Digital Commons Network^™

The Genetic Landscape And Clinical Implication Of Pediatric Moyamoya Angiopathy In An International Cohort, Yan-Hao Wei, Ren-Tang Bi, Yan-Mei Qiu, Chun-Lin Zhang, Jian-Zhuang Li, Ya-Nan Li, Bo Hu

Faculty, Staff and Student Publications

Ischemic stroke is a highly complex systemic disease characterized by intricate interactions between the brain and gastrointestinal tract. While our current understanding of these interactions primarily stems from experimental models, their relevance to human stroke outcomes is of considerable interest. After stroke, bidirectional communication between the brain and gastrointestinal tract initiates changes in the gastrointestinal microenvironment. These changes involve the activation of gastrointestinal immunity, disruption of the gastrointestinal barrier, and alterations in gastrointestinal microbiota. Importantly, experimental evidence suggests that these alterations facilitate the migration of gastrointestinal immune cells and cytokines across the damaged blood-brain barrier, ultimately infiltrating the ischemic brain. …

Timing Of Invasive Mechanical Ventilation And Death In Critically Ill Adults With Covid-19: A Multicenter Cohort Study, Adam Green, Jean-Sebastien Rachoin, Christa Schorr, Phil Dellinger, Jonathan D Casey, Isabel Park, Shruti Gupta, Rebecca M Baron, Shahzad Shaefi, Krystal Hunter, David E Leaf

Faculty, Staff and Student Publications

PURPOSE: To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality.

MATERIALS AND METHODS: The data for this study were derived from a multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death. Patients were followed until the first of hospital discharge, death, or 90 days. We adjusted for confounding using a multivariable Cox …

Resveratrol Rescues Cutaneous Radiation-Induced Dna Damage Via A Novel Ampk/Sirt7/Hmgb1 Regulatory Axis, Yi Jin, Xingyuan Liu, Xiaoting Liang, Jiabin Liu, Jieyu Liu, Zonglin Han, Qianxin Lu, Ke Wang, Bingyao Meng, Chunting Zhang, Minna Xu, Jian Guan, Li Ma, Liang Zhou

Faculty, Staff and Student Publications

Cutaneous radiation injury (CRI) interrupts the scheduled process of radiotherapy and even compromises the life quality of patients. However, the current clinical options for alleviating CRI are relatively limited. Resveratrol (RSV) has been shown to be a promising protective agent against CRI; yet the mechanisms of RSV enhancing radioresistance were not fully elucidated and limited its clinical application. In this study, we demonstrate RSV promotes cutaneous radioresistance mainly through SIRT7. During ionizing radiation (IR) treatment, RSV indirectly phosphorylates and activates SIRT7 through AMPK, which is critical for maintaining the genome stability of keratinocytes. Immunoprecipitation and mass spectrometry identified HMGB1 to …

Clinical Insights Into Small Cell Lung Cancer: Tumor Heterogeneity, Diagnosis, Therapy, And Future Directions, Zsolt Megyesfalvi, Carl M Gay, Helmut Popper, Robert Pirker, Gyula Ostoros, Simon Heeke, Christian Lang, Konrad Hoetzenecker, Anna Schwendenwein, Kristiina Boettiger, Paul A Bunn, Ferenc Renyi-Vamos, Karin Schelch, Helmut Prosch, Lauren A Byers, Fred R Hirsch, Balazs Dome

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or …

Enhancing The Therapeutic Activity Of Hyperimmune Igg Against Chikungunya Virus Using Fcγriiia Affinity Chromatography, Julie M Fox, Vicky Roy, Bronwyn M Gunn, Glen R Bolton, Daved H Fremont, Galit Alter, Michael S Diamond, Austin W Boesch

2020-Current year OA Pubs

INTRODUCTION: Chikungunya virus (CHIKV) is a re-emerging mosquito transmitted alphavirus of global concern. Neutralizing antibodies and antibody Fc-effector functions have been shown to reduce CHIKV disease and infection in animals. However, the ability to improve the therapeutic activity of CHIKV-specific polyclonal IgG by enhancing Fc-effector functions through modulation of IgG subclass and glycoforms remains unknown. Here, we evaluated the protective efficacy of CHIKV-immune IgG enriched for binding to Fc-gamma receptor IIIa (FcγRIIIa) to select for IgG with enhanced Fc effector functions.

