Digital Commons Network^™

A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we …

A Double Humanized Blt-Mice Model Featuring A Stable Human-Like Gut Microbiome And Human Immune System, Lance Daharsh, Jianshui Zhang, Amanda E. Ramer-Tait, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut …

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Annabel T. Olson, Zhigang Wang, Annabel Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and vi- ral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a com- mon pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vac- cinia virus protein B12, which otherwise impedes an early event in the …

Mta3-Sox2 Module Regulates Cancer Stemness And Contributes To Clinical Outcomes Of Tongue Carcinoma., Zhimeng Yao, Liang Du, Min Xu, Kai Li, Haipeng Guo, Guodong Ye, Dianzheng Zhang, Robert P Coppes, Hao Zhang

PCOM Scholarly Works

Cancer cell plasticity plays critical roles in both tumorigenesis and tumor progression. Metastasis-associated protein 3 (MTA3), a component of the nucleosome remodeling and histone deacetylase (NuRD) complex and multi-effect coregulator, can serve as a tumor suppressor in many cancer types. However, the role of MTA3 in tongue squamous cell cancer (TSCC) remains unclear although it is the most prevalent head and neck cancer and often with poor prognosis. By analyzing both published datasets and clinical specimens, we found that the level of MTA3 was lower in TSCC compared to normal tongue tissues. Data from gene set enrichment analysis (GSEA) also …

Targeting The Bcl-2 Family In B Cell Lymphoma., Clare M. Adams, Sean Clark-Garvey, Pierluigi Porcu, Christine M. Eischen

Department of Medical Oncology Faculty Papers

Although lymphoma is a very heterogeneous group of biologically complex malignancies, tumor cells across all B cell lymphoma subtypes share a set of underlying traits that promote the development and sustain malignant B cells. One of these traits, the ability to evade apoptosis, is essential for lymphoma development. Alterations in the Bcl-2 family of proteins, the key regulators of apoptosis, is a hallmark of B cell lymphoma. Significant efforts have been made over the last 30 years to advance knowledge of the biology, molecular mechanisms, and therapeutic potential of targeting Bcl-2 family members. In this review, we will highlight the …

Differences In The M1 And M2 Macrophage Subtypes Between The Sexes Determine Susceptibility To Francisella Tularensis Infection, Michelle Arlene Sanchez

Open Access Theses & Dissertations

Francisella tularensis is the causative agent of the human disease tularemia. It is highly infectious with as few as 10 microorganisms via inhalation causing a lethal infection. F. tularensis infects a variety of cell types, including macrophages and neutrophils, since it needs to enter, survive and proliferate in order to cause pathogenicity. Disease is the result of over activating the host's own inflammatory response initiated by the macrophage's response to infection.

Known differences exist in the intensity of the inflammatory response between the sexes which leads to differences in sensitivity to autoimmune and infectious disease. Males tend to be more …

Trypanosoma Cruzi Trypomastigote Glycosylphosphatidylinositol-Anchored Mucins And A Synthetic Alpha-Gal-Containing Neoglycoprotein As Potential Biomarkers And Vaccines For Chagas Disease, Igor Leandro Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease that kills or permanently disable thousands of people annually. About 6-8 million people are estimated to be infected worldwide. Although many efforts have been made for the development of an effective immunotherapy, currently there is no vaccine to prevent or treat CD in humans. Despite their toxicity, the two current drugs for CD, benznidazole (BZN) and nifurtimox (NFX), have medium-to-high efficacy in the chronic stage of the disease and could save or improve the lives of thousands of patients. However, negative seroconversion in treated patients, as …

Generation, Identification And Characterization Of Novel Monoclonal Antibodies Against Ctla-4, Pd-1 And Btla For The Treatment Of Cancer, Rosabril Acuna

Open Access Theses & Dissertations

Members of the CD28 co-inhibitory receptor family, Cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4), Program death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) are type I transmembrane proteins expressed on a variety of immune cells. Co- inhibitory receptors deliver "off" signals that play an important role in down regulating immune cell activation. Manipulation of inhibitory signals have shown to be a powerful strategy in the treatment of autoimmune diseases, infectious diseases and various forms of cancer. In fact, the FDA (Food and Drug Administration) has approved the use of monoclonal antibodies against CTLA-4 (Ipilimumab) for the treatment of metastatic melanoma, against …

