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The Role Of Efferent Reduction Of Cochlear Compression In The Detection Of Tones In Noise, Shaum Bhagat, Anusha Yellamsetty

Faculty Publications

Stimulation of medial olivocochlear (MOC) efferent neurons reduces basilar membrane (BM) sensitivity and increases the slope of BM input-output (I/O) functions in animal models. Decreased compression of I/O functions associated with activation of MOC efferent neurons may assist in extending the neural response to the tone above that of noise, leading to an improvement in masked thresholds. To evaluate this hypothesis, the distortion-product otoacoustic emission (DPOAE) I/O function, a proxy measure of BM compression, was examined in conditions with presentation of contralateral noise. DPOAE I/O functions were measured at f2 frequencies of 1000 and 2000 Hz in 16 normal-hearing adults. …

Other Tobacco Product Use Among Sexual Minority Young Adult Bar Patrons, Amanda Fallin-Bennett, Nadra E. Lisha, Pamela M. Ling

Nursing Faculty Publications

Introduction—Lesbian, gay, and bisexual (LGB) individuals smoke at rates 1.5–2 times higher than the general population, but less is known about LGB consumption of other tobacco products (OTPs) and gender differences. OTP use among young adult LGB bar patrons and the relationship among past quit attempts, intention to quit, and binge drinking with OTP use was examined.

Methods—A cross-sectional survey of young adults (aged 18–26) in bars/nightclubs in seven U.S. cities between 2012 and 2014 (N=8,010; 1,101 LGB participants) was analyzed in 2016. Logistic regressions examined current use of five OTPs (cigarillos, electronic cigarettes, hookah, chewing tobacco, and …

Advertising Exposure And Use Of E-Cigarettes Among Female Current And Former Tobacco Users Of Childbearing Age, Kristin Ashford, Emily Rayens, Amanda T. Wiggins, Mary Kay Rayens, Amanda Fallin-Bennett, Molly Malany Sayre

Nursing Faculty Publications

Objective: The study examined the relationship between exposure to e‐cigarette advertising and e‐cigarette use by pregnancy status, including use of flavored e‐cigarette products, among women of childbearing age.

Design: A cross‐sectional, correlational design was used.

Subjects: Female current or former tobacco users in Central and Eastern Kentucky, 18–45 years old (N = 194, 52% pregnant).

Measures: Demographics, pregnancy status, cigarette and e‐cigarette use, and exposure to e‐cigarette advertising.

Results: Younger age, white non‐Hispanic race, and greater exposure to e‐cigarette advertising were associated with a higher likelihood of ever using e‐cigarettes (p < .05 for each variable). Pregnancy was not associated with ever use (p = .11). Younger age was associated …

Amlexanox Enhances Premature Termination Codon Read-Through In Col7a1 And Expression Of Full Length Type Vii Collagen: Potential Therapy For Recessive Dystrophic Epidermolysis Bullosa., Velina S. Atanasova, Qiujie Jiang, Marco Prisco, Christina Gruber, Josefina Piñón Hofbauer, Mei Chen, Cristina Has, Leena Bruckner-Tuderman, John A. Mcgrath, Jouni Uitto, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder caused by the lack of functional type VII collagen, leading to skin fragility and subsequent trauma-induced separation of the epidermis from the underlying dermis. A total of 46% of patients with RDEB harbor at least one premature termination codon (PTC) mutation in COL7A1, and previous studies have shown that aminoglycosides are able to overcome RDEB PTC mutations by inducing "read-through" and incorporation of an amino acid at the PTC site. However, aminoglycoside toxicity will likely prevent widespread clinical application. Here the FDA-approved drug amlexanox was tested for its ability …

Intracranial Eeg Fluctuates Over Months After Implanting Electrodes In Human Brain., Hoameng Ung, Steven N. Baldassano, Hank Bink, Abba M. Krieger, Shawniqua Williams, Flavia Vitale, Chengyuan Wu, Dean Freestone, Ewan Nurse, Kent Leyde, Kathryn A. Davis, Mark Cook, Brian Litt

Department of Neurosurgery Faculty Papers

OBJECTIVE: Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings.