METHODS: Total IgG was isolated from CHIKV-immune convalescent donors with and without additional purification by FcγRIIIa affinity chromatography. The …

Targeting T Cell Checkpoints 41bb And Lag3 And Myeloid Cell Cxcr1/Cxcr2 Results In Antitumor Immunity And Durable Response In Pancreatic Cancer, Pat Gulhati, Aislyn Schalck, Shan Jiang, Xiaoying Shang, Chang-Jiun Wu, Pingping Hou, Sharia Hernandez Ruiz, Luisa Solis Soto, Edwin Parra, Haoqiang Ying, Jincheng Han, Prasenjit Dey, Jun Li, Pingna Deng, Emi Sei, Dean Y Maeda, John A Zebala, Denise J Spring, Michael Kim, Huamin Wang, Anirban Maitra, Dirk Moore, Karen Clise-Dwyer, Y Alan Wang, Nicholas E Navin, Ronald A Depinho

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is considered non-immunogenic, with trials showing its recalcitrance to PD1 and CTLA4 immune checkpoint therapies (ICTs). Here, we sought to systematically characterize the mechanisms underlying de novo ICT resistance and to identify effective therapeutic options for PDAC. We report that agonist 41BB and antagonist LAG3 ICT alone and in combination, increased survival and antitumor immunity, characterized by modulating T cell subsets with antitumor activity, increased T cell clonality and diversification, decreased immunosuppressive myeloid cells and increased antigen presentation/decreased immunosuppressive capability of myeloid cells. Translational analyses confirmed the expression of 41BB and LAG3 in human PDAC. Since …

Chimeric Rnas Reveal Putative Neoantigen Peptides For Developing Tumor Vaccines For Breast Cancer, Brandon Mistretta, Sakuni Rankothgedera, Micah Castillo, Mitchell Rao, Kimberly Holloway, Anjana Bhardwaj, Maha El Noafal, Constance Albarracin, Randa El-Zein, Hengameh Rezaei, Xiaoping Su, Rehan Akbani, Xiaoshan M Shao, Brian J Czerniecki, Rachel Karchin, Isabelle Bedrosian, Preethi H Gunaratne

Faculty, Staff and Student Publications

INTRODUCTION: We present here a strategy to identify immunogenic neoantigen candidates from unique amino acid sequences at the junctions of fusion proteins which can serve as targets in the development of tumor vaccines for the treatment of breastcancer.

METHOD: We mined the sequence reads of breast tumor tissue that are usually discarded as discordant paired-end reads and discovered cancer specific fusion transcripts using tissue from cancer free controls as reference. Binding affinity predictions of novel peptide sequences crossing the fusion junction were analyzed by the MHC Class I binding predictor, MHCnuggets. CD8+ T cell responses against the 15 peptides were …

Translating Energy Balance Research From The Bench To The Clinic To The Community: Parallel Animal-Human Studies In Cancer, Miriam B Garcia, Keri L Schadler, Joya Chandra, Steven K Clinton, Kerry S Courneya, Zobeida Cruz-Monserrate, Carrie R Daniel, Andrew J Dannenberg, Wendy Demark-Wahnefried, Mark W Dewhirst, Carol J Fabian, Stephen D Hursting, Melinda L Irwin, Neil M Iyengar, Jennifer L Mcquade, Kathryn H Schmitz, Karen Basen-Engquist

Faculty, Staff and Student Publications

Advances in energy balance and cancer research to date have largely occurred in siloed work in rodents or patients. However, substantial benefit can be derived from parallel studies in which animal models inform the design of clinical and population studies or in which clinical observations become the basis for animal studies. The conference Translating Energy Balance from Bench to Communities: Application of Parallel Animal-Human Studies in Cancer, held in July 2021, convened investigators from basic, translational/clinical, and population science research to share knowledge, examples of successful parallel studies, and strong research to move the field of energy balance and cancer …

The Involvement Of Kynurenine Pathway In Neurodegenerative Diseases, Lais B Martins, Ana L M Silveira, Antonio L Teixeira

Faculty, Staff and Student Publications

BACKGROUND: A growing body of evidence has shown the involvement of the kynurenine pathway (KP), the primary route of tryptophan (TRP) catabolism, in the pathophysiology of neuropsychiatric disorders.

