Digital Commons Network^™

A Deep Learning-Based Framework For Supporting Clinical Diagnosis Of Glioblastoma Subtypes, Sana Munquad, Tapas Si, Saurav Mallik, Asim Bikas Das, Zhongming Zhao

Faculty, Staff and Student Publications

Understanding molecular features that facilitate aggressive phenotypes in glioblastoma multiforme (GBM) remains a major clinical challenge. Accurate diagnosis of GBM subtypes, namely classical, proneural, and mesenchymal, and identification of specific molecular features are crucial for clinicians for systematic treatment. We develop a biologically interpretable and highly efficient deep learning framework based on a convolutional neural network for subtype identification. The classifiers were generated from high-throughput data of different molecular levels, i.e., transcriptome and methylome. Furthermore, an integrated subsystem of transcriptome and methylome data was also used to build the biologically relevant model. Our results show that deep learning model outperforms …

Crucial Roles Of Microrna-16-5p And Microrna-27b-3p In Ameloblast Differentiation Through Regulation Of Genes Associated With Amelogenesis Imperfecta, Akiko Suzuki, Hiroki Yoshioka, Teng Liu, Aania Gull, Naina Singh, Thanh Le, Zhongming Zhao, Junichi Iwata

Faculty, Staff and Student Publications

Amelogenesis imperfecta is a congenital disorder within a heterogeneous group of conditions characterized by enamel hypoplasia. Patients suffer from early tooth loss, social embarrassment, eating difficulties, and pain due to an abnormally thin, soft, fragile, and discolored enamel with poor aesthetics and functionality. The etiology of amelogenesis imperfecta is complicated by genetic interactions. To identify mouse amelogenesis imperfecta-related genes (mAIGenes) and their respective phenotypes, we conducted a systematic literature review and database search and found and curated 70 mAIGenes across all of the databases. Our pathway enrichment analysis indicated that these genes were enriched in tooth development-associated pathways, forming four …

The Wnt/Β-Catenin Pathway Regulates Expression Of The Genes Involved In Cell Cycle Progression And Mitochondrial Oxidative Phosphorylation In The Postmitotic Cardiac Myocytes, Melis Olcum, Sirisha M Cheedipudi, Leila Rouhi, Siyang Fan, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: Aging is associated with cardiac myocyte loss, sarcopenia, and cardiac dysfunction. Adult cardiac myocytes are postmitotic cells with an insufficient proliferative capacity to compensate for myocyte loss. The canonical WNT (cWNT) pathway is involved in the regulation of cell cycle reentry in various cell types. The effects of the cWNT pathway on the expression of genes involved in cell cycle reentry in the postmitotic cardiac myocytes are unknown.

AIM: The aim of the study was to identify genes whose expression is regulated by the β-catenin, the indispensable component to the cWNT signaling, in the postmitotic myocytes.

METHODS AND RESULTS: …

Prediction Of Intensive Care Unit Admission (>24h) After Surgery In Elective Noncardiac Surgical Patients Using Machine Learning Algorithms, Lan Lan, Fangwei Chen, Jiawei Luo, Mengjiao Li, Xuechao Hao, Yao Hu, Jin Yin, Tao Zhu, Xiaobo Zhou

Faculty, Staff and Student Publications

BACKGROUND: To develop a highly discriminative machine learning model for the prediction of intensive care unit admission (>24h) using the easily available preoperative information from electronic health records. An accurate prediction model for ICU admission after surgery is of great importance for surgical risk assessment and appropriate utilization of ICU resources.

METHOD: Data were collected retrospectively from a large hospital, comprising 135,442 adult patients who underwent surgery except for cardiac surgery between 1 January 2014, and 31 July 2018 in China. Multiple existing predictive machine learning algorithms were explored to construct the prediction model, including logistic regression, random forest, …

Epithelial Immunomodulation By Aerosolized Toll-Like Receptor Agonists Prevents Allergic Inflammation In Airway Mucosa In Mice, David L Goldblatt, Gabriella Valverde Ha, Shradha Wali, Vikram V Kulkarni, Michael K Longmire, Ana M Jaramillo, Rosha P Chittuluru, Adrienne Fouts, Margarita Martinez-Moczygemba, Jonathan T Lei, David P Huston, Michael J Tuvim, Burton F Dickey, Scott E Evans

