Diseases Commons^™

Machine Learning Prediction Of Glioblastoma Patient One-Year Survival, Andrew Du '20, Warren Mcgee, Jane Y. Wu

Student Publications & Research

Glioblastoma (GBM) is a grade IV astrocytoma formed primarily from cancerous astrocytes and sustained by intense angiogenesis. GBM often causes non-specific symptoms, creating difficulty for diagnosis. This study aimed to utilize machine learning techniques to provide an accurate one-year survival prognosis for GBM patients using clinical and genomic data from the Chinese Glioma Genome Atlas. Logistic regression (LR), support vector machines (SVM), random forest (RF), and ensemble models were used to identify and select predictors for GBM survival and to classify patients into those with an overall survival (OS) of less than one year and one year or greater. With …

Graphic Novels In Biology – A Novel Assessment Idea, Sowmya Anjur

Faculty Publications & Research

Galileo once said, “You cannot teach a man anything, you can only help him find it within himself.” (Goodreads, 2020). I have often pondered upon how best I could use this advice. I have been an educator for 24 years and have loved every minute of it. During this time, I have seen students of all cadres come and go, but they all have one thing in common - their innate fear of written assessments. In general, students in high school tend to have a different perspective on education than their adult counterparts - they tend to procrastinate, are usually …

The Effects Of Roundup On The Life History, Stress Response, And Immune Function Of The Yellow Fever Mosquito, Aedes Aegypti, Lindsay E. Martin

Honors Undergraduate Theses

Aedes aegypti mosquitoes, vectors for many human diseases, begin life as larvae developing in water, potentially exposed to runoff with herbicides and pesticides. This study serves as a novel investigation into the transstadial effects of exposure to Roundup on A. aegypti life history, immunity, and stress response and aims to account for these effects in an R0 model for vectorborne disease transmission. Prior work has shown that Roundup negatively affects mosquito life history. I hypothesized that larval exposure to the maximum sublethal dose of Roundup (7189µg/L) would negatively impact A. aegypti life history, immunity (candidate gene approach), and stress response …

Mast Cells As Novel Effector Cells In The Pathogenesis Of Chronic Graft-Versus-Host Disease, Ethan Strattan

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host-disease (GVHD), a condition wherein the donor cells recognize the patient tissues as non-self. GVHD can manifest anywhere from weeks to decades post-transplant and is classified as either acute or chronic GVHD, both of which are significant causes of transplant-related morbidity and mortality.

However, GVHD is a complex, multifactorial, and enigmatic disease. The factors driving GVHD at the cellular and molecular level are incompletely understood. Immunosuppression targeting T-cells has …

Why The Government Shouldn't Pay People To Get Vaccinated Against Covid-19, Ana Santos Rutschman

All Faculty Scholarship

As several pharmaceutical companies approach the Food and Drug Administration (FDA) seeking authorization to bring COVID-19 vaccines to market, concerns about vaccine mistrust cloud the prospects of imminent vaccination efforts across the globe. These concerns have prompted some commentators to suggest that governments may nudge vaccine uptake by paying people to get vaccinated against COVID-19. This post argues that, even if potentially viable, this idea is undesirable against the backdrop of a pandemic marked by the intertwined phenomena of health misinformation and mistrust in public health authorities. Even beyond the context of COVID-19, paying for vaccination is likely to remain …

Effet De L’Expertise Et Du Sexe Sur Les Contraintes À L’Épaule En Manutention, Etienne Goubault, Romain Martinez, Najoua Assila, Jennifer Dowling-Medley, Élodie Monga-Dubreuil, Sophie-Anne Scherrer, André Plamondon, Mickaël Begon

Rapports de recherche scientifique

L’atteinte de troubles musculosquelettiques (TMS) parmi les travailleurs et travailleuses au Québec était récemment estimée à 732 000 cas (Stock et al., 2014). Ces TMS sont associés aux activités professionnelles impliquant des efforts physiques prolongés, intenses et/ou répétitifs, telles que des tâches d’assemblage, de manutention, d’aide à la personne ou encore de maintien de posture prolongée sur un poste de travail. Les membres supérieurs, qui représentaient 30,1 % des cas de TMS déclarés et acceptés au Québec de 1998 à 2007 (Michel et al., 2010), sont les plus touchés après le dos. Plus particulièrement, l’épaule figure comme l’articulation …

