Digital Commons Network^™

Dlx2 Promotes Osteosarcoma Epithelial-Mesenchymal Transition And Doxorubicin Resistance By Enhancing Hoxc8-Cdh2 Axis, Boya Zhang, Xinhui Du, Yichao Fan, Guoxin Qu, Lon Kai Pang, Ruiying Zhao, Weitao Yao

Faculty, Staff and Student Publications

Metastasis and doxorubicin resistance are challenges in the clinical diagnosis and treatment of osteosarcoma, the mechanisms underlying these phenomena remain unclear. In this study, we found that DLX2 is highly expressed in metastatic osteosarcoma and is closely related to clinical prognosis. Knockdown of DLX2 inhibited tumor proliferation and migration in vitro and inhibited tumor growth in vivo. Mechanistically, we found that DLX2 enhanced the repression of CDH2 transcription by binding to HOXC8, thereby promoting the epithelial-mesenchymal transition in osteosarcoma cells. Through subsequent exploration, we found that targeting DLX2/HOXC8 signaling significantly restores the sensitivity of osteosarcoma cells to doxorubicin. In …

Pmca Screening Of Retropharyngeal Lymph Nodes In White-Tailed Deer And Comparisons With Elisa And Ihc, Rebeca Benavente, J Hunter Reed, Mitch Lockwood, Rodrigo Morales

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting cervids. CWD diagnosis is conducted through enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in retropharyngeal lymph nodes. Unfortunately, these techniques have limited sensitivity against the biomarker (CWD-prions). Two in vitro prion amplification techniques, real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), have shown promise in detecting CWD-prions in tissues and bodily fluids. Recent studies have demonstrated that RT-QuIC yields similar results compared to ELISA and IHC. Here, we analyzed 1003 retropharyngeal lymph nodes (RPLNs) from Texas white-tailed deer. PMCA detected CWD at a higher rate compared to ELISA/IHC, identified …

Membrane Anchoring Of The Diras3 N-Terminal Extension Permits Tumor Suppressor Function, Xiaowen Liang, Sung Yun Jung, Lon Wolf Fong, Gamze Bildik, Joshua P Gray, Weiqun Mao, Shuxing Zhang, Steven W Millward, Alemayehu A Gorfe, Yong Zhou, Zhen Lu, Robert C Bast

Faculty, Staff and Student Publications

DIRAS3 is an imprinted tumor suppressor gene encoding a GTPase that has a distinctive N-terminal extension (NTE) not found in other RAS proteins. This NTE and the prenylated C-terminus are required for DIRAS3-mediated inhibition of RAS/MAP signaling and PI3K activity at the plasma membrane. In this study, we applied biochemical, biophysical, and computational methods to characterize the structure and function of the NTE. The NTE peptide recognizes phosphoinositides PI(3,4,5)P3 and PI(4,5)P2 with rapid kinetics and strong affinity. Lipid binding induces NTE structural change from disorder to amphipathic helix. Mass spectrometry identified N-myristoylation of DIRAS3. All-atom molecular dynamic simulations predict DIRAS3 …

Rbfox2 Regulated Eya3 Isoforms Partner With Six4 Or Zbtb1 To Control Transcription During Myogenesis, Hannah J Wiedner, R Eric Blue, Matheus Sadovsky, C Allie Mills, Xander H T Wehrens, Laura E Herring, Jimena Giudice

Faculty, Staff and Students Publications

Alternative splicing is a prevalent gene-regulatory mechanism, with over 95% of multi-exon human genes estimated to be alternatively spliced. Here, we describe a tissue-specific, developmentally regulated, highly conserved, and disease-associated alternative splicing event in exon 7 of the eyes absent homolog 3 (Eya3) gene. We discovered that EYA3 expression is vital to the proliferation and differentiation of myoblasts. Genome-wide transcriptomic analysis and mass spectrometry-based proteomic studies identified SIX homeobox 4 (SIX4) and zinc finger and BTB-domain containing 1 (ZBTB1), as major transcription factors that interact with EYA3 to dictate gene expression. EYA3 isoforms differentially regulate transcription, indicating that …

