Digital Commons Network^™

Methylation-Directed Glycosylation Of Chromatin Factors Represses Retrotransposon Promoters, Mathieu Boulard, Sofia Rucli, John R. Edwards, Timothy H. Bestor

Open Access Publications

No abstract provided.

The Role Of Ct-Quantified Body Composition On Longitudinal Health-Related Quality Of Life In Colorectal Cancer Patients: The Colocare Study, Biljana Gigic, Graham A Colditz, Adetunji T Toriola, Et Al

Open Access Publications

BACKGROUND: Obesity, defined by body mass index (BMI), measured at colorectal cancer (CRC) diagnosis has been associated with postoperative complications and survival outcomes. However, BMI does not allow for a differentiation between fat and muscle mass. Computed tomography (CT)-defined body composition more accurately reflects different types of tissue and their associations with health-related quality of life (HRQoL) during the first year of disease, but this has not been investigated yet. We studied the role of visceral and subcutaneous fat area (VFA and SFA) and skeletal muscle mass (SMM) on longitudinally assessed HRQoL in CRC patients.

METHODS: A total of 138 …

Genomics Of Mpnst (Gem) Consortium: Rationale And Study Design For Multi-Omic Characterization Of Nf1-Associated And Sporadic Mpnsts, David T Miller, Angela C Hirbe, Et Al

Open Access Publications

The Genomics of Malignant Peripheral Nerve Sheath Tumor (GeM) Consortium is an international collaboration focusing on multi-omic analysis of malignant peripheral nerve sheath tumors (MPNSTs), the most aggressive tumor associated with neurofibromatosis type 1 (NF1). Here we present a summary of current knowledge gaps, a description of our consortium and the cohort we have assembled, and an overview of our plans for multi-omic analysis of these tumors. We propose that our analysis will lead to a better understanding of the order and timing of genetic events related to MPNST initiation and progression. Our ten institutions have assembled 96 fresh frozen …

Matriptase Cleaves Epcam And Trop2 In Keratinocytes, Destabilizing Both Proteins And Associated Claudins, Chuan-Jin Wu, Michael Lu, Xu Feng, Gaku Nakato, Mark C Udey

Open Access Publications

The homologs EpCAM and TROP2, which both interact with claudin-1 and claudin-7, are frequently coexpressed in epithelia including skin. Intestine uniquely expresses high levels of EpCAM but not TROP2. We previously identified EpCAM as a substrate of the membrane-anchored protease matriptase and linked HAI-2, matriptase, EpCAM and claudin-7 in a pathway that is pivotal for intestinal epithelial cells (IEC) homeostasis. Herein, we reveal that TROP2 is also a matriptase substrate. Matriptase cleaved TROP2 when purified recombinant proteins were mixed in vitro. TROP2, like EpCAM, was also cleaved after co-transfection of matriptase in 293T cells. Neither EpCAM nor TROP2 cleavage was …

Development And Evaluation Of Machine Learning Models For Voxel Dose Predictions In Online Adaptive Magnetic Resonance Guided Radiation Therapy, M Allan Thomas, Yabo Fu, Deshan Yang

Open Access Publications

PURPOSE: Daily online adaptive plan quality in magnetic resonance imaging guided radiation therapy (MRgRT) is difficult to assess in relation to the fully optimized, high quality plans traditionally established offline. Machine learning prediction models developed in this work are capable of predicting 3D dose distributions, enabling the evaluation of online adaptive plan quality to better inform adaptive decision-making in MRgRT.

METHODS: Artificial neural networks predicted 3D dose distributions from input variables related to patient anatomy, geometry, and target/organ-at-risk relationships in over 300 treatment plans from 53 patients receiving adaptive, linac-based MRgRT for abdominal cancers. The models do not include any …

Focal Dynamic Thermal Imaging For Label‑Free High‑Resolution Characterization Of Materials And Tissue Heterogeneity, Christine M. O'Brien, Hongyu Meng, Leonid Shmuylovich, Julia Carpenter, Praneeth Gogineni, Haini Zhang, Kevin Bishop, Suman B. Mondal, Gail P. Sudlow, Cheryl Bethea, Clyde Bethea, Samuel Achilefu

Open Access Publications

No abstract provided.

