Medicine and Health Sciences Commons^™

Multicenter, Phase 1 Study Of Etavopivat (Ft-4202) Treatment For Up To 12 Weeks In Patients With Sickle Cell Disease, Santosh L Saraf, Robert Hagar, Modupe Idowu, Ifeyinwa Osunkwo, Kimberly Cruz, Frans A Kuypers, R Clark Brown, James Geib, Maria Ribadeneira, Patricia Schroeder, Eric Wu, Sanjeev Forsyth, Patrick F Kelly, Theodosia A Kalfa, Marilyn J Telen

Faculty, Staff and Student Publications

Etavopivat is an investigational, once daily, oral, selective erythrocyte pyruvate kinase (PKR) activator. A multicenter, randomized, placebo-controlled, double-blind, 3-part, phase 1 study was conducted to characterize the safety and clinical activity of etavopivat. Thirty-six patients with sickle cell disease (SCD) were enrolled into 4 cohorts: 1 single-dose, 2 multiple ascending doses, and 1 open-label (OL). In the OL cohort, 15 patients (median age 33.0 years [range, 17-55]) received 400 mg etavopivat once daily for 12 weeks; 14 patients completed treatment. Consistent with the mechanism of PKR activation, increases in adenosine triphosphate and decreases in 2,3-diphosphoglycerate were observed and sustained over …

Neutralization Escape, Infectivity, And Membrane Fusion Of Jn1-Derived Sars-Cov-2 Slip, Flirt, And Kp2 Variants, Pei Li, Julia N Faraone, Cheng Chih Hsu, Michelle Chamblee, Yi-Min Zheng, Claire Carlin, Joseph S Bednash, Jeffrey C Horowitz, Rama K Mallampalli, Linda J Saif, Eugene M Oltz, Daniel Jones, Jianrong Li, Richard J Gumina, Kai Xu, Shan-Lu Liu

Faculty, Staff and Student Publications

We investigate JN.1-derived subvariants SLip, FLiRT, and KP.2 for neutralization by antibodies in vaccinated individuals, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients, or class III monoclonal antibody S309. Compared to JN.1, SLip, KP.2, and especially FLiRT exhibit increased resistance to bivalent-vaccinated and BA.2.86/JN.1-wave convalescent human sera. XBB.1.5 monovalent-vaccinated hamster sera robustly neutralize FLiRT and KP.2 but have reduced efficiency for SLip. All subvariants are resistant to S309 and show decreased infectivity, cell-cell fusion, and spike processing relative to JN.1. Modeling reveals that L455S and F456L in SLip reduce spike binding for ACE2, while R346T in FLiRT and KP.2 strengthens …

Pipe Dream: Remyelination Therapy For Multiple Sclerosis, Benjamin Deneen

Faculty, Staff and Students Publications

No abstract provided.

Trim44, A Novel Prognostic Marker, Supports The Survival Of Proteasome-Resistant Multiple Myeloma Cells, Trung Vu, Yuqin Wang, Annaliese Fowler, Anton Simieou, Nami Mccarty

Faculty, Staff and Student Publications

TRIM44, a tripartite motif (TRIM) family member, is pivotal in linking the ubiquitin-proteasome system (UPS) to autophagy in multiple myeloma (MM). However, its prognostic impact and therapeutic potential remain underexplored. Here, we report that TRIM44 overexpression is associated with poor prognosis in a Multiple Myeloma Research Foundation (MMRF) cohort of 858 patients, persisting across primary and recurrent MM cases. TRIM44 expression notably increases in advanced MM stages, indicating its potential role in disease progression. Single-cell RNA sequencing across MM stages showed significant TRIM44 upregulation in smoldering MM (SMM) and MM compared to normal bone marrow, especially in patients with t(4;14) …

Asthma And Hyperglycemia: Exploring The Interconnected Pathways, Dharani K Narendra, Sandhya Khurana

