lindsey Topham Wilson, Chris Packer, Jacob G. Young, Christopher R. Bowerbank, Richard E. Carlson

Biology Faculty Publications

Lavandula angustifolia Mill., lavender, is an aromatic plant in the Lamiaceae family. Lavender, which is native to the Mediterranean region but cultivated throughout the world, is an important economic plant. Several studies have investigated two aspects of this aromatic plant: (1) which pollinators, particularly bees, pollinate lavender, and (2) the composition of lavender essential oil. However, little research has been conducted to investigate how pollination affects either the yield or phytochemistry of lavender. The current study, which was conducted in North America, investigates which bee species visit lavender and how pollination affects plant chemistry, specifically the essential oil produced by …

Investigating The Immunomodulatory Effects Of Cdk8/19 Inhibitor Senexin631 In A Her2-Positive Breast Cancer Model, Stephen O'Rourke

Theses and Dissertations

HER2-positive (HER2⁺) breast cancer is aggressive and often develops resistance to anti-HER2 therapies. CDK8 and CDK19, transcription-associated cyclin-dependent kinases (tCDKs) in the Mediator complex, are dysregulated in HER2⁺ breast cancer, correlate with poor survival, and support transcriptional escape driving therapeutic resistance. Previous studies Previous studies in immune-deficient models demonstrated that CDK8/19 inhibition (CDK8/19i) reduces pro-tumor macrophages (M2Φs), but its role in immune-competent tumors and innate immune–mediated tumor control remains unclear. Since HER2⁺ tumors are often immunogenic and anti-HER2 therapies rely on innate immune activation, reprogramming immunosuppressive M2Φ toward an M1Φ-like phenotype could enhance antitumor immunity. We hypothesized that CDK8/19i modulates …

Mtap Immunohistochemistry As A Surrogate Marker Of Cdkn2a Loss In Brain Tumors: A Meta-Analysis And Literature Review, Antonio Dono, Diego Pichardo-Rojas, Leonardo Mendoza Mora, Pavel S Pichardo-Rojas, Luis A Marin-Castañeda, Abril Carrillo, Adrian Coria Medrano, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

Given the known relationship between CDKN2A homozygous deletion (HD) and worsened outcomes in both meningiomas and IDH-mutant astrocytomas, it is paramount to identify CDKN2A HD for accurate risk stratification of patients. Multiple array platforms can detect CDKN2A HD. However, these methods are expensive and are not readily available at every institution. To address this, we conducted a meta-analysis and literature review to evaluate 5'-methylthioadenosine phosphorylase (MTAP) expression determined by immunohistochemistry (IHC) as a surrogate of CDKN2A HD. Our study analyzed 7 cohort studies, 3 of which focused on meningiomas encompassing a total of 87 patients; and 4 studies were conducted …

Non-Invasive Tools For Analysis Of Plasma Membrane Protein Topology In Living Cells, Daria Savenkova, Leysan Bulatova, Vera Skripova, Ramziya Kiyamova, Mikhail Bogdanov

Faculty, Staff and Student Publications

Membrane protein topology studies offer guidance to membrane protein structure, folding, and function, serving as a credible scaffold for designing site-directed mutagenesis and biochemical experiments, helping to identify functionally significant extracellular and intracellular regions, modeling three-dimensional structures, and building reliable mechanistic models. Membrane protein structure as a function of given lipid composition and physiological state of the cell is best probed in whole intact cells. A described simple and advanced immunofluorescence protocol applied to the transmembrane orientation of extramembrane domains permits a topology analysis of plasma membrane proteins in their native state in living unperturbed eucaryotic cells. The accessibility of …

Long Akap18 Isoforms Anchor Ubiquitin Specific Proteinases And Coordinate Calcium Reuptake At The Sarcoplasmic Reticulum, Taeyeop Park, Katherine Forbush, Yong Li, Oscar Vivas, Kacey J Rosenthal, Jerome Falcone, Cassandra J Wong, James E Bruce, Claudia Moreno, Carmen W Dessauer, John D Scott

Faculty, Staff and Student Publications

Subcellular targeting of signaling enzymes influences where and when various modes of intracellular communication operate. Macromolecular complexes of signal transduction and signal termination elements favor reversible control of repetitive processes. This includes adrenergic stimulation of excitation–contraction coupling in the heart. Long isoforms of A-kinase anchoring protein 18 (AKAP18γ and δ) modulate this process via regulation of calcium uptake into the sarcoplasmic reticulum through the Ca2+ATPase 2a (SERCA2a). AKAP18 proximity-proteomic screening in cardiomyocytes identifies networks for protein kinase A (PKA) and ubiquitin-specific proteinases (USPs). A 2′phosphoesterase domain on AKAP18 interfaces with the USP4 isoform at the Z bands of sarcomeres. PKA …