OBJECTIVE: The study aims to provide a comprehensive and critical overview of the clinical evidence on the KP involvement in the pathophysiology of Alzheimer's disease (AD) and Parkinson's disease (PD), discussing therapeutic opportunities.

METHODS: We searched for studies investigating KP metabolites in human subjects with AD and/or PD.

RESULTS: Postmortem studies showed altered levels of KP metabolites in the brain of AD and PD patients compared with controls. Cross-sectional studies have reported …

Il-8 Produced Via Bidirectional Communication Between Prostate Cancer And M2 Macrophages As A Potential Diagnostic And Prognostic Biomarker, Huihui Fan, Zheng Tang, Yaling Tian, Qingsong Lv, Fangyin Zeng

Faculty, Staff and Student Publications

PURPOSE: Owing to the mortality associated with metastatic prostate cancer and the shortcomings of the current parameters in predicting the disease prognosis, we require the identification of viable biomarkers, which would help in the diagnosis and prognosis of the disease. We aimed to determine whether the interleukin-8 level in the tumor microenvironment could serve as a potential clinical diagnostic marker and prognostic factor for prostate cancer.

METHODS: The migration assay of prostate cancer cells was performed in an in vitro co-culture model. Cell lines PC3 and DU145 were divided into two groups and co-cultured with M0 and M2 macrophages, respectively. …

Targeting Immunosuppressive Ly6c+ Classical Monocytes Reverses Anti-Pd-1/Ctla-4 Immunotherapy Resistance, B Leticia Rodriguez, Limo Chen, Yanli Li, Shucheng Miao, David H Peng, Jared J Fradette, Lixia Diao, Jessica M Konen, Frank R Rojas Alvarez, Luisa M Solis, Xiaohui Yi, Aparna Padhye, Laura A Gibson, Joshua K Ochieng, Xiaofei Zhou, Jing Wang, Don L Gibbons

Faculty, Staff and Student Publications

Introduction: Despite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way …

Clinical Manifestations And Outcome Of Patients With Primary Amoebic Meningoencephalitis In Pakistan A Single-Center Experience, Shakeel Ur Rehman, Salman Farooq, Muhammad Bilal Tariq, Nosheen Nasir, Mohammad Wasay, Sobia Masood, Musa Karim

Faculty, Staff and Student Publications

Primary amoebic meningoencephalitis (PAM) is a rapidly progressing central nervous system (CNS) infection caused by Naegleria fowleri, a free-living amoeba found in warm freshwater. The disease progression is very rapid, and the outcome is nearly always fatal. We aim to describe the disease course in patients admitted with PAM in a tertiary care center in Karachi, Pakistan between the periods of 2010 to 2021. A total of 39 patients were included in the study, 33 males (84.6%). The median age of the patients was 34 years. The most frequent presenting complaint was fever, which was found in 37 patients (94.9%) …

Population-Based Mini-Mental State Examination Norms In Adults Of Mexican Heritage In The Cameron County Hispanic Cohort, Avram S Bukhbinder, Miriam Hinojosa, Kristofer Harris, Xiaojin Li, Christine M Farrell, Madison Shyer, Nathan Goodwin, Sahar Anjum, Omar Hasan, Susan Cooper, Lois Sciba, Amanda Falk Vargas, David H Hunter, Guadalupe J Ortiz, Karen Chung, Licong Cui, Guo-Qiang Zhang, Susan P Fisher-Hoch, Joseph B Mccormick, Paul E Schulz

Faculty, Staff and Student Publications

Background:

Accurately identifying cognitive changes in Mexican American (MA) adults using the Mini-Mental State Examination (MMSE) requires knowledge of population-based norms for the MMSE, a scale which has widespread use in research settings.

