Biomedical Informatics Commons^™

Successful Management Of Chromoblastomycosis Utilizing Conventional Antifungal Agents And Imiquimod Therapy, Jinjin Zheng, Shougang Liu, Zhenmou Xie, Yangxia Chen, Liyan Xi, Hongfang Liu, Yinghui Liu

Faculty, Staff and Student Publications

Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host's immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal …

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results Of A Multicenter, Randomized, Controlled Trial, Wei Dai, Yaqin Wang, Jia Liao, Xing Wei, Zhen Dai, Wei Xu, Yangjun Liu, Xin Shelley Wang, Cecilia Pompili, Hongfan Yu, Yang Pu, Yuqian Zhao, Bangrong Cao, Qifeng Wang, Wenhong Feng, Yuanqiang Zhang, Fang Liu, Yuanle Deng, Jin Zhou, Juan Li, Shaohua Xie, Run Xiang, Xiang Wang, Bo Tian, Xiaozun Yang, Bin Hu, Xiaoqin Liu, Tianpeng Xie, Xiaojun Yang, Xiang Zhuang, Guibin Qiao, Qiang Li, Qiuling Shi

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where …

Implementation Of A Health Information Technology Safety Classification System In The Veterans Health Administration’S Informatics Patient Safety Office, Danielle Kato, Joe Lucas, Dean F Sittig

Faculty, Staff and Student Publications

Objective: Implement the 5-type health information technology (HIT) patient safety concern classification system for HIT patient safety issues reported to the Veterans Health Administration's Informatics Patient Safety Office.

Materials and methods: A team of informatics safety analysts retrospectively classified 1 year of HIT patient safety issues by type of HIT patient safety concern using consensus discussions. The processes established during retrospective classification were then applied to incoming HIT safety issues moving forward.

Results: Of 140 issues retrospectively reviewed, 124 met the classification criteria. The majority were HIT failures (eg, software defects) (33.1%) or configuration and implementation problems (29.8%). Unmet user …

Understanding Enterprise Data Warehouses To Support Clinical And Translational Research: Impact, Sustainability, Demand Management, And Accessibility, Thomas R Campion, Catherine K Craven, David A Dorr, Elmer V Bernstam, Boyd M Knosp

Faculty, Staff and Student Publications

OBJECTIVES: Healthcare organizations, including Clinical and Translational Science Awards (CTSA) hubs funded by the National Institutes of Health, seek to enable secondary use of electronic health record (EHR) data through an enterprise data warehouse for research (EDW4R), but optimal approaches are unknown. In this qualitative study, our goal was to understand EDW4R impact, sustainability, demand management, and accessibility.

MATERIALS AND METHODS: We engaged a convenience sample of informatics leaders from CTSA hubs (n = 21) for semi-structured interviews and completed a directed content analysis of interview transcripts.

RESULTS: EDW4R have created institutional capacity for single- and multi-center studies, democratized access …

Neuroecological Links Of The Exposome And One Health, Agustin Ibanez, Lucia Melloni, Paweł Świeboda, William Hynes, Burcin Ikiz, Rym Ayadi, Massamba Thioye, Consuelo Walss-Bass, Bahar Güntekin, Jyoti Mishra, Mohamed Salama, Sarah Dunlop, Claudia Duran-Aniotz, Harris A Eyre

Faculty, Staff and Student Publications

This NeuroView assesses the interplay among exposome, One Health, and brain capital in health and disease. Physical and social exposomes affect brain health, and green brain skills are required for environmental health strategies. Ibanez et al. address current gaps and strategies needed in research, policy, and technology, offering a road map for stakeholders.

Challenges And Opportunities In Cancer Immunotherapy: A Society For Immunotherapy Of Cancer (Sitc) Strategic Vision, Leisha A Emens, Pedro J Romero, Ana Carrizosa Anderson, Tullia C Bruno, Christian M Capitini, Deborah Collyar, James L Gulley, Patrick Hwu, Avery D Posey, Ann W Silk, Jennifer A Wargo

Faculty, Staff and Student Publications

Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor …

L-Citrulline Supplementation Improves Arterial Blood Flow And Muscle Oxygenation During Handgrip Exercise In Hypertensive Postmenopausal Women, Yejin Kang, Katherine N Dillon, Mauricio A Martinez, Arun Maharaj, Stephen M Fischer, Arturo Figueroa