Faculty, Staff and Students Publications

The interplay between asthma and glucose metabolism disorders, such as hyperglycemia, has gained increasing attention due to the potential exacerbation of asthma symptoms and severity. This review explores the complex relationship between hyperglycemia and asthma, emphasizing the pathophysiological links, the impact of glucose metabolism disorders on asthma, and the effects of asthma medications on glucose levels. Hyperglycemia, often induced by asthma treatments like corticosteroids, has been associated with an increased risk of asthma exacerbations. This review delves into the pathophysiology underlying this association, highlighting the role of insulin resistance, metabolic syndrome, and obesity in both the development and management of …

Mitral Annular Disjunction And Its Progression During Childhood In Marfan Syndrome, Tam T Doan, Alejandra Iturralde Chavez, Santiago O Valdes, Justin D Weigand, James C Wilkinson, Anitha Parthiban, Sara B Stephens, Ricardo H Pignatelli, Shaine A Morris

Faculty, Staff and Students Publications

AIMS: Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood.

METHODS AND RESULTS: We included patientsMFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram-CMR agreement. Bland-Altman …

Clearing New Frontiers: Sinonasal Health And The Future Of Spaceflight, Faizaan I Khan, Isuru Somawardana, Roshan Dongre, Najm S Khan, Keyvon Rashidi, Samuel Razmi, David Hilmers, Omar G Ahmed, Masayoshi Takashima

Faculty, Staff and Students Publications

No abstract provided.

Meti: Deep Profiling Of Tumor Ecosystems By Integrating Cell Morphology And Spatial Transcriptomics, Jiahui Jiang, Yunhe Liu, Jiangjiang Qin, Jianfeng Chen, Jingjing Wu, Melissa P Pizzi, Rossana Lazcano, Kohei Yamashita, Zhiyuan Xu, Guangsheng Pei, Kyung Serk Cho, Yanshuo Chu, Ansam Sinjab, Fuduan Peng, Xinmiao Yan, Guangchun Han, Ruiping Wang, Enyu Dai, Yibo Dai, Bogdan A Czerniak, Andrew Futreal, Anirban Maitra, Alexander Lazar, Humam Kadara, Amir A Jazaeri, Xiangdong Cheng, Jaffer Ajani, Jianjun Gao, Jian Hu, Linghua Wang

Faculty, Staff and Student Publications

Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance …

Non-Coding Rnas In Peritoneal Carcinomatosis: From Bench To Bedside, Julia Bohosova, Nida Sarosh Ashraf, Ondrej Slaby, George A Calin

Faculty, Staff and Student Publications

Peritoneal carcinomatosis represents an advanced stage of tumors within the peritoneal cavity. Once considered an incurable terminal cancer metastasis, contemporary medicine is on the hunt for certain potentially curative options alongside the present day’s palliative disease management. However, for most patients, peritoneal carcinomatosis continues to pose a fatal late-stage prognosis with a grim future outlook. Over the past two decades, non-coding RNAs have garnered significant attention due to their undeniable significance in regulating cellular processes across all levels. Disruption of the intricate regulation led by non-coding RNAs has been demonstrated to have a substantial impact on various human diseases, particularly …

Experiences Of Parent Coaches In An Intervention For Parents Of Young Children Newly Diagnosed With Type 1 Diabetes, Carrie Tully, Manuela Sinisterra, Wendy Levy, Christine H Wang, John Barber, Hailey Inverso, Marisa E Hilliard, Maureen Monaghan, Randi Streisand

Faculty, Staff and Students Publications

Objectives: This paper explores parent coaching experiences supporting parents of young children newly diagnosed with type 1 diabetes in a clinical trial.

Methods: In a trial for 157 parents, those in the intervention arm (n = 116) were paired with a parent coach (n = 37; Mage = 37.9 years, SD = 3.9; 94.6% mothers, 81.1% White non-Hispanic). Parent coaches provided diabetes-specific social support. Parent coaches completed monthly surveys and satisfaction/feasibility surveys, with a subset (n = 7) undergoing qualitative interviews at the end of this study.