Faculty, Staff and Student Publications

Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells …

Comparison Of Three Exercise Interventions With And Without Gemcitabine Treatment On Pancreatic Tumor Growth In Mice: No Impact On Tumor Infiltrating Lymphocytes, Priti Gupta, Charles F Hodgman, Claudia Alvarez-Florez, Keri L Schadler, Melissa M Markofski, Daniel P O'Connor, Emily C Lavoy

Faculty, Staff and Student Publications

Exercise has been shown to slow pancreatic tumor growth, but whether exercise interventions of differing volume or intensity yield differential effects on tumor outcomes is unknown. In this study, we compared three exercise training interventions implemented with and without chemotherapy on pancreatic tumor growth in mice. Methods: Male C57BL/6 mice (6-8 weeks old) were subcutaneously inoculated with pancreatic ductal adenocarcinoma tumor cells (PDAC 4662). Upon tumor detection, mice received gemcitabine 15 mg/kg intraperitoneally 3 days/week and were assigned to exercise: high volume continuous exercise (HVCE), low volume continuous exercise (LVCE), high intensity interval training (HIIT), or sedentary (SED). HVCE ran …

B Cells Are Required To Generate Optimal Anti-Melanoma Immunity In Response To Checkpoint Blockade, Shubhra Singh, Jason Roszik, Neeraj Saini, Vipul Kumar Singh, Karishma Bavisi, Zhiqiang Wang, Long T Vien, Zixi Yang, Suprateek Kundu, Richard E Davis, Laura Bover, Adi Diab, Sattva S Neelapu, Willem W Overwijk, Kunal Rai, Manisha Singh

Faculty, Staff and Student Publications

Immunotherapies such as checkpoint blockade therapies are known to enhance anti-melanoma CD8+ T cell immunity, but only a fraction of patients treated with these therapies achieve durable immune response and disease control. It may be that CD8+ T cells need help from other immune cells to generate effective and long-lasting anti-tumor immunity or that CD8+ T cells alone are insufficient for complete tumor regression and cure. Melanoma contains significant numbers of B cells; however, the role of B cells in anti-melanoma immunity is controversial. In this study, B16 melanoma mouse models were used to determine the role of B cells …

Engineered Cord Blood Megakaryocytes Evade Killing By Allogeneic T-Cells For Refractory Thrombocytopenia, Bijender Kumar, Vahid Afshar-Kharghan, Mayela Mendt, Robert Sackstein, Mark R Tanner, Uday Popat, Jeremy Ramdial, May Daher, Juan Jimenez, Rafet Basar, Luciana Melo Garcia, Mayra Shanley, Mecit Kaplan, Xinhai Wan, Vandana Nandivada, Francia Reyes Silva, Vernikka Woods, April Gilbert, Ricardo Gonzalez-Delgado, Sunil Acharya, Paul Lin, Hind Rafei, Pinaki Prosad Banerjee, Elizabeth J Shpall

Faculty, Staff and Student Publications

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, …

Regenerative Medicine Technologies Applied To Transplant Medicine An Update, Astgik Petrosyan, Filippo Montali, Andrea Peloso, Antonio Citro, Lori N Byers, Catherine La Pointe, Mara Suleiman, Alice Marchetti, Eoin P Mcneill, Allison L Speer, Wai Hoe Ng, Xi Ren, Benedetta Bussolati, Laura Perin, Paolo Di Nardo, Vincenzo Cardinale, Jerome Duisit, Alexandra Rose Monetti, John Richard Savino, Amish Asthana, Giuseppe Orlando

Faculty, Staff and Student Publications

Regenerative medicine (RM) is changing how we think and practice transplant medicine. In regenerative medicine, the aim is to develop and employ methods to regenerate, restore or replace damaged/diseased tissues or organs. Regenerative medicine investigates using tools such as novel technologies or techniques, extracellular vesicles, cell-based therapies, and tissue-engineered constructs to design effective patient-specific treatments. This review illustrates current advancements in regenerative medicine that may pertain to transplant medicine. We highlight progress made and various tools designed and employed specifically for each tissue or organ, such as the kidney, heart, liver, lung, vasculature, gastrointestinal tract, and pancreas. By combing both …

Impairment Of Autophagy After Spinal Cord Injury Potentiates Neuroinflammation And Motor Function Deficit In Mice, Yun Li, Zhuofan Lei, Rodney M Ritzel, Junyun He, Hui Li, Harry M C Choi, Marta M Lipinski, Junfang Wu

Faculty, Staff and Student Publications

Autophagy is a catabolic process that degrades cytoplasmic constituents and organelles in the lysosome, thus serving an important role in cellular homeostasis and protection against insults. We previously reported that defects in autophagy contribute to neuronal cell damage in traumatic spinal cord injury (SCI). Recent data from other inflammatory models implicate autophagy in regulation of immune and inflammatory responses, with low levels of autophagic flux associated with pro-inflammatory phenotypes. In the present study, we examined the effects of genetically or pharmacologically manipulating autophagy on posttraumatic neuroinflammation and motor function after SCI in mice.