Bridging Cell Morphological Behaviors And Molecular Dynamics In Multi-Modal Spatial Omics With Morphlink, Jing Huang, Chenyang Yuan, Jiahui Jiang, Jianfeng Chen, Sunil S Badve, Yesim Gokmen-Polar, Rossana L Segura, Xinmiao Yan, Alexander Lazar, Jianjun Gao, Bing Yao, Michael Epstein, Linghua Wang, Jian Hu

Faculty, Staff and Student Publications

Multi-modal spatial omics data are invaluable for exploring complex cellular behaviors in diseases from both morphological and molecular perspectives. Current analytical methods primarily focus on clustering and classification, and do not adequately examine the relationship between cell morphology and molecular dynamics. Here, we present MorphLink, a framework designed to systematically identify disease-related morphological-molecular interplays. MorphLink has been evaluated across a wide array of datasets, showcasing its effectiveness in extracting and linking interpretable morphological features with various molecular measurements in spatial omics analyses. These linkages provide a transparent view of cellular behavior heterogeneity within tissue regions with similar cell type compositions, …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas F Mcelrath, Arun Jeyabalan, Arkady Khodursky, Alison B Moe, Manfred Lee, Maneesh Jain, Laura Goetzl, Elizabeth F Sutton, Pamela M Simmons, George R Saade, Antonio Saad, Luis D Pacheco, Esther Park-Hwang, Antonina I Frolova, Ebony B Carter, Ai-Ris Y Collier, Daniel G Kiefer, Vincenzo Berghella, Rupsa C Boelig, Michal A Elovitz, Cynthia Gyamfi-Bannerman, Joseph R Biggio, Kara Rood, William A Grobman, Carrie Haverty, Morten Rasmussen

Faculty, Staff and Student Publications

Importance: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

Objective: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

Design, setting, and participants: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

Practical Considerations For Using The Tite-Boin Design To Handle Late-Onset Toxicity Or Fast Accrual In Phase I Trials, Kai Chen, Ting-Yu Chen, Yiming Zhang, Ruitao Lin, Ying Yuan

Faculty, Staff and Student Publications

Conducting phase I trials is particularly challenging when dealing with late-onset dose-limiting toxicity (DLT) or when patient accrual is rapid relative to the DLT assessment window. In such cases, a new cohort may be ready for enrollment before the DLT assessments are complete for the current cohort, complicating dose assignment decisions. The time-to-event Bayesian optimal interval (TITE-BOIN) design was developed to address this issue by enabling real-time dose assignment for new cohorts, even when some enrolled patients' DLT data are still pending. This design has been increasingly adopted in practice. Upon reviewing trial protocols utilizing TITE-BOIN, we observed considerable variation …

The Landscape Of Malignant Transition: Unraveling Cancer Cell-Of-Origin And Heterogeneous Tissue Microenvironment, Ruihan Luo, Jiajia Liu, Tiangang Wang, Weiling Zhao, Yanfei Wang, Jianguo Wen, Hongyu Wang, Shanli Ding, Xiaobo Zhou

Faculty, Staff and Student Publications

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced …

Diagnostic Guidance For Chronic Complex Regional Pain Syndrome Type I And Type Ii From The American Society Of Interventional Physicians (Asipp), Christopher Gharibo, Miles Day, Steve M Aydin, Alan D Kaye, Salahadin Abdi, Sudhir Diwan, Lisa V Doan, Danielle Feng, Kris Ferguson, Kirolos Georges, Andrew Kaufman, Nebojsa Nick Knezevic, Sean Li, Franzes A Liongson, Devi Nampiaparampil, Annu Navani, Mahendra Sanapati, Michael E Schatman, Amol Soin, Peter S Staats, Giustino Varrassi, Jing Wang, Laxmaiah Manchikanti

Faculty, Staff and Student Publications

Background: Complex Regional Pain Syndrome (CRPS) is a challenging and often disabling condition marked by persistent pain, most commonly in a limb following injury or surgery. It presents with a wide array of symptoms, including intense pain, swelling, alterations in skin color and temperature, motor dysfunction, and trophic changes such as skin and tissue atrophy. While the precise cause of CRPS is not fully understood, it is thought to stem from abnormal nervous system activity, leading to heightened pain sensitivity and inflammatory responses. A thorough understanding of CRPS is essential for accurate diagnosis, effective treatment, and enhancing patients' quality of …

