Digital Commons Network^™

Unicentric Castleman Disease: Illustration Of Its Morphologic Spectrum And Review Of The Differential Diagnosis, Siba El Hussein, Andrew G Evans, Hong Fang, Wei Wang, L Jeffrey Medeiros

Faculty, Staff and Student Publications

Context: Unicentric Castleman disease (UCD) is a dynamic entity with a wide spectrum of morphologic findings. UCD can be further subdivided into hyaline-vascular and mixed/plasmacytic variants. Hyaline-vascular UCD has both follicular and interfollicular (stromal) changes, and occasionally these lesions show a skewed representation of either the follicular or stromal compartments. Plasmacytosis is usually minimal in the hyaline-vascular variant. The mixed/plasmacytic variant of UCD is composed of sheets of plasma cells often associated with a variable number of follicles with regressive changes.

Objective: To illustrate the differential diagnosis of UCD, as it is quite broad and includes lymphomas, plasma cell neoplasms, …

A Reinforcement Learning (Rl)-Motivated Simulation Framework For Evaluating Vancomycin Dosing Strategies, Bingyu Mao, Ziqian Xie, Laila Rasmy, Masayuki Nigo, Degui Zhi

Faculty, Staff and Student Publications

Achieving and maintaining the therapeutic range in vancomycin treatment is important for optimal outcomes. While guidelines and best practices based on empirical studies exist, the theoretical best dosing strategies under various conditions remain illusive. We developed an RL-based simulation framework using a deep learning two-compartment pharmacokinetic model (PK-RNN-2CM) and introduced the area under the time-concentration curve (AUC) reward score, which translates clinical guidelines into an RL reward. Ground truth time-concentration curves were generated from patient-specific data, and simulated curves were produced under different dosing strategies with optional noise perturbations to mimic real-world settings. Evaluation metrics included 24-hour AUC assessments and …

Characterizing Treatment Non-Responders And Responders In Completed Alzheimer's Disease Clinical Trials, Xiaoqian Jiang

Faculty, Staff and Student Publications

Characterizing differential responses to Alzheimer's disease (AD) drugs will provide better insights into personalized treatment strategies. Our study aims to identify heterogeneous treatment effects and pre-treatment features that moderate the treatment effect of Galantamine, Bapineuzumab, and Semagacestat from completed trial data. The causal forest method can capture heterogeneity in treatment responses. We applied causal forest modeling to estimate the treatment effect and identify efficacy moderators in each trial. We found several patient's pretreatment conditions that determined treatment efficacy. For example, in Galantamine trials, whole brain volume (1092.54 vs. 1060.67 ml, P < .001) and right hippocampal volume (2.43e-3 vs. 2.79e-3, P < .001) are significantly different between responsive and non-responsive subgroups. Overall, our implementation of causal forests in AD clinical trials reveals the heterogeneous treatment effects and different moderators for AD drug responses, highlighting promising personalized treatment based on patient-specific characteristics in AD research and drug development.

Parents' Stigmatizing Beliefs About The Hpv Vaccine And Their Association With Information Seeking Behavior And Vaccination Communication Behaviors, L Aubree Shay, Travis Teague, Erica Frost, Stanley W Spinner, Sally W Vernon

Faculty, Staff and Student Publications

Parents' stigmatizing beliefs about the HPV vaccine, such as beliefs that it promotes adolescent sexual activity, constitute a notable barrier to vaccine uptake. The purpose of this study is to describe the associations between parents' stigmatizing beliefs about the HPV vaccine, psychosocial antecedents to vaccination, and parents' intentions to vaccinate their children. Parents of vaccine-eligible children (

Predictive Metabolites For Incident Myocardial Infarction: A Two-Step Meta-Analysis Of Individual Patient Data From Six Cohorts Comprising 7897 Individuals From The Consortium Of Metabolomics Studies, Jie Hu, Rui Wang-Sattler, Gabi Kastenmüler, Birgit Linkohr, Clara Barrios, Marta Crespo, Christian Gieger, Annette Peters, Jackie Price, Kathryn M Rexrode, Bing Yu, Cristina Menni

Faculty, Staff and Student Publications

AIMS: Myocardial infarction (MI) is a major cause of death and disability worldwide. Most metabolomics studies investigating metabolites predicting MI are limited by the participant number and/or the demographic diversity. We sought to identify biomarkers of incident MI in the COnsortium of METabolomics Studies.

