Digital Commons Network^™

Variantsurvival: A Tool To Identify Genotype-Treatment Response, Thomas Krannich, Marina Herrera Sarrias, Hiba Ben Aribi, Moustafa Shokrof, Alfredo Iacoangeli, Ammar Al-Chalabi, Fritz J Sedlazeck, Ben Busby, Ahmad Al Khleifat

Faculty, Staff and Students Publications

Associated Data

Cloud-Native Distributed Genomic Pileup Operations, Marek Wiewiórka, Agnieszka Szmurło, Paweł Stankiewicz, Tomasz Gambin

Faculty, Staff and Students Publications

MOTIVATION: Pileup analysis is a building block of many bioinformatics pipelines, including variant calling and genotyping. This step tends to become a bottleneck of the entire assay since the straightforward pileup implementations involve processing of all base calls from all alignments sequentially. On the other hand, a distributed version of the algorithm faces the intrinsic challenge of splitting reads-oriented file formats into self-contained partitions to avoid costly data exchange between computational nodes.

RESULTS: Here, we present a scalable, distributed and efficient implementation of a pileup algorithm that is suitable for deploying in cloud computing environments. In particular, we implemented: (i) …

Ageing And Rejuvenation Of Tissue Stem Cells And Their Niches, Anne Brunet, Margaret A Goodell, Thomas A Rando

Faculty, Staff and Students Publications

Most adult organs contain regenerative stem cells, often organized in specific niches. Stem cell function is critical for tissue homeostasis and repair upon injury, and it is dependent on interactions with the niche. During ageing, stem cells decline in their regenerative potential and ability to give rise to differentiated cells in the tissue, which is associated with a deterioration of tissue integrity and health. Ageing-associated changes in regenerative tissue regions include defects in maintenance of stem cell quiescence, differentiation ability and bias, clonal expansion and infiltration of immune cells in the niche. In this Review, we discuss cellular and molecular …

A Population-Based Assessment Of Metastatic Hepatoblastoma In Texas Reveals Ethnic Disparities, Andres F Espinoza, Michael E Scheurer, Tiffany M Chambers, Sanjeev A Vasudevan, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Hepatoblastoma (HB) is the most common primary liver cancer in children with emerging evidence that incidence is increasing globally. While overall survival for low risk hepatoblastoma is >90%, children with metastatic disease have worse survival. As identifying factors associated with high-risk disease is critical for improving outcomes for these children, a need for a further understanding of the epidemiology of hepatoblastoma is warranted. Therefore, we conducted a population-based epidemiologic study of hepatoblastoma in Texas, a large state characterized by ethnic and geographic diversity.

METHODS: Information on children diagnosed with hepatoblastoma at 0-19 years of age for the period of …

Factors Associated With Nonsyndromic Anotia And Microtia, Texas, 1999–2014, Jeremy M Schraw, J P Woodhouse, Renata H Benjamin, Charles J Shumate, Joanne Nguyen, Mark A Canfield, A J Agopian, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few risk factors have been identified for nonsyndromic anotia/microtia (A/M).

METHODS: We obtained data on cases and a reference population of all livebirths in Texas for 1999-2014 from the Texas Birth Defects Registry (TBDR) and Texas vital records. We estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) for A/M (any, isolated, nonisolated, unilateral, and bilateral) using Poisson regression. We evaluated trends in prevalence rates using Joinpoint regression.

RESULTS: We identified 1,322 cases, of whom 982 (74.3%) had isolated and 1,175 (88.9%) had unilateral A/M. Prevalence was increased among males (PR: 1.3, 95% CI: 1.2-1.4), offspring of women with …

Oocyte-Specific Wee1-Like Protein Kinase 2 Is Dispensable For Fertility In Mice, Kaori Nozawa, Zian Liao, Yuhkoh Satouh, Ting Geng, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Wee1-like protein kinase 2 (WEE2) is an oocyte-specific protein tyrosine kinase involved in the regulation of oocyte meiotic arrest in humans. As such, it has been proposed as a candidate for non-hormonal female contraception although pre-clinical models have not been reported. Therefore, we developed two novel knockout mouse models using CRISPR/Cas9 to test loss-of-function of Wee2 on female fertility. A frameshift mutation at the Wee2 translation start codon in exon 2 had no effect on litter size, litter production, or the ability of oocytes to maintain prophase I arrest. Because of the lack of a reproductive phenotype, we additionally generated …

