Digital Commons Network^™

Life Among The Sand Grains, Will M. Ballentine, N. G. Roberts, M. K. Yap-Chiongco, K. M. Halanych, K. M. Kocot

Biology Faculty Works

Have you ever played with sand at the beach? Did you know you were also playing with thousands of tiny animals? The sand in the ocean is home to many small creatures called meiofauna, but you can only see them under a magnifying glass or microscope. Meiofauna are so tiny that sand grains seem like boulders to them. Meiofauna are too small to move these boulders, so they wriggle through spaces between them. Living in such tight spaces has led them to evolve long, skinny body shapes like worms. They also have special body parts to grip sand grains and …

Conformation And Membrane Topology Of The N-Terminal Ectodomain Of Influenza A M2 Protein, Kyra C. Roepke , '24, Kathleen P. Howard

Chemistry & Biochemistry Faculty Works

The N-terminal ectodomain of the influenza A M2 protein is a target for universal influenza vaccine development and novel antiviral strategies. Despite the significance of this domain, it is poorly understood and most structural studies of the M2 protein have disregarded the N-terminal ectodomain in their analyses. Here, we report conformational properties and describe insights into the membrane topology of sites along the N-terminal ectodomain. Full-length M2 protein is embedded in lipid bilayer nanodiscs and studied using site-directed spin labeling electron paramagnetic resonance spectroscopy. Results are consistent with a turn in the middle of the ectodomain that changes in proximity …

Development Of The Navigation Guide Evidence-To-Decision Framework For Environmental Health: Version 1.0, Nicholas Chartres, Max T. Aung, Sustan L. Norris, Courtney Cooper, Lia A. Bero, Roger Chou, Devon C. Payne-Sturges, Wendy E. Wagner, Jessica W. Reyes, Lisa M. Askie, Daniel A. Axelrad, Deysi Flores Vigo, Jill E. Johnston, Juleen Lam, Keeve E. Nachman, Eva Rehfuess, Rachel Rothschild, Patrice Sutton, Lauren Zeise, Tracey J. Woodruff

Articles

Environmental exposures, including widespread industrial pollution, impact human health and are amplified in more highly exposed communities. Policy and regulatory frameworks for making decisions and recommendations on interventions to mitigate or prevent exposures tend to narrowly focus on exposure and some health-related data related to risks. Typically, such frameworks do not consider other factors, including essentiality, health equity, and distribution of benefits and costs. Further, decisions and recommendations lack transparency regarding how they were developed. We developed the Navigation Guide Evidence-to-Decision Framework for Environmental Health (E2DFEH) to provide a structured and transparent framework incorporating a range of scientific information and …

Higher Amounts Of Habitual Physical Activity Changes The Relationship Between Hot Flashes And Subclinical Cardiovascular Disease Risk, Sarah Witkowski, Tint Tha Ra Wun, Jo Sophia Brunzelle, Sara Buszkiewicz, Lorna Murphy, Randi L. Garcia, Lynnette Leidy Sievert

Exercise and Sport Studies: Faculty Publications

The menopausal transition is associated with increased risk for cardiovascular disease (CVD). Hot flashes (HF), a cardinal symptom of menopause, have been associated with increased CVD risk, particularly in perimenopausal women. Flow-mediated dilation (FMD) is an indicator of endothelial function and a subclinical CVD risk factor. Lower FMD has been associated with more HF. As moderate to vigorous physical activity (MVPA) is recognized to reduce CVD risk, our goal was to determine whether higher levels of MVPA change the relationship between HF and FMD in perimenopausal women. Healthy perimenopausal women had HF measured objectively using sternal skin conductance for 24 …

Ivy Proteins As Guardians Of Bacterial Cell Wall Integrity: Regulation Of Lytic Transglycosylases Explored, Aamna Aijaz, Trinity E. Alamutu, Vy T. Dao, Nathaniel R. Davis, Michael D. Landers, Nykolas K. Mackevicius, Liliana Ortiz, Irina F. Padilla-Montoya, Kacy J. Smith, Maria L. Snyder, Anthony J. Stefanie, Blaise M. Williams, Thomas C. Leeper

