Digital Commons Network^™

Different Genetic Mechanisms Mediate Spontaneous Versus Uvr-Induced Malignant Melanoma, Blake Ferguson, Herlina Y. Handoko, Pamela Mukhopadhyay, Arash Chitsazan, Lois Balmer, Grant Morahan, Graeme J. Walker

Research outputs 2014 to 2021

Genetic variation conferring resistance and susceptibility to carcinogen-induced tumorigenesis is frequently studied in mice. We have now turned this idea to melanoma using the collaborative cross (CC), a resource of mouse strains designed to discover genes for complex diseases. We studied melanoma-prone transgenic progeny across seventy CC genetic backgrounds. We mapped a strong quantitative trait locus for rapid onset spontaneous melanoma onset to Prkdc, a gene involved in detection and repair of DNA damage. In contrast, rapid onset UVR-induced melanoma was linked to the ribosomal subunit gene Rrp15. Ribosome biogenesis was upregulated in skin shortly after UVR exposure. …

Effects Of Am80 Compared To Ac261066 In A High Fat Diet Mouse Model Of Liver Disease, Marta Melis, Xiao-Han Tang, Steven E. Trasino, Viral M. Patel, Daniel J. Stummer, Jose Jessurun, Lorraine J. Gudas

Publications and Research

The roles of retinoids in nonalcoholic fatty liver disease (NAFLD) remain unclear and a better understanding may lead to therapies that prevent or limit NAFLD progression. We examined the actions of retinoic acid receptor (RAR) agonists- AM80 for RARαand AC261066 for RARβ2- in a murine model of NAFLD. We fed wild type C57Bl/6 mice a chow or a 45% high fat diet (HFD) for 12 weeks, followed by 4 additional weeks with the HFD+AM80; HFD +AC261066; or HFD. The HFD+AM80 group showed greater hyperglycemia and glucose intolerance compared to other groups. Histopathological evaluation of the livers showed the highest degree …

Global Epidemiology Of Lung Cancer., Julie A. Barta, Md, Charles A. Powell, Juan P. Wisnivesky

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

While lung cancer has been the leading cause of cancer-related deaths for many years in the United States, incidence and mortality statistics - among other measures - vary widely worldwide. The aim of this study was to review the evidence on lung cancer epidemiology, including data of international scope with comparisons of economically, socially, and biologically different patient groups. In industrialized nations, evolving social and cultural smoking patterns have led to rising or plateauing rates of lung cancer in women, lagging the long-declining smoking and cancer incidence rates in men. In contrast, emerging economies vary widely in smoking practices and …

Static And Dynamic Postural Control Deficits In Aging Fragile X Mental Retardation 1 (Fmr1) Gene Premutation Carriers., Zheng Wang, Pravin Khemani, Lauren M Schmitt, Su Lui, Matthew W Mosconi

Articles, Abstracts, and Reports

BACKGROUND: Individuals with premutation alleles of the fragile X mental retardation 1 (FMR1) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in FMR1 premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS.

METHODS: We examined postural stability in 18 premutation carriers ages 46-77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG …

Microrna-4719 And Microrna-6756-5p Correlate With Castration-Resistant Prostate Cancer Progression Through Interleukin-24 Regulation, Dibash K. Das, Leah Persaud, Moira Sauane

Publications and Research

Prostate cancer (PCa) is the second leading cause of cancer death in the United States. The five-year survival rate for men diagnosed with localized PCa is nearly 100%, yet for those diagnosed with aggressive PCa, it is less than 30%. The pleiotropic cytokine Interleukin-24 (IL-24) has been shown to specifically kill PCa cells compared to normal cells when overexpressed in both in vitro and in vivo studies. Despite this, the mechanisms regulating IL-24 in PCa are not well understood. Since specific microRNAs (miRNAs) are dysregulated in PCa, we used miRNA target prediction algorithm tools to identify miR-4719 and miR-6556-5p as …

Gene Co-Expression Networks Analysis Reveal Novel Molecular Endotypes In Alpha-1 Antitrypsin Deficiency, Jen-Hwa Chu, Wenlan Zang

Yale Day of Data

Rationale:Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that predisposes to early onset pulmonary emphysema and airways obstruction. The exact mechanism through which AATD leads to lung disease is incompletely understood.

Objectives: To investigate the effect of AAT genotype and augmentation therapy on bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) transcriptome, while examining the link between gene expression profiles, and clinical features of AATD.

