Medicine and Health Sciences Commons^™

Mechanism And Rational Combinations With Gp-2250, A Novel Oxathiazine Derivative, In Ovarian Cancer, Mark S Kim, Deanna Glassman, Katelyn F Handley, Adrian Lankenau Ahumada, Nicholas B Jennings, Emine Bayraktar, Katherine Foster, Robiya Joseph, Sanghoon Lee, Robert L Coleman, Anil K Sood

Faculty, Staff and Student Publications

BACKGROUND: GP-2250, a novel analog of taurultam (TRLT), has emerged as a potent anti-neoplastic drug; however, the mechanisms underlying its effects are not well understood. Here, we investigated the mechanism of action and the biological effects of GP-2250 using in vitro and in vivo models.

METHODS: We carried out a series of in vitro (MTT assay, Annexin V/PI assay, colony formation assay, reverse-phase protein array [RPPA], and HRLC/IC analysis) to determine the biological activity of GP-2250 and investigate the mechanism of action. In vivo experiments were carried out to determine the therapeutic efficacy of GP-2250 alone and in combination with …

Autophagic Signaling Promotes Systems-Wide Remodeling In Skeletal Muscle Upon Oncometabolic Stress By D2-Hg, Yaqi Gao, Kyoungmin Kim, Heidi Vitrac, Rebecca L Salazar, Benjamin D Gould, Daniel Soedkamp, Weston Spivia, Koen Raedschelders, An Q Dinh, Anna G Guzman, Lin Tan, Stavros Azinas, David J R Taylor, Walter Schiffer, Daniel Mcnavish, Helen B Burks, Roberta A Gottlieb, Philip L Lorenzi, Blake M Hanson, Jennifer E Van Eyk, Heinrich Taegtmeyer, Anja Karlstaedt

Faculty, Staff and Student Publications

OBJECTIVES: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by D2-HG activates autophagy and drives skeletal muscle loss.

METHODS: We quantified genomic, metabolomic, and proteomic changes in …

#Hashtagthis – Everything You Need To Know About Launching Your Gynecologic Oncology Social Media Research Career: A Report From Gynecologic Oncology Reports And Society Of Gynecologic Oncology Education Committee, Megan L Hutchcraft, Eric Rios-Doria, Tiffany Y Sia, Eleonora Teplinsky, Shannon N Westin, Gregg Nelson

Faculty, Staff and Student Publications

On February 6th, 2024, Gynecologic Oncology Reports and the Society of Gynecologic Oncology Education Committee co-hosted a webinar about ways to use social media for career enhancement and for dissemination of research. During the discussion, we reviewed:i.how to identify one's goals, target audience, and select a social media platform.ii.how to navigate the negatives of social media.iii.how to develop one's online academic brand.iv.how to use social media for academic promotion and career advancement.v.how to use social media as a research tool.vi.how to use visual tools to bring attention to one's research.The objective of this report is to review the literature on …

A Biallelic Variant Of The Rna Exosome Gene, Exosc4, Associated With Neurodevelopmental Defects Impairs Rna Exosome Function And Translation, Milo B Fasken, Sara W Leung, Lauryn A Cureton, Maha Al-Awadi, Adila Al-Kindy, Ambro Van Hoof, Sohail Khoshnevis, Homa Ghalei, Almundher Al-Maawali, Anita H Corbett

Faculty, Staff and Student Publications

The RNA exosome is an evolutionarily conserved complex required for both precise RNA processing and decay. Pathogenic variants in EXOSC genes, which encode structural subunits of this complex, are linked to several autosomal recessive disorders. Here, we describe a missense allele of the EXOSC4 gene that causes a collection of clinical features in two affected siblings. This missense variant (NM_019037.3: exon3:c.560T>C) changes a leucine residue within a conserved region of EXOSC4 to proline (p.Leu187Pro). The two affected individuals show prenatal growth restriction, failure to thrive, global developmental delay, intracerebral and basal ganglia calcifications, and kidney failure. Homozygosity for the …

Nf1 Mutation Disrupts Activity-Dependent Oligodendroglial Plasticity And Motor Learning In Mice, Yuan Pan, Jared D Hysinger, Belgin Yalçın, James J Lennon, Youkyeong Gloria Byun, Preethi Raghavan, Nicole F Schindler, Corina Anastasaki, Jit Chatterjee, Lijun Ni, Haojun Xu, Karen Malacon, Samin M Jahan, Alexis E Ivec, Benjamin E Aghoghovwia, Christopher W Mount, Surya Nagaraja, Suzanne Scheaffer, Laura D Attardi, David H Gutmann, Michelle Monje