Disease Modeling Of Adamts9-Related Nephropathy Using Kidney Organoids Reveals Its Roles In Tubular Cells And Podocytes, Seyoung Yu, Yo Jun Choi, John Hoon Rim, Hye-Youn Kim, Nasim Bekheirnia, Sarah Jane Swartz, Hongzheng Dai, Shen Linda Gu, Soyeon Lee, Ryuichi Nishinakamura, Friedhelm Hildebrandt, Mir Reza Bekheirnia, Heon Yung Gee

Faculty, Staff and Students Publications

INTRODUCTION: Mutations in ADAMTS9 cause nephronophthisis-related ciliopathies (NPHP-RC), which are characterized by multiple developmental defects and kidney diseases. Patients with NPHP-RC usually have normal glomeruli and negligible or no proteinuria. Herein, we identified novel compound-heterozygous ADAMTS9 variants in two siblings with NPHP-RC who had glomerular manifestations, including proteinuria.

METHODS: To investigate whether ADAMTS9 dysfunction causes NPHP and glomerulopathy, we differentiated ADAMTS9 knockout human induced pluripotent stem cells (hiPSCs) into kidney organoids. Single-cell RNA sequencing was utilized to elucidate the gene expression profiles from the ADAMTS9 knockout kidney organoids.

RESULTS:ADAMTS9 knockout had no effect on nephron differentiation; however, it reduced …

Codon-Optimized Tdp-43 Mediates Neurodegeneration In A Drosophila Model Of Als/Ftld, Tanzeen Yusuff, Ya-Chu Chang, Tzu-Kang Sang, George R Jackson, Shreyasi Chatterjee

Faculty, Staff and Students Publications

Transactive response DNA binding protein-43 (TDP-43) is known to mediate neurodegeneration associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The exact mechanism by which TDP-43 exerts toxicity in the brains, spinal cord, and lower motor neurons of affected patients remains unclear. In a novel Drosophila melanogaster model, we report gain-of-function phenotypes due to misexpression of insect codon-optimized version of human wild-type TDP-43 (CO-TDP-43) using both the binary GAL4/UAS system and direct promoter fusion constructs. The CO-TDP-43 model showed robust tissue specific phenotypes in the adult eye, wing, and bristles in the notum. Compared to non-codon optimized …

Establishing An Online Resource To Facilitate Global Collaboration And Inclusion Of Underrepresented Populations: Experience From The Mjff Global Genetic Parkinson’S Disease Project, Eva-Juliane Vollstedt, Harutyun Madoev, Anna Aasly, Azlina Ahmad-Annuar, Bashayer Al-Mubarak, Roy N Alcalay, Victoria Alvarez, Ignacio Amorin, Grazia Annesi, David Arkadir, Soraya Bardien, Roger A Barker, Melinda Barkhuizen, A Nazli Basak, Vincenzo Bonifati, Agnita Boon, Laura Brighina, Kathrin Brockmann, Andrea Carmine Belin, Jonathan Carr, Jordi Clarimon, Mario Cornejo-Olivas, Leonor Correia Guedes, Jean-Christophe Corvol, David Crosiers, Joana Damásio, Parimal Das, Patricia De Carvalho Aguiar, Anna De Rosa, Jolanta Dorszewska, Sibel Ertan, Rosangela Ferese, Joaquim Ferreira, Emilia Gatto, Gençer Genç, Nir Giladi, Pilar Gómez-Garre, Hasmet Hanagasi, Nobutaka Hattori, Faycal Hentati, Dorota Hoffman-Zacharska, Sergey N Illarioshkin, Joseph Jankovic, Silvia Jesús, Valtteri Kaasinen, Anneke Kievit, Peter Klivenyi, Vladimir Kostic, Dariusz Koziorowski, Andrea A Kühn, Anthony E Lang, Shen-Yang Lim, Chin-Hsien Lin, Katja Lohmann, Vladana Markovic, Mika Henrik Martikainen, George Mellick, Marcelo Merello, Lukasz Milanowski, Pablo Mir, Özgür Öztop-Çakmak, Márcia Mattos Gonçalves Pimentel, Teeratorn Pulkes, Andreas Puschmann, Ekaterina Rogaeva, Esther M Sammler, Maria Skaalum Petersen, Matej Skorvanek, Mariana Spitz, Oksana Suchowersky, Ai Huey Tan, Pichet Termsarasab, Avner Thaler, Vitor Tumas, Enza Maria Valente, Bart Van De Warrenburg, Caroline H Williams-Gray, Ruey-Mei Wu, Baorong Zhang, Alexander Zimprich, Justin Solle, Shalini Padmanabhan, Christine Klein