Applying Dimensional Psychopathology: Transdiagnostic Associations Among Regional Homogeneity, Leptin And Depressive Symptoms, Yan-Ge Wei, Jia Duan, Fay Y. Womer, Yue Zhu, Zhiyang Yin, Lingling Cui, Chao Li, Zhuang Liu, Shengnan Wei, Xiaowei Jiang, Yanbo Zhang, Xizhe Zhang, Yanqing Tang, Fei Wang

Open Access Publications

No abstract provided.

Neutron Activation Of Gadolinium For Ion Therapy: A Monte Carlo Study Of Charged Particle Beams, Kurt W. Van Delinder, Rao Khan, James L. Gräfe

Open Access Publications

No abstract provided.

Competitive Tight-Binding Inhibition Of Vkorc1 Underlies Warfarin Dosage Variation And Antidotal Efficacy, Shuang Li, Shixuan Liu, Xiaoran Roger Liu, Mengru Mira Zhang, Weikai Li

Open Access Publications

No abstract provided.

Nanotherapy Delivery Of C-Myc Inhibitor Targets Protumor Macrophages And Preserves Antitumor Macrophages In Breast Cancer, Alison K. Esser, Michael H. Ross, Francesca Fontana, Xinming Su, Ariel Gabay, Gregory C. Fox, Yalin Xu, Jingyu Xiang, Anne H. Schmieder, Xiaoxia Yang, Grace Cui, Michael Scott, Samuel Achilefu, Jay Chauhan, Steven Fletcher, Gregory M. Lanza, Katherine N. Weilbaecher

Open Access Publications

No abstract provided.

Maternal Activation Of The Egfr Prevents Translocation Of Gut-Residing Pathogenic Escherichia Coli In A Model Of Late-Onset Neonatal Sepsis, Kathryn A. Knoop, Paige E. Coughlin, Alexandria N. Floyd, I. Malick Ndao, Carla Hall-Moore, Nurmohammad Shaikh, Andrew J. Gasparrini, Brigida Rusconi, Marilyn Escobedo, Misty Good, Barbara B. Warner, Phillip I. Tarr, Rodney D. Newberry

Open Access Publications

No abstract provided.

Tumor Burden, Inflammation, And Product Attributes Determine Outcomes Of Axicabtagene Ciloleucel In Large B-Cell Lymphoma, Frederick L. Locke, Armin Ghobadi, Et Al.

Open Access Publications

No abstract provided.

The Gut Microbiome Defines Social Group Membership In Honey Bee Colonies, Cassondra L Vernier, Iris M Chin, Boahemaa Adu-Oppong, Joshua J Krupp, Joel Levine, Gautam Dantas, Yehuda Ben-Shahar

Open Access Publications

In the honey bee, genetically related colony members innately develop colony-specific cuticular hydrocarbon profiles, which serve as pheromonal nestmate recognition cues. Yet, despite high intracolony relatedness, the innate development of colony-specific chemical signatures by individual colony members is largely determined by the colony environment, rather than solely relying on genetic variants shared by nestmates. Therefore, it is puzzling how a nongenic factor could drive the innate development of a quantitative trait that is shared by members of the same colony. Here, we provide one solution to this conundrum by showing that nestmate recognition cues in honey bees are defined, at …

Leukocyte Telomere Length Is Unrelated To Cognitive Performance Among Non-Demented And Demented Persons: An Examination Of Long Life Family Study Participants, Adiba Ashrafi, Stephanie Cosentino, Min S Kang, Joseph H Lee, Nicole Schupf, Stacy L Andersen, Kaare Christensen, Michael A Province, Bharat Thyagarajan, Joseph M Zmuda, Lawrence S Honig

Open Access Publications

OBJECTIVE: Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient dementia.

METHOD: Enrolled subjects belong to the Long Life Family Study (LLFS), a multi-generational cohort study, where enrollment was predicated upon exceptional family longevity. Included subjects had valid cognitive and telomere data at baseline. Exclusion criteria were age ≤ 60 years, outlying LTL, and missing sociodemographic/clinical information. Analyses were performed using linear regression with …

Chemical Effects Of Dicect Staining Protocols On Fluid-Preserved Avian Specimens, Catherine M. Early, Ashley C. Morhardt, Timothy P. Cleland, Christopher M. Milensky, Gwénaëlle M. Kavich, Helen F. James