APPROACH: Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for …

Incidence, Risks, And Types Of Infections In Pediatric Long-Term Care Facilities, Lisa Saiman, Philip Maykowski, Meghan Murray, Bevin Cohen, Natalie Neu, Gordon R. Hutcheon, Elaine Larson

NYMC Faculty Publications

Importance: The population of infants, children, and adolescents cared for at pediatric long-term care facilities is increasing in complexity and size and thus consumes substantial health care resources. Infections are a significant cause of morbidity and mortality in this population, but few recent data describe their incidence and effects.

Objectives: To describe the types of infections diagnosed in residents of pediatric long-term care facilities, calculate infection rates, and identify risk factors for respiratory tract infections (RTIs).

Design, Setting, and Participants: This prospective cohort study, which was part of a larger trial called Keep It Clean for Kids, was conducted from …

Increasing Use Of Allogeneic Hematopoietic Cell Transplantation In Patients Aged 70 Years And Older In The United States, Lori Muffly, Marcelo C. Pasquini, Michael Martens, Ruta Brazauskas, Xiaochun Zhu, Kehinde Adekola, Mahmoud Aljurf, Karen K. Ballen, Ashish Bajel, Frederic Baron, Minoo Battiwalla, Amer Beitinjaneh, Jean-Yves Cahn, Mathew Carabasi, Yi-Bin Chen, Saurabh Chhabra, Stefan Ciurea, Edward Copelan, Anita D'Souza, John Edwards, James Foran, Cesar O. Freytes, Henry C. Fung, Robert Peter Gale, Sergio Giralt, Shahrukh K. Hashmi, Gerhard C. Hildebrandt, Vincent Ho, Ann Jakubowski, Hillard Lazarus

Internal Medicine Faculty Publications

In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥ 70 years with hematologic malignancies across the United States. Adults ≥ 70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥ 70 years underwent HCT across 103 transplant centers. The number and proportion of allografts …

Pulmonary Tumor Embolism Secondary To Soft Tissue And Bone Sarcomas: A Case Report And Literature Review., Nicholas Latchana, Vincent C Daniel, Robert W Gould, Raphael E Pollock

Oncology Articles

BACKGROUND: Tumor embolisms (TE) are an underappreciated source of pulmonary embolisms in sarcoma. Most evidence in the literature is limited to case reports and none have described the presence of TE secondary to myxofibrosarcoma. We report the first case of myxofibrosarcoma TE and perform a review of the literature for TE secondary to bone and soft tissue sarcomas (STS).

CASE PRESENTATION: A 36-year-old female presented with debilitating pain of the right upper extremity secondary to a recurrent soft tissue sarcoma. She had distant metastasis to the lung. An MRI revealed a 25-cm shoulder mass involving the proximal arm muscles with …

Challenges And Considerations Related To Studying Dementia In Blacks/African Americans, Eseosa T. Ighodaro, Peter T. Nelson, Walter A. Kukull, Frederick A. Schmitt, Erin L. Abner, Allison M. Caban-Holt, Shoshana H. Bardach, Derrick C. Hord, Crystal M. Glover, Gregory A. Jicha, Linda J. Van Eldik, Alexander X. Byrd, Anita Fernander

Neuroscience Faculty Publications

Blacks/African Americans have been reported to be ~2–4 times more likely to develop clinical Alzheimer’s disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses. Here we provide a selected historical background, discuss challenges, present opportunities, and suggest considerations for studying health outcomes among racial/ethnic …

Smartscope2: Simultaneous Imaging And Reconstruction Of Neuronal Morphology., Brian Long, Zhi Zhou, Ali Cetin, Jonathan Ting, Ryder Gwinn, Bosiljka Tasic, Tanya Daigle, Ed Lein, Hongkui Zeng, Peter Saggau, Michael Hawrylycz, Hanchuan Peng

Articles, Abstracts, and Reports

Quantitative analysis of neuronal morphology is critical in cell type classification and for deciphering how structure gives rise to function in the brain. Most current approaches to imaging and tracing neuronal 3D morphology are data intensive. We introduce SmartScope2, the first open source, automated neuron reconstruction machine integrating online image analysis with automated multiphoton imaging. SmartScope2 takes advantage of a neuron's sparse morphology to improve imaging speed and reduce image data stored, transferred and analyzed. We show that SmartScope2 is able to produce the complex 3D morphology of human and mouse cortical neurons with six-fold reduction in image data requirements …