Faculty, Staff and Student Publications

Endothelial dysfunction decreases exercise limb blood flow (BF) and muscle oxygenation. Acute L-Citrulline supplementation (CIT) improves muscle tissue oxygen saturation index (TSI) and deoxygenated hemoglobin (HHb) during exercise. Although CIT improves endothelial function (flow-mediated dilation [FMD]) in hypertensive women, the impact of CIT on exercise BF and muscle oxygenation (TSI) and extraction (HHb) are unknown. We examined the effects of CIT (10 g/day) and a placebo for 4 weeks on blood pressure (BP), arterial vasodilation (FMD, BF, and vascular conductance [VC]), and forearm muscle oxygenation (TSI and HHb) at rest and during exercise in 22 hypertensive postmenopausal women. Compared to …

Targeting Mcl1-Driven Anti-Apoptotic Pathways Overcomes Blast Progression After Hypomethylating Agent Failure In Chronic Myelomonocytic Leukemia, Guillermo Montalban-Bravo, Natthakan Thongon, Juan Jose Rodriguez-Sevilla, Feiyang Ma, Irene Ganan-Gomez, Hui Yang, Yi June Kim, Vera Adema, Bethany Wildeman, Tomoyuki Tanaka, Faezeh Darbaniyan, Gheath Al-Atrash, Karen Dwyer, Sanam Loghavi, Rashmi Kanagal-Shamanna, Xingzhi Song, Jianhua Zhang, Koichi Takahashi, Hagop Kantarjian, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

RAS pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk of resistance to and progression after hypomethylating agent (HMA) therapy, the current standard of care for the disease. Here, using single-cell, multi-omics technologies, we seek to dissect the biological mechanisms underlying the initiation and progression of RAS pathway-mutated CMML. We identify that RAS pathway mutations induce transcriptional reprogramming of hematopoietic stem and progenitor cells (HSPCs) and downstream monocytic populations in response to cell-intrinsic and -extrinsic inflammatory signaling that also impair the functions of immune cells. HSPCs expand at disease …

Phase 2 Study Of Neoadjuvant Enzalutamide And Paclitaxel For Luminal Androgen Receptor-Enriched Tnbc: Trial Results And Insights Into “Arness”, Bora Lim, Sahil Seth, Clinton Yam, Lei Huo, Takeo Fujii, Jangsoon Lee, Roland Bassett, Sara Nasser, Lisa Ravenberg, Jason White, Alyson Clayborn, Gil Guerra, Jennifer K Litton, Senthil Damodaran, Rachel Layman, Vicente Valero, Debasish Tripathy, Michael Lewis, Lacey E Dobrolecki, Jonathan Lei, Rosalind Candelaria, Banu Arun, Gaiane Rauch, Li Zhao, Jianhua Zhang, Qingqing Ding, W Fraser Symmans, Jeffrey T Chang, Alastair M Thompson, Stacy L Moulder, Naoto T Ueno

Faculty, Staff and Student Publications

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a …

Sod1 Is A Synthetic-Lethal Target In Ppm1d-Mutant Leukemia Cells, Linda Zhang, Joanne I Hsu, Etienne D Braekeleer, Chun-Wei Chen, Tajhal D Patel, Alejandra G Martell, Anna G Guzman, Katharina Wohlan, Sarah M Waldvogel, Hidetaka Uryu, Ayala Tovy, Elsa Callen, Rebecca L Murdaugh, Rosemary Richard, Sandra Jansen, Lisenka Vissers, Bert B A De Vries, Andre Nussenzweig, Shixia Huang, Cristian Coarfa, Jamie Anastas, Koichi Takahashi, George Vassiliou, Margaret A Goodell

Faculty, Staff and Student Publications

The DNA damage response is critical for maintaining genome integrity and is commonly disrupted in the development of cancer. PPM1D (protein phosphatase Mg2+/Mn2+-dependent 1D) is a master negative regulator of the response; gain-of-function mutations and amplifications of PPM1D are found across several human cancers making it a relevant pharmacological target. Here, we used CRISPR/Cas9 screening to identify synthetic-lethal dependencies of PPM1D, uncovering superoxide dismutase-1 (SOD1) as a potential target for PPM1D-mutant cells. We revealed a dysregulated redox landscape characterized by elevated levels of reactive oxygen species and a compromised response to oxidative stress in PPM1D-mutant cells. Altogether, our …