Association Between Trigeminal Neuralgia And Degenerative Cervical Myelopathy: A Cross‐Sectional Study Using Us Data, Robert J. Trager

Faculty Scholarship

Background: Limited research has suggested that trigeminal neuralgia (TN), an often-idiopathic pain disorder affecting the face and head, may arise from compression of the cervical spinal cord due to involvement of the spinal trigeminal tract. We hypothesized that adults with TN would have a greater likelihood of concurrent degenerative cervical myelopathy (DCM) compared to matched adults without TN. Methods: We retrieved de-identified data from a US network (TriNetX, Inc.) including medical records of >113 million patients, with a query date of October 1, 2023, and data spanning the previous 20 years. We created two groups of adults (aged ≥18 years): …

Primary Care Patient Interest In Multi-Cancer Early Detection For Cancer Screening, Ronald Myers, Mie Hallman, Ayako Shimada, Melissa Dicarlo, Kaitlyn Davis, William Leach, Hattie Jackson, Amanda Indictor, Christopher Chambers

Department of Medical Oncology Faculty Papers

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. …

Cytomulate: Accurate And Efficient Simulation Of Cytof Data, Yuqiu Yang, Kaiwen Wang, Zeyu Lu, Tao Wang, Xinlei Wang

Faculty, Staff and Student Publications

Recently, many analysis tools have been devised to offer insights into data generated via cytometry by time-of-flight (CyTOF). However, objective evaluations of these methods remain absent as most evaluations are conducted against real data where the ground truth is generally unknown. In this paper, we develop Cytomulate, a reproducible and accurate simulation algorithm of CyTOF data, which could serve as a foundation for future method development and evaluation. We demonstrate that Cytomulate can capture various characteristics of CyTOF data and is superior in learning overall data distributions than single-cell RNA-seq-oriented methods such as scDesign2, Splatter, and generative models like LAMBDA.

Pharmacokinetics And Safety Of A Single Dose Of Telavancin In Pediatric Subjects 2-17 Years Of Age., John S. Bradley, Jennifer Goldman, Laura P. James, Byron Kaelin, Breanne H Y Gibson, Antonio Arrieta

Manuscripts, Articles, Book Chapters and Other Papers

Antimicrobial resistance increases infection morbidity in both adults and children, necessitating the development of new therapeutic options. Telavancin, an antibiotic approved in the United States for certain bacterial infections in adults, has not been examined in pediatric patients. The objectives of this study were to evaluate the short-term safety and pharmacokinetics (PK) of a single intravenous infusion of telavancin in pediatric patients. Single-dose safety and PK of 10 mg/kg telavancin was investigated in pediatric subjects >12 months to ≤17 years of age with known or suspected bacterial infection. Plasma was collected up to 24-h post-infusion and analyzed for concentrations of …

Baseline Extracellular Vesicle Mirna-30c And Autophagic Ctcs Predict Chemoradiotherapy Resistance And Outcomes In Patients With Lung Cancer, Diego De Miguel-Perez, Francisco Gabriel Ortega, Rosario Guerrero Tejada, Antonio Martínez-Única, Christine B Peterson, Alessandro Russo, Muthukumar Gunasekaran, Andres F Cardona, Victor Amezcua, Jose Antonio Lorente, Jose Expósito Hernández, Christian Rolfo, Maria Jose Serrano

Faculty, Staff and Student Publications

Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 …

Nad+ Rescues Aging-Induced Blood-Brain Barrier Damage Via The Cx43-Parp1 Axis, Rui Zhan, Xia Meng, Dongping Tian, Jie Xu, Hongtu Cui, Jialei Yang, Yangkai Xu, Mingming Shi, Jing Xue, Weiwei Yu, Gaofei Hu, Ke Li, Xiaoxiao Ge, Qi Zhang, Mingming Zhao, Jianyong Du, Xin Guo, Wenli Xu, Yang Gao, Changyu Yao, Fan Chen, Yue Chen, Wenxin Shan, Yujie Zhu, Liang Ji, Bing Pan, Yan Yu, Wenguang Li, Xuyang Zhao, Qihua He, Xiaohui Liu, Yue Huang, Shengyou Liao, Bin Zhou, Dehua Chui, Y Eugene Chen, Zheng Sun, Erdan Dong, Yongjun Wang, Lemin Zheng