Methods: We performed RNA-Seq on RNA extracted from BAL and PBMC on samples obtained from 89 AATD patients enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Differential …

Demethylation By Low-Dose 5-Aza-2'-Deoxycytidine Impairs 3d Melanoma Invasion Partially Through Mir-199a-3p Expression Revealing The Role Of This Mir In Melanoma., Cécile Desjobert, Arnaud Carrier, Audrey Delmas, Diego M Marzese, Antoine Daunay, Florence Busato, Arnaud Pillon, Jörg Tost, Joëlle Riond, Gilles Favre, Chantal Etievant, Paola B Arimondo

Articles, Abstracts, and Reports

BACKGROUND: Efficient treatments against metastatic melanoma dissemination are still lacking. Here, we report that low-cytotoxic concentrations of 5-aza-2'-deoxycytidine, a DNA demethylating agent, prevent in vitro 3D invasiveness of metastatic melanoma cells and reduce lung metastasis formation in vivo.

RESULTS: We unravelled that this beneficial effect is in part due to MIR-199A2 re-expression by promoter demethylation. Alone, this miR showed an anti-invasive and anti-metastatic effect. Throughout integration of micro-RNA target prediction databases with transcriptomic analysis after 5-aza-2'-deoxycytidine treatments, we found that miR-199a-3p downregulates set of genes significantly involved in invasion/migration processes. In addition, analysis of data from melanoma patients showed a …

Model-Based Virtual Patient Analysis Of Human Liver Regeneration Predicts Critical Perioperative Factors Controlling The Dynamic Mode Of Response To Resection., Babita Verma, Pushpavanam Subramaniam, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Liver has the unique ability to regenerate following injury, with a wide range of variability of the regenerative response across individuals. Existing computational models of the liver regeneration are largely tuned based on rodent data and hence it is not clear how well these models capture the dynamics of human liver regeneration. Recent availability of human liver volumetry time series data has enabled new opportunities to tune the computational models for human-relevant time scales, and to predict factors that can significantly alter the dynamics of liver regeneration following a resection.

METHODS: We utilized a mathematical model that integrates signaling …

The Use Of Dietary Interventions In Pediatric Patients, Shirin Madzhidova, Lusine Sedrakyan

PCOM Scholarly Works

Complementary and alternative treatment approaches are becoming more common among children with chronic conditions. The prevalence of CAM use among US adults was estimated to be around 42% in 2015 and around 44% to 50% among adults with neurologic disorders. Studies demonstrate that children with certain chronic illnesses such as asthma, cancer, genetic disorders, attention-deficit/hyperactivity disorder (ADHD), and other neurodevelopmental disorders are treated with complementary and alternative treatments at higher rates. Dietary therapies are gaining increasing popularity in the mainstream population. Although the majority of "fad" diets do not have enough supporting evidence, some dietary therapies have been utilized for …

Comparative Analysis Of Us Real-World Dosing Patterns And Direct Infusion-Related Costs For Matched Cohorts Of Rheumatoid Arthritis Patients Treated With Infliximab Or Intravenous Golimumab., Lorie A. Ellis, Elisabetta Malangone-Monaco, Helen Varker, Diana Stetsovsky, Maureen Kubacki, Raphael J. Dehoratius, Shelly Kafka

Department of Medicine Faculty Papers

Purpose: The objectives of this study were to evaluate and compare treatment patterns and infusion-related health care resource expenditures for rheumatoid arthritis (RA) patients initiating golimumab for intravenous use (GLM-IV) and infliximab (IFX) therapy and to assess cost implications from the commercial perspective.

Methods: Adult RA patients with a new episode of GLM-IV or IFX treatment between January 1, 2014 and March 31, 2016 were identified from MarketScan databases and evaluated for maintenance infusion intervals and related costs of treatment. IFX and GLM-IV patients were matched 1:1 on index medication treatment duration, gender, payer type, prior biologic use, and post-index …

Who Speaks For Me?: Addressing Variability In Informed Consent Practices For Minimal Risk Research Involving Foster Youth, Mary V. Greiner, Sarah J. Beal, Antonio Allen, Vikash Patel, Jareen Meinzen-Derr, Armand Antommaria

Journal of Health Disparities Research and Practice

Background: Youth in protective custody (i.e., foster care) are at higher risk for poorer physical and mental health outcomes compared with those who are not. These differences may be due in part to the lack of research on the population to create evidence-based recommendations for health care delivery. A potential contributor to this lack of research is difficulties in obtaining informed consent for empirical studies in this population. The objective of this study was to describe the approaches to obtaining informed consent in minimal risk studies of foster youth and provide recommendations for future requirements.