Methods: Young adult male C57BL/6, CX3CR1-GFP, autophagy …

Anatomy And Function Of Ventral Tegmental Area Glutamate Neurons, Jing Cai, Qingchun Tong

Faculty, Staff and Student Publications

The ventral tegmental area (VTA) is well known for regulating reward consumption, learning, memory, and addiction behaviors through mediating dopamine (DA) release in downstream regions. Other than DA neurons, the VTA is known to be heterogeneous and contains other types of neurons, including glutamate neurons. In contrast to the well-studied and established functions of DA neurons, the role of VTA glutamate neurons is understudied, presumably due to their relatively small quantity and a lack of effective means to study them. Yet, emerging studies have begun to reveal the importance of glutamate release from VTA neurons in regulating diverse behavioral repertoire …

Use Of The Fully Spectroscopic Pixelated Cadmium Telluride Detector For Benchtop X-Ray Fluorescence Computed Tomography, Sandun Jayarathna, Hem Moktan, Sang Hyun Cho

Faculty, Staff and Student Publications

In this work, we integrated a commercially-available fully-spectroscopic pixelated cadmium telluride (CdTe) detector system as a two-dimensional (2D) array detector into our existing benchtop cone-beam x-ray fluorescence computed tomography (XFCT) system. After integrating this detector, known as High-Energy X-ray Imaging Technology (HEXITEC), we performed quantitative imaging of gold nanoparticle (GNP) distribution in a small animal-sized phantom using our benchtop XFCT system. Owing to the upgraded detector component within our benchtop XFCT system, we were able to conduct this phantom imaging in an unprecedented manner by volumetric XFCT scans followed by XFCT image reconstruction in 3D. The current results showed that …

Cgas-Sting Pathway Targeted Therapies And Their Applications In The Treatment Of High-Grade Glioma, Shashwat Tripathi, Hinda Najem, Akanksha Sanjay Mahajan, Peng Zhang, Justin T Low, Alexander H Stegh, Michael A Curran, David M Ashley, Charles David James, Amy B Heimberger

Faculty, Staff and Student Publications

Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches …

Behavioural Immune Landscapes Of Inflammation, Georgiana Crainiciuc, Miguel Palomino-Segura, Miguel Molina-Moreno, Jon Sicilia, David G Aragones, Jackson Liang Yao Li, Rodrigo Madurga, José M Adrover, Alejandra Aroca-Crevillén, Sandra Martin-Salamanca, Alfonso Serrano Del Valle, Sandra D Castillo, Heidi C E Welch, Oliver Soehnlein, Mariona Graupera, Fátima Sánchez-Cabo, Alexander Zarbock, Thomas E Smithgall, Mauro Di Pilato, Thorsten R Mempel, Pierre-Louis Tharaux, Santiago F González, Angel Ayuso-Sacido, Lai Guan Ng, Gabriel F Calvo, Iván González-Díaz, Fernando Díaz-De-María, Andrés Hidalgo

Faculty, Staff and Student Publications

Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues1,2. These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream 'behavioural' outputs3-5. Here we used 4D live imaging to record tens to hundreds of morpho-kinetic parameters describing the dynamics of individual leukocytes at sites of active inflammation. By analysing more than 100,000 reconstructions of cell shapes and tracks over time, we obtained behavioural descriptors of individual cells and used these high-dimensional datasets to build behavioural landscapes. These landscapes recognized leukocyte …

Association Of Proton Pump Inhibitor Use With Survival Outcomes In Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review And Meta-Analysis, Baoqing Chen, Chen Yang, Mihnea P Dragomir, Dongmei Chi, Wenyan Chen, David Horst, George A Calin, Qiaoqiao Li

Faculty, Staff and Student Publications

Background: Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients.

Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI …

Defective Dna Polymerase Beta Invoke A Cytosolic Dna Mediated Inflammatory Response, Shengyuan Zhao, Julia A Goewey Ruiz, Manu Sebastian, Dawit Kidane

Faculty, Staff and Student Publications

Base excision repair (BER) has evolved to maintain the genomic integrity of DNA following endogenous and exogenous agent induced DNA base damage. In contrast, aberrant BER induces genomic instability, promotes malignant transformation and can even trigger cancer development. Previously, we have shown that deoxyribo-5'-phosphate (dRP) lyase deficient DNA polymerase beta (POLB) causes replication associated genomic instability and sensitivity to both endogenous and exogenous DNA damaging agents. Specifically, it has been established that this loss of dRP lyase function promotes inflammation associated gastric cancer. However, the way that aberrant POLB impacts the immune signaling and inflammatory responses is still unknown. Here …

Quaking But Not Parkin Is The Major Tumor Suppressor In 6q Deleted Region In Glioblastoma, Fatma Betul Aksoy Yasar, Takashi Shingu, Daniel B Zamler, Mohammad Fayyad Zaman, Derek Lin Chien, Qiang Zhang, Jiangong Ren, Jian Hu

Faculty, Staff and Student Publications

Glioblastoma (GBM) is a high-grade, aggressive brain tumor with dismal median survival time of 15 months. Chromosome 6q (Ch6q) is a hotspot of genomic alterations, which is commonly deleted or hyper-methylated in GBM. Two neighboring genes in this region, QKI and PRKN have been appointed as tumor suppressors in GBM. While a genetically modified mouse model (GEMM) of GBM has been successfully generated with Qk deletion in the central nervous system (CNS), in vivo genetic evidence supporting the tumor suppressor function of Prkn has not been established. In the present study, we generated a mouse model with Prkn-null allele …

Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Intra-Tumoral Nerve-Tracing In A Novel Syngeneic Model Of High-Grade Serous Ovarian Carcinoma, Jeffrey L Barr, Allison Kruse, Anthony C Restaino, Natalia Tulina, Sarah Stuckelberger, Samuel J Vermeer, Caitlin S Williamson, Daniel W Vermeer, Marianna Madeo, Jillian Stamp, Maria Bell, Mark Morgan, Ju-Yoon Yoon, Marilyn A Mitchell, Anna Budina, Dalia K Omran, Lauren E Schwartz, Ronny Drapkin, Paola D Vermeer

Faculty, Staff and Student Publications

Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. …

Epigenome-Wide Association Study Of Serum Urate Reveals Insights Into Urate Co-Regulation And The Slc2a9 Locus, Adrienne Tin, Pascal Schlosser, Pamela R Matias-Garcia, Chris H L Thio, Roby Joehanes, Hongbo Liu, Zhi Yu, Antoine Weihs, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L Min, Victoria L Halperin Kuhns, Adebowale A Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Jan Bressler, Monique M B Breteler, Cristian Carmeli, Layal Chaker, Josef Coresh, Tanguy Corre, Adolfo Correa, Simon R Cox, Graciela E Delgado, Kai-Uwe Eckardt, Arif B Ekici, Karlhans Endlich, James S Floyd, Eliza Fraszczyk, Xu Gao, Xīn Gào, Allan C Gelber, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L Grove, Sarah E Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A Hurme, Shih-Jen Hwang, Sharon L R Kardia, Silva Kasela, Marcus E Kleber, Wolfgang Koenig, Jaspal S Kooner, Florian Kronenberg, Brigitte Kühnel, Christine Ladd-Acosta, Terho Lehtimäki, Lars Lind, Dan Liu, Donald M Lloyd-Jones, Stefan Lorkowski, Ake T Lu, Riccardo E Marioni, Winfried März, Daniel L Mccartney, Karlijn A C Meeks, Lili Milani, Pashupati P Mishra, Matthias Nauck, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M Psaty, Olli T Raitakari, Scott M Ratliff, Alex P Reiner, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A Smith, Nona Sotoodehnia, Hannah R Stocker, Silvia Stringhini, Johan Sundström, Brenton R Swenson, Joyce B J Van Meurs, Jana V Van Vliet-Ostaptchouk, Andrea Venema, Uwe Völker, Juliane Winkelmann, Bruce H R Wolffenbuttel, Wei Zhao, Yinan Zheng, Marie Loh, Harold Snieder, Melanie Waldenberger, Daniel Levy, Shreeram Akilesh, Owen M Woodward, Katalin Susztak, Alexander Teumer, Anna Köttgen

Faculty, Staff and Student Publications

Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.