Objective:

To describe the distribution of MMSE scores in a large cohort of MA adults, assess the impact of MMSE requirements on their clinical trial eligibility, and explore which factors are most strongly associated with their MMSE scores.

Methods:

Visits between 2004–2021 in the Cameron County Hispanic Cohort were analyzed. Eligible participants were ≥18 years old and of Mexican descent. MMSE distributions before and after stratification by …

Hermann ("Hugh") Blaschko (1900-1993): Father Of Catecholamine Metabolism, Heinrich Taegtmeyer, Jiries Ganim, Anne B Leuppi-Taegtmeyer

Faculty, Staff and Student Publications

No abstract provided.

Inhibition Of Yap/Taz-Driven Tead Activity Prevents Growth Of Nf2-Null Schwannoma And Meningioma, Liyam Laraba, Lily Hillson, Julio Grimm De Guibert, Amy Hewitt, Maisie R Jaques, Tracy T Tang, Leonard Post, Emanuela Ercolano, Ganesha Rai, Shyh-Ming Yang, Daniel J Jagger, Waldemar Woznica, Philip Edwards, Aditya G Shivane, C Oliver Hanemann, David B Parkinson

Peninsula Medical School

Schwannoma tumours typically arise on the eighth cranial nerve and are mostly caused by loss of the tumour suppressor Merlin (NF2). There are no approved chemotherapies for these tumours and the surgical removal of the tumour carries a high risk of damage to the eighth or other close cranial nerve tissue. New treatments for schwannoma and other NF2-null tumours such as meningioma are urgently required. Using a combination of human primary tumour cells and mouse models of schwannoma, we have examined the role of the Hippo signalling pathway in driving tumour cell growth. Using both genetic ablation of the Hippo …

Supplementary Feeding And Infection Control In Pregnant Adolescents-A Secondary Analysis Of A Randomized Trial Among Malnourished Women In Sierra Leone, Aminata S Koroma, Mariama Ellie, Kadiatu Bangura, Per O Iversen, David T Hendrixson, Kevin Stephenson, Mark J Manary

2020-Current year OA Pubs

Undernutrition during pregnancy in adolescence confers a high risk of maternal morbidity and adverse birth outcomes, particularly in low-resource settings. In a secondary analysis, we hypothesized that younger undernourished pregnant adolescents (<18 years) would benefit more than undernourished pregnant adults (>20 years) from the intervention of supplementary food and anti-infective treatments. The original trial in Sierra Leone enrolled 236 younger adolescents (<18 years), 454 older adolescents (aged 18-19 years), and 741 adults (≥20 years), all with a mid-upper arm circumference ≤23 cm. Younger adolescents had lower final fundal height as well as smaller newborns (-0.3 kg; 95% confidence interval [CI], -0.3, -0.2; p < 0.001) and shorter newborns (-1.1 cm; 95% CI, -1.5, -0.7; p < 0.001) than adults. The intervention's effect varied significantly between maternal age groups: adults benefited more than younger adolescents with respect to newborn birth weight (difference in difference, 166 g; 95% CI, 26, 306; interaction p = 0.02), birth length (difference in difference, 7.4 mm; 95% CI, 0.1, 14.8; interaction p = 0.047), and risk for low birth weight (<2.5 kg) (interaction p = 0.019). The differences in response persisted despite adjustments for maternal anthropometry, the number of prior pregnancies, and human immunodeficiency virus status. Older adolescents similarly benefited more than younger adolescents, though differences did not reach statistical significance. In conclusion, newborns born to younger adolescent mothers had worse outcomes than those born to adult mothers, and adults and their newborns benefited more from the intervention than younger adolescents.

Dual-Task Upper Extremity Motor Performance Measured By Video Processing As Cognitive-Motor Markers For Older Adults, Changhong Wang, Mohsen Zahiri, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Introduction: The use of dual-task model such as dual-task gait has been extensively studied to assess cognitive-motor performance among older adults. However, space restriction and safety factor limit its applications in remote assessment. To address the gap, we propose a video processing-based approach to remotely quantify cognitive-motor performance using a 20-s repetitive elbow flexion-extension test with dual-task condition, called video-based motoric-cognitive meter (MCM).