Methods: We conducted a …

Antisense Oligonucleotides Targeting Angiotensinogen: Insights From Animal Studies, Chia-Hua Wu, Ya Wang, Murong Ma, Adam E. Mullick, Rosanne M. Crooke, Mark J. Graham, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

Angiotensinogen (AGT) is the unique substrate of all angiotensin peptides. We review the recent preclinical research of AGT antisense oligonucleotides (ASOs), a rapidly evolving therapeutic approach. The scope of the research findings not only opens doors for potentially new therapeutics of hypertension and many other diseases, but also provides insights into understanding critical physiological and pathophysiological roles mediated by AGT.

Allogeneic Hematopoietic Cell Transplantation Provides Effective Salvage Despite Refractory Disease Or Failed Prior Autologous Transplant In Angioimmunoblastic T-Cell Lymphoma: A Cibmtr Analysis, Narendranath Epperla, Kwang W. Ahn, Carlos Litovich, Sairah Ahmed, Minoo Battiwalla, Jonathon B. Cohen, Parastoo Dahi, Nosha Farhadfar, Umar Farooq, Cesar O. Freytes, Nilanjan Ghosh, Bradley Haverkos, Alex Herrera, Mark Hertzberg, Gerhard C. Hildebrandt, David Inwards, Mohamed A. Kharfan-Dabaja, Farhad Khimani, Hillard Lazarus, Aleksandr Lazaryan, Lazaros Lekakis, Hemant Murthy, Sunita Nathan, Taiga Nishihori, Attaphol Pawarode, Tim Prestidge, Praveen Ramakrishnan, Andrew R. Rezvani, Rizwan Romee, Nirav N. Shah

Internal Medicine Faculty Publications

Background: There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.

Methods: We evaluated 249 adult AITL patients who received their first allo-HCT during 2000–2016.

Results: The median patient age was 56 years (range = 21–77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 …

Radiation Dose Estimation By Completely Automated Interpretation Of The Dicentric Chromosome Assay, Peter Rogan, Yanxin Li, Ben Shirley, Ruth Wilkins, Farrah Norton, Joan Knoll

Biochemistry Publications

Accuracy of the automated dicentric chromosome (DC) assay relies on metaphase image selection. This study validates a software framework to find the best image selection models that mitigate inter-sample variability. Evaluation methods to determine model quality include the Poisson goodness-of-fit of DC distributions for each sample, residuals after calibration curve fitting and leave-one-out dose estimation errors. The process iteratively searches a pool of selection model candidates by modifying statistical and filter cut-offs to rank the best candidates according to their respective evaluation scores. Evaluation scores minimize the sum of squared errors relative to the actual radiation dose of the calibration …

Csf Inflammatory Markers Differ In Gram-Positive Versus Gram-Negative Shunt Infections., Gwenn L. Skar, David C. Synhorst, Matthew Beaver, Jessica N. Snowden

Manuscripts, Articles, Book Chapters and Other Papers

Background: Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection.

Methods: We conducted a retrospective chart review of children with …

Dachshund Depletion Disrupts Mammary Gland Development And Diverts The Composition Of The Mammary Gland Progenitor Pool., Xuanmao Jiao, Zhiping Li, Min Wang, Sanjay Katiyar, Gabriele Di Sante, Mehdi Farshchian, Andrew P. South, Cinzia Cocola, Daniele Colombo, Rolland Reinbold, Ileana Zucchi, Kongming Wu, Ira Tabas, Benjamin T. Spike, Richard G. Pestell

Department of Dermatology and Cutaneous Biology Faculty Papers

DACH1 abundance is reduced in human malignancies, including breast cancer. Herein DACH1 was detected among multipotent fetal mammary stem cells in the embryo, among mixed lineage precursors, and in adult basal cells and (ERα⁺) luminal progenitors. Dach1 gene deletion at 6 weeks in transgenic mice reduced ductal branching, reduced the proportion of mammary basal cells (Lin⁻ CD24^med CD29^high) and reduced abundance of basal cytokeratin 5, whereas DACH1 overexpression induced ductal branching, increased Gata3 and Notch1, and expanded mammosphere formation in LA-7 breast cells. Mammary gland-transforming growth factor β (TGF-β) activity, known to reduce ductal …

Functional And Structural Studies Of Tolloid-Like 1 Mutants Associated With Atrial-Septal Defect 6., Lukasz Sieron, Marta Lesiak, Izabela Schisler, Zofia Drzazga, Andrzej Fertala, Aleksander L. Sieron