Open Access Publications

Diffusible iodine-based contrast-enhanced computed tomography (diceCT) techniques allow visualization of soft tissues of fluid-preserved specimens in three dimensions without dissection or histology. Two popular diceCT stains, iodine-potassium iodide (I2KI) dissolved in water and elemental iodine (I2) dissolved in 100% ethanol (EtOH), yield striking results. Despite the widespread use of these stains in clinical and biological fields, the molecular mechanisms that result in color change and radiopacity attributed to iodine staining are poorly understood. Requests to apply these stains to anatomical specimens preserved in natural history museums are increasing, yet curators have little information about the potential for degradation of treated …

Rev-Erb Agonism Improves Liver Pathology In A Mouse Model Of Nash, Kristine Griffett, Gonzalo Bedia-Diaz, Bahaa Elgendy, Thomas P. Burris

Open Access Publications

Non-alcoholic fatty liver disease (NAFLD) affects a significant number of people worldwide and currently there are no pharmacological treatments. NAFLD often presents with obesity, insulin resistance, and in some cases cardiovascular diseases. There is a clear need for treatment options to alleviate this disease since it often progresses to much more the much more severe non-alcoholic steatohepatitis (NASH). The REV-ERB nuclear receptor is a transcriptional repressor that regulates physiological processes involved in the development of NAFLD including lipogenesis and inflammation. We hypothesized that pharmacologically activating REV-ERB would suppress the progression of fatty liver in a mouse model of NASH. Using …

Functional Profiling Of Fsh And Estradiol In Ovarian Granulosa Cell Tumors, Ulla-Maija Haltia, Marjut Pihlajoki, Noora Andersson, Lotta Mäkinen, Johanna Tapper, Alejandra Cervera, Hugo M. Horlings, Ursula Turpeinen, Mikko Anttonen, Ralf Bützow, Leila Unkila-Kallio, Olli Carpén, David B. Wilson, Markku Heikinheimo, Anniina Färkkilä

Open Access Publications

Adult-type granulosa cell tumors (AGCTs) are sex-cord derived neoplasms with a propensity for late relapse. Hormonal modulators have been used empirically in the treatment of recurrent AGCT, albeit with limited success. To provide a more rigorous foundation for hormonal therapy in AGCT, we used a multimodal approach to characterize the expressions of key hormone biomarkers in 175 tumor specimens and 51 serum samples using RNA sequencing, immunohistochemistry, RNA

Effects Of Personality On The Developmental Trajectories Of Academic Burnout Among Korean Medical Students, Han Chae, C. Robert Cloninger, Soon Jin Lee

Open Access Publications

No abstract provided.

Evaluation Of Naturalistic Driving Behavior Using In-Vehicle Monitoring Technology In Preclinical And Early Alzheimer's Disease, Jennifer D Davis, Ganesh M Babulal, George D Papandonatos, Erin M Burke, Christopher B Rosnick, Brian R Ott, Catherine M Roe

Open Access Publications

Cognitive impairment is a significant risk factor for hazardous driving among older drivers with Alzheimer's dementia, but little is known about how the driving behavior of mildly symptomatic compares with those in the preclinical, asymptomatic phase of Alzheimer's disease (AD). This study utilized two in-car technologies to characterize driving behavior in symptomatic and preclinical AD. The goals of this pilot study were to (1) describe unsafe driving behaviors in individuals with symptomatic early AD using G-force triggered video capture and (2) compare the driving habits of these symptomatic AD drivers to two groups of cognitively normal drivers, those with and …

High-Throughput Analysis Of Adaptation Using Barcoded Strains Of Saccharomyces Cerevisiae, Vincent J Fasanello, Ping Liu, Carlos A Botero, Justin C Fay

Open Access Publications

Background: Experimental evolution of microbes can be used to empirically address a wide range of questions about evolution and is increasingly employed to study complex phenomena ranging from genetic evolution to evolutionary rescue. Regardless of experimental aims, fitness assays are a central component of this type of research, and low-throughput often limits the scope and complexity of experimental evolution studies. We created an experimental evolution system in

Results: We first confirm that barcode insertions do not alter fitness and that barcode sequencing can be used to efficiently detect fitness differences via pooled competition-based fitness assays. Next, we examine the effects …

Human Ipsc-Derived Neuronal Cells From Ctbp1-Mutated Patients Reveal Altered Expression Of Neurodevelopmental Gene Networks, S Vijayalingam, Eric Tycksen, Christina A Gurnett, Et Al

