Medicine and Health Sciences Commons^™

The Mitochondrial Deoxyguanosine Kinase Is Required For Cancer Cell Stemness In Lung Adenocarcinoma, Shengchen Lin, Chongbiao Huang, Jianwei Sun, Oana Bollt, Xiuchao Wang, Eric Martine, Jiaxin Kang, Matthew D. Taylor, Bin Fang, Pankaj K. Singh, John Koomen, Jihui Hao, Shengyu Yang

Journal Articles: Eppley Institute

The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. …

Human Islet Response To Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study, Ahmed M. Abdellatif, Heather Jensen Smith, Robert Z. Harms, Nora Sarvetnick

Journal Articles: Eppley Institute

Type 1 diabetes (T1D) is a chronic autoimmune disease that results from destruction of pancreatic β-cells. T1D subjects were recently shown to harbor distinct intestinal microbiome profiles. Based on these findings, the role of gut bacteria in T1D is being intensively investigated. The mechanism connecting intestinal microbial homeostasis with the development of T1D is unknown. Specific gut bacteria such as Bacteroides dorei (BD) and Ruminococcus gnavus (RG) show markedly increased abundance prior to the development of autoimmunity. One hypothesis is that these bacteria might traverse the damaged gut barrier, and their constituents elicit a response from human islets that causes …

Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein

Journal Articles: Eppley Institute

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …

Mapping Of Lymphatic Filariasis In Loiasis Areas: A New Strategy Shows No Evidence For Wuchereria Bancrofti Endemicity In Cameroon, Samuel Wanji, Mathias Eyong Esum, Abdel Jelil Njouendou, Amuam Andrew Mbeng, Patrick W Chounna Ndongmo, Raphael Awah Abong, Jerome Fru, Fanny F. Fombad, Gordon Takop Nchanji, Glory Ngongeh, Narcisse V. Ngandjui, Peter Ivo Enyong, Helen Storey, Kurt C. Curtis, Kerstin Fischer, Joseph R. Fauver, Daphne Lew, Charles W. Goss, Peter U. Fischer

Journal Articles: Epidemiology

BACKGROUND: Mapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemic areas may be inaccurate.

METHODOLOGY/PRINCIPAL FINDINGS: In order to develop an LF mapping strategy for areas with high loiasis prevalence, we collected day blood samples from 5,001 subjects residing in 50 villages that make up 6 health districts throughout Cameroon. Antigen testing using Filarial Test Strip (FTS, a novel platform that uses …

Consequences Of Pathogen Lists: Why Some Diseases May Continue To Plague Us, David Brett-Major, Trina Racine, Gary P. Kobinger

Journal Articles: Epidemiology

The current strategy used by many funding agencies for determining how money is spent on research to help prevent infectious disease outbreaks is based on pathogen-specific priority lists. Listing disease threats provides focus for business and research planning conducive to specific goals of developing a drug, or a vaccine, or other particular product. But, this singular type of focus has consequences. This perspective explores the consequences of lists, and describes how parallel programming independent of disease lists that address what we need to do to prevent and mitigate emerging disease risks may provide benefits out of reach of a singular …

New Filovirus Disease Classification And Nomenclature, Jens H. Kuhn, Takuya Adachi, Neill K.J. Adhikari, Jose R. Arribas, Ibrahima Elhadj Bah, Daniel G. Bausch, Nahid Bhadelia, Matthias Borchert, Arne Broch Brantsæter, David Brett-Major, Timothy H. Burgess, Daniel S. Chertow, Christopher G. Chute, Theodore J. Cieslak, Robert Colebunders, Ian Crozier, Richard T. Davey, Hilde De Clerck, Rafael Delgado, Laura Evans, Mosoka Fallah, William A. Fischer, Tom E. Fletcher, Robert A. Fowler, Thomas Grünewald, Andy Hall, Angela L. Hewlett, Andy I.M. Hoepelman, Catherine F. Houlihan, Giuseppe Ippolito, Shevin T. Jacob, Michael Jacobs, Robert Jakob, Frederique A. Jacquerioz, Laurent Kaiser, Andre C. Kalil, Rashidatu F. Kamara, Jimmy Kapetshi, Hans-Dieter Klenk, Gary Kobinger, Mark G. Kortepeter, Colleen S. Kraft, Thomas Kratz, Henry S. Kyobe Bosa, Marta Lado, François Lamontagne, H. Cliff Lane, Leslie Lobel, Julius Lutwama, G. Marshall Lyon, Moses B.F. Massaquoi, Thomas A. Massaquoi, Aneesh K. Mehta, Vital Mondonge Makuma, Srinivas Murthy, Tonny Seikikongo Musoke, Jean-Jacques Muyembe-Tamfum, Phiona Nakyeyune, Carolina Nanclares, Miriam Nanyunja, Justus Nsio-Mbeta, Tim O'Dempsey, Janusz T. Pawęska, Clarence J. Peters, Peter Piot, Christophe Rapp, Bertrand Renaud, Bruce Ribner, Pardis C. Sabeti, John S. Schieffelin, Werner Slenczka, Moses J. Soka, Armand Sprecher, James Strong, Robert Swanepoel, Timothy M. Uyeki, Michel Van Herp, Pauline Vetter, David A. Wohl, Timo Wolf, Anja Wolz, Alie H. Wurie, Zabulon Yoti

Journal Articles: Epidemiology

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.