Methods: Eighteen older participants (age: 78.6 ± 6.5 years) who were clinically diagnosed as having either mild cognitive impairment or dementia were included in this study. Participants were asked to perform 20-s repetitive elbow flexion-extension exercise with …

Neuroanatomical Correlates Of The Late Positive Potential In Youth With Pediatric Bipolar Disorder, Alessio Simonetti, Marijn Lijffijt, Sherin Kurian, Johanna Saxena, Delfina Janiri, Marianna Mazza, Giulio Carriero, Lorenzo Moccia, Benson Mwangi, Alan C Swann, Jair C Soares

Faculty, Staff and Student Publications

BACKGROUND: The late positive potential (LPP) could be a marker of emotion dysregulation in youth with pediatric bipolar disorder (PBD). However, the neuroanatomical correlates of the LPP are still not clarified.

OBJECTIVE: To provide cortical and deep gray matter correlates of the LPP in youth, specifically, youth with PBD.

METHODS: Twenty-four 7 to 17 years-old children with PBD and 28 healthy controls (HC) underwent cortical thickness and deep gray matter volumes measurements through magnetic resonance imaging and LPP measurement elicited by passively viewing emotional faces through electroencephalography. T-tests compared group differences in LPP, cortical thickness, and deep gray matter volumes. …

Functional Divergence Of The Sarcomeric Myosin, Myh7b, Supports Species-Specific Biological Roles, Lindsey A. Lee, Samantha K. Barrick, Artur Meller, Jonathan Walklate, Jeffrey M. Lotthammer, Jian Wei Tay, W. Tom Stump, Gregory Bowman, Michael A. Geeves, Michael J. Greenberg, Leslie A Leinwand

2020-Current year OA Pubs

Myosin heavy chain 7b (MYH7b) is an evolutionarily ancient member of the sarcomeric myosin family, which typically supports striated muscle function. However, in mammals, alternative splicing prevents MYH7b protein production in cardiac and most skeletal muscles and limits expression to a subset of specialized muscles and certain nonmuscle environments. In contrast, MYH7b protein is abundant in python cardiac and skeletal muscles. Although the MYH7b expression pattern diverges in mammals versus reptiles, MYH7b shares high sequence identity across species. So, it remains unclear how mammalian MYH7b function may differ from that of other sarcomeric myosins and whether human and python MYH7b …

Unmet Needs And Coping Strategies Of Older Underserved Veterans During The Covid-19 Pandemic, Trenton M Haltom, Joyce Tiong, Tracy L Evans, Nipa Kamdar, Gala True, Mark E Kunik

Faculty, Staff and Students Publications

INTRODUCTION: The COVID-19 pandemic has had profound impacts on people with diabetes, a group with high morbidity and mortality. Factors like race, age, income, Veteran-status, and limited or interrupted resources early in the COVID-19 pandemic compounded risks for negative health outcomes. Our objective was to characterize the experiences and needs of under-resourced Veterans with type 2 diabetes during the COVID-19 pandemic.

METHODS: We conducted semi-structured qualitative interviews (March through September 2021) with U.S. military Veterans with diabetes. Transcripts were analyzed using a team-based, iterative process of summarizing and coding to identify key themes. Participants included Veterans (n = 25) who …

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 …

Meta-Analysis Of Chest Compression-Only Versus Conventional Cardiopulmonary Resuscitation By Bystanders For Adult With Out-Of-Hospital Cardiac Arrest, Karol Bielski, Jacek Smereka, Jaroslaw Chmielewski, Michal Pruc, Francesco Chirico, Aleksandra Gasecka, Nataliia Litvinova, Milosz J Jaguszewski, Grazyna Nowak-Starz, Zubaid Rafique, Frank W Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: According to the guidelines of cardiopulmonary resuscitation (CPR) conducted by bystanders, two methods of CPR are feasible: standard CPR (sCPR) with mouth-to-mouth ventilations and continuous chest compression-only CPR (CCC) without rescue breathing. The goal herein, was to evaluate the effect of sCPR (30:2) and CCC on resuscitation outcomes in patients with out-of-hospital cardiac arrest (OHCA) patients.