Faculty, Staff and Student Publications

Neurogenetic disorders, such as neurofibromatosis type 1 (NF1), can cause cognitive and motor impairments, traditionally attributed to intrinsic neuronal defects such as disruption of synaptic function. Activity-regulated oligodendroglial plasticity also contributes to cognitive and motor functions by tuning neural circuit dynamics. However, the relevance of oligodendroglial plasticity to neurological dysfunction in NF1 is unclear. Here we explore the contribution of oligodendrocyte progenitor cells (OPCs) to pathological features of the NF1 syndrome in mice. Both male and female littermates (4-24 weeks of age) were used equally in this study. We demonstrate that mice with global or OPC-specific Nf1 heterozygosity exhibit defects …

A Visualization And Radiation Treatment Plan Quality Scoring Method For Triage In A Population-Based Context, Alexandra O Leone, Abdallah S R Mohamed, Clifton D Fuller, Christine B Peterson, Adam S Garden, Anna Lee, Lauren L Mayo, Amy C Moreno, Jay P Reddy, Karen Hoffman, Joshua S Niedzielski, Laurence E Court, Thomas J Whitaker

Faculty, Staff and Student Publications

PURPOSE: Our purpose was to develop a clinically intuitive and easily understandable scoring method using statistical metrics to visually determine the quality of a radiation treatment plan.

METHODS AND MATERIALS: Data from 111 patients with head and neck cancer were used to establish a percentile-based scoring system for treatment plan quality evaluation on both a plan-by-plan and objective-by-objective basis. The percentile scores for each clinical objective and the overall treatment plan score were then visualized using a daisy plot. To validate our scoring method, 6 physicians were recruited to assess 60 plans, each using a scoring table consisting of a …

Safety And Activity Of Lenalidomide In Combination With Obinutuzumab In Patients With Relapsed Indolent Non-Hodgkin Lymphoma: A Single Group, Open-Label, Phase 1/2 Trial, Ashwath Gurumurthi, Collin K Chin, Lei Feng, Nathan H Fowler, Paolo Strati, Fredrick B Hagemeister, Luis E Fayad, Jason R Westin, Chizobam Obi, Janine Arafat, Ranjit Nair, Raphael E Steiner, Sattva S Neelapu, Christopher R Flowers, Loretta J Nastoupil

Faculty, Staff and Student Publications

BACKGROUND: Rituximab and lenalidomide is a preferred option for relapsed indolent B cell non-Hodgkin lymphoma. Obinutuzumab may be a superior combination partner with lenalidomide given enhanced antibody dependent cellular cytotoxicity and phagocytosis compared to rituximab. Our aim was to determine the recommended phase 2 dose, safety, and activity of lenalidomide in combination with fixed dose of obinutuzumab in relapsed and refractory indolent B cell non-Hodgkin lymphoma.

METHODS: In this single-arm, open-label, phase 1/2 trial, we enrolled patients with relapsed or refractory WHO Grade 1-3A follicular lymphoma, marginal zone lymphoma and small lymphocytic lymphoma and adequate performance status (ECOG 0-2) at …

Assessing The State Of Obesity Care: Quality, Access, Guidelines, And Standards, Lee M Kaplan, Caroline M Apovian, Jamy D Ard, David B Allison, Louis J Aronne, Rachel L Batterham, Luca Busetto, Dror Dicker, Deborah B Horn, Aaron S Kelly, Jeffrey I Mechanick, Jonathan Q Purnell, Ximena Ramos-Salas, Assessing The State Of Obesity Care Writing Group

Faculty, Staff and Student Publications

BACKGROUND: An international panel of obesity medicine experts from multiple professional organizations examined patterns of obesity care and current obesity treatment guidelines to identify areas requiring updating in response to emerging science and clinical evidence.

AIMS: The panel focused on multiple medical health and societal issues influencing effective treatment of obesity and identified several unmet needs in the definition, assessment, and care of obesity.

METHODS: The panel was held in Leesburg, Virginia in September 2019.