Department of Orthopaedic Surgery Faculty Papers

Inactive mammalian tolloid-like 1 (tll1) and mutations detected in tolloid-like 1 (TLL1) have been linked to the lack of the heart septa formation in mice and to a similar human inborn condition called atrial-septal defect 6 (ASD6; OMIM 613087, formerly ASD II). Previously, we reported four point mutations in TLL1 found in approximately 20% of ASD6 patients. Three mutations in the coding sequence were M182L, V238A, and I629V. In this work, we present the effects of these mutations on TLL1 function. Three recombinant cDNA constructs carrying the mutations and one wild-type construct were prepared and then expressed in HT-1080 cells. …

Assessing The Utilization Of High-Resolution 2-Field Hla Typing In Solid Organ Transplantation., Yanping Huang, Anh Dinh, Steven Heron, Allison Gasiewski, Carolina Kneib, Hilary Mehler, Michael T. Mignogno, Ryan Morlen, Larissa Slavich, Ethan Kentzel, Edward C. Frackelton, Jamie L. Duke, Deborah Ferriola, Timothy Mosbruger, Olga A. Timofeeva, Steven S. Geier, Dimitri Monos

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

HLA typing in solid organ transplantation (SOT) is necessary for determining HLA-matching status between donor-recipient pairs and assessing patients' anti-HLA antibody profiles. Histocompatibility has traditionally been evaluated based on serologically defined HLA antigens. The evolution of HLA typing and antibody identification technologies, however, has revealed many limitations with using serologic equivalents for assessing compatibility in SOT. The significant improvements to HLA typing introduced by next-generation sequencing (NGS) require an assessment of the impact of this technology on SOT. We have assessed the role of high-resolution 2-field HLA typing (HR-2F) in SOT by retrospectively evaluating NGS-typed pre- and post-SOT cases. HR-2F …

Enhancing Cognitive Engagement Of Pre-Clinical Undergraduate Medical Students Via Video Cases And Interactive Quizzes In Problem-Based Learning, Syeda Sadia Fatima, Kulsoom Ghias, Kauser Jabeen, Saniya Sabzwari

Department of Biological & Biomedical Sciences

Background: Problem-based learning (PBL) is one of the main pedagogical approaches utilized in the undergraduate medical education (UGME) program at a private medical college in Karachi, Pakistan. Video-enhanced cases and formative assessments were introduced at the end of PBL sessions to evaluate their effectiveness in enhancing student engagement.
Methods: A mixed methods study was conducted with Year 2 medical students (n=102; divided into 11 groups) and faculty (n=11) facilitating the PBL process. Of the 10 PBL cases, five were converted to video-enhanced cases and five were kept as paper-based, “traditional” cases. “Micro” videos were used to introduce clinical scenarios, augmented …

Star-Related Lipid Transfer Protein 10 (Stard10): A Novel Key Player In Alcohol-Induced Breast Cancer Progression, Andrea Floris, Jia Luo, Jacqueline A. Frank, Jennifer Zhou, Sandro Orrù, Michela Biancolella, Sabina Pucci, Augusto Orlandi, Paolo Campagna, Antonella Balzano, Komal Ramani, Maria Lauda Tomasi

Pharmacology and Nutritional Sciences Faculty Publications

Background: Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events. Interestingly, STARD10 has been described to be highly expressed in 35–40% of ERBB2-positive breast …

Understanding And Improving Patient Satisfaction In Orthopaedic Surgical Procedures: A Review, Paul J. Johnson

UNM Orthopaedic Research Journal

Orthopaedic surgeons and their hospitals are being evaluated and reimbursed according to their ability to provide patient satisfaction. It behooves physicians to learn how patient satisfaction is evaluated, how patient satisfaction may be improved, and how improvements in patient satisfaction may positively influence patient outcomes both subjectively and objectively. The purpose of this review is to illuminate how evaluation works, how patient factors may affect or correlate with increased satisfaction, and how physicians can improve actions to enhance patient satisfaction. Notably, studies have found that improved care coordination, nursing follow-up, provider listening skills, providing realistic yet positive expectations, and sitting …

Periprosthetic Joint Infections: A Review, Jay J. Wojcik

UNM Orthopaedic Research Journal

No abstract provided.