The Kennesaw Journal of Undergraduate Research

Lytic transglycosylases (LTs) are bacterial enzymes involved in biosynthesis and maintenance of the peptidoglycan cell wall. LTs are reported to be regulated by two paralogs of Inhibitor of Vertebrate Lysozymes: Ivyp1 and Ivyp2. This study investigated the regulatory dynamics between the soluble LT (SltB1), and Ivy paralogs as putative regulators in Pseudomonas aeruginosa (PA). The secondary objective was to delineate the critical roles played by a glutamic acid at position 135 in SltB1 and a histidine at position 62 in Ivyp1 in governing their molecular interaction through site directed mutagenesis. Isolated SltB1 shows no lytic activity in our assay, in …

Delphi-Driven Consensus Definition For Mesenchymal Stromal Cells And Clinical Reporting Guidelines For Mesenchymal Stromal Cell-Based Therapeutics, Laurent Renesme, Kelly D. Cobey, Manoj M. Lalu, Tania M. Bubela, Raghavan Chinnadurai, John De Vos, Rod Dunbar, Dean Fergusson, Daniel Freund, Jacques Galipeau

Office of the Provost

Background aims: Despite promising results in pre-clinical studies, mesenchymal stromal cells (MSCs) face significant challenges in clinical translation. A scoping review by our group highlighted two key issues contributing to this gap: (i) lack of a clear and consensus definition for MSCs and (ii) under-reporting of critical parameters in MSC clinical studies. To address these issues, we conducted a modified Delphi study to establish and implement a consensus definition for MSCs and develop reporting guidelines for MSC clinical studies.
Methods: A steering committee of 22 international experts, including stakeholders from different MSC research fields, participated in the three Delphi rounds. …

Inhibition Of Lysine Deacetylase Activity Impacts Formation Of The Vitamin D Receptor Activation Complex, Shannon Dwyer

Theses and Dissertations

The vitamin D endocrine system is responsible for the regulation of many biological processes including bone metabolism, calcium homeostasis, cell proliferation and cell differentiation. Alterations to the vitamin D signaling pathway are associated with several diseases including bone diseases, diabetes, cardiovascular diseases, autoimmune diseases, and cancer. Vitamin D precursors are chemically modified to become the biologically active hormone, calcitriol. Calcitriol binds to the vitamin D receptor (VDR), a member of the nuclear hormone receptor (NHR) superfamily. VDR forms a heterodimer with retinoid X receptor (RXR) and together they bind to promoters containing vitamin D response elements (VDREs) to activate transcription …

Watershed Land Use Decreases The Nitrogen Limitation Of Benthic Algal Growth In Coastal Wetlands Of A Large Oligotrophic Lake, Matthew J. Cooper, Michele C. Wheeler

Open Access Publishing Support Funded Articles

Introduction:

Identifying patterns in the primary limiting nutrients of basal trophic levels such as benthic algae can inform the prediction of potential ecological responses to anthropogenic nutrient loading. In coastal wetlands of the Laurentian Great Lakes, reduced concentrations of reactive nitrogen species such as ammonium and nitrate may limit algal growth, especially when nutrient loading is minimal. However, the response of benthic algae to macronutrient inputs remains understudied, especially in Lake Superior coastal wetlands.

Methods:

We conducted nutrient amendment assays using nutrient diffusing substrate devices in 25 coastal wetlands along the southwestern shore of Lake Superior in the spring, summer, …

Product Testing: Research Shows Benefits Of Biostimulants May Vary By Variety, Prakriti Nepal, Youping Sun, Milena Oliveira

Plants, Soils and Climate Student Research

The use of plant biostimulants is showing some promise as a potential means of helping onion crops thrive despite certain environmental challenges, according to new research at Utah State University.