METHODS AND RESULTS: We included 7897 individuals aged on average 66 years from six intercontinental cohorts with blood metabolomic profiling (n = 1428 metabolites, of which 168 were present in at least three cohorts with over 80% prevalence) and MI information (1373 cases). We performed a two-stage individual patient data meta-analysis. We first assessed the associations …

Altered Outer Retinal Structure, Electrophysiology And Visual Perception In Parkinson's Disease, Bao N Nguyen

Faculty, Staff and Student Publications

BACKGROUND: Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation.

OBJECTIVE: To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing.

METHODS: Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = …

Structural Basis For Dna Proofreading, Gina Buchel, Ashok Nayak, Karl Herbine, Azadeh Sarfallah, Viktoriia Sokolova, Angelica Zamudio-Ochoa, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the corrected DNA terminus returns has remained elusive. Here, we present an ensemble of nine high-resolution structures representing human mitochondrial DNA polymerase Gamma, Polγ, captured during consecutive proofreading steps. The structures reveal key events, including mismatched base recognition, its dissociation from the polymerase site, forward translocation of DNAP, alterations in DNA trajectory, repositioning and refolding of elements for primer separation, DNAP backtracking, and displacement …

Using Long-Read Cage Sequencing To Profile Cryptic-Promoter-Derived Transcripts And Their Contribution To The Immunopeptidome, Ju Heon Maeng, H Josh Jang, Alan Y Du, Shin-Cheng Tzeng, Ting Wang

2020-Current year OA Pubs

Recent studies have shown that the noncoding genome can produce unannotated proteins as antigens that induce immune response. One major source of this activity is the aberrant epigenetic reactivation of transposable elements (TEs). In tumors, TEs often provide cryptic or alternate promoters, which can generate transcripts that encode tumor-specific unannotated proteins. Thus, TE-derived transcripts (TE transcripts) have the potential to produce tumor-specific, but recurrent, antigens shared among many tumors. Identification of TE-derived tumor antigens holds the promise to improve cancer immunotherapy approaches; however, current genomics and computational tools are not optimized for their detection. Here we combined CAGE technology with …

Single-Pulse Electrical Stimulation Artifact Removal Using The Novel Matching Pursuit-Based Artifact Reconstruction And Removal Method (Mparrm), Tao Xie, Thomas J Foutz, Markus Adamek, James R Swift, Cory S Inman, Joseph R Manns, Eric C Leuthardt, Jon T Willie, Peter Brunner

2020-Current year OA Pubs

No abstract provided.

People Are Less Myopic About Future Than Past Collective Outcomes

Faculty, Staff and Student Publications

Myopia involves giving disproportionate weight to outcomes that occur close to the present. Myopia in people's evaluations of political outcomes and proposals threatens effective policymaking. It can lead to inefficient spending just before elections, cause inaction on important future policy challenges, and create incentives for government interventions aimed at boosting short-term performance at the expense of long-term welfare. But, are people generally myopic? Existing evidence comes mostly from studies that disregard either the future or collective outcomes. Political science characterizes people as myopic based on how they retrospectively evaluate collective outcomes, such as the state of the economy. Behavioral economics …

Genomic Loci Influence Patterns Of Structural Covariance In The Human Brain, Junhao Wen, Aristeidis Sotiras, Daniel S Marcus, Pamela Lamontagne, John C Morris, Et Al.