Design For Transtibial Modifiable Socket For Immediate Postoperative Prosthesis, Matthew N. Rush, Evan Hagin, Jane Nguyen, Victoria Lujan, Rebecca A. Dutton, Christina Salas

UNM Orthopaedic Research Journal

Amputations are long-standing surgical procedures that have been performed for centuries; however, very little attention and urgency have been given to immediate restoration of movement and return to a normal lifestyle. In many cases, the time between amputation and prosthetic fitting can pause recovery and development of new routines. To increase recovery, immediate postoperative prostheses (IPOPs) have been developed yet these are under-utilized because of concerns for wound healing and complications with vascular diseases. Subsequently, we designed a transtibial IPOP that utilizes an ergonomic modifiable socket that allows for examination, wound care, and in situ edema control. Additionally, the IPOP …

Fellows And Chiefs, Unm Department Of Orthopaedic Surgery

UNM Orthopaedic Research Journal

No abstract provided.

Division Of Research, Unm Department Of Orthopaedic Surgery

UNM Orthopaedic Research Journal

No abstract provided.

Enhancing The Effectiveness Of Special Olympics Minnesota’S Health Promotion Programming, Avery R. Bajema, Laura Marie Hayes, Kelsey B. Kostreba, Shelly Winslow

All Electronic Theses and Dissertations

Nearly 3% of the world’s population have an intellectual disability. A link exists between intellectual disability and higher rates of chronic and preventable diseases, which is partially attributed to lack of health education geared toward individuals with intellectual disability. Health promotion programs can provide health-related resources and education. Health promotion programs are often standardized, making it challenging to meet the various learning needs of individuals with intellectual disability. Special Olympics is the largest organization that provides health-related programming for those with intellectual disability. In Minnesota, the Special Olympics branch known as Health Promotion has reported difficulty with meeting the goal …

A Qualitative Examination Of Vaccine Hesitancy Among Mothers, Alicia L. Benner, Annie Vasterling, Teia Wolter

All Electronic Theses and Dissertations

Vaccine hesitancy describes the reluctance to vaccinate or the delay of vaccines (World Health Organization [WHO], 2017a). Various factors contribute to vaccine hesitancy for patients (Salmon, Dudley, Glanz, & Somer, 2015), and multiple sources are used by patients to gain vaccine information (Salmon et al., 2015), making it difficult for healthcare providers to address vaccine hesitancy. This research was conducted to identify factors that cause mothers to be vaccine hesitant and information sources used to support the mothers’ vaccination beliefs. Phone interviews were conducted with twelve vaccine hesitant mothers. Participants were asked if the following factors contributed to their vaccine …

A Community Outreach Project Addressing Mental Health, Obesity, And Asthma In Underserved Saint Paul Youth, Anna Ehnstrom, Ellie Hoopman, Caitlin Olson

All Electronic Theses and Dissertations

Due to a lack of resources, awareness, and reinforcement of information, underserved youth are predisposed to unique health concerns. The health disparities prevalent among children living in poverty are many, but the topics of focus for this community outreach project include mental health, obesity, and asthma. Supplemental health education curriculum has the potential to alleviate the health disparities prevalent among such a vulnerable population (Thomas & Aggleton, 2016). To address the health disparities present specifically among underserved youth in St. Paul, MN, the group partnered with the after-school tutoring program at Central Baptist Church to provide education on the topics …

Patient Disclosure Of Complementary And Alternative Medicine And The Patient-Provider Relationship, Kathryn V. Ortmann, Norsha Scheil, Thomas Stearns

All Electronic Theses and Dissertations

Complementary and alternative medicine (CAM) is becoming increasingly prevalent in the United States, with notable usage of supplements, deep breathing exercises, and chiropractic care. Despite this influx of CAM, nearly half of patients do not report their CAM use to their medical provider (Jou & Johnson, 2016). Disclosing these practices to a medical provider is pertinent to patient safety, as a number of potential drug interactions and side effects are associated with different CAM practices. Current literature illustrates specific provider attributes help facilitate an open dialogue with patients, or more specifically, a positive patient-provider relationship. This research study examines if …

Assessing The Use Of Pre-Treatment Medications In The Management Of Infusion-Related Reactions In An Outpatient Infusion Center, Alyssa Boesche, Alyssa Augst, Bill Kuhlman

Pharmacy Posters

Introduction

• Infusion-related reactions (IRRs) are well-known adverse drug reactions of many biological agents and antineoplastic medications
• While typically mild-to-moderate in intensity, IRRs can be severe, with potentially life-threatening consequences requiring urgent interventions
• Appropriate use of pre-treatment medications, such as corticosteroids, antihistamines, intravenous fluids, and antiemetics reduces the incidence and severity of IRRs

Purpose

• Evaluate the use of pre-treatment medications in patients with experienced IRRs at an outpatient infusion center
• Identify opportunities to improve treatment plans and reduce the occurrence of IRRs