RESULTS: The panelists recommended addressing these unmet needs in obesity medicine through research, education, evaluation of delivery and payment of care, and updating clinical practice …

Molecular Responses In Decitabine- And Decitabine/ Venetoclax-Treated Patients With Acute Myeloid Leukemia And Myelodysplastic Syndromes, Agata Gruszczynska, Abhishek Maiti, Christopher A Miller, Sai Mukund Ramakrishnan, Daniel C Link, Geoffrey L Uy, Allegra A Petti, Kala Hayes, Courtney D Dinardo, Farhad Ravandi, Timothy J Ley, David H Spencer, Feng Gao, Marina Y Konopleva, John S Welch

Faculty, Staff and Student Publications

No abstract provided.

Using Gps-Defined Venue-Based Affiliation Networks Among Black Sexually Minoritized Men And Transgender Women To Identify Locations For Hiv Prevention Interventions, Yen-Tyng Chen, Cho-Hee Shrader, Dustin T Duncan, Abby E Rudolph, Seann D Regan, Byoungjun Kim, Jade Pagkas-Bather, Justin Knox, Kayo Fujimoto, John A Schneider

Faculty, Staff and Student Publications

Purpose: HIV biomedical intervention uptake is suboptimal among Black sexually minoritized men (SMM) and transgender women (TW). Venues where people meet and interact shape HIV-related risk and prevention behaviors. We aimed to construct GPS-defined venue-based affiliation networks and identify the unique set of venues that could maximize reach of HIV biomedical interventions among Black SMM and TW.

Methods: We used baseline survey and GPS data from 272 Black SMM and TW in the Neighborhoods and Networks (N2) Cohort Study in Chicago, Illinois (2018-2019). We mapped participants' GPS data to the nearest pre-identified SMM- and TW-friendly venue (n = 222) to …

Trends In Central Nervous System-Active Polypharmacy Among People With Multiple Sclerosis, Hayden Naizer, Joseph Wozny, Trudy Millard Krause, Ethan Huson, Leorah Freeman

Faculty, Staff and Student Publications

BACKGROUND: People with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS.

OBJECTIVE: The objective is to measure the prevalence of CNS-active polypharmacy in pwMS.

METHODS: This serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants.

RESULTS: The …

"The Hotel Of 10,000 Stars": The Impact Of Social-Structural Determinants Of Health Among Im/Migrant Shrimpers In The Gulf Of Mexico, Shannon Guillot-Wright, Lacy Davis, Linh Truong, Heide Castañeda, Anabel Rodriguez

Faculty, Staff and Student Publications

Objectives. To identify appropriate interventions to prevent injury, we conducted a qualitative study among commercial shrimp fishermen in the Gulf of Mexico.

Methods. Using qualitative and participatory research methods, including interviews, photovoice, and workplace observations in southeast Texas and the Rio Grande Valley in Texas, we examined the social‒structural dimensions that contribute to physical and psychological injury.

Results. We found that multiple layers of vulnerability and danger exist among shrimpers with interacting themes: (1) recognizing risk, (2) precarious employment, and (3) psychological distress.

Conclusions. Our results add to the growing body of knowledge that emphasizes the negative health impacts of …

Does Every Move Really Count Towards Better Health?, Andrea Ramirez Varela, Pedro C Hallal

Faculty, Staff and Student Publications

No abstract provided.

Sexual Debut In Early Adolescence And Individual, School, And Neighborhood Social Capital, Camila Cribb Fabersunne, Carly Milliren, Mark A Schuster, Marc N Elliott, Susan Tortolero Emery, Paula M Cuccaro, Susan L Davies, Tracy Richmond

Faculty, Staff and Student Publications

Purpose: Sexual debut in early adolescence is associated with poor health outcomes in adulthood. We examined the associations of social capital within families, schools, and neighborhoods with early sexual debut.

Methods: Using data from the Healthy Passages cohort, a longitudinal multilevel study of adolescents, we performed a series of cross-classified multilevel logistic regression models to examine (1) the relative contribution of schools and neighborhoods to the variance and (2) the association of markers of social cohesion/social capital in families, schools, and neighborhoods with sexual debut by 10th grade.