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage., Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John D'Orazio, D Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K St Clair, Luksana Chaiswing

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off-target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage by …

Analysis Of 26 Studies Of The Impact Of Coconut Oil On Lipid Parameters: Beyond Total And Ldl Cholesterol, Mary T. Newport, Fabian M. Dayrit

Chemistry Faculty Publications

Coconut oil (CNO) is often characterized as an “artery-clogging fat” because it is a predominantly saturated fat that ostensibly raises total cholesterol (TChol) and LDL cholesterol (LDL-C). Whereas previous analyses assessed CNO based on the relative effects on lipid parameters against other fats and oils, this analysis focuses on the effects of CNO itself. Here, we review the literature on CNO and analyze 984 lipid profile data sets from 26 CNO studies conducted over the past 40 years. This analysis shows considerable heterogeneity among CNO studies regarding participant selection, the amount consumed, and the study duration. The analysis reveals that, …

Frequency-Dependent Assembly Processes Determine The Coexistence And Relative Abundance Of Tropical Plant Species, David M. Defilippis, Joseph A. Lamanna, Stefan A. Schnitzer

Biological Sciences Faculty Research and Publications

Testing the extent to which ecological communities are structured by deterministic (niche-based) assembly processes, resulting in predictable species abundance and composition, is a fundamental goal of ecology. Here we use a 10-year dataset of 55,156 lianas comprising 86 species in an old-growth tropical forest in Panama to test whether community assembly is consistent with niche-based assembly processes. We find that species diversity and community composition was maintained because species conformed to four general requirements of coexistence theory: (1) species have negative conspecific frequency-dependent feedback that control their local population size; (2) species have a stronger negative effect on their own …

Long-Term Agricultural Management Reduces Abundance And Alters Community Structure Of Ground Beetles (Coleoptera: Carabidae), Cynthia M. Fiser, Nathan L. Haan, Douglas A. Landis

Entomology Faculty Publications

Carabid beetles (Coleoptera: Carabidae) are beneficial predators and bioindicators of ground-dwelling arthropod diversity in agricultural landscapes. We studied changes in community composition, activity density, and diversity of carabids in a long-term agroecosystem study spanning 30 years in the US Midwest. We contrasted carabid community metrics measured by pitfall trap sampling in two conservation-oriented treatments in a corn-soybean-wheat rotation. One treatment uses conventional practices but with reduced agrochemical inputs (Reduced Input), while the other has no synthetic inputs (Biologically Based). Since a 1994–95 study on the same site, in 2019 overall carabid activity density had declined a minimum of 58–76 % …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Attenuation Of Vitamin E On Haloxyfop-R-Methyl Ester-Induced Hepatic Oxidative Stress In Orally Exposed Rats., Omolara D. Falodun

STEM for Success Resources

No abstract provided.

Marine Protected Species Identification Guide 2025, Department Of Primary Industries And Regional Development, Western Australia

Fisheries Occasional Publications

The Western Australian aquatic environment is home to a number of species that are protected under international agreements and national or state legislation. Many of these species occur in areas where fishing takes place, sometimes resulting in interactions between fishers and protected species. An interaction is considered to be any physical contact between a person, fishing vessel or fishing gear and a protected species, including captures, entanglements and collisions.

This guide has been developed to help you identify some common marine protected species in Western Australia that you may encounter while fishing.

It has been divided into 5 sections:

• …

Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn-Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger

Markey Cancer Center Faculty Publications

MYCN-amplification is a genetic hallmark of ~40% of high-risk neuroblastomas (NBs). Altered glycosylation is a common feature of adult cancer progression, but little is known about how genetic signatures such as MYCN-amplification alter glycosylation profiles. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased core fucosylated glycan abundance within neuroblast-rich regions of human MYCN-amplified NB tumors. GDP-mannose 4,6-dehydratase (GMDS) is responsible for the first-committed and rate-limiting step of de novo GDP-fucose synthesis. High GMDS expression was found to be associated with poor patient survival, advanced stage disease, and MYCN-amplification in human NB tumors. Chromatin immunoprecipitation and promoter reporter assays …

A Microrna-Regulated Transcriptional State Defines Intratumoral Cd8+ T Cells That Respond To Immunotherapy, William W. Tang, Ben Battistone, Kaylyn M. Bauer, Allison M. Weis, Cindy Barba, Muhammad Zaki Hidayatullah Fadlullah, Arevik Ghazaryan, Van B. Tran, Soh-Hyun Lee, Z. Busra Agir, Morgan C. Nelson, Emmanuel Stephen Victor, Amber Thibeaux, Colton Hernandez, Jacob Tantalla, Aik C. Tan, Dinesh Rao, Matthew Williams, Micah J. Drummond, Ellen J. Beswick, June L. Round, H. Atakan Ekiz, Warren P/ Voth, Ryan M. O’Connell