Genetic And Cellular Models For The Study Of Ptk2b And Adam10 In Adaptive Thermogenesis And Metabolism, Jared S. Farrar

Theses and Dissertations

In a cellular model, we demonstrate that the non-receptor protein tyrosine kinase 2 beta (PTK2B) plays a critical role in mouse cultured beige adipocyte differentiation. CRISPR/Cas9-mediated knock-out of Ptk2b results in non-differentiating white adipocytes and differentiated beige adipocytes with significantly reduced thermogenic gene and protein expression, enlarged lipid droplet size, and altered mitochondrial respiration. Together, these data in a cell culture system provide evidence for a role of PTK2B in the differentiation of mouse beige adipocytes.

In the process of developing a new mouse model utilizing the adipocyte selective Adipoq-Cre transgenic mouse, strong genetic linkage between a gene …

The Role Of Manganese In Streptococcus Sanguinis, Tanya M. Puccio

Theses and Dissertations

Streptococcus sanguinis is primarily associated with oral health as a commensal bacterium. As an opportunistic pathogen, S. sanguinis is capable of colonizing heart valve vegetations, leading to the disease infective endocarditis. Previous studies from our lab have identified the high-affinity manganese transporter SsaACB as important for endocarditis virulence. The impact that manganese depletion has on S. sanguinis had never been evaluated and a secondary manganese transporter has not been identified. Thus, we employed the use of a fermentor to control large-scale growth over time and depleted manganese in an ΔssaACB mutant using a metal chelator, EDTA. The changes in …

Ndrg1 And Myelin-Related Disease: Alcoholism And Chemotherapy-Induced Neuropathy, Guy Harris

Theses and Dissertations

Alcohol use disorder (AUD) is a prevalent neuropsychiatric disease with profound health, social, and economic consequences. With an estimated 50% heritability, identifying genes that engender risk and contribute to the underlying neurobiological mechanisms represents an important first step in developing effective treatments. Gene expression studies are an important source of candidate genes for studying AUD, providing windows into the molecular machinery engaged by the brain in response to ethanol. Our laboratory has implicated N-myc down-regulated gene 1 (Ndrg1) as a potential candidate gene that modulates ethanol-induced changes in myelin-related gene expression and acute sensitivity to ethanol. Analysis of …

Novel Strategies To Overcome Carboplatin Resistance In Triple Negative Breast Cancer Using Patient Derived Xenografts, Mohammad A. Al Zubi

Theses and Dissertations

Triple-negative breast cancer (TNBC) patients have a poor prognosis and rely on chemotherapeutic treatment as standard of care. Often, they develop chemotherapy resistance, which leaves them without more therapeutic options, like targeted therapy. New models have been developed to test targeted inhibitors in human tumors, and they are known as patient-derived xenografts (PDX). These tumors are obtained from patients, then established and maintained in mice where they areused for tumor studies. In this work, we characterized 14 PDXs for their primary tumor growth rate and investigated metastatic propensity using spontaneous and experiment metastasis models. We utilized RNA-sequencing to characterize contributions …

Analysis Of Genetic Structure And Pathogen Dynamics Of Ixodes Scapularis In Southwestern Virginia, Leemu Jackson

Undergraduate Honors Theses

Ixodes scapularis, or the blacklegged tick, is the primary vector of Borrelia burgdorferi. This pathogen is the causative agent of Lyme disease, the most common vector-transmitted disease in the United States. Although I. scapularis is distributed throughout the eastern U.S., Lyme disease is only considered endemic in the northeastern region of the country. Prior to 2007, Lyme disease was uncommon in Virginia, but since then cases of Lyme disease have increased dramatically with a hotspot forming in the Roanoke-Blacksburg area. The purpose of the current study was to determine whether B. burgdorferi prevalence and the genetic structure of I. …

Tick-Borne Infections In New Hampshire: An Evaluation Of The Diagnostic Process In A Local Patient Population, Katherine Anderson