Open Access Publications

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Meningioma: A Review Of Clinicopathological And Molecular Aspects, Kristin Huntoon, Angus Martin Shaw Toland, Sonika Dahiya

Open Access Publications

Meningiomas are the most the common primary brain tumors in adults, representing approximately a third of all intracranial neoplasms. They classically are found to be more common in females, with the exception of higher grades that have a predilection for males, and patients of older age. Meningiomas can also be seen as a spectrum of inherited syndromes such as neurofibromatosis 2 as well as ionizing radiation. In general, the 5-year survival for a WHO grade I meningioma exceeds 80%; however, survival is greatly reduced in anaplastic meningiomas. The standard of care for meningiomas in a surgically-accessible location is gross total …

Coronavirus Proteins As Ion Channels: Current And Potential Research, Conor Mcclenaghan, Alex Hanson, Sun-Joo Lee, Colin G Nichols

Open Access Publications

Coronavirus (CoV) outbreaks have recently emerged as a global public health threat due to their exceptional zoonotic potential - a feature arising from their ability to infect a diverse range of potential hosts combined with their high capacity for mutation and recombination. After Severe Acute Respiratory Syndrome (SARS) CoV-1 in 2003 and Middle East Respiratory Syndrome (MERS) CoV in 2012, with the current SARS-CoV-2 pandemic we are now in the midst of the third deadly international CoV outbreak in less than 20 years. Coronavirus outbreaks present a critical threat to global public health and an urgent necessity for therapeutic options. …

Fenofibrate Prevents Iron Induced Activation Of Canonical Wnt/Β-Catenin And Oxidative Stress Signaling In The Retina, Ashok Mandala, Austin Armstrong, Becky Girresch, Jiyao Zhu, Aruna Chilakala, Sanmathi Chavalmane, Kapil Chaudhary, Pratim Biswas, Judith Ogilvie, Jaya P. Gnana-Prakasam

Open Access Publications

No abstract provided.

Comprehensive Profiling Of Extracellular Rna In Hpv‑Induced Cancers Using An Improved Pipeline For Small Rna‑Seq Analysis, Fangjia Tong, Arlise Andress, Gongyu Tang, Ping Liu, Xiaowei Wang

Open Access Publications

No abstract provided.

Protocol For A Proof-Of-Concept Observational Study Evaluating The Potential Utility And Acceptability Of A Telemedicine Solution For The Post-Anesthesia Care Unit, Thaddeus P Budelier, Christopher Ryan King, Shreya Goswami, Anchal Bansal, Stephen H Gregory, Troy S Wildes, Joanna Abraham, Sherry L Mckinnon, Amy Cooper, Ivan Kangrga, Jackie L Martin Jr., Melissa Milbrandt, Alex S Evers, Michael S Avidan

Open Access Publications

No abstract provided.

Primary Cilia As The Nexus Of Biophysical And Hedgehog Signaling At The Tendon Enthesis, Fei Fang, Andrea G Schwartz, Emily R Moore, Mckenzie E Sup, Stavros Thomopoulos

Open Access Publications

The tendon enthesis is a fibrocartilaginous tissue critical for transfer of muscle forces to bone. Enthesis pathologies are common, and surgical repair of tendon to bone is plagued by high failure rates. At the root of these failures is a gap in knowledge of how the tendon enthesis is formed and maintained. We tested the hypothesis that the primary cilium is a hub for transducing biophysical and hedgehog (Hh) signals to regulate tendon enthesis formation and adaptation to loading. Primary cilia were necessary for enthesis development, and cilia assembly was coincident with Hh signaling and enthesis mineralization. Cilia responded inversely …

A Harmonized Meta-Knowledgebase Of Clinical Interpretations Of Somatic Genomic Variants In Cancer, Alex H. Wagner, Kilannin Krysiak, Malachi Griffith, Obi L. Griffith, Et Al.

Open Access Publications

No abstract provided.

Diet Modifies Pioglitazone’S Influence On Hepatic Pparγ-Regulated Mitochondrial Gene Expression, Sakil Kulkarni, Jiansheng Huang, Eric Tycksen, Paul F. Cliften, David A. Rudnick

Open Access Publications

No abstract provided.

Expanding The Genetic Architecture Of Nicotine Dependence And Its Shared Genetics With Multiple Traits, Bryan C. Quach, Michael J. Bray, Pamela Madden, Laura J. Bierut, Nancy L. Saccone, Et Al.

Open Access Publications

No abstract provided.