Markey Cancer Center Faculty Publications

The rising incidence of advanced-stage colorectal cancer (CRC) and poor survival outcomes necessitate new and effective therapies. Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, show promise, yet clinical determinants of a positive response are suboptimal. Here, we identify microRNA-155 (miR-155) as necessary for CD8 + T cell-infiltrated tumors through an unbiased in vivo CRISPR-Cas9 screen identifying functional tumor antigen-specific CD8+ T cell-expressed microRNAs. T cell miR-155 is required for anti-PD-1 responses and for a vital intratumor CD8 + T cell differentiation cascade by repressing Ship-1, inhibiting Tcf-1 and stemness, and subsequently enhancing Cxcr6 expression, anti-tumor immunity, and effector functions. Based …

Staying Sane In The Membrane: Neutral Sphingomyelinase 2 As A Master Regulator Of Plasma Membrane Ceramide, Zainuddin Quadri, Erhard Bieberich

Markey Cancer Center Faculty Publications

Ceramide, a key signaling sphingolipid in the plasma membrane, plays a pivotal role in fundamental cellular processes such as adhesion, polarity, and programmed cell death. The generation of plasma membrane ceramide is largely attributed to the activity of two types of sphingomyelinases: neutral sphingomyelinase 2 (nSMase2, Smpd3) and acid sphingomyelinase (aSMase, Smpd1). While many studies have explored ceramide generation following experimental activation of these enzymes, the mechanisms governing basal or steady- state ceramide levels have remained poorly understood. Using an innovative mass spectrometry approach developed in the Canals’ lab, the team has quantified the distinct contributions of nSMase2 and aSMase …

Gdp-Mannose 4,6-Dehydratase Is A Key Driver Of Mycn- Amplified Neuroblastoma Core Fucosylation And Tumorigenesis, Beibei Zhu, Michelle G. Pitts, Michael D. Buoncristiani, Lindsay T. Bryant, Oscar Lopez-Nunez, Juan P. Gurria, Cameron Shedlock, Roberto Ribas, Shannon Keohane, Jinpeng Liu, Chi Wang, Matthew S. Gentry, Nathan R. Shelman, Derek B. Allison, B. Mark Evers, Ramon C. Sun, Eric J. Rellinger

Markey Cancer Center Faculty Publications

MYCN-amplification is a genetic hallmark of ~40% of high-risk neuroblastomas (NBs). Altered glycosylation is a common feature of adult cancer progression, but little is known about how genetic signatures such as MYCN-amplification alter glycosylation profiles. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased core fucosylated glycan abundance within neuroblast-rich regions of human MYCN-amplified NB tumors. GDP-mannose 4,6-dehydratase (GMDS) is responsible for the first-committed and rate-limiting step of de novo GDP-fucose synthesis. High GMDS expression was found to be associated with poor patient survival, advanced stage disease, and MYCN-amplification in human NB tumors. Chromatin immunoprecipitation and promoter reporter assays …

Decoding Cancer Etiology With Cellular Reprogramming, Mo-Fan Huang, Megan E Fisher, Trinh T T Phan, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Student Publications

Cancer research remains clinically unmet in many areas due to limited access to patient samples and the lack of reliable model systems that truly reflect human cancer biology. The emergence of patient-derived induced pluripotent stem cells and engineered human pluripotent stem cells (hPSCs) has helped overcome these challenges, offering a versatile alternative platform for advancing cancer research. These hPSCs are already proving to be valuable models for studying specific cancer driver mutations, offering insights into cancer origins, pathogenesis, tumor heterogeneity, clonal evolution, and facilitating drug discovery and testing. This article reviews recent progress in utilizing hPSCs for clinically relevant cancer …

Chemoresistance-Motility Signature Of Molecular Evolution To Chemotherapy In Non-Muscle-Invasive Bladder Cancer And Its Clinical Implications, Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem

Faculty, Staff and Student Publications

Non-muscle-invasive bladder cancer (NMIBC) often recurs and can progress to MIBC due to resistance to treatments like intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). Therefore, we established the Gemcitabine-Resistant Cells (GRCs) to study the molecular evolution under external pressure. A 63-gene Chemoresistance-Motility (CrM) signature was created to identify stage-specific traits of GRCs. This signature was tested on 1846 samples using log-rank tests and Cox regression to evaluate clinical utility. Early and intermediate resistance stages showed increased cell motility and metastatic potential. FAK, PI3K-AKT, and TGFβ pathways were activated first, followed by MAPK signaling. Single-cell analysis and experiments utilizing the CrM signature …

Association Of Serum Endocannabinoid Levels With Pancreatitis And Pancreatitis-Related Pain, Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli

Faculty, Staff and Student Publications

No abstract provided.

A Statistical Framework For Multi-Trait Rare Variant Analysis In Large-Scale Whole-Genome Sequencing Studies, Xihao Li, Han Chen, Margaret Sunitha Selvaraj, Eric Van Buren, Hufeng Zhou, Yuxuan Wang, Ryan Sun, Zachary R Mccaw, Zhi Yu, Min-Zhi Jiang, Daniel Dicorpo, Sheila M Gaynor, Rounak Dey, Donna K Arnett, Emelia J Benjamin, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Jennifer A Brody, Brian E Cade, April P Carson, Jenna C Carlson, Nathalie Chami, Yii-Der Ida Chen, Joanne E Curran, Paul S De Vries, Myriam Fornage, Nora Franceschini, Barry I Freedman, Charles Gu, Nancy L Heard-Costa, Jiang He, Lifang Hou, Yi-Jen Hung, Marguerite R Irvin, Robert C Kaplan, Sharon L R Kardia, Tanika N Kelly, Iain Konigsberg, Charles Kooperberg, Brian G Kral, Changwei Li, Yun Li, Honghuang Lin, Ching-Ti Liu, Ruth J F Loos, Michael C Mahaney, Lisa W Martin, Rasika A Mathias, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Take Naseri, Kari E North, Nicholette D Palmer, Patricia A Peyser, Bruce M Psaty, Susan Redline, Alexander P Reiner, Stephen S Rich, Colleen M Sitlani, Jennifer A Smith, Kent D Taylor, Hemant K Tiwari, Ramachandran S Vasan, Satupa'itea Viali, Zhe Wang, Jennifer Wessel, Lisa R Yanek, Bing Yu, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Josée Dupuis, James B Meigs, Paul L Auer, Laura M Raffield, Alisa K Manning, Kenneth M Rice, Jerome I Rotter, Gina M Peloso, Pradeep Natarajan, Zilin Li, Zhonghua Liu, Xihong Lin

Faculty, Staff and Student Publications

Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally scalable analytical pipeline for functionally informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple …

Molecular Profiling Of Bladder Cancer Xenografts Defines Relevant Molecular Subtypes And Provides A Resource For Biomarker Discovery, Sharada Mokkapati, Ganiraju Manyam, Alexis R Steinmetz, Côme Tholomier, Alberto Martini, Woonyoung Choi, Bogdon Czerniak, Byron H Lee, Colin P Dinney, David J Mcconkey

Faculty, Staff and Student Publications

Bladder cancer (BLCA) genomic profiling has identified molecular subtypes with distinct clinical characteristics and variable sensitivities to frontline therapy. BLCAs can be categorized into luminal or basal subtypes based on their gene expression. We comprehensively characterized nine human BLCA cell lines (UC3, UC6, UC9, UC13, UC14, T24, SCaBER, RT4V6 and RT112) into molecular subtypes using orthotopic xenograft models. Patient-derived, luciferase-tagged BLCA cell lines were cultured in vitro and engrafted into bladders of NSG mice. Tumor growth was monitored using bioluminescence imaging and mRNA-based molecular classification was used to characterize xenografts into molecular subtypes. RNAseq analysis and basal, luminal, and epithelial-mesenchymal …

On The Acceptance, Commissioning, And Quality Assurance Of Electron Flash Units, Allison Palmiero, Kevin Liu, Julie Colnot, Nitish Chopra, Denae Neill, Luke Connell, Brett Velasquez, Albert C Koong, Steven H Lin, Peter Balter, Ramesh Tailor, Charlotte Robert, Jean-François Germond, Patrik Gonçalves Jorge, Reiner Geyer, Sam Beddar, Raphael Moeckli, Emil Schüler