Faculty, Staff and Students Publications

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, …

Δfosb Is Part Of A Homeostatic Mechanism That Protects The Epileptic Brain From Further Deterioration, Jerome Clasadonte, Tania Deprez, Gabriel S Stephens, Georges Mairet-Coello, Pierre-Yves Cortin, Maxime Boutier, Aurore Frey, Jeannie Chin, Marek Rajman

Faculty, Staff and Students Publications

Activity induced transcription factor ΔFosB plays a key role in different CNS disorders including epilepsy, Alzheimer's disease, and addiction. Recent findings suggest that ΔFosB drives cognitive deficits in epilepsy and together with the emergence of small molecule inhibitors of ΔFosB activity makes it an interesting therapeutic target. However, whether ΔFosB contributes to pathophysiology or provides protection in drug-resistant epilepsy is still unclear. In this study, ΔFosB was specifically downregulated by delivering AAV-shRNA into the hippocampus of chronically epileptic mice using the drug-resistant pilocarpine model of mesial temporal epilepsy (mTLE). Immunohistochemistry analyses showed that prolonged downregulation of ΔFosB led to exacerbation …

5-Aminolevulinic Acid, Fluorescein Sodium, And Indocyanine Green For Glioma Margin Detection: Analysis Of Operating Wide-Field And Confocal Microscopy In Glioma Models Of Various Grades, Evgenii Belykh, Liudmila Bardonova, Irakliy Abramov, Vadim A Byvaltsev, Talgat Kerymbayev, Kwanha Yu, Debbie R Healey, Ernesto Luna-Melendez, Benjamin Deneen, Shwetal Mehta, James K Liu, Mark C Preul

Faculty, Staff and Students Publications

INTRODUCTION: Surgical resection remains the first-line treatment for gliomas. Several fluorescent dyes are currently in use to augment intraoperative tumor visualization, but information on their comparative effectiveness is lacking. We performed systematic assessment of fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), and indocyanine green (ICG) fluorescence in various glioma models using advanced fluorescence imaging techniques.

METHODS: Four glioma models were used: GL261 (high-grade model), GB3 (low-grade model), and an

RESULTS: Our systematic analysis showed that wide-field imaging of highly malignant gliomas is equally efficient with 5-ALA, FNa, and ICG, although FNa is associated with more false-positive staining of …

Primary Spinal Intramedullary Anaplastic Ganglioglioma In A Pediatric Patient, Huy Dang, Abdul Basit Khan, Nisha Gadgil, Marc Prablek, Frank Y Lin, Melissa M Blessing, Guillermo Aldave, David Bauer

Faculty, Staff and Students Publications

BACKGROUND: Gangliogliomas (GGs) are rare tumors of the central nervous system composed of neoplastic neural and glial cells and are typically low-grade. Intramedullary spinal anaplastic GGs (AGG) are rare, poorly understood, and often aggressive tumors that can result in widespread progression along the craniospinal axis. Due to the rarity of these tumors, data are lacking to guide clinical and pathologic diagnosis and standard of care treatment. Here, we present a case of pediatric spinal AGG to provide information on our institutional approach to work-up and to highlight unique molecular pathology.