The Role Of P62/Imp2 In Hepatocellular Carcinoma Progression, Mengtao Xing

Open Access Theses & Dissertations

The family of insulin- like growth factor 2 mRNA binding proteins (IMPs) contains three members: IMP1, p62/IMP2 and IMP3. All these proteins are oncofetal proteins, expressed during embryogenesis and lost in most tissues in adults. However, p62/IMP2 were found overexpressed in various cancers but its function in carcinogenesis remains to be investigated. Our previous studies found that p62/IMP2 was not only overexpressed in hepatocellular carcinoma (HCC) tissues, but also overexpressed in HCC cell lines. To explore the biological roles of p62/IMP2 in HCC progression, p62/IMP2 was knockout in two p62/IMP2 positive HCC cell lines (SNU449, HepG2). Due to the low …

Melatonin Enhances Sorafenib-Induced Cytotoxicity In Flt3-Itd Acute Myeloid Leukemia Cells By Redox Modification, Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Hua Wang, Fufu Zheng, Dingbo Shi, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with an internal tandem duplication in Fms-related tyrosine kinase 3 (FLT3-ITD) is identified as a subgroup with poor outcome and intrinsic resistance to chemotherapy and therefore urgent need for development of novel therapeutic strategies.

Methods: The antitumor effects of melatonin alone or combined with sorafenib were evaluated via flow cytometry and immunoblotting assays in FLT-ITD AML cells. Also, the ex vivo and in vivo models were used to test the synergistic effects of melatonin and sorafenib against leukemia with FLT3/ITD mutation.

Results: Our study shows for the first time that melatonin inhibits proliferation and induces apoptosis …

A Feasibility Study Of Diffusion Weighted Imaging And Parametric Response Map Analysis For Treatment Response Prediction In Nasopharyngeal Cancer, Titiya Jirawatwanith

Chulalongkorn University Theses and Dissertations (Chula ETD)

Diffusion-weighted imaging (DWI) is an MRI technique which provides functional information of tissue by detecting microscopic motion of water molecules. The change of apparent diffusion coefficient (ADC) derived from DWI was used as an imaging biomarker for treatment response prediction in cancers. However, it was based on whole-tumor analysis which did not reflect heterogeneity within the tumor. To overcome this limitation, a new method called parametric response map (PRM) analysis was proposed to evaluate response by quantifying voxel-wise changes in ADC. Here we investigated the use of PRM analysis on ADC from DWI as an imaging biomarker for treatment response …

Dosimetric Comparison Between Single And Double Isocenters Volumetric Arc Therapy For Stereotactic Radiotherapy With Multiple Targets, Wai Lwin Lwin Kyaw

Chulalongkorn University Theses and Dissertations (Chula ETD)

The purpose of this study was to evaluate the dosimetric effects between single isocenter (SI) and double isocenters (DI) VMAT SRT of multiple brain metastases. There are two parts of study, which were experimental for energy selection, technique comparison and clinical part to use appropriate technique. As the first part, three lesions with 3 cm distance apart and 1 cm size for all lesions were created as standard plan by varying energy. Twelve VMAT SRT plans by varying energy with 6 MV, 10 MV, 6 FFF and 10 FFF were planned on simulated three lesions of CT image. 18 VMAT …

Diuretic, Natriuretic, And Vasodepressor Activity Of A Lipid Fraction Enhanced In Medium Of Cultured Mouse Medullary Interstitial Cells By A Selective Faah Inhibitor, Zdravka P. Daneva