Practical Considerations Of Dissolved Oxygen Levels For Platelet Function Under Hypoxia, Branden Kusanto, Andrew Gordon, Leigh Naylor-Adamson, Lloyd Atkinson, Charlie Coupland, Zoe Booth, Yusra Ahmed, Isabel M Pires, Graeme J Stasiuk, Roger Sturmey, Simon D J Calaminus, Mònica Arman

Faculty, Staff and Student Publications

Investigating human platelet function in low-oxygen environments is important in multiple settings, including hypobaric hypoxia (e.g., high altitude), sea level hypoxia-related disease, and thrombus stability. These studies often involve drawing blood from which platelets are isolated and analysed at atmospheric conditions or re-exposed to low oxygen levels in hypoxia chambers before testing. However, it remains unknown how the in vitro handling of the samples itself changes their dissolved oxygen concentration, which might affect platelet function and experimental results. Here, we prepared healthy donor platelet-rich plasma and washed platelet (WP) suspensions and exposed them to 2% oxygen. We found that the …

Dietary Supplementation Of Bacillus-Based Probiotics On The Growth Performance, Gut Morphology, Intestinal Microbiota And Immune Response In Low Biosecurity Broiler Chickens, Mohammad Arif, Md Akteruzzaman, Tuhin-Al-Ferdous, Sk Shaheenur Islam, Bidhan Chandra Das, Mahbubul Pratik Siddique, S M Lutful Kabir

Faculty, Staff and Student Publications

A feeding trial was conducted to evaluate the effects of Bacillus-based probiotics on growth performance, intestinal histo-morphology, gut microbial population and immune response in broilers. A total of 2000 Hubbard Classic day-old chicks were randomly enrolled in four experimental groups and 4 replicates of 500 birds in each group, and reared for 35 days under a low- level of biosecurity measures. The trial groups were assigned treatment-1 (T1): basal diet(control), treatment-2 (T2): basal diet plus Bacillus licheniformis (DSM17236), treatment-3 (T3): basal diet plus Bacillus subtilis (PB6), and treatment-4 (T4) basal diet plus 4% Flavomycin. All four groups were fed …

Tavr In Older Adults: Moving Toward A Comprehensive Geriatric Assessment And Away From Chronological Age: Jacc Family Series, Joy M Schmitz, Scott D Lane, Michael F Weaver, Ponnada A Narayana, Khader M Hasan, Delisa D Russell, Robert Suchting, Charles E Green

Faculty, Staff and Student Publications

Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This …

Pre-Exposure Prophylaxis With Various Doses Of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure To Covid-19: A Randomized Controlled Trial, Fibhaa Syed, Muhammad Hassan, Mohammad Ali Arif, Sadia Batool, Rauf Niazi, Ume E Laila, Sadia Ashraf, Junaid Arshad

Faculty, Staff and Student Publications

Objective This trial aimed to evaluate the safety and efficacy of pre-exposure prophylaxis (PrEP) with various hydroxychloroquine (HCQ) doses against a placebo among healthcare personnel (HCP) with high-risk exposure to coronavirus disease 2019 (COVID 19). Methods A phase II, randomized, placebo-controlled trial was conducted including 200 subjects with no active or past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (antibody testing and reverse transcription-polymerase chain reaction (RT-PCR) were taken at the time of enrollment). Subjects of experimental groups one to three received HCQ in various doses and the control group received a placebo. The study outcomes in terms of …

Evaluation Of Bone Formation On Orthopedic Implant Surfaces Using An Ex-Vivo Bone Bioreactor System, Rupak Dua, Hugh Jones, Philip C Noble

Faculty, Staff and Student Publications

Recent advances in materials and manufacturing processes have allowed the fabrication of intricate implant surfaces to facilitate bony attachment. However, refinement and evaluation of these new design strategies are hindered by the cost and complications of animal studies, particularly during early iterations in the development process. To address this problem, we have previously constructed and validated an ex-vivo bone bioreactor culture system that can maintain the viability of bone samples for an extended period ex-vivo. In this study, we investigated the mineralization of a titanium wire mesh scaffold under both static and dynamic culturing using our ex vivo bioreactor system. …