2020-Current year OA Pubs

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and …

Lidocaine Induces Apoptosis In Head And Neck Squamous Cell Carcinoma Through Activation Of Bitter Taste Receptor T2r14, Zoey A Miller, Arielle Mueller, Taebeom Kim, Jennifer F Jolivert, Ray Z Ma, April Park, Kevin T Nead, Ryan M Carey, Robert J Lee

Faculty, Staff and Student Publications

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis. Lidocaine is a local anesthetic that also activates bitter taste receptor 14 (T2R14). Lidocaine has some anti-cancer effects, but the mechanisms are unclear. Here, we find that lidocaine causes intracellular Ca

Microcalcification Crystallography As A Potential Marker Of Dcis Recurrence, Zoey A Miller, Arielle Mueller, Taebeom Kim, Jennifer F Jolivert, Ray Z Ma, April Park, Kevin T Nead, Ryan M Carey, Robert J Lee

Faculty, Staff and Student Publications

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis. Lidocaine is a local anesthetic that also activates bitter taste receptor 14 (T2R14). Lidocaine has some anti-cancer effects, but the mechanisms are unclear. Here, we find that lidocaine causes intracellular Ca

Para-Infectious Brain Injury In Covid-19 Persists At Follow-Up Despite Attenuated Cytokine And Autoantibody Responses, Robyn Williams, Parul Sharma, Krishanthi Subramaniam, Greta K Wood, Ceryce Collie, Richard Digby, Alexander Ren, Emma Norton, Maya Leibowitz, Soraya Ebrahimi, Andrew Fower, Hannah Fox, Esteban Tato, Mark A Ellul, Geraint Sunderland, Marie Held, Claire Hetherington, Franklyn N Egbe, Alish Palmos, Kathy Stirrups, Alexander Grundmann, Anne-Cecile Chiollaz, Jean-Charles Sanchez, James P Stewart, Michael Griffiths, Tom Solomon, Gerome Breen, Alasdair J Coles, Nathalie Kingston, John R Bradley, Patrick F Chinnery, Jonathan Cavanagh, Sarosh R Irani, Angela Vincent, J Kenneth Baillie, Peter J Openshaw, Malcolm G Semple, Covid-Cns Consortium, Isaric4c Investigators, Leonie S Taams, David K Menon

Faculty, Staff and Student Publications

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common …

Leptin Decreases Gluconeogenesis And Gluconeogenic Substrate Availability In Patients With Lipodystrophy, Emmanuel Quaye, Shaji Chacko, Megan Startzell, Rebecca J Brown

Children’s Nutrition Research Center Staff Publications

Context: The effects of leptin, an adipocyte-derived hormone that signals overall energy sufficiency, can only be studied in leptin-deficient conditions. In patients with lipodystrophy, a rare disease and unique model of leptin deficiency, treatment with recombinant leptin (metreleptin) improves glycemia and decreases energy expenditure. We hypothesized that these improvements might be mediated by reduced gluconeogenesis (GNG), an energy-requiring process.

Objective: To determine the effects of metreleptin on GNG and GNG substrates.

Methods: This was a single-arm prospective study of metreleptin administration in 15 patients with lipodystrophy, 9 of whom had data on GNG (NIH, 2013-2018). We analyzed total GNG, insulin-mediated …

Efficacy And Safety Of Teprotumumab In Patients With Thyroid Eye Disease Of Long Duration And Low Disease Activity, Raymond S Douglas, Steven Couch, Sara T Wester, Brian T Fowler, Catherine Y Liu, Prem S Subramanian, Rosa Tang, Quang T Nguyen, Robi N Maamari, Shoaib Ugradar, Kate Hsu, Michael Karon, Marius N Stan

2020-Current year OA Pubs

CONTEXT: Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials.

OBJECTIVE: We present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED.