Using "Outbreak Science" To Strengthen The Use Of Models During Epidemics., Caitlin Rivers, Jean-Paul Chretien, Steven Riley, Julie A. Pavlin, Alexandra Woodward, David Brett-Major, Irina Maljkovic Berry, Lindsay Morton, Richard G. Jarman, Matthew Biggerstaff, Michael A. Johansson, Nicholas G. Reich, Diane Meyer, Michael R. Snyder, Simon Pollett

Journal Articles: Epidemiology

Infectious disease modeling has played a prominent role in recent outbreaks, yet integrating these analyses into public health decision-making has been challenging. We recommend establishing ‘outbreak science’ as an inter-disciplinary field to improve applied epidemic modeling.

Barriers Of Colorectal Cancer Screening In Rural Usa: A Systematic Review, Hongmei Wang, Shreya Roy, Jungyoon Kim, Evi A. Farazi, Mohammad Siahpush, Dejun Su

Journal Articles: Epidemiology

INTRODUCTION: Colorectal cancer (CRC) screening rates are lower in rural areas in the USA. To guide the design of interventions to improve CRC screening, a systematic review was conducted to identify CRC screening barriers for rural populations.

METHODS: A search was conducted in four literature databases - Medline, CINAHL, Embase, and Scopus - for articles from 1998 to 2017 that examine CRC screening barriers in rural areas. This review included a total of 27 articles reporting perceived CRC screening barriers by rural residents or providers or examining factors associated with CRC screening of rural populations in the USA.

RESULTS: The …

The Impact Of Travel Time On Colorectal Cancer Stage At Diagnosis In A Privately Insured Population, Mesnad Alyabsi, Mary Charlton, Jane L. Meza, K. M. Monirul Islam, Amr Soliman, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

BACKGROUND: Rural residents are less likely to receive screening for colorectal cancer (CRC) than urban residents. However, the mechanisms underlying this disparity, especially among people aged 50-64 years old with private health insurance, are not well understood. We examined the impact of travel time on stage at CRC diagnosis.

METHODS: This retrospective cohort study used data from the Blue Cross and Blue Shield of Nebraska. Members of this private insurance company aged 50-64 years, diagnosed with CRC during the period 2012-2016, and continuously enrolled in the insurance plan for at least 6 months prior to CRC diagnosis, were selected for …

Improving Behavioral Health Workforce Supply And Needs Estimates Using Active Surveillance Data, Shinobu Watanabe-Galloway, Li-Wu Chen, Kate Trout, David Palm, Marlene Deras, Zaeema Naveed

Journal Articles: Epidemiology

INTRODUCTION: Previous studies show that supply of behavioral health professionals in rural areas is inadequate to meet the need. Measuring shortage using licensure data on psychiatrists is a common approach. Although inexpensive, the licensure data have many limitations. An alternative is to implement an active surveillance system, which uses licensure data in addition to active data collection to obtain timely and detailed information.

METHODS: Nebraska Health Professions Tracking Service (HPTS) data were used to examine differences in workforce supply estimates between the passive (licensure data only) and active (HPTS data) surveillance systems. The impact of these differences on the designation …

Risk Mitigation For Travelers: Managing Endemic And Emerging Threats, Shannon M. Wood, David Brett-Major

Journal Articles: Epidemiology

International travel continues to increase in numbers and complexity. Despite the availability of pretravel health advice, travelers remain at risk for exposure to common organisms as well as emerging pathogens. With low rates of travel clinic utilization, it is important for the general practitioner to remain aware of the importance of travel health, risk factors unique to individual patients, and evolving threats. This review highlights important considerations when evaluating ill travelers, incorporating emerging infectious threats.

Effect Of Abo Blood Group On Asymptomatic, Uncomplicated And Placental Plasmodium Falciparum Infection: Systematic Review And Meta-Analysis, Abraham Degarege, Merhawi T. Gebrezgi, Consuelo M. Beck-Sague, Mats Wahlgren, Luiz Carlos De Mattos, Purnima Madhivanan

Journal Articles: Epidemiology

BACKGROUND: Malaria clinical outcomes vary by erythrocyte characteristics, including ABO blood group, but the effect of ABO blood group on asymptomatic, uncomplicated and placental Plasmodium falciparum (P. falciparum) infection remains unclear. We explored effects of ABO blood group on asymptomatic, uncomplicated and placental falciparum infection in the published literature.

METHODS: A systematic review and meta-analysis was performed using the preferred reporting items for systematic reviews and meta-analyses guidelines. Articles in Pubmed, Embase, Web of Science, CINAHL and Cochrane Library published before February 04, 2017 were searched without restriction. Studies were included if they reported P. falciparum infection incidence or prevalence, …

Improving Socioeconomic Status May Reduce The Burden Of Malaria In Sub Saharan Africa: A Systematic Review And Meta-Analysis, Abraham Degarege, Kristopher Fennie, Dawit Degarege, Shasank Chennupati, Purnima Madhivanan

Journal Articles: Epidemiology

BACKGROUND: A clear understanding of the effects of housing structure, education, occupation, income, and wealth on malaria can help to better design socioeconomic interventions to control the disease. This literature review summarizes the relationship of housing structure, educational level, occupation, income, and wealth with the epidemiology of malaria in sub-Saharan Africa (SSA).

METHODS: A systematic review and meta-analysis was conducted following the preferred reporting items for systematic reviews and meta-analyses guidelines. The protocol for this study is registered in PROSPERO (ID=CRD42017056070), an international database of prospectively registered systematic reviews. On January 16, 2016, available literature was searched in PubMed, Embase, …