Results: There were 2262 contacts between participants and their parent coaches, averaging …

Improved High Quality Sand Fly Assemblies Enabled By Ultra Low Input Long Read Sequencing, Michelle Huang, Sarah Kingan, Douglas Shoue, Oanh Nguyen, Lutz Froenicke, Brendan Galvin, Christine Lambert, Ruqayya Khan, Chirag Maheshwari, David Weisz, Gareth Maslen, Helen Davison, Erez Lieberman Aiden, Jonas Korlach, Olga Dudchenko, Mary Ann Mcdowell, Stephen Richards

Faculty, Staff and Students Publications

Phlebotomine sand flies are the vectors of leishmaniasis, a neglected tropical disease. High-quality reference genomes are an important tool for understanding the biology and eco-evolutionary dynamics underpinning disease epidemiology. Previous leishmaniasis vector reference sequences were limited by sequencing technologies available at the time and inadequate for high-resolution genomic inquiry. Here, we present updated reference assemblies of two sand flies, Phlebotomus papatasi and Lutzomyia longipalpis. These chromosome-level assemblies were generated using an ultra-low input library protocol, PacBio HiFi long reads, and Hi-C technology. The new P. papatasi reference has a final assembly span of 351.6 Mb and contig and scaffold N50s …

The Icf Syndrome Protein Cdca7 Harbors A Unique Dna Binding Domain That Recognizes A Cpg Dyad In The Context Of A Non-B Dna, Swanand Hardikar, Ren Ren, Zhengzhou Ying, Jujun Zhou, John R Horton, Matthew D Bramble, Bin Liu, Yue Lu, Bigang Liu, Luis Della Coletta, Jianjun Shen, Jiameng Dan, Xing Zhang, Xiaodong Cheng, Taiping Chen

Faculty, Staff and Student Publications

CDCA7, encoding a protein with a carboxyl-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, a disease related to hypomethylation of juxtacentromeric satellite DNA. How CDCA7 directs DNA methylation to juxtacentromeric regions is unknown. Here, we show that the CDCA7 CRD adopts a unique zinc-binding structure that recognizes a CpG dyad in a non-B DNA formed by two sequence motifs. CDCA7, but not ICF mutants, preferentially binds the non-B DNA with strand-specific CpG hemi-methylation. The unmethylated sequence motif is highly enriched at centromeres of human chromosomes, whereas the methylated motif is distributed throughout …

Lung Cell Transplantation For Pulmonary Fibrosis, Irit Milman Krentsis, Yangxi Zheng, Chava Rosen, Sarah Y Shin, Christa Blagdon, Einav Shoshan, Yuan Qi, Jing Wang, Sandeep K Yadav, Esther Bachar Lustig, Elias Shetzen, Burton F Dickey, Harry Karmouty-Quintana, Yair Reisner

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors …

Therapeutic Antisense Oligonucleotides In Oncology: From Bench To Bedside, Elif Çakan, Olivia D Lara, Anna Szymanowska, Emine Bayraktar, Arturo Chavez-Reyes, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo

Faculty, Staff and Student Publications

Advancements in our comprehension of tumor biology and chemoresistance have spurred the development of treatments that precisely target specific molecules within the body. Despite the expanding landscape of therapeutic options, there persists a demand for innovative approaches to address unmet clinical needs. RNA therapeutics have emerged as a promising frontier in this realm, offering novel avenues for intervention such as RNA interference and the utilization of antisense oligonucleotides (ASOs). ASOs represent a versatile class of therapeutics capable of selectively targeting messenger RNAs (mRNAs) and silencing disease-associated proteins, thereby disrupting pathogenic processes at the molecular level. Recent advancements in chemical modification …

Heartmate 3 As A Bridge To Transplant In An Adult With Failing Fontan Circulation, Kengo Z. Soghoyan, Stephen Cook, Maya Guglin

The VAD Journal

Mechanical circulatory support devices have demonstrated efficacy in adult congenital patients with biventricular repairs. The off-label use of ventricular assist devices may be invaluable for managing end-stage single ventricle failure. We present the case of a 27-year-old male who developed heart failure, congestive hepatopathy, and, ultimately, cardiogenic shock. He received a HeartMate 3 (Abbott, Chicago, IL, USA) without complications one year after the surgery.