Growth And Weight Gain In Children With Juvenile Idiopathic Arthritis: Results From The Reacch-Out Cohort., Jaime Guzman, Tristan Kerr, Leanne M Ward, Jinhui Ma, Kiem Oen, Alan M Rosenberg, Brian M Feldman, Gilles Boire, Kristin Houghton, Paul Dancey, Rosie Scuccimarri, Alessandra Bruns, Adam M Huber, Karen Watanabe Duffy, Natalie J Shiff, Roberta A Berard, Deborah M Levy, Elizabeth Stringer, Kimberly Morishita, Nicole Johnson, David A Cabral, Maggie Larché, Ross E Petty, Ronald M Laxer, Earl Silverman, Paivi Miettunen, Anne-Laure Chetaille, Elie Haddad, Lynn Spiegel, Stuart E Turvey, Heinrike Schmeling, Bianca Lang, Janet Ellsworth, Suzanne E Ramsey, Johannes Roth, Sarah Campillo, Susanne Benseler, Gaëlle Chédeville, Rayfel Schneider, Shirley M L Tse, Roxana Bolaria, Katherine Gross, Debbie Feldman, Bonnie Cameron, Roman Jurencak, Jean Dorval, Claire Leblanc, Claire St Cyr, Michele Gibbon, Rae S M Yeung, Ciarán M Duffy, Lori B Tucker

Paediatrics Publications

BACKGROUND: With modern treatments, the effect of juvenile idiopathic arthritis (JIA) on growth may be less than previously reported. Our objective was to describe height, weight and body mass index (BMI) development in a contemporary JIA inception cohort.

METHODS: Canadian children newly-diagnosed with JIA 2005-2010 had weight and height measurements every 6 months for 2 years, then yearly up to 5 years. These measurements were used to calculate mean age- and sex-standardized Z-scores, and estimate prevalence and cumulative incidence of growth impairments, and the impact of disease activity and corticosteroids on growth.

RESULTS: One thousand one hundred forty seven children …

Effect Of Natriuretic Peptide-Guided Therapy On Hospitalization Or Cardiovascular Mortality In High-Risk Patients With Heart Failure And Reduced Ejection Fraction: A Randomized Clinical Trial., G. Michael Felker, Kevin J. Anstrom, Kirkwood F. Adams, Justin A Ezekowitz, Mona Fiuzat, Nancy Houston-Miller, James L. Januzzi, Daniel B. Mark, Ileana L. Piña, Gayle Passmore, David J. Whellan, Hongqiu Yang, Lawton S. Cooper, Eric S. Leifer, Patrice Desvigne-Nickens, Christopher M O'Connor

Department of Medicine Faculty Papers

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results.

Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF).

Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in …

Multi-Laboratory Assessment Of Reproducibility, Qualitative And Quantitative Performance Of Swath-Mass Spectrometry., Ben C Collins, Christie L Hunter, Yansheng Liu, Birgit Schilling, George Rosenberger, Samuel L Bader, Daniel W Chan, Bradford W Gibson, Anne-Claude Gingras, Jason M Held, Mio Hirayama-Kurogi, Guixue Hou, Christoph Krisp, Brett Larsen, Liang Lin, Siqi Liu, Mark P Molloy, Robert L Moritz, Sumio Ohtsuki, Ralph Schlapbach, Nathalie Selevsek, Stefani N Thomas, Shin-Cheng Tzeng, Hui Zhang, Ruedi Aebersold

Articles, Abstracts, and Reports

Quantitative proteomics employing mass spectrometry is an indispensable tool in life science research. Targeted proteomics has emerged as a powerful approach for reproducible quantification but is limited in the number of proteins quantified. SWATH-mass spectrometry consists of data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics (accuracy, sensitivity, and selectivity) of targeted proteomics at large scale. While previous SWATH-mass spectrometry studies have shown high intra-lab reproducibility, this has not been evaluated between labs. In this multi-laboratory evaluation study including 11 sites worldwide, we demonstrate that using SWATH-mass spectrometry data acquisition we can consistently …

Strategies To Improve Interdisciplinary Communication In An Acute Care Inpatient Pediatric Unit, Sarah Thompson, Haley Pelletier, Barbara Bush Children's Hospital-Inpatient, Maine Medical Center, Suneela Nayak, Ruth Hanselman, Stephen Tyzik

MaineHealth Maine Medical Center

Interdisciplinary patient rounding has been shown to improve patient and family satisfaction as well as reduce patient length of stay and readmission rates. In an acute care inpatient pediatric unit, baseline metrics demonstrated that 100% of the time, nursing was not included in these rounds thus resulting in sub optimal communication.