CASE DESCRIPTION: A 13-year-old female presented with signs of spinal …

Linked-Read Based Analysis Of The Medulloblastoma Genome, Melissa Zwaig, Michael J Johnston, John J Y Lee, Hamza Farooq, Marco Gallo, Nada Jabado, Michael D Taylor, Jiannis Ragoussis

Faculty, Staff and Students Publications

INTRODUCTION: Medulloblastoma is the most common type of malignant pediatric brain tumor with group 4 medulloblastomas (G4 MBs) accounting for 40% of cases. However, the molecular mechanisms that underlie this subgroup are still poorly understood. Point mutations are detected in a large number of genes at low incidence per gene while the detection of complex structural variants in recurrently affected genes typically requires the application of long-read technologies.

METHODS: Here, we applied linked-read sequencing, which combines the long-range genome information of long-read sequencing with the high base pair accuracy of short read sequencing and very low sample input requirements.

RESULTS: …

Role Of Adrenomedullin2/ Intermedin In Pregnancy Induced Vascular And Metabolic Adaptation In Mice, Chandra Yallampalli, Ancizar Betancourt, Akansha Mishra, Kathleen A Pennington, Simone Hernandez Ruano, Moises Tacam, Madhu Chauhan

Faculty, Staff and Students Publications

Introduction: Adrenomedullin2 (AM2) shares its receptor with Calcitonin gene related peptide and adrenomedullin with overlapping but distinct biological functions. Goal of this study was to assess the specific role of Adrenomedullin2 (AM2) in pregnancy induced vascular and metabolic adaptation using AM2 knockout mice (AM2 ^−/−).

Method : The AM2 ^−/− mice were successfully generated using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Nuclease Cas nine system. Phenotype of pregnant AM2 ^−/− mice was assessed with respect to its fertility, blood pressure regulation, vascular health and metabolic adaptations and compared to the wild type littermates (AM2 ^+/+).

Results …

Editorial: Molecular Mechanisms In Ocular Development And Disease, Rajalekshmy Shyam, Daisy Y Shu, Elizabeth Zuniga-Sanchez, Deepika Vasudevan

Faculty, Staff and Students Publications

No abstract provided.

Growth And Differentiation Factor 15 (Gdf15) Levels Predict Adverse Respiratory Outcomes In Premature Neonates, Faeq Almudares, Joseph Hagan, Xinpu Chen, Sridevi Devaraj, Bhagavatula Moorthy, Krithika Lingappan

Faculty, Staff and Students Publications

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved …

Sox9 Governs Gastric Mucous Neck Cell Identity And Is Required For Injury-Induced Metaplasia, Spencer G Willet, Nattapon Thanintorn, Helen Mcneill, Sung-Ho Huh, David M Ornitz, Won Jae Huh, Stella G Hoft, Richard J Dipaolo, Jason C Mills

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Acute and chronic gastric injury induces alterations in differentiation within the corpus of the stomach called pyloric metaplasia. Pyloric metaplasia is characterized by the death of parietal cells and reprogramming of mitotically quiescent zymogenic chief cells into proliferative, mucin-rich spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Overall, pyloric metaplastic units show increased proliferation and specific expansion of mucous lineages, both by proliferation of normal mucous neck cells and recruitment of SPEM cells. Here, we identify Sox9 as a potential gene of interest in the regulation of mucous neck and SPEM cell identity in the stomach.

METHODS: We used immunostaining …

Novel Banana Lectin Car-T Cells To Target Pancreatic Tumors And Tumor-Associated Stroma, Mary K Mckenna, Ada Ozcan, Daniel Brenner, Norihiro Watanabe, Maureen Legendre, Dafydd G Thomas, Christopher Ashwood, Richard D Cummings, Challice Bonifant, David M Markovitz, Malcolm K Brenner

Faculty, Staff and Students Publications

BACKGROUND: Cell therapies for solid tumors are thwarted by the hostile tumor microenvironment (TME) and by heterogeneous expression of tumor target antigens. We address both limitations with a novel class of chimeric antigen receptors based on plant lectins, which recognize the aberrant sugar residues that are a 'hallmark' of both malignant and associated stromal cells. We have expressed in T cells a modified lectin from banana, H84T BanLec, attached to a chimeric antigen receptor (H84T-CAR) that recognizes high-mannose (asparagine residue with five to nine mannoses). Here, we tested the efficacy of our novel H84T CAR in models of pancreatic ductal …