Faculty, Staff and Students Publications

Blood-brain barrier (BBB) function deteriorates during aging, contributing to cognitive impairment and neurodegeneration. It is unclear what drives BBB leakage in aging and how it can be prevented. Using single-nucleus transcriptomics, we identified decreased connexin 43 (CX43) expression in cadherin-5

The Role Of Noncoding Rnas In Pancreatic Birth Defects, Ziyue Zoey Yang, Ronald J Parchem

Faculty, Staff and Students Publications

Congenital defects in the pancreas can cause severe health issues such as pancreatic cancer and diabetes which require lifelong treatment. Regenerating healthy pancreatic cells to replace malfunctioning cells has been considered a promising cure for pancreatic diseases including birth defects. However, such therapies are currently unavailable in the clinic. The developmental gene regulatory network underlying pancreatic development must be reactivated for in vivo regeneration and recapitulated in vitro for cell replacement therapy. Thus, understanding the mechanisms driving pancreatic development will pave the way for regenerative therapies. Pancreatic progenitor cells are the precursors of all pancreatic cells which use epigenetic changes …

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …

Circulating Tumor Dna Monitoring On Chemo-Immunotherapy For Risk Stratification In Advanced Non-Small Cell Lung Cancer, Bruna Pellini, Russell W Madison, Merrida A Childress, Shoshana T Miller, Ole Gjoerup, Jason Cheng, Richard S P Huang, Michael Krainock, Pratyush Gupta, Wei Zou, David S Shames, Solomon Moshkevich, Marcus Ballinger, Minetta C Liu, Amanda Young, Minu K Srivastava, Geoffrey R Oxnard, Mark A Socinski

Faculty, Staff and Student Publications

PURPOSE: Chemoimmunotherapy (chemoIO) is a prevalent first-line treatment for advanced driver-negative non-small cell lung cancer (NSCLC), with maintenance therapy given after induction. However, there is significant clinical variability in the duration, dosing, and timing of maintenance therapy after induction chemoIO. We used circulating tumor DNA (ctDNA) monitoring to inform outcomes in patients with advanced NSCLC receiving chemoIO.

EXPERIMENTAL DESIGN: This retrospective study included 221 patients from a phase III trial of atezolizumab+carboplatin+nab-paclitaxel versus carboplatin+nab-paclitaxel in squamous NSCLC (IMpower131). ctDNA monitoring used the FoundationOne Tracker involving comprehensive genomic profiling of pretreatment tumor tissue, variant selection using an algorithm to exclude nontumor …

Novel Clinical Trial Designs With Dose Optimization To Improve Long-Term Outcomes, Peter F Thall, Yong Zang, Andrew G Chapple, Ying Yuan, Ruitao Lin, David Marin, Pavlos Msaouel

Faculty, Staff and Student Publications

Conventional designs for choosing a dose for a new therapy may select doses that are unsafe or ineffective and fail to optimize progression-free survival time, overall survival time, or response/remission duration. We explain and illustrate limitations of conventional dose-finding designs and make four recommendations to address these problems. When feasible, a dose-finding design should account for long-term outcomes, include screening rules that drop unsafe or ineffective doses, enroll an adequate sample size, and randomize patients among doses. As illustrations, we review three designs that include one or more of these features. The first illustration is a trial that randomized patients …

Dhodh: A Promising Target In The Treatment Of T-Cell Acute Lymphoblastic Leukemia, Amy N Sexauer, Gabriela Alexe, Karin Gustafsson, Elizabeth Zanetakos, Jelena Milosevic, Mary Ayres, Varsha Gandhi, Yana Pikman, Kimberly Stegmaier, David B Sykes