Honors Theses and Capstones

Overall, approximately 95 percent of reported cases of vector-borne disease were associated with ticks, making these the most medically important group of arthropods in the United States.¹ Despite the prevalence of tick-borne infections, the process for the diagnosis of this condition is not well studied. This study aims to analyze data from a pool of 100 patients who underwent testing for tick-borne disease in the same institution in Dover, New Hampshire during the most recent peak tick season of 2019. Information utilized in this study included: patient age, sex, location of testing (inpatient versus outpatient), diagnostic testing methods used …

The Case For Face Shields: Improving The Covid-19 Public Health Policy Toolkit, Timothy L. Wiemken, Ana Santos Rutschman, Robert Gatter

All Faculty Scholarship

As the United States battles the later stages of the first wave of COVID-19 and faces the prospect of future waves, it is time to consider the practical utility of face shields as an alternative or complement to face masks in the policy guidance. Without face shields specifically noted in national guidance, many areas may be reluctant to allow their use as an alternative to cloth face masks, even with sufficient modification.

In this piece, we discuss the benefits of face shields as a substitute to face masks in the context of public health policy. We further discuss the implications …

The Oral Microbiome And Its Effects On Human Systemic Diseases, Hee Chang Shin

Biology and Microbiology Graduate Students Plan B Research Projects

In the past decade, scientists and healthcare professionals have gained interest in the microbiome and its function as part of the human body. The two most diverse microbiome environments are found in the gut and the oral cavity. While the gut microbiome has been investigated more deeply and continues to be a great interest, the oral microbiome is in comparison a more recent subject with fewer reports on the topic. The purpose of this review paper is to highlight the main human systemic diseases associated with the oral microbiome and to discuss how our understanding of the oral microbiome’s effect …

Parkinson’S Disease: Current Treatment Options, Luke Kovaleski

Biology and Microbiology Graduate Students Plan B Research Projects

Parkinson’s Disease is a neurodegenerative disease that is caused by a lack of dopamine. This lack of dopamine has many effects on a person’s body who has Parkinson’s Disease including loss of motor control, slowed movement (bradykinesia), changes in speech, impaired posture and balance, and muscle rigidity. The object of this paper is to explore some of the many different options for treatment of symptoms of Parkinson’s Disease that are currently available. There is not one over-arching treatment that can alleviate the symptoms that are caused by Parkinson’s Disease. However, if multiple treatments are used together, a patient who is …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Donor Age Effects On The Proliferative And Chondrogenic/Osteogenic Differentiation Performance Of Equine Bone Marrow- And Adipose Tissue Derived Mesenchymal Stem Cells In Culture, Jasmin Bagge

Theses and Dissertations--Veterinary Science

Orthopedic injuries are a major cause of lameness and morbidity in horses. Bone marrow (BM)- and adipose tissue (AT) derived mesenchymal stem cells (MSCs) have shown potential to facilitate the repair of orthopedic injuries and are being used increasingly in veterinary clinics. Presently, the use of MSCs as a therapy for equine patients is most commonly applied as autologous transplants, using BM- and AT-MSCs harvested from the patient shortly after the time of injury. Cell-based therapies are therefore delayed to enable primary cell numbers to be expanded in culture. Of concern, however, are human and rodent studies that have shown …

Comparative Chondrogenesis Of Interzone And Anlagen Cells In Equine Skeletal Development, Chanhee Mok

Theses and Dissertations--Veterinary Science

At the presumptive sites of future synovial joints during mammalian skeletogenesis, articular cartilage develops from interzone located between the cartilaginous anlagen of bones. Thus, two types of cartilaginous tissues differentiate in close proximity. While anlagen cartilage is transient, progressing through endochondral ossification to form bones, articular cartilage is stable and functions throughout life to facilitate both low friction movement and load distribution. Despite important life-long functional properties, articular cartilage has a very limited intrinsic ability to repair structural defects. On the other hand, structural lesions in bones generally heal well by forming a cartilaginous callus and recapitulating endochondral ossification to …

Optimisation Of Estrogen Receptor Subtype-Selectivity Of A 4-Aryl-4h-Chromene Scaffold Previously Identified By Virtual Screening, Miriam Carr, Andrew Knox, Daniel Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas Mccabe, Brendan Twamley, Daniela Zisterer, David Lloyd, Mary Meegan

Articles

4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and β with low nanomolar affinity and <20-fold selectivity for α over β and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERβ (compound 42; 170-fold selectivity).