METHODS: This study was a systematic review and meta-analysis. Using standardized criteria, Pub- Med, Web of Science, Scopus, EMBASE and Cochrane Collaboration were searched for trials assessing the effect of sCPR vs. CCC on resuscitation outcomes after adult OHCA. Random-effects model meta-analysis was …

Multiomics, Artificial Intelligence, And Precision Medicine In Perinatology, Mohan Pammi, Nima Aghaeepour, Josef Neu

Faculty, Staff and Students Publications

Technological advances in omics evaluation, bioinformatics, and artificial intelligence have made us rethink ways to improve patient outcomes. Collective quantification and characterization of biological data including genomics, epigenomics, metabolomics, and proteomics is now feasible at low cost with rapid turnover. Significant advances in the integration methods of these multiomics data sets by machine learning promise us a holistic view of disease pathogenesis and yield biomarkers for disease diagnosis and prognosis. Using machine learning tools and algorithms, it is possible to integrate multiomics data with clinical information to develop predictive models that identify risk before the condition is clinically apparent, thus …

Spatial Analysis Of Nanoparticle Distribution In Human Breast Xenografts Reveals Nanoparticles Targeted To Cancer Cells Localized With Tumor-Associated Stromal Cells, Sean Healy, Elizabeth T Henderson, Suqi Ke, Jacqueline Kelly, Brian W Simons, Chen Hu, Robert Ivkov, Preethi Korangath

Faculty, Staff and Students Publications

The biological influence of physicochemical parameters of “targeted” nanoparticles on their delivery to cancer tumors remains poorly understood. A comparative analysis of nanoparticle distributions in tumors following systemic delivery across several models can provide valuable insights.

Methods: Bionized nanoferrite nanoparticles (iron oxide core coated with starch), either conjugated with a targeted anti-HER2 antibody (BH), or unconjugated (BP), were intravenously injected into athymic nude or NOD-scid gamma (NSG) female mice bearing one of five human breast cancer tumor xenografts growing in a mammary fat pad. Tumors were harvested 24 hours after nanoparticle injection, fixed, mounted, and stained. We performed detailed histopathology …

Repair Of Complex Ovine Segmental Mandibulectomy Utilizing Customized Tissue Engineered Bony Flaps, Emma Watson, Hannah A Pearce, Katie J Hogan, Natasja W M Van Dijk, Mollie M Smoak, Sergio Barrios, Brandon T Smith, Alexander M Tatara, Timothy C Woernley, Jonathan Shum, Craig B Pearl, James C Melville, Tang Ho, Issa A Hanna, Nagi Demian, Jeroen J J P Van Den Beucken, John A Jansen, Mark E Wong, Antonios G Mikos

Faculty, Staff and Student Publications

Craniofacial defects require a treatment approach that provides both robust tissues to withstand the forces of mastication and high geometric fidelity that allows restoration of facial architecture. When the surrounding soft tissue is compromised either through lack of quantity (insufficient soft tissue to enclose a graft) or quality (insufficient vascularity or inducible cells), a vascularized construct is needed for reconstruction. Tissue engineering using customized 3D printed bioreactors enables the generation of mechanically robust, vascularized bony tissues of the desired geometry. While this approach has been shown to be effective when utilized for reconstruction of non-load bearing ovine angular defects and …

Multiomics In Primary And Metastatic Breast Tumors From The Aurora Us Network Finds Microenvironment And Epigenetic Drivers Of Metastasis, Susana Garcia-Recio, Toshinori Hinoue, Gregory L Wheeler, Benjamin J Kelly, Ana C Garrido-Castro, Tomas Pascual, Aguirre A De Cubas, Youli Xia, Brooke M Felsheim, Marni B Mcclure, Andrei Rajkovic, Ezgi Karaesmen, Markia A Smith, Cheng Fan, Paula I Gonzalez Ericsson, Melinda E Sanders, Chad J Creighton, Jay Bowen, Kristen Leraas, Robyn T Burns, Sara Coppens, Amy Wheless, Salma Rezk, Amy L Garrett, Joel S Parker, Kelly K Foy, Hui Shen, Ben H Park, Ian Krop, Carey Anders, Julie Gastier-Foster, Mothaffar F Rimawi, Rita Nanda, Nancy U Lin, Claudine Isaacs, P Kelly Marcom, Anna Maria Storniolo, Fergus J Couch, Uma Chandran, Michael Davis, Jonathan Silverstein, Alexander Ropelewski, Minetta C Liu, Susan G Hilsenbeck, Larry Norton, Andrea L Richardson, W Fraser Symmans, Antonio C Wolff, Nancy E Davidson, Lisa A Carey, Adrian V Lee, Justin M Balko, Katherine A Hoadley, Peter W Laird, Elaine R Mardis, Tari A King, Charles M Perou