Results: There were 4,001 youth participants nested in 115 schools and 751 …

Enolase Inhibitors As Therapeutic Leads For Naegleria Fowleri Infection, Jillian E Milanes, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian N Dominy, Daniel C Whitehead, Steven W Millward, Madison Bolejack, Roger Shek, Logan Tillery, Isabelle Q Phan, Bart Staker, E Ashley Moseman, Xiang Zhang, Xipeng Ma, Audriy Jebet, Xinmin Yin, James C Morris

Faculty, Staff and Student Publications

Infections with the pathogenic free-living amoebae Naegleria fowleri can lead to life-threatening illnesses including catastrophic primary amoebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen. Recently, human enolase 2 (ENO2) phosphonate inhibitors have been developed as lead agents to treat glioblastoma multiforme (GBM). These compounds, which cure GBM in a rodent model, are well-tolerated in mammals because enolase 1 (ENO1) is the predominant isoform used …

Recommendations And Implementation Considerations For The Routine Collection Of Sexual Orientation And Gender Identity Data In Research And Practice, Irene Tamí-Maury, Thomas J Millett

Faculty, Staff and Student Publications

No abstract provided.

Plasma Proteins Associated With Plant-Based Diets: Results From The Atherosclerosis Risk In Communities (Aric) Study And Framingham Heart Study (Fhs), Hyunju Kim, Jingsha Chen, Brenton Prescott, Maura E Walker, Morgan E Grams, Bing Yu, Ramachandran S Vasan, James S Floyd, Nona Sotoodehnia, Nicholas L Smith, Dan E Arking, Josef Coresh, Casey M Rebholz

Faculty, Staff and Student Publications

Background & aims: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort.

Methods: ARIC Study participants at visit 3 (1993-1995) with completed food frequency questionnaire (FFQ) data and proteomics …

Past-Year Hiv Testing, Current Antiretroviral Therapy Use, And Participation In Services For People Who Inject Drugs, Itunu Sokale, Johnny Wilkerson, Paige Wermuth, Folefac Atem, Janet Burnett, Cyprian Wejnert, Salma Khuwaja, Catherine Troisi

Faculty, Staff and Student Publications

Evaluating routine HIV testing and treatment and use of services for people who inject drugs (PWID) is critical to curb the ongoing HIV epidemic. We analyzed data from the 2018 National HIV Behavioral Surveillance of PWID aged 18 years or older, recruited using respondent-driven sampling and offered anonymous HIV testing after survey. We performed bivariate and multivariable analyses with log-linked Poisson regression of the generalized linear models to examine the associations between demographics and PWID service use, past-year HIV testing, and current antiretroviral therapy (ART) use. Among 10,311 HIV-negative PWID, 56% reported past-year HIV testing, and of the 553 HIV-positive …

Analyzing Heterogeneity In Biomarker Discriminative Performance Through Partial Time-Dependent Receiver Operating Characteristic Curve Modeling, Xinyang Jiang, Wen Li, Kang Wang, Ruosha Li, Jing Ning

Faculty, Staff and Student Publications

This study investigates the heterogeneity of a biomarker's discriminative performance for predicting subsequent time-to-event outcomes across different patient subgroups. While the area under the curve (AUC) for the time-dependent receiver operating characteristic curve is commonly used to assess biomarker performance, the partial time-dependent AUC (PAUC) provides insights that are often more pertinent for population screening and diagnostic testing. To achieve this objective, we propose a regression model tailored for PAUC and develop two distinct estimation procedures for discrete and continuous covariates, employing a pseudo-partial likelihood method. Simulation studies are conducted to assess the performance of these procedures across various scenarios. …

E-Cigarette Use Reasons And Associated E-Cigarette Use Dependence Among College Students: A Longitudinal Examination, Tzung-Shiang Ou, Anne Buu, James J Yang, Hsien-Chang Lin

Faculty, Staff and Student Publications

Objective: Previous studies have established an understanding of reasons for e-cigarette use and associated e-cigarette use patterns such as use frequency, yet the critical extension to associated e-cigarette dependence outcome remains under-researched. This study used longitudinal data to examine whether the reasons for e-cigarette use predict a higher/lower level of e-cigarette dependence.

Methods: This study recruited college students who were current e-cigarette users from Fall 2019 to Fall 2020 (four semesters) at three public universities in the Midwest and South of the U.S. Those who participated for at least two semesters were included (N = 366). Data were collected using …

Mapping The Single-Cell Differentiation Landscape Of Osteosarcoma, Danh D Truong, Corey Weistuch, Kevin A Murgas, Prasad Admane, Bridgette L King, Jes Chauviere Lee, Salah-E Lamhamedi-Cherradi, Jyothishmathi Swaminathan, Najat C Daw, Nancy Gordon, Vidya Gopalakrishnan, Richard G Gorlick, Neeta Somaiah, Joseph O Deasy, Antonios G Mikos, Allen Tannenbaum, Joseph Ludwig

Faculty, Staff and Student Publications

Purpose: The genetic intratumoral heterogeneity observed in human osteosarcomas poses challenges for drug development and the study of cell fate, plasticity, and differentiation, which are processes linked to tumor grade, cell metastasis, and survival.