Active Learning Pipeline To Identify Candidate Terms For A Cdss Ontology, Xia Jing, Rohan Goli, Keerthana Komatineni, Shailesh Alluri, Nina Hubig, Hua Min, Yang Gong, Dean F Sittig, Paul Biondich, David Robinson, Christian Nøhr, Arild Faxvaag, Adam Wright, Timothy Law, Lior Rennert, Ronald Gimbel

Faculty, Staff and Student Publications

Ontology is essential for achieving health information and information technology application interoperability in the biomedical fields and beyond. Traditionally, ontology construction is carried out manually by human domain experts (HDE). Here, we explore an active learning approach to automatically identify candidate terms from publications, with manual verification later as a part of a deep learning model training and learning process. We introduce the overall architecture of the active learning pipeline and present some preliminary results. This work is a critical and complementary component in addition to manually building the ontology, especially during the long-term maintenance stage.

Perceptions Of Hiv-Related Comorbidities And Usability Of A Virtual Environment For Cardiovascular Disease Prevention Education In Sexual Minority Men With Hiv: Formative Phases Of A Pilot Randomized Controlled Trial, S Raquel Ramos, Harmony Reynolds, Constance Johnson, Gail Melkus, Trace Kershaw, Julian F Thayer, Allison Vorderstrasse

Faculty, Staff and Student Publications

Background: Sexual minority men with HIV are at an increased risk of cardiovascular disease (CVD) and have been underrepresented in behavioral research and clinical trials.

Objective: This study aims to explore perceptions of HIV-related comorbidities and assess the interest in and usability of a virtual environment for CVD prevention education in Black and Latinx sexual minority men with HIV.

Methods: This is a 3-phase pilot behavioral randomized controlled trial. We report on formative phases 1 and 2 that informed virtual environment content and features using qualitative interviews, usability testing, and beta testing with a total of 25 individuals. In phase …

Sexannodb, A Knowledgebase Of Sex-Specific Regulations From Multi-Omics Data Of Human Cancers, Mengyuan Yang, Yuzhou Feng, Jiajia Liu, Hong Wang, Sijia Wu, Weiling Zhao, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Background

Sexual differences across molecular levels profoundly impact cancer biology and outcomes. Patient gender significantly influences drug responses, with divergent reactions between men and women to the same drugs. Despite databases on sex differences in human tissues, understanding regulations of sex disparities in cancer is limited. These resources lack detailed mechanistic studies on sex-biased molecules.

Methods

In this study, we conducted a comprehensive examination of molecular distinctions and regulatory networks across 27 cancer types, delving into sex-biased effects. Our analyses encompassed sex-biased competitive endogenous RNA networks, regulatory networks involving sex-biased RNA binding protein-exon skipping events, sex-biased transcription factor-gene regulatory networks, …

A Data Pipeline For Enhancing Quality Of Maude-Based Studies, Yuheng Shi, Yue Yu, Yubo Feng, Yang Gong

Faculty, Staff and Student Publications

The increasing use of MAUDE reports in patient safety research highlights the importance of understanding the processing and dissemination of open-access MAUDE data. However, the absence of a structured data pipeline undermines the reproducibility and transparency of studies relying on MAUDE data. In response, we conducted a comprehensive analysis of a recent study on endoscopic clips, assessing methodologies and results. We advocate for implementing an extract, transform, and load (ETL) pipeline, utilizing openFDA and integrating keyword search strategies and data visualization techniques. This approach aims to enhance the quality of MAUDE-based studies, ensuring their reproducibility and transparency. Moreover, ETL serves …

Challenges And Opportunities Of Artificial Intelligence In Cdss And Patient Safety, Yang Gong, Hua Min, Xia Jing, Ping Yu