Nrf1 Association With Auts2-Polycomb Mediates Specific Gene Activation In The Brain, Sanxiong Liu, Kimberly A Aldinger, Chi Vicky Cheng, Takae Kiyama, Mitali Dave, Hanna K Mcnamara, Wukui Zhao, James M Stafford, Nicolas Descostes, Pedro Lee, Stefano G Caraffi, Ivan Ivanovski, Edoardo Errichiello, Christiane Zweier, Orsetta Zuffardi, Michael Schneider, Antigone S Papavasiliou, M Scott Perry, Jennifer Humberson, Megan T Cho, Astrid Weber, Andrew Swale, Tudor C Badea, Chai-An Mao, Livia Garavelli, William B Dobyns, Danny Reinberg

Faculty, Staff and Student Publications

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its …

Evaluating The Efficacy Of Automated Smoking Treatment For People With Hiv: Protocol For A Randomized Controlled Trial, Damon J Vidrine, Thanh C Bui, Michael S Businelle, Ya-Chen Tina Shih, Steven K Sutton, Lokesh Shahani, Diana Stewart Hoover, Kristina Bowles, Jennifer I Vidrine

Faculty, Staff and Student Publications

BACKGROUND: Smoking prevalence rates among people with HIV are nearly 3 times higher than those in the general population. Nevertheless, few smoking cessation trials targeting smokers with HIV have been reported in the literature. Efforts to develop and evaluate sustainable, low-cost, and evidence-based cessation interventions for people with HIV are needed. Given the widespread proliferation of mobile phones, the potential of using mobile health apps to improve the reach and efficacy of cessation interventions is promising, but evidence of efficacy is lacking, particularly among people with HIV.

OBJECTIVE: This study will consist of a 2-group randomized controlled trial to evaluate …

Candida Albicans Elicits Protective Allergic Responses Via Platelet Mediated T Helper 2 And T Helper 17 Cell Polarization, Yifan Wu, Zhimin Zeng, Yubiao Guo, Lizhen Song, Jill E Weatherhead, Xinyan Huang, Yuying Zeng, Lynn Bimler, Cheng-Yen Chang, John M Knight, Christian Valladolid, Hua Sun, Miguel A Cruz, Bernhard Hube, Julian R Naglik, Amber U Luong, Farrah Kheradmand, David B Corry

Faculty, Staff and Student Publications

Fungal airway infection (airway mycosis) is an important cause of allergic airway diseases such as asthma, but the mechanisms by which fungi trigger asthmatic reactions are poorly understood. Here, we leverage wild-type and mutant Candida albicans to determine how this common fungus elicits characteristic Th2 and Th17 cell-dependent allergic airway disease in mice. We demonstrate that rather than proteinases that are essential virulence factors for molds, C. albicans instead promoted allergic airway disease through the peptide toxin candidalysin. Candidalysin activated platelets through the Von Willebrand factor (VWF) receptor GP1bα to release the Wnt antagonist Dickkopf-1 (Dkk-1) to drive Th2 and …

Identification Of An Atp/P2x7/Mast Cell Pathway Mediating Ozone-Induced Bronchial Hyperresponsiveness, Xiaomei Kong, William C Bennett, Corey M Jania, Kelly D Chason, Zachary German, Jennifer Adouli, Samuel D Budney, Brandon T Oby, Catharina Van Heusden, Eduardo R Lazarowski, Ilona Jaspers, Scott H Randell, Barry A Hedgespeth, Glenn Cruse, Xiaoyang Hua, Stephen A Schworer, Gregory J Smith, Samir Np Kelada, Stephen L Tilley

Faculty, Staff and Student Publications

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast …

Hop2 Interacts With The Transcription Factor Cebpα And Suppresses Adipocyte Differentiation, Tonghui Lin, Yang Zhang, Tingting Zhang, Rita A Steckler, Xiangli Yang

Faculty, Staff and Student Publications

CCAAT enhancer binding protein (CEBP) transcription factors (TFs) are known to promote adipocyte differentiation; however, suppressors of CEBP TFs have not been reported thus far. Here, we find that homologous chromosome pairing protein 2 (Hop2) functions as an inhibitor for the TF CEBPα. We found that Hop2 mRNA is highly and specifically expressed in adipose tissue, and that ectopic Hop2 expression suppresses reporter activity induced by CEBP as revealed by DNA transfection. Recombinant and ectopically expressed Hop2 was shown to interact with CEBPα in pull-down and coimmunoprecipitation assays, and interaction between endogenous Hop2 and CEBPα was observed in the nuclei …