Experimental design: To pinpoint errors in osteosarcoma differentiation, we transcriptionally profiled 31,527 cells from a tissue-engineered model that directs mesenchymal stem cells toward adipogenic and osteoblastic fates. Incorporating preexisting chondrocyte data, we applied trajectory analysis and non-negative matrix factorization to generate the first human mesenchymal differentiation atlas.

Results: This "roadmap" served as a reference to delineate the cellular composition of morphologically complex osteosarcoma tumors and quantify …

A 3d Dual-Echo Spiral Sequence For Simultaneous Dynamic Susceptibility Contrast And Dynamic Contrast-Enhanced Mri With Single Bolus Injection, Zhiqiang Li, Dinghui Wang, Melvyn B Ooi, Poonam Choudhary, Sudarshan Ragunathan, John P Karis, James G Pipe, C Chad Quarles, Ashley M Stokes

Faculty, Staff and Student Publications

Purpose: Perfusion MRI reveals important tumor physiological and pathophysiologic information, making it a critical component in managing brain tumor patients. This study aimed to develop a dual-echo 3D spiral technique with a single-bolus scheme to simultaneously acquire both dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) data and overcome the limitations of current EPI-based techniques.

Methods: A 3D spiral-based technique with dual-echo acquisition was implemented and optimized on a 3T MRI scanner with a spiral staircase trajectory and through-plane SENSE acceleration for improved speed and image quality, in-plane variable-density undersampling combined with a sliding-window acquisition and reconstruction approach for increased …

Sleep Disturbance As A Precursor To Anxiety, Depression, And Ptsd Among Rural Kenyans: A Cross-Lagged Panel Analysis From A Rural Kenyan Interventional Cohort, Michael L Goodman, Miryoung Lee, Andrew Springer, Vanessa Schick, Elizabeth Vaughan, Christine Markham, Stanley Gitari, Fridah Mukiri

Faculty, Staff and Student Publications

Sleep quality is essential to biopsychosocial functioning, yet there remains limited longitudinal research on sleep and mental or social well-being within low- or middle-income countries. This study utilised longitudinal cohort data from a community-based empowerment programme in Meru County, Kenya to assess cross-lagged correlations between sleep disturbance, social support, symptoms of depression, anxiety, and posttraumatic stress. Participants (n = 373; 92% women; age range 18-86 years) who reported more sleep disturbance at T1 reported significantly more symptoms of depression, anxiety, and PTSD, and significantly less social support at T2 (average 11 weeks later), controlling for all within-time correlations across measures, …

Clinicians’ Perceptions Of Care Partner Involvement In Health Priorities Identification For People Living With Dementia, Joan K Monin, Emily Mroz, Kalisha Bonds Johnson, Rafael Samper-Ternent, Thi Vu, Mary Tinetti

Faculty, Staff and Student Publications

No abstract provided.

In Utero Exposure To Antihistamines And Risk Of Hepatocellular Carcinoma In A Multigenerational Cohort, Caitlin C Murphy, Karim Seif El Dahan, Amit G Singal, Piera M Cirillo, Nickilou Y Krigbaum, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Growing evidence suggests that liver disease originates in early life. Antihistamines cross the placenta and are frequently prescribed to pregnant women to treat nausea and vomiting, as well as allergy and asthma symptoms. Exposure to antihistamines in utero may impact the developing liver by reprogramming or inducing epigenetic changes in fetal hepatocytes.