Faculty, Staff and Student Publications

Ensuring patient safety in healthcare involves training professionals and implementing clinical decision support systems (CDSS) and health IT solutions to reduce errors and adverse events. The integration of artificial intelligence (AI) into health IT has revolutionized clinical settings by enabling real-time insights and personalized recommendations. However, the use of health IT can lead to unintended consequences that are not adequately addressed during training and implementation. These consequences can hinder the maximization of benefits and limit equitable access to healthcare. In this paper, we explore the impact of AI on CDSS and health IT, discuss the challenges in educating clinical informaticians, …

Loss Of Symmetric Cell Division Of Apical Neural Progenitors Drives Dennd5a-Related Developmental And Epileptic Encephalopathy, Emily Banks, Vincent Francis, Sheng-Jia Lin, Fares Kharfallah, Vladimir Fonov, Maxime Lévesque, Chanshuai Han, Gopinath Kulasekaran, Marius Tuznik, Armin Bayati, Reem Al-Khater, Fowzan S Alkuraya, Loukas Argyriou, Meisam Babaei, Melanie Bahlo, Behnoosh Bakhshoodeh, Eileen Barr, Lauren Bartik, Mahmoud Bassiony, Miriam Bertrand, Dominique Braun, Rebecca Buchert, Mauro Budetta, Maxime Cadieux-Dion, Daniel G Calame, Heidi Cope, Donna Cushing, Stephanie Efthymiou, Marwa Abd Elmaksoud, Huda G El Said, Tawfiq Froukh, Harinder K Gill, Joseph G Gleeson, Laura Gogoll, Elaine S-Y Goh, Vykuntaraju K Gowda, Tobias B Haack, Mais O Hashem, Stefan Hauser, Trevor L Hoffman, Jacob S Hogue, Akimoto Hosokawa, Henry Houlden, Kevin Huang, Stephanie Huynh, Ehsan G Karimiani, Silke Kaulfuß, G Christoph Korenke, Amy Kritzer, Hane Lee, James R Lupski, Elysa J Marco, Kirsty Mcwalter, Arakel Minassian, Berge A Minassian, David Murphy, Juanita Neira-Fresneda, Hope Northrup, Denis M Nyaga, Barbara Oehl-Jaschkowitz, Matthew Osmond, Richard Person, Davut Pehlivan, Cassidy Petree, Lynette G Sadleir, Carol Saunders, Ludger Schoels, Vandana Shashi, Rebecca C Spillmann, Varunvenkat M Srinivasan, Paria N Torbati, Tulay Tos, Maha S Zaki, Dihong Zhou, Christiane Zweier, Jean-François Trempe, Thomas M Durcan, Ziv Gan-Or, Massimo Avoli, Cesar Alves, Gaurav K Varshney, Reza Maroofian, David A Rudko, Peter S Mcpherson

Faculty, Staff and Student Publications

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells …

Clinical Features And Disease Progression In Older Individuals With Rett Syndrome, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Cary Fu, Robin C Ryther, Steven A Skinner, David N Lieberman, Timothy Feyma, Arthur Beisang, Peter Heydemann, Sarika U Peters, Amitha Ananth, Alan K Percy