The goal of this performance improvement project was to attain increased nursing participation. Data collection demonstrated several reasons for lack of participation and corrective actions were instituted. After undertaking this KPI goal and utilizing operational excellence, 95% of the time, nurses were called to morning rounds with the medical …

Strategies To Improve Control Of Blood A1c In Diabetics, Jennifer Aronson, Leanne Bellino, Elizabeth Eisenhardt, Diane Bryant, Haley Pelletier, Internal Medicine Team, Adult Outpatient Clinic

MaineHealth Maine Medical Center

A1c monitoring is an important aspect of controlling the health of a diabetic patient. An adult internal medicine clinic noted that the percentage of their diabetic patients who had an A1c higher than 9 or no reading within the past year exceeded the national average. As a result, operational excellence methods were implemented with the overall goal to reduce their percentage to 18% or less.

A root cause analysis identified several deficiencies to includelack of essential equipment, variations in

staff education and the absence of daily reminders.

Post KPI implementations, an overall decrease in the percentage of patients with poorly …

Identification Strategies For The Very High Fall Risk Patient In An Acute Inpatient Psychiatric Unit, P6 Inpatient Geri-Med Psychiatry, Haley Pelletier, Suneela Nayak, Stephen Tyzik, Ruth Hanselman

MaineHealth Maine Medical Center

Patients falling as a result of geriatric and psychiatric impairments are at a much higher risk than the average patient population. An acute care inpatient psychiatric team used baseline metrics to demonstrate increasing fall rates per month that surpassed the unit’s target number. As a result, a quality improvement project around falls was felt to be warranted.

The overall goal of this study was to improve patient safety by reducing falls for their very high risk fall population. A root cause analysis determined that this population was not being properly identified and several tools were developed and employed to better …

Improving Type And Screen Specimen Collection Prior To Elective Surgery, Nordx Blood Bank Staff, Haley Pelletier, Suneela Nayak, Stephen Tyzik, Ruth Hanselman

MaineHealth Maine Medical Center

To avoid delays in the availability of compatible blood for elective surgery patients requiring transfusion, a type and screen specimen should be completed at least 24 hours prior to surgery. Baseline metrics in an acute care inpatient blood bank demonstrated a significant number of cases with no type or screen completed.

The objective of this KPI was to prevent any delays in providing compatible blood products to scheduled surgical patients. Several internal and external system issues were identified as a result of a root cause analysis and a number of actions were initiated.

Outcomes have been positive. Data collection post …

Delirium Reduction Strategies For The Critically Ill, June Chaves, Sam Canonico, Will Cheney, Tammy Corey, Gil Fraser, Alex Kowalewski, Jen Low, Cardiac Intensive Care Unit, Haley Pelletier, Cathy Palleschi, Stephen Tyzik, Suneela Nayak, Ruth Hanselman

MaineHealth Maine Medical Center

Delirium, an acute and fluctuating disturbance of consciousness and cognition, is a common manifestation of acute brain dysfunction in critically ill patients. Patients with delirium have longer hospital stays and a lower 6-month survival rate than do patients without delirium. Preliminary research suggests that delirium may be associated with cognitive impairment that persists months to years after discharge.

In a large acute care hospital, the cardiac intensive care staff became interested in mitigating their unit’s high delirium rate of ventilated patients. At baseline, many members of the healthcare team did not believe that delirium could be prevented and the predominant …

Improving Cardiology Patient Flow In Nuclear Medicine, Kelly Haar, Hannah Sullivan, Kathryn Laverdiere, Nuclear Medicine Department, Haley Pelletier, Stephen Tyzik, Suneela Nayak, Ruth Hanselman

MaineHealth Maine Medical Center

At baseline, a nuclear medicine department found it difficult to complete cardiac stress tests within scheduled times. Using the performance improvement process, a nuclear medicine department looked to improve patient experience related to wait times for this test.

Two goals were identified and a root cause analysis was initiated. After identifying some process issues, two KPIs were developed to address them.

A root cause analysis identified some processing issues and two KPIs were instituted to address them.