Repeat Controlled Human Plasmodium Falciparum Infections Delay Bloodstream Patency And Reduce Symptoms, Patricia Ferrer, Andrea A Berry, Allison N Bucsan, Surendra K Prajapati, Karthik Krishnan, Michelle C Barbeau, David M Rickert, Sandra Mendoza Guerrero, Miho Usui, Yonas Abebe, Asha Patil, Sumana Chakravarty, Peter F Billingsley, Faith Pa'ahana-Brown, Kathy Strauss, Biraj Shrestha, Effie Nomicos, Gregory A Deye, B Kim Lee Sim, Stephen L Hoffman, Kim C Williamson, Kirsten E Lyke

Faculty, Staff and Student Publications

Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody …

Real World Predictors Of Response And 24-Month Survival In High-Grade Tp53-Mutated Myeloid Neoplasms, Amandeep Kaur, Alexandra E Rojek, Emily Symes, Mariam T Nawas, Anand A Patel, Jay L Patel, Payal Sojitra, Barina Aqil, Madina Sukhanova, Megan E Mcnerney, Leo P Wu, Aibek Akmatbekov, Jeremy Segal, Melissa Y Tjota, Sandeep Gurbuxani, Jason X Cheng, Su-Yeon Yeon, Harini V Ravisankar, Carrie Fitzpatrick, Angela Lager, Michael W Drazer, Caner Saygin, Pankhuri Wanjari, Panagiotis Katsonis, Olivier Lichtarge, Jane E Churpek, Sharmila B Ghosh, Ami B Patel, Madhu P Menon, Daniel A Arber, Peng Wang, Girish Venkataraman

Faculty, Staff and Students Publications

Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 …

Diverse Mentoring Connections Across Institutional Boundaries In The Biomedical Sciences: Innovative Graph Database Analysis, Toufeeq Ahmed Syed, Erika L Thompson, Zainab Latif, Jay Johnson, Damaris Javier, Katie Stinson, Gabrielle Saleh, Jamboor K Vishwanatha

Faculty, Staff and Student Publications

BACKGROUND: With an overarching goal of increasing diversity and inclusion in biomedical sciences, the National Research Mentoring Network (NRMN) developed a web-based national mentoring platform (MyNRMN) that seeks to connect mentors and mentees to support the persistence of underrepresented minorities in the biomedical sciences. As of May 15, 2024, the MyNRMN platform, which provides mentoring, networking, and professional development tools, has facilitated more than 12,100 unique mentoring connections between faculty, students, and researchers in the biomedical domain.

OBJECTIVE: This study aimed to examine the large-scale mentoring connections facilitated by our web-based platform between students (mentees) and faculty (mentors) across institutional …

Sting Agonist 8803 Reprograms The Immune Microenvironment And Increases Survival In Preclinical Models Of Glioblastoma, Hinda Najem, Spencer T Lea, Shashwat Tripathi, Lisa Hurley, Chao-Hsien Chen, Ivana William, Moloud Sooreshjani, Michelle Bowie, Genevieve Hartley, Corey Dussold, Sebastian Pacheco, Crismita Dmello, Catalina Lee-Chang, Kathleen Mccortney, Alicia Steffens, Jordain Walshon, Martina Ott, Jun Wei, Anantha Marisetty, Irina Balyasnikova, Roger Stupp, Rimas V Lukas, Jian Hu, Charles David James, Craig M Horbinski, Maciej S Lesniak, David M Ashley, Waldemar Priebe, Leonidas C Platanias, Michael A Curran, Amy B Heimberger

Faculty, Staff and Student Publications

STING agonists can reprogram the tumor microenvironment to induce immunological clearance within the central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and the Ivy Glioblastoma Atlas, STING expression was found in myeloid populations and in the perivascular space. The STING agonist 8803 increased median survival in multiple preclinical models of glioblastoma, including QPP8, an immune checkpoint blockade-resistant model, where 100% of mice were cured. Ex vivo flow cytometry profiling during the therapeutic window demonstrated increases in myeloid tumor trafficking and activation, alongside enhancement of CD8+ T cell and NK effector responses. Treatment with 8803 reprogrammed microglia to express costimulatory CD80/CD86 …

Prevalence And Relevant Factors Of Nocturia And Its Impact On Sleep Quality In Chinese University Students, Yakai Liu, Zhenwei Zhang, Huijie Hu, Xiangfei He, Pengchao Xu, Qifeng Dou, Cuiping Song, Huiqing Zhang, Israel Franco, Konstantinos Kamperis, Søren Rittig, Jianguo Wen