METHODS: This randomized double-masked, placebo-controlled trial, conducted at 11 US centers, enrolled adult participants with TED duration of 2 to 10 years, Clinical Activity Score (CAS) ≤ 1 or no additional inflammation or progression in proptosis/diplopia for ≥1 year, proptosis ≥3 mm from before TED and/or from normal, euthyroid/mildly hypo/hyperthyroid, no prior …

Evaluation Of A Targeted Covid-19 Community Outreach Intervention: Case Report For Precision Public Health, Michelle Jones, Susan P Fisher-Hoch

Faculty, Staff and Student Publications

BACKGROUND: Cameron County, a low-income south Texas-Mexico border county marked by severe health disparities, was consistently among the top counties with the highest COVID-19 mortality in Texas at the onset of the pandemic. The disparity in COVID-19 burden within Texas counties revealed the need for effective interventions to address the specific needs of local health departments and their communities. Publicly available COVID-19 surveillance data were not sufficiently timely or granular to deliver such targeted interventions. An agency-academic collaboration in Cameron used novel geographic information science methods to produce granular COVID-19 surveillance data. These data were used to strategically target an …

Colonization Of Larval Zebrafish (Danio Rerio) With Adherent-Invasive Escherichia Coli Prevents Recovery Of The Intestinal Mucosa From Drug-Induced Enterocolitis, Erika Flores, Soumita Dutta, Rachel Bosserman, Ambro Van Hoof, Anne-Marie Krachler

Faculty, Staff and Student Publications

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections …

Colonization Of Larval Zebrafish (Danio Rerio) With Adherent-Invasive Escherichia Coli Prevents Recovery Of The Intestinal Mucosa From Drug-Induced Enterocolitis, Anne-Marie Krachler

Faculty, Staff and Student Publications

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections …

Bacterial Outer Membrane Vesicles Provide An Alternative Pathway For Trafficking Of Escherichia Coli O157 Type Iii Secreted Effectors To Epithelial Cells, Anne Marie Krachler

Faculty, Staff and Student Publications

Outer membrane vesicles (OMVs) are proteoliposomes shed by Gram-negative bacteria. Their secretion is enhanced by the transition into the intra-host milieu, and OMVs play critical roles during pathogenesis. Enterohemorrhagic Escherichia coli O157 (EHEC) can cause diarrheal disease in humans, and soluble toxins including Shiga-like toxins that contribute to disease severity and clinical complications like hemolytic uremic syndrome have been shown to be OMV associated. In addition to Shiga-like toxins, EHEC produces a type III secretion system (T3SS), and T3SS effectors are associated with colonization and disease severity in vivo. Here, we show that type III secreted substrates including translocators …

Mirna-211 Maintains Metabolic Homeostasis In Medulloblastoma Through Its Target Gene Long-Chain Acyl-Coa Synthetase 4, Kandarp Joshi, Olivier Saulnier, Rudramani Pokhrel, Bongyong Lee, Wathsala Liyanage, Haritha Kunhiraman, Stacie Stapleton, Ignacio Gonzalez-Gomez, Rangaramanujam M Kannan, Tanja Eisemann, Elayaraja Kolanthai, Sudipta Seal, Timothy J Garrett, Saed Abbasi, Kimberly Bockley, Justin Hanes, Prem Chapagain, George Jallo, Robert J Wechsler-Reya, Michael D Taylor, Charles G Eberhart, Animesh Ray, Ranjan J Perera

Faculty, Staff and Students Publications

The prognosis of childhood medulloblastoma (MB) is often poor, and it usually requires aggressive therapy that adversely affects quality of life. microRNA-211 (miR-211) was previously identified as an important regulator of cells that descend from neural cells. Since medulloblastomas primarily affect cells with similar ontogeny, we investigated the role and mechanism of miR-211 in MB. Here we showed that miR-211 expression was highly downregulated in cell lines, PDXs, and clinical samples of different MB subgroups (SHH, Group 3, and Group 4) compared to normal cerebellum. miR-211 gene was ectopically expressed in transgenic cells from MB subgroups, and they were subjected …