As a result, one outcome was to hire an additional physician assistant to address the barrier of inadequate cardiology coverage. Next steps include …

Communication Of Medication Side Effects In An Acute Care Hospital, Deb Bachand, Rachel Caiola, R6 Neurology Med-Surg Unit, Haley Pelletier, Brendan Lilley, Suneela Nayak, Ruth Hanselman, Stephen Tyzik

MaineHealth Maine Medical Center

COMMUNICATION OF MEDICATION SIDE EFFECTS IN AN ACUTE CARE HOSPITAL

Effective patient education of prescribed medication side effects improves patient safety and reduces overall risk. On an acute care hospital unit, nursing staff felt previous attempts at this education had been ineffective as demonstrated by their HCAHPs scores for communication about medications.

A root cause analysis demonstrated some flaws and several countermeasures were instituted. The goal of this KPI project was to attain a higher than national average for the specific HCAHPs score.

Post KPI inception, the unit’s HCAHPs data showed steady improvement. Within one month, the goal of an …

Rational Confederation Of Genes And Diseases: Ngs Interpretation Via Genecards, Malacards And Varelect., Noa Rappaport, Simon Fishilevich, Ron Nudel, Michal Twik, Frida Belinky, Inbar Plaschkes, Tsippi Iny Stein, Dana Cohen, Danit Oz-Levi, Marilyn Safran, Doron Lancet

Articles, Abstracts, and Reports

BACKGROUND: A key challenge in the realm of human disease research is next generation sequencing (NGS) interpretation, whereby identified filtered variant-harboring genes are associated with a patient's disease phenotypes. This necessitates bioinformatics tools linked to comprehensive knowledgebases. The GeneCards suite databases, which include GeneCards (human genes), MalaCards (human diseases) and PathCards (human pathways) together with additional tools, are presented with the focus on MalaCards utility for NGS interpretation as well as for large scale bioinformatic analyses.

RESULTS: VarElect, our NGS interpretation tool, leverages the broad information in the GeneCards suite databases. MalaCards algorithms unify disease-related terms and annotations from 69 …

Human Milk And Allergic Diseases: An Unsolved Puzzle, Daniel Munblit, Diego G. Peroni, Alba Boix-Amorós, Peter S. Hsu, Belinda Van't Land, Melvin C. L. Gay, Anastasia Kolotilina, Chrysanthi Skevaki, Robert J. Boyle, Maria C. Collado, Johan Garssen, Donna T. Geddes, Ralph Nanan, Carolyn Slupsky, Ganesa Wegienka, Anita L. Kozyrskyj, John O. Warner

Public Health Sciences Articles

There is conflicting evidence on the protective role of breastfeeding in relation to the development of allergic sensitisation and allergic disease. Studies vary in methodology and definition of outcomes, which lead to considerable heterogeneity. Human milk composition varies both within and between individuals, which may partially explain conflicting data. It is known that human milk composition is very complex and contains variable levels of immune active molecules, oligosaccharides, metabolites, vitamins and other nutrients and microbial content. Existing evidence suggests that modulation of human breast milk composition has potential for preventing allergic diseases in early life. In this review, we discuss …

Tia1 Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia Promote Phase Separation And Alter Stress Granule Dynamics., Ian R. Mackenzie, Alexandra M. Nicholson, Mohona Sarkar, James Messing, Maria D. Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B. Perkerson, Aishe Kurti, Billie J. Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R. Hsiung, Charles Krieger, Melissa E. Murray, Masato Kato, John D. Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A. Zivkovic, Veronica Hirsch-Reinshagen, Raymond P. Roos, Stephan Züchner, Neill R. Graff-Radford, Ronald C. Petersen, Richard J. Caselli, Zbigniew K. Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W. Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B. Boylan, J. Paul Taylor, Rosa Rademakers

Department of Neurology Faculty Papers

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10

Interleukin-6 (Il-6) Rs1800796 And Cyclin Dependent Kinase Inhibitor (Cdkn2a/Cdkn2b) Rs2383207 Are Associated With Ischemic Stroke In Indigenous West African Men, Rufus Akinyemi, Donna K. Arnett, Hemant K. Tiwari, Bruce Ovbiagele, Fred Sarfo, Vinodh Srinivasasainagendra, Marguerite Ryan Irvin, Abiodun Adeoye, Rodney T. Perry, Albert Akpalu, Carolyn Jenkins, Lukman Owolabi, Reginald Obiako, Kolawole Wahab, Emmanuel Sanya, Morenikeji Komolafe, Michael Fawale, Philip Adebayo, Godwin Osaigbovo, Taofiki Sunmonu, Paul Olowoyo, Innocent Chukwuonye, Yahaya Obiabo, Onoja Akpa, Sylvia Melikam, Raelle Saulson, Raj Kalaria, Adesola Ogunniyi, Mayowa Owolabi

Epidemiology and Environmental Health Faculty Publications

Background—Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub – Saharan African populations. Interleukin–6 polymorphisms have been previously associated with ischemic stroke in some non-African populations.