Structural Biology Of The Enterovirus Replication-Linked 5'-Cloverleaf Rna And Associated Virus Proteins, Steven M. Pascal, Ravindranath Garimella, Meghan S. Warden, Komala Ponniah

Chemistry & Biochemistry Faculty Publications

Although enteroviruses are associated with a wide variety of diseases and conditions, their mode of replication is well conserved. Their genome is carried as a single, positive-sense RNA strand. At the 5′ end of the strand is an approximately 90-nucleotide self-complementary region called the 5′ cloverleaf, or the oriL. This noncoding region serves as a platform upon which host and virus proteins, including the 3B, 3C, and 3D virus proteins, assemble in order to initiate replication of a negative-sense RNA strand. The negative strand in turn serves as a template for synthesis of multiple positive-sense RNA strands. Building on structural …

Antibacterial, Antifungal, Antioxidant Activity And Polyphenol Content Of Aerial Parts And Bulbs Of Allium Schugnanicum., Saidbeg Satorov, F. Mirzoeva, Sh. Kurbonbekova, Sh. Satorov, M. Vakhidova, Vyacheslav Dushenkov

Publications and Research

Objective: То study of antibacterial, antifungal and antioxidant activity, and content of polyphenols in the bulb and aerial parts of an endemic species of onion A. schugnanicum. Methods: An ethanol-based extract was prepared from fresh plants. Total polyphenolic content (Folin) and ABTS antioxidant capacity assays were used to characterized extracts. Extracts obtained from bulbs, peduncle, and seeds demonstrated antibacterial activity against the reference Staphylococcus aureus (ATCC 4929), Pseudomonas aeruginosa (ATCC 4930) and Klebsiella pneumoniae (ATCC 4927) strains, as well as against the hospital strains of the same types of bacteria, i.e. strains isolated from inpatient surgical patients. Results: The study …

Investigating The Morphology Of Iprgcs In Control Vs. Glaucomatous Retinas, Samantha Cook

Williams Honors College, Honors Research Projects

Glaucoma is a build-up of pressure in the eye that leads to the gradual loss of sight. The intention of this study was to investigate how glaucoma affects intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). These cells contain melanopsin, a photopigment, that enables the cells to react to light. Four-month-old control and five-month-old glaucoma mice retinas were dissected, stained using primary and secondary antibodies, then traced using ImageJ’s Simple Neurite Tracer. There were no significant differences in soma size, total dendritic length, dendritic field size, and dendritic field diameter between control and glaucoma ipRGCs. However, further research is needed to provide …

Assessing Morphology Of Iprgcs After Traumatic Brain Injury, Brian Foresi, Matt Smith

Williams Honors College, Honors Research Projects

ipRGCs are retinal ganglion cells that project to visual processing centers of the brain for nonimage forming visual functions. The relation of ipRGCs to tramatic brain injury (TBI) is emerging as data has been published describing ipRGC functional changes in TBI affected military veterans. Major symptomologies of concussions, a mild form of TBI, also overlap with the function governed by sites in the brain with major ipRGC projection percentages. Assesing if a morphological change is occuring in the ipRGCs after a TBI could support the idea of a pathological mechanism of the injury. This study could also indicate further relevance …

The Functional Importance Of Methyl Cpg Binding Domain Proteins 2 And 3 In Regulating Fetal Hemoglobin Expression In Human Adult Erythroid Cells, Alexander Azzo

Theses and Dissertations

Humans undergo two developmental switches in the predominantly expressed β-like globin chain during embryogenesis and fetal development. The first switch from embryonic (ε) to fetal (γ) occurs around week 5 of embryonic development, while the second switch from fetal to adult (β) globin occurs shortly after birth. By adulthood, fetal hemoglobin represents only 1-2% of total hemoglobin in the blood. As sufficiently elevated levels of fetal hemoglobin are beneficial for improving clinical outcomes in sickle cell disease and β-thalassemia, the mechanisms that enforce silencing of fetal hemoglobin expression postnatally are of great clinical significance. The methyl-CpG binding domain protein MBD2 …