Faculty, Staff and Student Publications

Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) have a poor prognosis with few therapeutic options. With the goal of identifying novel therapeutic targets, we used data from the Dependency Map project to identify dihydroorotate dehydrogenase (DHODH) as one of the top metabolic dependencies in T-ALL. DHODH catalyzes the fourth step of de novo pyrimidine nucleotide synthesis. Small molecule inhibition of DHODH rapidly leads to the depletion of intracellular pyrimidine pools and forces cells to rely on extracellular salvage. In the absence of sufficient salvage, this intracellular nucleotide starvation results in the inhibition of DNA and RNA synthesis, …

The Landscape Of Alterations From 1407 Ultra-Rare Sarcomas From The Aacr Genie Database: Clinical Implications, Ryan A Denu, Justin T Moyers, Mohamed A Gouda, Anthony P Conley, Alexander J Lazar, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Ultra-rare sarcomas (URS) comprise a group of orphan diseases with an incidence of ≤1/1,000,000 people per year. We aimed to assess clinically actionable genomic alterations in URS.

Experimental design: Data were extracted from the GENIE database using cBioPortal. OncoKB was used to assess for clinical actionability of mutations. Tumor mutational burden (TMB) was inferred from clinical sequencing data.

Results: Soft tissue (ST) URS made up 23.5% of ST sarcoma cases, and bone URS made up 16.5% of bone sarcoma cases. The most commonly mutated gene in all four groups was TP53. The most common fusions involved EWSR1. The most …

Gasdermin D Permeabilization Of Mitochondrial Inner And Outer Membranes Accelerates And Enhances Pyroptosis, Rui Miao, Cong Jiang, Winston Y Chang, Haiwei Zhang, Jinsu An, Felicia Ho, Pengcheng Chen, Han Zhang, Caroline Junqueira, Dulguun Amgalan, Felix G Liang, Junbing Zhang, Charles L Evavold, Iva Hafner-Bratkovič, Zhibin Zhang, Pietro Fontana, Shiyu Xia, Markus Waldeck-Weiermair, Youdong Pan, Thomas Michel, Liron Bar-Peled, Hao Wu, Jonathan C Kagan, Richard N Kitsis, Peng Zhang, Xing Liu, Judy Lieberman

Faculty, Staff and Student Publications

Gasdermin D (GSDMD)-activated inflammatory cell death (pyroptosis) causes mitochondrial damage, but its underlying mechanism and functional consequences are largely unknown. Here, we show that the N-terminal pore-forming GSDMD fragment (GSDMD-NT) rapidly damaged both inner and outer mitochondrial membranes (OMMs) leading to reduced mitochondrial numbers, mitophagy, ROS, loss of transmembrane potential, attenuated oxidative phosphorylation (OXPHOS), and release of mitochondrial proteins and DNA from the matrix and intermembrane space. Mitochondrial damage occurred as soon as GSDMD was cleaved prior to plasma membrane damage. Mitochondrial damage was independent of the B-cell lymphoma 2 family and depended on GSDMD-NT binding to cardiolipin. Canonical and …

Post-Acute Sequelae Of Covid-19 (Pasc) In Pediatrics: Factors That Impact Symptom Severity And Referral To Treatment., Catherine Soprano, Ryan Ngo, Casey A Konys, Ashley Bazier, Katherine Salamon

Department of Medicine Faculty Papers

The post-acute sequelae of COVID-19 (PASC) is a complex condition. While there are emerging studies on its effects in adults, there is scarce research regarding the long-term effects of COVID-19 infection among youth. Several researchers have likened long-haul COVID-19 to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and postural orthostatic tachycardia syndrome (POTS). In adults, the prognosis for these diagnoses is less promising than that in youth; however, there is currently very little information available on the presentation of youth with PASC. A better understanding of the specific symptom presentation for youth diagnosed with PASC is necessary. Retrospective chart reviews were conducted …

Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lisa E. Nigrovic, Nathan Kuppermann, Simona Ghetti, Jeff E. Schunk, Michael J. Stoner, Arleta Rewers, Julie K. Mcmanemy, Kimberly S. Quayle, Jennifer L. Trainor, Leah Tzimenatos, Jonathan E. Bennett, Maria Y. Kwok, Sage R. Myers, Kathleen M. Brown, T. Charles Casper, Cody S. Olsen, Nicole S. Glaser

Department of Emergency Medicine Faculty Papers

Background.