Faculty, Staff and Students Publications

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different …

Early Rhombic Lip Protogenin+Ve Stem Cells In A Human-Specific Neurovascular Niche Initiate And Maintain Group 3 Medulloblastoma, Abhirami Visvanathan, Olivier Saulnier, Chuan Chen, Parthiv Haldipur, Wilda Orisme, Alberto Delaidelli, Seungmin Shin, Jake Millman, Andrew Bryant, Namal Abeysundara, Xujia Wu, Liam D Hendrikse, Vikas Patil, Zahedeh Bashardanesh, Joseph Golser, Bryn G Livingston, Takuma Nakashima, Yusuke Funakoshi, Winnie Ong, Alexandra Rasnitsyn, Kimberly A Aldinger, Cory M Richman, Randy Van Ommeren, John J Y Lee, Michelle Ly, Maria C Vladoiu, Kaitlin Kharas, Polina Balin, Anders W Erickson, Vernon Fong, Jiao Zhang, Raúl A Suárez, Hao Wang, Ning Huang, Jonelle G Pallota, Tajana Douglas, Joonas Haapasalo, Ferechte Razavi, Evelina Silvestri, Olga Sirbu, Samantha Worme, Michelle M Kameda-Smith, Xiaochong Wu, Craig Daniels, Antony K Michaelraj, Aparna Bhaduri, Daniel Schramek, Hiromichi Suzuki, Livia Garzia, Nabil Ahmed, Claudia L Kleinman, Lincoln D Stein, Peter Dirks, Christopher Dunham, Nada Jabado, Jeremy N Rich, Wei Li, Poul H Sorensen, Robert J Wechsler-Reya, William A Weiss, Kathleen J Millen, David W Ellison, Dimiter S Dimitrov, Michael D Taylor

Faculty, Staff and Students Publications

We identify a population of PRTG+ve MYChigh NESTINlow stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RLVZ). Oncogenic transformation of early Prtg+ve rhombic lip stem cells initiate Group 3 Medulloblastoma (Gr3-MB)-like tumors. PRTG+ve stem-cells grow adjacent to a human specific interposed vascular plexus in the RLVZ, a phenotype which is recapitulated in Gr3-MB, but not other types of medulloblastoma. Co-culture of Gr3-MB with endothelial cells promotes tumor stem-cell growth, with the endothelial cells adopting an immature phenotype. Targeting the PRTGhigh compartment of Gr3-MB in vivo using either the diphtheria …

The Dna Repair Pathway As A Therapeutic Target To Synergize With Trastuzumab Deruxtecan In Her2-Targeted Antibody-Drug Conjugate-Resistant Her2-Overexpressing Breast Cancer, Jangsoon Lee, Kumiko Kida, Jiwon Koh, Huey Liu, Ganiraju C Manyam, Young Jin Gi, Dileep R Rampa, Asha S Multani, Jing Wang, Gitanjali Jayachandran, Dae-Won Lee, James M Reuben, Aysegul Sahin, Lei Huo, Debu Tripathy, Seock-Ah Im, Naoto T Ueno

Faculty, Staff and Student Publications

Background: Anti-HER2 therapies, including the HER2 antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have led to improved survival outcomes in patients with HER2-overexpressing (HER2+) metastatic breast cancer. However, intrinsic or acquired resistance to anti-HER2-based therapies remains a clinical challenge in these patients, as there is no standard of care following disease progression. The purpose of this study was to elucidate the mechanisms of resistance to T-DM1 and T-DXd in HER2+ BC patients and preclinical models and identify targets whose inhibition enhances the antitumor activity of T-DXd in HER2-directed ADC-resistant HER2+ breast cancer in vitro and in vivo. …

Transcriptome Profiling Of Pediatric Extracranial Solid Tumors And Lymphomas Enables Rapid Low-Cost Diagnostic Classification, Kofi B Opoku, Teresa Santiago, Priya Kumar, Sophia M Roush, Yuri Fedoriw, Tamiwe Tomoka, Vasiliki Leventaki, Larissa V Furtado, Nickhill Bhakta, Thomas B Alexander, Jeremy R Wang

Faculty, Staff and Student Publications

Approximately 80% of pediatric tumors occur in low- and middle-income countries (LMIC), where diagnostic tools essential for treatment decisions are often unavailable or incomplete. Development of cost-effective molecular diagnostics will help bridge the cancer diagnostic gap and ultimately improve pediatric cancer outcomes in LMIC settings. We investigated the feasibility of using nanopore whole transcriptome sequencing on formalin-fixed paraffin embedded (FFPE)-derived RNA and a composite machine learning model for pediatric solid tumor diagnosis. Transcriptome cDNA sequencing was performed on a heterogenous set of 221 FFPE and 32 fresh frozen pediatric solid tumor and lymphoma specimens on Oxford Nanopore Technologies' sequencing platforms. …