Use Of Pefloxacin As A Surrogate Marker To Detect Ciprofloxacin Susceptibility In Salmonella Enterica Serotypes Typhi And Paratyphi A, Safia Moin, Mohammad Zeeshan, Sidra Laiq, Ahmed Raheem, Afia Zafar

Department of Pathology and Laboratory Medicine

Objective: To determine the use of pefloxacin as a surrogate marker to detect fluoroquinolone (ciprofloxacin) susceptibility against Salmonella enterica serotypes Typhi and Paratyphi A.
Methods: The prospective, descriptive cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from September 2016 to March 2018, and comprised Salmonella Typhi and Paratyphi A isolates of blood cultures. Disk susceptibility tests and broth microdilution to test minimum inhibitory concentration were performed as per standard guidelines. Data was analysed using SPSS 21.
Results: Of the 138 isolates, 91(66%) were intermediate resistant to ciprofloxacin but were resistant to pefloxacin, 42(30%) were resistant to both …

Comments On The Preliminary Framework For Equitable Allocation Of Covid-19 Vaccine, Ana Santos Rutschman, Julia Barnes-Weise, Robert Gatter, Timothy L. Wiemken

All Faculty Scholarship

On September 1, 2020 the National Academies released a draft framework for Equitable Allocation of a COVID-19 Vaccine. In this response, we analyze the proposed framework and highlight several areas.

Among the proposed changes, we highlight the need for the following interventions. The final framework for distribution of COVID-19 vaccines should give a higher priority to populations made most vulnerable by the social determinants of health. It should incorporate more geography-based approaches in at least some of the four proposed phases of vaccine distribution. It should address the possibility of a vaccine being made available through an emergency use authorization …

Mucosa-Associated Microbiota In Barrett’S Esophagus, Dysplasia, And Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls, Shajan Peter, Amanda Pendergraft,, William Vanderpol, Mel Wilcox, Kondal R. Kyanam Kabir Baig, Casey Morrow, Jacques Izard, Peter J. Mannon

Department of Food Science and Technology: Faculty Publications

Introduction: Alterations in the composition of the human gut microbiome and its metabolites have been linked to gut epithelial neoplasia. We hypothesized that differences in mucosa-adherent Barrett’s microbiota could link to risk factors, providing risk of progression to neoplasia.

Methods: Paired biopsies from both diseased and nonaffected esophagus (as well as gastric cardia and gastric juice for comparison) from patients with intestinal metaplasia (n = 10), low grade dysplasia (n = 10), high grade dysplasia (n = 10), esophageal adenocarcinoma (n = 12), and controls (n = 10) were processed for mucosa-associated bacteria …

Urban Food Sovereignty: Urgent Need For Agroecology And Systems Thinking In A Post-Covid-19 Future, Ali Loker, Charles A. Francis

Department of Agronomy and Horticulture: Faculty Publications

The current COVID-19 pandemic has brought attention to challenges associated with our dominant industrial food system in the U.S. The general public now has more appreciation for farm workers and meatpacking employees, as well as those in grocery stores and in food transportation who are suddenly recognized as essential frontline workers. It apparently takes a crisis for us to focus clearly on the fragility of this system and the lives of people on whom we depend. In this commentary we discuss the definition of food sovereignty, how it manifests in urban areas, and how the COVID-19 pandemic can trigger viable …

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal …

Observing The Effects Of Antimalarial Drug Availability On Women’S Work Absenteeism, Rei Imada

CMC Senior Theses

This study aims to provide insight on how availability of antimalarial drugs can help alleviate the economic burden of malaria. Much of the existing literature that looks into the effects of antimalarial drug availability focuses on the associated health benefits, but fails to draw a link to the economic benefits that may also be incurred. Using data from the 2015-2016 Tanzania Demographic and Health Survey and Malaria Indicator Survey, this study performs a series of multiple regressions to observe how increased availability of artemisinin-based combination therapies (ACTs), a front-line antimalarial drug in most African countries, affects likelihood of work absenteeism …