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of childhood diabetes. However, the influence of demographic factors on presentation are not well-defined.

Methods.

We included children from 12 centers who were <18 years with DKA (glucose > 300 mg/dL, serum pH < 7.25, or serum bicarbonate <15 mEq/L) enrolled in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Trial. Data were also collected for children who presented to the centers during the enrollment period but were not enrolled due to disease or treatment-related reasons. We compared demographic, clinical, and biochemical findings among children with newly and previously diagnosed diabetes and children in different age groups.

Results.

Of the 1,679 DKA episodes in 1,553 children, 799 (47.5%) episodes occurred in children with newly diagnosed diabetes and 396 (23.6%) were severe (pH < 7.1). Newly diagnosed children <6 years of age were not more likely to have severe DKA in terms of pH, but had more severe hypocarbia and higher blood urea nitrogen levels, factors previously associated with the risk of cerebral injury. Lower socioeconomic status (SES) (based on family income and maternal education level) were associated with more severe DKA in new onset children, and recurrent DKA in the previously diagnosed children.

Conclusions.

Greater efforts are needed to identify the children with diabetes early and to prevent recurrent DKA, particularly among children in low-SES groups. Young children with DKA may need more intensive monitoring due to higher …

Identification Of Exosome Protein Panels As Predictive Biomarkers For Non-Small Cell Lung Cancer, Bin Luo, Zujun Que, Xinyi Lu, Dan Qi, Zhi Qiao, Yun Yang, Fangfang Qian, Yi Jiang, Yan Li, Ronghu Ke, Xiaoyun Shen, Hua Xiao, Hegen Li, Erxi Wu, Jianhui Tian

Children’s Nutrition Research Center Staff Publications

Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes.

Methods: Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes.

Results: …

Tumor-Resident Lactobacillus Iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring, Lauren E Colbert, Molly B El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J Lynn, Timothy A Harris, Jacob H Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K Bronk, Julie Sammouri, Ananta V Yanamandra, Adilene V Olvera, Lily G Carlin, Travis Sims, Andrea Y Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O Abana, Hannah X Li, Patricia J Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M Ramondetta, Andrew M Futreal, Kathleen M Schmeler, Geena Mathew, Stephanie Dorta-Estremera, Jianhua Zhang, Xiaogang Wu, Nadim J Ajami, Matthew Wong, Cullen Taniguchi, Joseph F Petrosino, K Jagannadha Sastry, Pablo C Okhuysen, Sara A Martinez, Lin Tan, Iqbal Mahmud, Philip L Lorenzi, Jennifer A Wargo, Ann H Klopp

Faculty, Staff and Student Publications

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other …

Wire Snare Close Loop: A Novel Technique To Retrieve Embolized Devices, Manish Bansal, Gary E Stapleton, Srinath T Gowda, Athar M Qureshi

Faculty, Staff and Students Publications

No abstract provided.

Microplastics In Different Tissues Of A Commonly Consumed Fish, Mohammad Belal Hossain, Farjana Haque Pingki, Md Abdus Samad Azad, As-Ad Ujjaman Nur, Partho Banik, Bilal Ahamad Paray, Takaomi Arai, Jimmy Yu

Faculty, Staff and Student Publications

Microplastics (MPs) ingestion by fish signifies a worldwide threat to human health but limited research has examined their existence within the consumable portions (muscle) of fish. Thus, this study was undertaken to unveil the prevalence, characterization, and contamination extent of MPs across various body tissues, including the muscle of the king mackerel (S. guttatus) from the lower Meghna estuary in Bangladesh-a pioneering investigation in this region. In our analysis, we identified a total of 487 MPs, with an average abundance of 48.7 ± 20.3 MPs/individual. These MPs were distributed across different tissues, with respective concentrations of 0.84 ± …