Faculty, Staff and Student Publications

Background and purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an …

A Phase Ib Trial Of Selinexor In Combination With Immune Checkpoint Blockade In Patients With Advanced Renal Cell Carcinoma, Omar Alhalabi, Mohamed A Gouda, Denái R Milton, Hassan Ahmed Momin, Bulent Yilmaz, Bettzy Stephen, Chinenye Lynette Ejezie, Justin Tyler Moyers, Serdar A Gurses, Jeffrey How, Siqing Fu, Jordi Rodon, David S Hong, Sarina A Piha-Paul, Vivek Subbiah, Ecaterina Elena Dumbrava, Daniel D Karp, Filip Janku, Funda Meric-Bernstam, Nizar M Tannir, Aung Naing

Faculty, Staff and Student Publications

Background: Selinexor (SEL) is a nuclear exportin 1 inhibitor that blocks the transport of nuclear proteins, including tumor suppressors, to the cytoplasm. Preclinical data suggest that the combination of SEL with checkpoint blockade may result in improved response to immunotherapy.

Methods: NCT02419495 was a multiarm phase IB study of SEL in combination with other standard regimens in patients with advanced malignancies. Arm M utilized twice weekly oral SEL and intravenous nivolumab (NIVO). Arm N utilized weekly oral SEL with NIVO plus ipilimumab (IPI). The primary objective of this study was to evaluate the safety of SEL + NIVO and SEL …

Frailty And Sleep In Adult Survivors Of Childhood Cancer: A Childhood Cancer Survivor Study Report, Lauren C Daniel, Margaret M Lubas, Huiqi Wang, Mariana Szklo-Coxe, Kirsten K Ness, Annalynn M Williams, Daniel A Mulrooney, Rebecca Howell, Wendy Leisenring, Yutaka Yasui, Leslie L Robison, Gregory T Armstrong, Eric J Chow, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

Background: Young adult survivors of childhood cancer exhibit rates of frailty similar to adults several decades older without a cancer history. Frailty has been associated with sleep disturbances in non-cancer populations, but the relationship has not been examined in childhood cancer survivors who are known to exhibit elevated rates of sleep problems.

Aims: Examine associations between frailty and poor sleep quality in long-term survivors of childhood cancer.

Methods: This study utilized data from 9044 participants (> 5 years from diagnosis, Mage = 40.8 years [SD = 9.5]) in the Childhood Cancer Survivor Study. Survivors' frailty status, chronic health conditions (CHC), …

Hsp90: Bringing It All Together, Georgios Ioannis Karras, Giorgio Colombo, Andrea N Kravats

Faculty, Staff and Student Publications

Heat-shock protein 90 (Hsp90) is an ancient and multifaceted protein-folding machine essential for most organisms. The past 40 years have uncovered remarkable complexity in the regulation and function of Hsp90, which dwarfs most other machines in the cell in sophistication. Here, we propose four analogies to illustrate Hsp90's sophistication: a multifunctional Swiss Army knife, an automobile engine and its controls, a switchboard acting as a hub and directing signals, and an orchestra conductor setting the tempo of a symphony. Although each of these analogies represents some key Hsp90 activities, none of them captures the entirety of Hsp90's complexity. Together, these …

Stereotactic Body Radiotherapy Vs Sorafenib Alone In Hepatocellular Carcinoma: The Nrg Oncology/Rtog 1112 Phase 3 Randomized Clinical Trial, Laura A Dawson, Kathryn A Winter, Jennifer J Knox, Andrew X Zhu, Sunil Krishnan, Chandan Guha, Lisa A Kachnic, Michael T Gillin, Theodore S Hong, Timothy D Craig, Terence M Williams, Ali Hosni, Eric Chen, Anne M Noonan, Eugene J Koay, Rishi Sinha, Michael I Lock, Nitin Ohri, Jennifer A Dorth, Guila Delouya, Anand Swaminath, Jennifer Moughan, Christopher H Crane

Faculty, Staff and Student Publications

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, setting, and participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, …