Theses and Dissertations

The relationship between the endocannabinoid system in the renal medulla and the long-term regulation of blood pressure is not well understood. To investigate the possible role of the endocannabinoid system in renomedullary interstitial cells, mouse medullary interstitial cells (MMICs) were obtained, cultured and characterized for their responses to treatment with a selective inhibitor of fatty acid amide hydrolase (FAAH), PF-3845. Treatment of MMICs with PF-3845 increased cytoplasmic lipid granules detected by Sudan Black B staining and multilamellar bodies identified by transmission electron microscopy. HPLC analyses of lipid extracts of MMIC culture medium revealed a 205nm-absorbing peak that showed responsiveness to …

Perceived Impact Of Ambient Operating Room Noise By Certified Registered Nurse Anesthetists, Marianne S. Cosgrove

Theses and Dissertations

It is widely acknowledged that elevated levels of noise are commonplace in the healthcare environment, particularly in high acuity areas such as the operating room (OR). Excessive ambient noise may pose a threat to patient safety by adversely impacting provider performance and interfering with communication among perioperative care team members. With respect to the certified registered nurse anesthetist (CRNA), increased ambient OR noise may engender distractibility, diminish situation awareness and cause untoward health effects, thereby increasing the possibility for the occurrence of error and patient injury.

This research project analytically examines the perceived impact of ambient noise in the operating …

Adaptation Of The Streptococcal Collagen-Like Protein 1, Scl1, Of Group A Streptococcus To Recognize Fibronectin Type Iii Repeats, Dudley H. Mcnitt

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: Group A Streptococcus (GAS) is responsible more than 700 million infections worldwide each year. Most of these infections start with initial colonization of the throat and skin, which is augmented by surface adhesins. The streptococcal collagen-like protein 1 (Scl1) is a major adhesin expressed by GAS that contains an N-terminal sequence-variable (V) domain, protruded away from the cell surface by the collagen domain. The Scl-V domain is comprised of three pairs of anti-parallel α-helices interconnected by surface-exposed loops. For attachment, GAS adhesins require a portal of entry, such as a wound or breach in the epithelium, to enter …

Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D.

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-coding RNAs (NcRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been found to be involved in a variety of critical biological processes, and dysregulation of ncRNAs have been involved with several human diseases including cancer.

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and a subset of head and neck cancers. The expression of the viral oncoproteins E6 and E7 is essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins and regulation of …

Reviewers' Responses To Medical Research Articles, Saba Sohail, Jamshed Akhtar

Department of Radiology

Objective: To document the reviewers' responses in terms of reviewers' demographic and professional characteristics, promptness of reply, and duration of reply to the request to review medical research articles for a general biomedical research journal.
Study design: Cross-sectional, observational study.
Place and duration of study: Department of Publications, College of Physicians and Surgeons Pakistan (CPSP), from October to December 2015.
Methodology: Peer reviewed articles edited by a single staff editor were included. Editorials and correspondence were excluded. Manuscript category, discipline, and the total number of reviewers per manuscript were noted. Responses were divided into no response, regrets, and responded, i.e. …

Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges To Clinical Application, Henry Caplan, Scott D Olson, Akshita Kumar, Mitchell George, Karthik S Prabhakara, Pamela Wenzel, Supinder Bedi, Naama E Toledano-Furman, Fabio Triolo, Julian Kamhieh-Milz, Guido Moll, Charles S Cox

Faculty, Staff and Student Publications

For several decades, multipotent mesenchymal stromal cells (MSCs) have been extensively studied for their therapeutic potential across a wide range of diseases. In the preclinical setting, MSCs demonstrate consistent ability to promote tissue healing, down-regulate excessive inflammation and improve outcomes in animal models. Several proposed mechanisms of action have been posited and demonstrated across an array of in vitro models. However, translation into clinical practice has proven considerably more difficult. A number of prominent well-funded late-phase clinical trials have failed, thus calling out for new efforts to optimize product delivery in the clinical setting. In this review, we discuss novel …

Risk Factors Associated With Myopia In Schoolchildren In Ireland, Síofra Harrington, Jim Stack, Veronica O'Dwyer

Articles

Aim To examine the demographic and social factors associated with myopia in schoolchildren in Ireland.