Transcriptomic Analyses Of Ovarian Clear-Cell Carcinoma With Concurrent Endometriosis, Kaitlyn E Collins, Xiyin Wang, Yuliya Klymenko, Noah B Davis, Maria C Martinez, Chi Zhang, Kaman So, Aaron Buechlein, Douglas B Rusch, Chad J Creighton, Shannon M Hawkins

Faculty, Staff and Students Publications

INTRODUCTION: Endometriosis, a benign inflammatory disease whereby endometrial-like tissue grows outside the uterus, is a risk factor for endometriosis-associated ovarian cancers. In particular, ovarian endometriomas, cystic lesions of deeply invasive endometriosis, are considered the precursor lesion for ovarian clear-cell carcinoma (OCCC).

METHODS: To explore this transcriptomic landscape, OCCC from women with pathology-proven concurrent endometriosis (n = 4) were compared to benign endometriomas (n = 4) by bulk RNA and small-RNA sequencing.

RESULTS: Analysis of protein-coding genes identified 2449 upregulated and 3131 downregulated protein-coding genes (DESeq2, P< 0.05, log2 fold-change > |1|) in OCCC with concurrent endometriosis compared to endometriomas. Gene set enrichment …

Allogeneic Haematopoietic Cell Transplant In Patients With Relapsed/Refractory Anaplastic Large Cell Lymphoma, Fateeha Furqan, Kwang W Ahn, Yue Chen, Manmeet Kaur, Syed A Abutalib, Nausheen Ahmed, Sairah Ahmed, Mohamed A Kharfan-Dabaja, Johnathan Friedberg, Tara Gregory, Laquisa Hill, Cole Sterling, Stephan K Barta, Mazyar Shadman, Miguel-Angel Perales, Jasmine Zain, Alex F Herrera, Craig Sauter, Mehdi Hamadani

Faculty, Staff and Students Publications

The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic haematopoietic cell transplantation (allo-HCT) in systemic R/R ALCL are not available. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we evaluated outcomes of 182 adults (aged ≥18 years) with R/R ALCL undergoing allo-HCT between 2008 and 2019. Non-relapse mortality (NRM), disease relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modelled using Cox proportional hazards models. The median (range) follow-up of survivors was 62 (3-148) months. The 1-year NRM was 18%. The 5-year REL, PFS and OS …

Sex-Specific Associations Between Urinary Bisphenols Concentrations During Pregnancy And Problematic Child Behaviors At Age 2 Years, Sarah Dee Geiger, Salma Musaad, Jennifer Hill, Andréa Aguiar, Susan Schantz

Faculty, Staff and Students Publications

Effects of prenatal bisphenol A (BPA) exposure on child behavior are mixed with some reports suggesting increased problematic behaviors in girls (e.g., aggression and emotional reactivity) and in boys (i.e., externalizing behaviors), while other reports suggest decreased problematic behaviors in girls. Little is known about the potential impact of pregnancy bisphenol S (BPS) exposure on child behavior. In a prospective cohort study (n=68), five maternal spot urine samples collected across pregnancy were pooled and analyzed for BPA and BPS. Child behavior at 2 years was assessed using the Child Behavior Checklist (CBCL). Linear regression models were used to assess associations …

The Role Of Supervised School Therapy In Poorly Controlled Asthma In Children, Muppala Raju, Malvika Sagar, Andrew Bush, Eugene Quaye, Shekhar Ghamande, Sonal Malhotra, Mercedes E Arroliga

Faculty, Staff and Students Publications

BACKGROUND: In children, nonadherence to inhaled corticosteroid (ICS) therapy leads to poor asthma control and complications.

METHODS: We evaluated the benefit from initiation of ICS administration once daily at school. We retrospectively chose patients from our pediatric pulmonary clinic who had poorly controlled asthma and prescribed ICS daily. For the study period, we examined the number of corticosteroid courses, emergency room visits, hospital admissions, symptom history, and pulmonary function tests.