METHODS: We examined in utero exposure to antihistamines and the risk of HCC in the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in the East Bay, CA, between 1959 and 1966 (n=14,507 mothers and 18,751 liveborn offspring). We reviewed mothers' medical records …

Sequential Inhibition Of Parp And Bet As A Rational Therapeutic Strategy For Glioblastoma, Xin Peng, Xin Huang, Shaolu Zhang, Naixin Zhang, Shengfan Huang, Yingying Wang, Zhenxing Zhong, Shan Zhu, Haiwang Gao, Zixiang Yu, Xiaotong Yan, Zhennan Tao, Yuxiang Dai, Zhe Zhang, Xi Chen, Feng Wang, Francois X Claret, Moshe Elkabets, Ning Ji, Yuxu Zhong, Dexin Kong

Faculty, Staff and Student Publications

PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient-derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can …

Disparities In Exposure To Tobacco On Television Or Streaming Platforms, Henry K Onyeaka, Onyema G Chido-Amajuoyi, Itunu Sokale, Kobi V Ajayi, A Eden Evins, Hermioni L Amonoo, Sanjay Shete

Faculty, Staff and Student Publications

Importance: With the rise in popularity of streaming platforms concerns about exposure to tobacco advertising and promotion have emerged. While tobacco marketing and promotion through traditional television (TV) media channels has been extensively studied, less is known about exposure to tobacco through TV or streaming platforms and its associated factors.

Objective: To examine the prevalence and factors associated with exposure to tobacco products advertised, marketed, or promoted on TV or streaming platforms among US adults.

Design, setting, and participants: This cross-sectional study used data from the National Cancer Institute's Health Information National Trends Survey (HINTS 6), conducted from March 7 …

Smyd5 Methylation Of Rpl40 Links Ribosomal Output To Gastric Cancer, Juhyung Park, Jibo Wu, Krzysztof J Szkop, Jinho Jeong, Predrag Jovanovic, Dylan Husmann, Natasha M Flores, Joel W Francis, Ying-Jiun C Chen, Ana Morales Benitez, Emily Zahn, Shumei Song, Jaffer A Ajani, Linghua Wang, Kamini Singh, Ola Larsson, Benjamin A Garcia, Ivan Topisirovic, Or Gozani, Pawel K Mazur

Faculty, Staff and Student Publications

Dysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis1,2. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 (rpL40) at lysine 22 (rpL40K22me3) by the lysine methyltransferase SMYD5 regulates mRNA translation output to promote malignant progression of gastric adenocarcinoma (GAC) with lethal peritoneal ascites. A biochemical-proteomics strategy identifies the monoubiquitin fusion protein partner rpL40 (ref. 3) as the principal physiological substrate of SMYD5 across diverse samples. Inhibiting the SMYD5-rpL40K22me3 axis in GAC cell lines reprogrammes …

Benchmarking Lung Cancer Screening Programmes With Adaptive Screening Frequency Against The Optimal Screening Schedules Derived From The Engage Framework: A Comparative Microsimulation Study, Mehdi Hemmati, Sayaka Ishizawa, Rafael Meza, Edwin Ostrin, Samir M Hanash, Mara Antonoff, Andrew J Schaefer, Martin C Tammemägi, Iakovos Toumazis

Faculty, Staff and Student Publications

Background: Lung cancer screening recommendations employ annual frequency for eligible individuals, despite evidence that it may not be universally optimal. The impact of imposing a structure on the screening frequency remains unknown. The ENGAGE framework, a validated framework that offers fully dynamic, analytically optimal, personalised lung cancer screening recommendations, could be used to assess the impact of screening structure on the effectiveness and efficiency of lung cancer screening.

Methods: In this comparative microsimulation study, we benchmarked alternative clinically relevant structured lung cancer screening programmes employing a fixed (annual or biennial) or adaptive (start with annual/biennial screening and then switch to …

Accelerated Tumor Progression After Covid-19 Infection In Patients With Glioblastoma: A Retrospective Case-Control Study, Timothy A Gregory, Stephanie R Knight, Ashley E Aaroe, Kaitlin N Highsmith, Zachary C Janatpour, Barbara J O'Brien, Nazanin K Majd, Monica E Loghin, Chirag B Patel, Shiao-Pei Weathers, Vinay K Puduvalli, Carlos Kamiya-Matsuoka

Faculty, Staff and Student Publications

Background: We observed rapid tumor progression following COVID-19 infection among patients with glioblastoma and sought to systematically characterize their disease course in a retrospective case-control study.

Methods: Using an institutional database, we retrospectively identified a series of COVID-19-positive glioblastoma cases and matched them by age and sex 1:2 to glioblastoma controls who had a negative COVID-19 test during their disease course. Demographic and clinical data were analyzed. Hyperprogression was defined using modified response evaluation criteria in solid tumors criteria. Time to progression and overall survival were estimated using the Kaplan-Meier method.

Results: Thirty-two glioblastoma cases with positive COVID-19 testing were …