Methods Thirty-seven schools participated, representing a mix of urban and rural schools and schools in socioeconomically disadvantaged and non-disadvantaged areas in Ireland. Examination included cyclopleged autorefraction (1% cyclopentolate hydrochloride). Height and weight of participants were measured. Parents filled in a participant’s lifestyle questionnaire, including questions on daily screen time use and daylight exposure. Myopia was defined as spherical equivalent ≤−0.50 D.

Results Data from 1626 participants (881 boys, 745 girls) in two age groups, 6–7 years (728) and 12–13 years (898), were examined. Myopia prevalence …

Sexual Behaviours Of Adolescents In Creek Town, Cross River State, Nigeria, Kabiru K. Salami, Rowland E. Edet

Department of Sociology: Faculty Publications

Risky sexual behaviors of adolescents in Creek Town have not been fully profiled. This study investigated the sexual behaviors of adolescents and their various dimensions in Creek Town, in Cross River State, Nigeria. This cross-sectional survey design adopted multi-stage sampling procedure to administer a 112-items questionnaire to 422 adolescents, to elicit information on their sexual behaviors and practices. Four focus group discussion sessions were also conducted with in-school and out-of-school adolescents. The mean age of adolescents was 17 years. Majority (65.4%) of the adolescents were sexually active. The mean age at sexual debut was 15 years for both male and …

Effect Of Neoadjuvant Chemoradiation On Preoperative Pulmonary Physiology, Postoperative Respiratory Complications And Quality Of Life In Patients With Oesophageal Cancer, J. A. Elliott, L. O'Byrne, G. Foley, C. F. Murphy, Suzanne Doyle, S. King, E. M. Guinan, N. Ravi, V. Reynolds

Articles

Background: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer.

Methods: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose–volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41⋅4Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity …

Subjective And Objective Assessment Of Taste And Smell Sensation In Advanced Cancer, Niamh Mcgettigan, Pauline Uí Dhuibhir, Michelle Barrett, Jessica Sui, Lucy Balding, Stephen Higgins, Norma O'Leary, Aileen Kennedy, Declan Walsh

Articles

Context: Taste and smell abnormalities (TSA) occur throughout the cancer trajectory regardless of cancer primary site and contribute to cancer-associated malnutrition. TSA etiology is poorly understood. Tumor-related inflammation is a possible cause. Objective: This study examined the prevalence, characteristics, and severity of TSA in advanced cancer and explored the relationship between TSA and nutritional status. No previous study combined subjective and objective measures for both taste and smell assessment in this population. Method: Consecutive advanced cancer hospice patients were recruited. A modified version of the “Taste and Smell Survey” assessed subjective TSA. Validated taste strips and “Sniffin’ …

Pain, Severity, And Attentional Capacity Following Acute Musculoskeletal Injury, Rebekah F. Roessler

College of Graduate Studies: Theses & Dissertations

Background: As recreational activities grow in popularity, there is a concurrent rise in musculoskeletal injury. Injury severity is determined through clinical evaluation and defined by a grading scale. Pain is included in the definition of each injury grade, despite the lack of any conclusive evidence relating injury severity and the associated pain. Additionally, previous studies report impairments in cognitive performance due to chronic and acute pain. The aim of this study is to determine the relationship between the perceived pain intensity and the clinically diagnosed severity of an acute musculoskeletal injury, and to determine if attentional capacity is influenced by …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Cultural Practices And The Transmission Of Ebola In Sierra Leone: Lessons Learned From A Medical Anthropology Perspective, Abubakarr Jalloh

Dissertations and Theses @ UNI

The link between culture and infectious diseases has long been established. This is primarily due to the notion that culture shapes and influences people’s beliefs, actions, and ways of life. Such beliefs and their accompanying actions ultimately contribute to people’s risk of contracting an infectious disease. As such, there is a need for a cultural perspective in understanding infectious diseases because human behavior plays a significant role in the emergent, transmission, and spread of such diseases. This study explores the cultural practices that may have contributed to the transmission of Ebola Virus Disease (EVD) in Sierra Leone during the 2013-2016 …