Aim—Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6 and CDKN2A- CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study.

Methods—Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known …

Epigenetic Regulation Of Kpc1 Ubiquitin Ligase Affects The Nf-Κb Pathway In Melanoma., Yuuki Iida, Aaron Ciechanover, Diego M Marzese, Keisuke Hata, Matias Bustos, Shigeshi Ono, Jinhua Wang, Matthew P Salomon, Kevin Tran, Stella Lam, Sandy Hsu, Nellie Nelson, Yelena Kravtsova-Ivantsiv, Gordon B Mills, Michael A Davies, Dave S B Hoon

Articles, Abstracts, and Reports

Purpose: Abnormal activation of the NF-κB pathway induces a more aggressive phenotype of cutaneous melanoma. Understanding the mechanisms involved in melanoma NF-κB activation may identify novel targets for this pathway. KPC1, an E3 ubiquitin ligase, is a regulator of the NF-κB pathway. The objective of this study was to investigate the mechanisms regulating KPC1 expression and its clinical impact in melanoma.Experimental Design: The clinical impact of KPC1 expression and its epigenetic regulation were assessed in large cohorts of clinically well-annotated melanoma tissues (tissue microarrays; n = 137, JWCI cohort; n = 40) and The Cancer Genome Atlas database (TCGA …

Selective Inhibitors Of Human Mpges-1 From Structure-Based Computational Screening, Ziyuan Zhou, Yaxia Yuan, Shuo Zhou, Kai Ding, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Human mPGES-1 is recognized as a promising target for next generation of anti-inflammatory drugs. Although various mPGES-1 inhibitors have been reported in literature, few have entered clinical trials and none has been proven clinically useful so far. It is highly desired for developing the next generation of therapeutics for inflammation-related diseases to design and discover novel inhibitors of mPGES-1 with new scaffolds. Here, we report the identification of a series of new, potent and selective inhibitors of human mPGES-1 with diverse scaffolds through combined computational and experimental studies. The computationally modeled binding structures of these new inhibitors with mPGES-1 provide …

Estimation Of Exposure Distribution Adjusting For Association Between Exposure Level And Detection Limit, Yuchen Yang, Brent J. Shelton, Thomas Tucker, Li Li, Richard Kryscio, Li Chen

Statistics Faculty Publications

In environmental exposure studies, it is common to observe a portion of exposure measurements to fall below experimentally determined detection limits (DLs). The reverse Kaplan–Meier estimator, which mimics the well‐known Kaplan–Meier estimator for right‐censored survival data with the scale reversed, has been recommended for estimating the exposure distribution for the data subject to DLs because it does not require any distributional assumption. However, the reverse Kaplan–Meier estimator requires the independence assumption between the exposure level and DL and can lead to biased results when this assumption is violated. We propose a kernel‐smoothed nonparametric estimator for the exposure distribution without imposing …

Posttranscriptional Upregulation Of Idh1 By Hur Establishes A Powerful Survival Phenotype In Pancreatic Cancer Cells., Mahsa Zarei, Shruti Lal, Seth J. Parker, Avinoam Nevler, Ali Vaziri-Gohar, Katerina Dukleska, Nicole C. Mambelli-Lisboa, Cynthia Moffat, Fernando F Blanco, Saswati N. Chand, Masaya Jimbo, Joseph A. Cozzitorto, Wei Jiang, Charles J. Yeo, Eric R. Londin, Erin L. Seifert, Christian M. Metallo, Jonathan R. Brody, Jordan M. Winter

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C > 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal …

Integrative Analysis Identifies Four Molecular And Clinical Subsets In Uveal Melanoma., A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman

Articles, Abstracts, and Reports

Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.

Building Virtual Communities Of Practice For Health, Bruce Struminger, Sanjeev Arora, Sarah Zalud-Cerrato, David Lowrance, Tedd Ellerbrock

Project ECHO Bibliography

No abstract provided.