RESULTS: Thirty-four patients who satisfied the inclusion criteria began the intervention. Preintervention, there were a mean number of 2.6 oral corticosteroid courses compared to 2 courses in the year following …

Long-Term Neuropsychological Outcomes In Children With Febrile Infection-Related Epilepsy Syndrome (Fires) Treated With Anakinra, Anima Shrestha, E Lynne Wood, Gretchen Berrios-Siervo, Coral M Stredny, Katrina Boyer, Clemente Vega, Srishti Nangia, Eyal Muscal, Krista Eschbach

Faculty, Staff and Students Publications

BACKGROUND: Febrile-infection related epilepsy syndrome (FIRES) is a rare epilepsy syndrome in which a previously healthy individual develops refractory status epilepticus in the setting of a preceding febrile illness. There are limited data regarding detailed long-term outcomes. This study aims to describe the long-term neuropsychological outcomes in a series of pediatric patients with FIRES.

METHODS: This is a retrospective multi-center case series of pediatric patients with a diagnosis of FIRES treated acutely with anakinra who had neuropsychological testing at least 12 months after status epilepticus onset. Each patient underwent comprehensive neuropsychological evaluation as part of routine clinical care. Additional data …

Global Regulatory Reforms To Promote Equitable Vaccine Access In The Next Pandemic, Richard Mahoney, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Students Publications

There is broad consensus that the global response to the Covid-19 pandemic was inadequate, leading to unacceptable levels of avoidable morbidity and mortality. Three strategic missteps led to the lack of equitable vaccine access: The heavy reliance on commercial vaccine manufacturers in high-income countries (HICs) versus low- and middle-income countries (LMICs); the emergence of vaccine nationalism restricting and delaying the supply of vaccines to LMICs; and an inadequate support or recognition for LMIC national regulatory authorities. To avoid these inequities in a future pandemic, we focus on three successful vaccine development and technology transfer case studies-the Hepatitis B vaccine produced …

Vaccine-Linked Chemotherapy Improves Cardiac Structure And Function In A Mouse Model Of Chronic Chagas Disease, Kathryn M Jones, Elise N Mangin, Corey L Reynolds, Liliana E Villanueva, Julio Vladimir Cruz, Leroy Versteeg, Brian Keegan, April Kendricks, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez

Faculty, Staff and Students Publications

INTRODUCTION: Chagas disease, caused by chronic infection with the protozoan parasite Trypanosoma cruzi, affects 6-7 million people worldwide. The major clinical manifestation of Chagas disease is chronic Chagasic cardiomyopathy (CCC), which encompasses a spectrum of symptoms including arrhythmias, hypertrophy, dilated cardiomyopathy, heart failure, and sudden death. Current treatment is limited to two antiparasitic drugs, benznidazole (BNZ) and nifurtimox, but both have limited efficacy to halt the progression of CCC. We developed a vaccine-linked chemotherapy strategy using our vaccine consisting of recombinant Tc24-C4 protein and a TLR-4 agonist adjuvant in a stable squalene emulsion, in combination with low dose benznidazole treatment. …

Prevalence Of Trypanosoma Cruzi, The Etiologic Agent Of Chagas Disease, Infection In Texas Skunks (Mammalia: Mephitidae), Bonnie E Gulas-Wroblewski, Rodion Gorchakov, Rebecca B Kairis, Robert C Dowler, Kristy O Murray

Faculty, Staff and Students Publications

Background:

Chagas disease is one of the world's most neglected tropical diseases, infecting over six million people across the Americas. The hemoparasite Trypanosoma cruzi is the etiological agent for the disease, circulating in domestic, peridomestic, and sylvatic transmission cycles that are maintained by triatomine vectors and a diversity of wild and synanthropic hosts. Public health and wildlife management interventions targeting the interruption of T. cruzi transmission rely on an understanding of the dynamics driving the ecology of this zoonotic pathogen. One wildlife host that purportedly plays a role in the transmission of Chagas disease within the southern United States is …