Single-Cell Analysis Differentiates The Effects Of P53 Mutation And P53 Loss On Cell Compositions Of Oncogenic Kras-Driven Pancreatic Cancer, Xinlei Sun, Daowei Yang, Yang Chen

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignant disease with a dismal prognosis. In the past decades, a plethora of genetically engineered mouse models (GEMMs) with autochthonous pancreatic tumor development have greatly facilitated studies of pancreatic cancer. Commonly used GEMMs of PDAC often harbor the oncogenic KRAS driver mutation (KrasG12D), in combination with either p53 mutation by knock-in strategy (Trp53R172H) or p53 loss by conditional knockout (Trp53cKO) strategy, in pancreatic cell lineages. However, the systematic comparison of the tumor microenvironment between KrasG12D; Trp53R172H (KPmut) mouse models and KrasG12D; Trp53cKO (KPloss) mouse models …

The Importance Of A Healthy Microbiome In Pregnancy And Infancy And Microbiota Treatment To Reverse Dysbiosis For Improved Health, Herbert L Dupont, Madeleine Mary Hines Salge

Faculty, Staff and Student Publications

BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.

METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).

RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during …

An Overview Of The Immune Modulatory Properties Of Long Non-Coding Rnas And Their Potential Use As Therapeutic Targets In Cancer, Moises Martinez-Castillo, Abdelrahman M Elsayed, Gabriel López-Berestein, Paola Amero, Cristian Rodríguez-Aguayo

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field …

Increase In Hnrnpa1 Expression Suffices To Kill Motor Neurons In Transgenic Rats, Xionghao Liu, Tingting Zhang, Qinxue Wu, Cao Huang, Xu-Gang Xia, Hongxia Zhou, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. …

Targeting The Αvβ3/Ngr2 Pathway In Neuroendocrine Prostate Cancer, Anna Testa, Fabio Quaglia, Nicole M. Naranjo, Cecilia E. Verrillo, Christopher D. Shields, Stephen Lin, Maxwell W. Pickles, Drini F. Hamza, Tami Von Schalscha, David A. Cheresh, Benjamin E Leiby, Qin Liu, Jianyi Ding, William K. Kelly, D. Craig Hooper, Eva Corey, Edward F. Plow, Dario C. Altieri, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in …

Improving Cervical Cancer Screening Rates In The Primary Care Setting, Esmeralda Young

Student Scholarly Projects

Practice Problem: Cervical cancer screening with Pap is the recommended standard practice for women aged 21 to 65. The project aimed to increase low cervical cancer screening rates at a primary care clinic.

PICOT: The PICOT question that guided this project was: (P) In women 21 to 65 years old in the primary care setting (I), does proactive pre-scheduling of cervical cancer screenings (C) compared to current standard practice (O) affect cervical cancer screening rates (T) over eight weeks?

Evidence: The evidence strongly supported improving cervical cancer screening among the targeted population. Studies showed that Pap smear screening reduced the …

Role Of Soluble Urokinase Type Plasminogen Activator Receptor (Supar) In Predicting Mortality, Readmission, Length Of Stay And Discharge In Emergency Patients: A Systematic Review And Meta Analysis, Syeda Tayyaba Rehan, Hassan Ul Hussain, Eman Ali, Kanwal Ashok Kumar, Shehroze Tabassum, Muhammad Hasanain, Asim Shaikh, Gibran Ali, Zohaib Yousaf, Muhammad Sohaib Asghar

Section of Internal Medicine

Background: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus, serves as a useful tool for ED physicians. Our study aims to analyze the efficacy of suPAR in predicting these prognostic markers in ED.
Methods: We performed a comprehensive search on 6 databases from the inception to 30th November 2022, to select the following eligibility criteria; a) observation or triage trial studies investigating the role of suPAR levels in predicting: 30 day and 90-day mortality, 30-day readmission, early discharge (within 24hr), and LOS in patients coming to …