Faculty, Staff and Student Publications

The purpose of this study was to investigate the prevalence and relevant factors of nocturia and its impact on sleep quality in university students in Mainland China. A large-scale survey was conducted on 14,000 university students from 3 universities in Henan province, China by using an anonymous questionnaire. The questionnaire collected the information from the past six months. The relationships between the prevalence of nocturia and its relevant factors were evaluated. A total of 13,874 questionnaires were collected and 13,104 qualified for statistical analysis. A total of 659 students suffered from clinically relevant nocturia (CRN) (4.56% in male and 5.34% …

Deepcg: A Cell Graph Model For Predicting Prognosis In Lung Adenocarcinoma, Baoyi Zhang, Chenyang Li, Jia Wu, Jianjun Zhang, Chao Cheng

Faculty, Staff and Student Publications

Lung cancer is the first leading cause of cancer-related death in the United States, with lung adenocarcinoma as the major subtype accounting for 40% of all cases. To improve patient survival, image-based prognostic models were developed due to the ready availability of pathological images at diagnosis. However, the application of these models is hampered by two main challenges: the lack of publicly available image datasets with high-quality survival information and the poor interpretability of conventional convolutional neural network models. Here, we integrated matched transcriptomic and H&E staining data from TCGA (The Cancer Genome Atlas) to develop an image-based prognostic model, …

Variance-Components Tests For Genetic Association With Multiple Interval-Censored Outcomes, Jaihee Choi, Zhichao Xu, Ryan Sun

Faculty, Staff and Student Publications

Massive genetic compendiums such as the UK Biobank have become an invaluable resource for identifying genetic variants that are associated with complex diseases. Due to the difficulties of massive data collection, a common practice of these compendiums is to collect interval-censored data. One challenge in analyzing such data is the lack of methodology available for genetic association studies with interval-censored data. Genetic effects are difficult to detect because of their rare and weak nature, and often the time-to-event outcomes are transformed to binary phenotypes for access to more powerful signal detection approaches. However transforming the data to binary outcomes can …

Developmental Milestones And Daily Living Skills In Individuals With Angelman Syndrome, Anjali Sadhwani, Sonya Powers, Anne Wheeler, Hillary Miller, Sarah Nelson Potter, Sarika U Peters, Carlos A Bacino, Steven A Skinner, Logan K Wink, Craig A Erickson, Lynne M Bird, Wen-Hann Tan

Faculty, Staff and Students Publications

BACKGROUND: Angelman syndrome (AS) is a neurodevelopmental disorder associated with severe global developmental delay. However, the ages at which different developmental skills are achieved in these individuals remain unclear. We seek to determine the probability and the age of acquisition of specific developmental milestones and daily living skills in individuals with AS across the different molecular subtypes, viz. class I deletion, class II deletion, uniparental disomy, imprinting defect, and UBE3A variants.

METHODS: Caregivers participating in a longitudinal multicenter Angelman Syndrome Natural History Study completed a questionnaire regarding the age at which their children achieved specific developmental milestones and daily living …

Persistent Gram-Negative Bloodstream Infection Increases The Risk Of Recurrent Bloodstream Infection With The Same Species, Paa Kwesi Ankrah, Andrew Bock, Felicia Ruffin, Blake M Hanson, Cesar A Arias, Stacey A Maskarinec, Joshua Parsons, Vance G Fowler, Joshua T Thaden

Faculty, Staff and Student Publications

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P = .04). Persistent GN-BSI may be a marker of complicated infection.

Immunotherapy In Locally Advanced Cervical Cancer: Integrating Keynote-A18 Into Management Strategies, Jeffrey A How, Amir A Jazaeri

Faculty, Staff and Student Publications

In locally advanced cervical cancer (LACC), the benefit of PD-1 blockade was unknown. In KEYNOTE-A18, Lorusso et al.1 compared the efficacy and safety of adding pembrolizumab to chemoradiation in LACC and demonstrated favorable outcomes. Given multiple approved indications of pembrolizumab in cervical cancer, strategies for optimal integration into management will be needed to maximize overall survival.

Supporting Ontario Public Health Units To Address Adverse Childhood Experiences In Pandemic Recovery Planning: A Priority-Setting Exercise, Kimberly B Harding, Erica Di Ruggiero, Erick Gonzalez, Amanda Hicks, Daniel W Harrington, Sarah Carsley

Faculty, Staff and Student Publications

BACKGROUND: Adverse childhood experiences (ACEs) are potentially traumatic exposures experienced during childhood, for example, neglect. There is growing evidence that the coronavirus disease 2019 (COVID-19) pandemic and related socioeconomic conditions contributed to an increased risk of ACEs. As public health programs/services are re-evaluated and restored following the state of emergency, it is important to plan using an ACEs-informed lens. The aim of this study was to identify and prioritize initiatives or activities that Public Health Ontario (PHO) could undertake to support Ontario public health units' work towards ACEs-informed pandemic recovery plans.