The Role Of Gdf5 In Regulating Enthesopathy Development In The Hyp Mouse Model Of Xlh, Melissa Sorsby, Shaza Almardini, Ahmad Alayyat, Ashleigh Hughes, Shreya Venkat, Mansoor Rahman, Jiana Baker, Rakshya Rana, Vicki Rosen, Eva S Liu

Staff and Researcher Publications

X-linked hypophosphatemia (XLH) is caused by mutations in PHEX, leading to rickets and osteomalacia. Adults affected with XLH develop a mineralization of the bone-tendon attachment site (enthesis), called enthesopathy, which causes significant pain and impaired movement. Entheses in mice with XLH (Hyp) have enhanced bone morphogenetic protein (BMP) and Indian hedgehog (IHH) signaling. Treatment of Hyp mice with the BMP signaling blocker palovarotene attenuated BMP/IHH signaling in Hyp entheses, thus indicating that BMP signaling plays a pathogenic role in enthesopathy development and that IHH signaling is activated by BMP signaling in entheses. It was previously shown that mRNA expression of …

Comparing Visualization Performance Of Liquid Embolic Agents Using A Novel Injectable Phantom, J Ryan Mason, Cristina Dodge, Adam Beardsley, Susan Hilsenbeck, Goetz Benndorf

Center for Medical Ethics and Health Policy Staff Publications

Background: Radiographic visualization of liquid embolic agents (LEAs) during embolization procedures in neurovascular territory represents a crucial feature to ensure efficacy and safety for the patients during endovascular treatment of arteriovenous shunting lesions. Radiopacity of available LEAs varies significantly and limited methods are currently available for comparison. The purpose of this study was to compare the contrast resolution (CR) during injection under blank roadmap of various LEAs, as well as standard contrast material.

Methods: An injectable angiographic phantom was designed consisting of parallel tubings between 313 and 1000 micron. Under roadmap, eight radiopaque liquid agents were injected and analyzed: Onyx18®, …

Needs Of Family Caregivers Of Hospitalised Adults With Dementia During Care Transitions: A Qualitative Study In A Us Department Of Veterans Affairs Hospital, Molly J Horstman, Tracy L Evans, Crystal Guo, Mandi Sonnenfeld, Aanand D Naik, Alan Stevens, Mark E Kunik

Faculty, Staff and Student Publications

OBJECTIVE: To identify the needs of caregivers of hospitalised adults with dementia in the hospital and during care transitions.

DESIGN: Pragmatic qualitative inquiry with semi-structured interviews.

SETTING: Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, USA.

PARTICIPANTS: 12 family caregivers (family member (n=11); friend (n=1)) and 15 health professionals (hospital medicine physicians (n=4), inpatient nurse case managers (n=2), social workers (n=4), outpatient geriatrics providers (n=2), a primary care provider (n=1), geriatric psychiatrists (n=2)) were interviewed. Caregivers were recruited while their care recipient was hospitalised and were interviewed at least 2 weeks after the care recipient was discharged from …

Mitral Annular Disjunction And "Pseudo" Mitral Annular Disjunction In Mitral Valve Prolapse, Tam T Doan, Shaine A Morris

Faculty, Staff and Students Publications

No abstract provided.

Right Ventricle-Pulmonary Artery Conduit Replacement Resolves Anomalous Single Coronary Stenosis In Repaired Tetralogy Of Fallot, Karl Kristian Lundin, Edward Hickey, Prakash Masand, Vivian Dimas, Katherine Bohard Salciccioli

Faculty, Staff and Students Publications

A 41-year-old man with repaired tetralogy of Fallot and a single coronary artery (CA) arising anteriorly presented with dyspnea in the setting of moderate right ventricle-pulmonary artery conduit (RV-PAC) stenosis and moderate-to-severe extrinsic left main CA compression between the aorta and RV-PAC. His CA stenosis resolved after successful RV-PAC replacement.