Ovarian Cancer Risk And Survival According To Tumor Sex Hormone Receptor Expression: An Ovarian Cancer Association Consortium And Ovarian Tumor Tissue Analysis Consortium Pooled Analysis, Zhuxuan Fu, Lauren Borho, Sarah E Taylor, Linda E Kelemen, Anna Defazio, Penelope M Webb, Martin Köbel, Nicola S Meagher, Renhua Na, Antonis C Antoniou, Alison H Brand, Catherine J Kennedy, Nikilyn Nevins, Paul D P Pharoah, Yurii B Shvetsov, Stacey J Winham, Jennifer Alsop, Matthias W Beckmann, Adelyn Bolithon, Jessica Boros, David D L Bowtell, James D Brenton, Michael E Carney, Anita Chudecka-Głaz, Linda S Cook, Cezary Cybulski, Peter A Fasching, Sian Fereday, Renée T Fortner, María J García, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Arndt Hartmann, Brenda Y Hernandez, Estrid Høgdall, David G Huntsman, Allan Jensen, Mercedes Jimenez-Linan, Janine M Joseph, Beth Y Karlan, Ewa Kaznowska, Susanne K Kjaer, Tomasz Kluz, Jennifer M Koziak, Jenny Lester, Teri A Longacre, Maria Lycke, Valerie Mcguire, Kirsten B Moysich, Rachel A Murphy, Sandra Orsulic, Susan J Ramus, Cristina Rodríguez-Antona, Joseph H Rothstein, Spinder Samra, Weiva Sieh, Helen Steed, Karin Sundfeldt, Aline Talhouk, Jan Uciński, Chen Wang, Nicolas Wentzensen, Alice S Whittemore, Lynne R Wilkens, Thomas Songer, Maria Mori Brooks, Lu Tang, Francesmary Modugno

Faculty, Staff and Student Publications

Objective: Many epithelial ovarian cancer (EOC) risk factors relate to sex hormones. The association between these factors and the expression of androgen receptor (AR), estrogen receptor-α (ER), and progesterone receptor (PR) in tumors is unknown.

Method: We linked epidemiologic, AR/ER/PR tumor expression, and survival data from 19 studies in the Ovarian Cancer Association Consortium (OCAC; 4762 cases, 20,888 controls) and the Ovarian Tumor Tissue Analysis (OTTA) consortium (5737 cases). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) between hormonally-linked factors and tumor AR/ER/PR expression using polytomous logistic regression. We assessed survival by AR/ER/PR tumor expression overall and …

Bayesian Inference Of Fitness Landscapes Via Tree-Structured Branching Processes, Xiang Ge Luo, Jack Kuipers, Kevin Rupp, Koichi Takahashi, Niko Beerenwinkel

Faculty, Staff and Student Publications

Motivation: The complex dynamics of cancer evolution, driven by mutation and selection, underlies the molecular heterogeneity observed in tumors. The evolutionary histories of tumors of different patients can be encoded as mutation trees and reconstructed in high resolution from single-cell sequencing data, offering crucial insights for studying fitness effects of and epistasis among mutations. Existing models, however, either fail to separate mutation and selection or neglect the evolutionary histories encoded by the tumor phylogenetic trees.

Results: We introduce FiTree, a tree-structured multi-type branching process model with epistatic fitness parameterization and a Bayesian inference scheme to learn fitness landscapes from single-cell …

Βiv Spectrin Abundancy, Cellular Distribution And Sensitivity To Akt/Gsk3 Regulation In Schizophrenia, Jessica Di Re, Michela Marini, Syed Ibrar Hussain, Aditya K Singh, Akshaya Venkatesh, Musaad A Alshammari, Tahani K Alshammari, Abdul-Rizaq Ali Hamoud, Ali Sajid Imami, Zahra Haghighijoo, Nickolas Fularcyzk, Laura Stertz, Derek Hawes, Angela Mosebarger, Jordan Jernigan, Claire Chaljub, Ralda Nehme, Consuelo Walss-Bass, Anton Schulmann, Marquis P Vawter, Robert Mccullumsmith, Robert D Damoiseaux, Agenor Limon, Demetrio Labate, Michael F Wells, Fernanda Laezza

Faculty, Staff and Student Publications

Schizophrenia (SCZ) is a complex psychiatric disorder with unclear biological mechanisms. Spectrins, cytoskeletal proteins linked to neurodevelopmental disorders, are regulated by the AKT/GSK3 pathway, which is implicated in SCZ. However, the impact of SCZ-related dysregulation of this pathway on spectrin expression and distribution remains unexplored. Here, we show that βIV spectrin protein levels were reduced in neurons of the dorsolateral prefrontal cortex in SCZ postmortem samples compared to healthy control (HC) from the Human Brain Collection Core (HBCC). To investigate potential links between βIV spectrin and the AKT/GSK3 pathway, we analyzed the PsychEncode dataset, revealing elevated SPTBN4 and AKT2 mRNA …