METHODS: The Child Health and Nutrition Research Initiative method …

Ikzf1 And Ubr4 Gene Variants Drive Autoimmunity And Th2 Polarization In Igg4-Related Disease, Qingxiang Liu, Yanyan Zheng, Ines Sturmlechner, Abhinav Jain, Maryam Own, Qiankun Yang, Huimin Zhang, Filippo Pinto E Vairo, Karen Cerosaletti, Jane H Buckner, Kenneth J Warrington, Matthew J Koster, Cornelia M Weyand, Jörg J Goronzy

Faculty, Staff and Student Publications

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, …

Durable Objective Response To Lurbinectedin In Small Cell Bladder Cancer With Tp53 Mutation: A Molecular-Directed Strategy, Mohammad Jad Moussa, Jaanki Khandelwal, Nathaniel R Wilson, Sagar A Naik, Vivek Subbiah, Matthew T Campbell, Pavlos Msaouel, Parminder Singh, Omar Alhalabi

Faculty, Staff and Student Publications

Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following …

Small Rna Signatures Of Acute Ischemic Stroke In L1cam Positive Extracellular Vesicles, Bharti Manwani, Nivetha Brathaban, Abiya Baqai, Yashee Munshi, Hilda W Ahnstedt, Mengqi Zhang, Kajsa Arkelius, Ted Llera, Edilberto Amorim, Fanny M Elahi, Neel S Singhal

Faculty, Staff and Student Publications

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms. Interestingly, small RNA sequencing of plasma L1EVs from patients with stroke and control patients (n = 28) identified micro(mi)RNAs known to be enriched in the brain. Weighted gene co-expression network analysis (WGCNA) revealed small RNA …

Slow Proliferation Of Bap1-Deficient Uveal Melanoma Cells Is Associated With Reduced S6 Signaling And Resistance To Nutrient Stress, Vivian Chua, Melisa Lopez-Anton, Mizue Terai, Ryota Tanaka, Usman Baqai, Timothy J Purwin, Jelan I Haj, Francis J Waltrich, Isabella Trachtenberg, Kristine Luo, Rohith Tudi, Angela Jeon, Anna Han, Inna Chervoneva, Michael A Davies, Julio A Aguirre-Ghiso, Takami Sato, Andrew E Aplin

Faculty, Staff and Student Publications

Uveal melanoma (UM) is the deadliest form of eye cancer in adults. Inactivating mutations and/or loss of expression of the gene encoding BRCA1-associated protein 1 (BAP1) in UM tumors are associated with an increased risk of metastasis. To investigate the mechanisms underlying this risk, we explored the functional consequences of BAP1 deficiency. UM cell lines expressing mutant BAP1 grew more slowly than those expressing wild-type BAP1 in culture and in vivo. The ability of BAP1 reconstitution to restore cell proliferation in BAP1-deficient cells required its deubiquitylase activity. Proteomic analysis showed that BAP1-deficient cells had decreased phosphorylation of ribosomal S6 and …

Collaborative Modeling To Compare Different Breast Cancer Screening Strategies: A Decision Analysis For The Us Preventive Services Task Force, Amy Trentham-Dietz, Christina Hunter Chapman, Jinani Jayasekera, Kathryn P Lowry, Brandy M Heckman-Stoddard, John M Hampton, Jennifer L Caswell-Jin, Ronald E Gangnon, Ying Lu, Hui Huang, Sarah Stein, Liyang Sun, Eugenio J Gil Quessep, Yuanliang Yang, Yifan Lu, Juhee Song, Diego F Muñoz, Yisheng Li, Allison W Kurian, Karla Kerlikowske, Ellen S O'Meara, Brian L Sprague, Anna N A Tosteson, Eric J Feuer, Donald Berry, Sylvia K Plevritis, Xuelin Huang, Harry J De Koning, Nicolien T Van Ravesteyn, Sandra J Lee, Oguzhan Alagoz, Clyde B Schechter, Natasha K Stout, Diana L Miglioretti, Jeanne S Mandelblatt

Faculty, Staff and Student Publications

IMPORTANCE: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known.