Participant Perceptions Of Changes In Psychosocial Domains Following Participation In An Adaptive Deep Brain Stimulation Trial, Amanda R Merner, Kristin Kostick-Quenet, Tiffany A Campbell, Michelle T Pham, Clarissa E Sanchez, Laura Torgerson, Jill Robinson, Stacey Pereira, Simon Outram, Barbara A Koenig, Philip A Starr, Aysegul Gunduz, Kelly D Foote, Michael S Okun, Wayne Goodman, Amy L Mcguire, Peter Zuk, Gabriel Lázaro-Muñoz

Faculty, Staff and Students Publications

BACKGROUND: There has been substantial controversy in the neuroethics literature regarding the extent to which deep brain stimulation (DBS) impacts dimensions of personality, mood, and behavior.

OBJECTIVE/HYPOTHESIS: Despite extensive debate in the theoretical literature, there remains a paucity of empirical data available to support or refute claims related to the psychosocial changes following DBS.

METHODS: A mixed-methods approach was used to examine the perspectives of patients who underwent DBS regarding changes to their personality, authenticity, autonomy, risk-taking, and overall quality of life.

RESULTS: Patients (n = 21) who were enrolled in adaptive DBS trials for Parkinson's disease, essential tremor, obsessive-compulsive …

Modeling Suicidality With Multimodal Impulsivity Characterization In Participants With Mental Health Disorder, Nidal Moukaddam, Bishal Lamichhane, Ramiro Salas, Wayne Goodman, Ashutosh Sabharwal

Faculty, Staff and Students Publications

INTRODUCTION: Suicide is one of the leading causes of death across different age groups. The persistence of suicidal ideation and the progression of suicidal ideations to action could be related to impulsivity, the tendency to act on urges with low temporal latency, and little forethought. Quantifying impulsivity could thus help suicidality estimation and risk assessments in ideation-to-action suicidality frameworks.

METHODS: To model suicidality with impulsivity quantification, we obtained questionnaires, behavioral tests, heart rate variability (HRV), and resting state functional magnetic resonance imaging measurements from 34 participants with mood disorders. The participants were categorized into three suicidality groups based on their …

Risk Factors Of Local Control In Adrenal Metastases Treated By Stereotactic Body Radiation Therapy – A Systematic Review And Meta-Analysis, Xuehong Liao, Kazushi Kishi, Kaixin Du, Ritsuko Komaki, Junetsu Mizoe, Gosuke Aikawa, Wei Zheng, Chao Pan

Faculty, Staff and Students Publications

PURPOSE: This study is aimed to explore risk factors affect the therapy outcomes of adrenal metastases (AM) for stereotactic body radiation therapy (SBRT) and guide clinical dose selection.

METHODS AND MATERIALS: PubMed, Embase and Web of Science were searched in September 22, 2022 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Subgroup analysis and meta-regression were used to search for sources of heterogeneity and identify risky outcomes factors. Publication bias test and sensitivity analysis were also conducted.

RESULTS: Thirty-three studies with full text from 2009 to 2022 about AM with SBRT on 1483 patients were …

Pre-Treatment Inflamed Tumor Immune Microenvironment Is Associated With Folfirinox Response In Pancreatic Cancer, Zachary Gao, Sung Wook Kang, Derek Erstad, Joseph Azar, George Van Buren, William Fisher, Zequn Sun, Mark P Rubinstein, Hyun-Sung Lee, E Ramsay Camp

Faculty, Staff and Students Publications

INTRODUCTION: Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with limited response to both chemotherapy and immunotherapy. Pre-treatment tumor features within the tumor immune microenvironment (TiME) may influence treatment response. We hypothesized that the pre-treatment TiME composition differs between metastatic and primary lesions and would be associated with response to modified FOLFIRINOX (mFFX) or gemcitabine-based (Gem-based) therapy.

METHODS: Using RNAseq data from a cohort of treatment-naïve, advanced PDAC patients in the COMPASS trial, differential gene expression analysis of key immunomodulatory genes in were analyzed based on multiple parameters including tumor site, response to mFFX, and response to Gem-based treatment. The relative …