Faculty, Staff and Students Publications

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER

Peptidylarginine Deiminase 2 Citrullinates Mzb1 And Promotes The Secretion Of Igm And Iga, Benjamin Geary, Bo Sun, Ronak R Tilvawala, Leonard Barasa, Konstantin Tsoyi, Ivan O Rosas, Paul R Thompson, I-Cheng Ho

Faculty, Staff and Students Publications

INTRODUCTION: MZB1 is an endoplasmic reticulum residential protein preferentially expressed in plasma cells, marginal zone and B1 B cells. Recent studies on murine B cells show that it interacts with the tail piece of IgM and IgA heavy chain and promotes the secretion of these two classes of immunoglobulin. However, its role in primary human B cells has yet to be determined and how its function is regulated is still unknown. The conversion of peptidylarginine to peptidylcitrulline, also known as citrullination, by peptidylarginine deiminases (PADs) can critically influence the function of proteins in immune cells, such as neutrophils and T …

An Overview: The Diversified Role Of Mitochondria In Cancer Metabolism, Yu'e Liu, Yihong Sun, Yadong Guo, Xiaoyun Shi, Xi Chen, Wenfeng Feng, Lei-Lei Wu, Jin Zhang, Shibo Yu, Yi Wang, Yufeng Shi

Faculty, Staff and Students Publications

Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling. They are essential not only in the process of ATP synthesis, lipid metabolism and nucleic acid metabolism, but also in tumor development and metastasis. Mutations in mtDNA are commonly found in cancer cells to promote the rewiring of bioenergetics and biosynthesis, various metabolites especially oncometabolites in mitochondria regulate tumor metabolism and progression. And mutation of enzymes in the TCA cycle leads to the unusual accumulation of certain metabolites and oncometabolites. Mitochondria have been demonstrated as the target for cancer treatment. Cancer cells rely on two main energy …

Biological Embedding Of Early Trauma: The Role Of Higher Prefrontal Synaptic Strength, Amanda J F Tamman, Lihong Jiang, Christopher L Averill, Graeme F Mason, Lynnette A Averill, Chadi G Abdallah

Staff and Researcher Publications

Background: Early trauma predicts poor psychological and physical health. Glutamatergic synaptic processes offer one avenue for understanding this relationship, given glutamate's abundance and involvement in reward and stress sensitivity, emotion, and learning. Trauma-induced glutamatergic excitotoxicity may alter neuroplasticity and approach/avoidance tendencies, increasing risk for psychiatric disorders. Studies examine upstream or downstream effects instead of glutamatergic synaptic processes in vivo, limiting understanding of how trauma affects the brain.Objective: In a pilot study using a previously published data set, we examine associations between early trauma and a proposed measure of synaptic strength in vivo in one of the largest human …

Peripherally-Induced Movement Disorders: An Update, Abhishek Lenka, Joseph Jankovic

Faculty, Staff and Students Publications

BACKGROUND: Peripherally-induced movement disorders (PIMD) should be considered when involuntary or abnormal movements emerge shortly after an injury to a body part. A close topographic and temporal association between peripheral injury and onset of the movement disorders is crucial to diagnosing PIMD. PIMD is under-recognized and often misdiagnosed as functional movement disorder, although both may co-exist. Given the considerable diagnostic, therapeutic, and psychosocial-legal challenges associated with PIMD, it is crucial to update the clinical and scientific information about this important movement disorder.

METHODS: A comprehensive PubMed search through a broad range of keywords and combinations was performed in February 2023 …