Epidemiology, Clinical Features And Outcomes Of Patients With Sickle Cell Disease Hospitalized With Influenza, Kyle P. Openo

College of Graduate Studies: Theses & Dissertations

Influenza is a respiratory viral infection responsible for annual epidemics, periodic pandemics and regularly causes substantial morbidity, mortality and economic burden worldwide. In the United States alone, influenza causes between 9.2 – 35.6 million cases, 140,000 to 710,000 hospitalizations and 12,000 – 56,000 deaths annually. Individuals with comorbid health conditions are at increased risk of hospitalization and severe outcomes from influenza infection and were recommended for vaccination prior to universal vaccine recommendations. Individuals with sickle cell disease (SCD) have been included in this group for decades though limited data existed to describe influenza among those with SCD. Recent studies showed …

Blended Learning Mediated Fostering Of Students’ Engagement In An Undergraduate Medical Education Module, Lena Jafri, Hafsa Majid, Salman Siddiqi, Najmul Islam, Faraz Khurshid

Department of Pathology and Laboratory Medicine

Introduction: The study investigated students’ perception of introducing blended learning strategies to engage and motivate them towards lecture halls and Problem Based Learning (PBL) sessions for improving the quality of the overall students’ learning experience.
Methods: A prospective study was conducted at the Aga Khan University Medical College involving a total of one hundred four (104) year II medical students for the Endocrine and Reproduction module in the academic year 2018. This module ran for six weeks. Modifications in teaching methods were made for this module introduced after approval from Endocrine & Reproduction module, year II and curriculum committees. Written …

An Ensemble Of Flexible Conformations Underlies Mechanotransduction By The Cadherin–Catenin Adhesion Complex, Martin Bush, Bashir M. Alhanshali, Shuo Qian, Christopher B. Stanley, William T. Heller, Tsutomu Matsui, Thomas M. Weiss, Iain D. Nicholl, Thomas Walz, David J. E. Callaway, Zimei Bu

Publications and Research

The cadherin–catenin adhesion complex is the central component of the cell–cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the α-catenin•β-catenin•epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible “tongue” that is inserted into α-catenin and participates in the …

A Systems Thinking Approach For Eliciting Mental Models From Visual Boundary Objects In Hydropolitical Contexts: A Case Study From The Pilcomayo River Basin, Riveraine S. Walters, Erin S. Kenzie, Alexander E. Metzger, William Jesse Baltutis, Kakali B. Chakrabarti, Shana Lee Hirsch, Bethany Laursen

Complex Systems Faculty Publications and Presentations

Transboundary collaborations related to international freshwater are critical for ensuring equitable, efficient, and sustainable shared access to our planet’s most fundamental resources. Visual artifacts, such as knowledge maps, functioning as boundary objects, are used in hydropolitical contexts to convey understandings and facilitate discussion across scales about challenges and opportunities from multiple perspectives. Such focal points for discussion are valuable in creating shared, socially negotiated priorities and integrating diverse and often disparate cultural perspectives that naturally exist in the context of international transboundary water resources. Visual boundary objects can also represent the collective mental models of the actor countries and transboundary …

Genomic Prediction Of Relapse In Recipients Of Allogeneic Haematopoietic Stem Cell Transplantation., J Ritari, K Hyvärinen, S Koskela, M Itälä-Remes, R Niittyvuopio, A Nihtinen, U Salmenniemi, M Putkonen, L Volin, T Kwan, T Pastinen, J Partanen

Manuscripts, Articles, Book Chapters and Other Papers

Allogeneic haematopoietic stem cell transplantation currently represents the primary potentially curative treatment for cancers of the blood and bone marrow. While relapse occurs in approximately 30% of patients, few risk-modifying genetic variants have been identified. The present study evaluates the predictive potential of patient genetics on relapse risk in a genome-wide manner. We studied 151 graft recipients with HLA-matched sibling donors by sequencing the whole-exome, active immunoregulatory regions, and the full MHC region. To assess the predictive capability and contributions of SNPs and INDELs, we employed machine learning and a feature selection approach in a cross-validation framework to discover the …