OBJECTIVE: To estimate outcomes of various mammography screening strategies.

DESIGN, SETTING, AND POPULATION: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses.

EXPOSURES: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or …

Tmprss2 Is A Tumor Suppressor And Its Downregulation Promotes Antitumor Immunity And Immunotherapy Response In Lung Adenocarcinoma, Zhixian Liu, Qiqi Lu, Zhilan Zhang, Qiushi Feng, Xiaosheng Wang

Faculty, Staff and Student Publications

Background: TMPRSS2, a key molecule for SARS-CoV-2 invading human host cells, has an association with cancer. However, its association with lung cancer remains insufficiently unexplored.

Methods: In five bulk transcriptomics datasets, one single-cell RNA sequencing (scRNA-seq) dataset and one proteomics dataset for lung adenocarcinoma (LUAD), we explored associations between TMPRSS2 expression and immune signatures, tumor progression phenotypes, genomic features, and clinical prognosis in LUAD by the bioinformatics approach. Furthermore, we performed experimental validation of the bioinformatics findings.

Results: TMPRSS2 expression levels correlated negatively with the enrichment levels of both immune-stimulatory and immune-inhibitory signatures, while they correlated positively with the ratios …

Role Of Ethanolamine Utilization And Bacterial Microcompartment Formation In Listeria Monocytogenes Intracellular Infection, Ayan Chatterjee, Karan Gautam Kaval, Danielle A Garsin

Faculty, Staff and Student Publications

Ethanolamine (EA) affects the colonization and pathogenicity of certain human bacterial pathogens in the gastrointestinal tract. However, EA can also affect the intracellular survival and replication of host cell invasive bacteria such as Listeria monocytogenes (LMO) and Salmonella enterica serovar Typhimurium (S. Typhimurium). The EA utilization (eut) genes can be categorized as regulatory, enzymatic, or structural, and previous work in LMO showed that loss of genes encoding functions for the enzymatic breakdown of EA inhibited LMO intracellular replication. In this work, we sought to further characterize the role of EA utilization during LMO infection of host …

Therapy-Related Chronic Myelomonocytic Leukemia Does Not Have The High-Risk Features Of A Therapy-Related Neoplasm, Alex Bataller, Georgina Gener-Ricos, Emmanuel Almanza-Huante, Kelly S Chien, Samuel Urrutia, Alexandre Bazinet, Juan Jose Rodriguez-Sevilla, Danielle Hammond, Koji Sasaki, Koichi Takahashi, Courtney D Dinardo, Farhad Ravandi, Gautam Borthakur, Tapan M Kadia, Rashmi Kanagal-Shamanna, Hagop M Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo

Faculty, Staff and Student Publications

Therapy-related myeloid neoplasms (t-MNs) arise after exposure to cytotoxic therapies and are associated with high-risk genetic features and poor outcomes. We analyzed a cohort of patients with therapy-related chronic myelomonocytic leukemia (tCMML; n = 71) and compared its features to that of de novo CMML (dnCMML; n = 461). Median time from cytotoxic therapy to tCMML diagnosis was 6.5 years. Compared with dnCMML, chromosome-7 abnormalities (4% vs 13%; P = .005) but not complex karyotype (3% vs 7%; P = .15), were more frequent in tCMML. tCMML was characterized by higher TP53 mutation frequency (4% vs 12%; P = .04) …

Determining The Optimal Dosage Of Dexmedetomidine For Smooth Emergence In Older Patients Undergoing Spinal Surgery: A Study Of 44 Cases, Hyoeun Ahn, Yun Jeong Chae, Gyu Bin Choi, Min Gyu Lee, Ji Young Yoo

Faculty, Staff and Student Publications

BACKGROUND Emergence agitation, or delirium, occurs during early recovery from general anesthesia and involves disorientation, excitation, and uncontrolled physical movements. Dexmedetomidine is an alpha agonist that has sedative, anxiolytic, analgesic, and sympatholytic activities and is used as a continuous infusion to prevent emergence agitation. This study aimed to evaluate patients aged 65 years and older undergoing general anesthesia to determine the 90% effective dose (ED90) of dexmedetomidine continuous intraoperative infusion to prevent emergence agitation. MATERIAL AND METHODS We enrolled 44 patients aged 65 years and older undergoing spinal surgery under general anesthesia. Dexmedetomidine administration commenced 30 minutes before surgery completion, …