Blue-Shift Photoconversion Of Near-Infrared Fluorescent Proteins For Labeling And Tracking In Living Cells And Organisms, Francesca Pennacchietti, Jonatan Alvelid, Rodrigo A Morales, Martina Damenti, Dirk Ollech, Daria M Shcherbakova, Vladislav V Verkhusha, Ilaria Testa

Faculty, Staff and Student Publications

Photolabeling of intracellular molecules is an invaluable approach to studying various dynamic processes in living cells with high spatiotemporal precision. Among fluorescent proteins, photoconvertible mechanisms and their products are in the visible spectrum (400-650 nm), limiting their in vivo and multiplexed applications. Here we report the phenomenon of near-infrared to far-red photoconversion in the miRFP family of near infrared fluorescent proteins engineered from bacterial phytochromes. This photoconversion is induced by near-infrared light through a non-linear process, further allowing optical sectioning. Photoconverted miRFP species emit fluorescence at 650 nm enabling photolabeling entirely performed in the near-infrared range. We use miRFPs as …

Biomarkers Of Affective Dysregulation Associated With In Utero Exposure To Etoh, Armine Darbinyan

Faculty, Staff and Student Publications

INTRODUCTION: Children with fetal alcohol spectrum disorders (FASD) exhibit behavioral and affective dysregulation, including hyperactivity and depression. The mechanisms are not known, but they could conceivably be due to postnatal social or environmental factors. However, we postulate that, more likely, the affective dysregulation is associated with the effects of EtOH exposure on the development of fetal serotonergic (5-HT) and/or dopaminergic (DA) pathways, i.e., pathways that in postnatal life are believed to regulate mood. Many women who use alcohol (ethanol, EtOH) during pregnancy suffer from depression and take selective serotonin reuptake inhibitors (SSRIs), which might influence these monoaminergic pathways in the …

A Comparison Of Depressive Symptom Self-Reported Measures In The Texas Youth Depression And Suicide Research Network (Tx-Ydsrn), Beth D Kennard, Graham J Emslie, Holli Slater, Taryn L Mayes, Melissa Defilippis, Cynthia Garza, Eric A Storch, Sarah M Wakefield, Madhukar H Trivedi

Faculty, Staff and Students Publications

Objective: To evaluate psychometrically and provide crosswalks between 3 self-report measures of depressive symptomatology in youth in psychiatric care settings. Ratings included the Patient Health Questionnaire for Adolescents (PHQ-A), a widely used 9-item self-report; the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16); and the 5-item Very Quick Inventory of Depressive Symptomatology-Self-Report (VQIDS-SR5), a recent effort to create a bridge from the QIDS-SR16 to clinical practice.

Methods: Data from the Texas Youth Depression and Suicide Research Network Registry (August 26, 2020-May 11, 2022) were included in this work. At first visit, 795 depressed or suicidal adolescent (12-20 years of age) psychiatric …

Genetic And Epigenetic Features Of Bilateral Wilms Tumor Predisposition In Patients From The Children’S Oncology Group Aren18b5-Q, Andrew J Murphy, Changde Cheng, Justin Williams, Timothy I Shaw, Emilia M Pinto, Jack Brzezinski, Brett Tornwall, Vicki Huff, Andrew L Hong, Elizabeth A Mullen, Brian Crompton, Jeffrey S Dome, Conrad V Fernandez, James I Geller, Peter F Ehrlich, Heather Mulder, Ninad Oak, Jamie Maciezsek, Carolyn M Jablonowski, Andrew M Fleming, Prahalathan Pichavaram, Christopher L Morton, John Easton, Kim E Nichols, Michael R Clay, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P Zambetti, Zhaoming Wang, Andrew M Davidoff, Xiang Chen

Faculty, Staff and Student Publications

Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of …

Pathway Centric Analysis For Single-Cell Rna-Seq And Spatial Transcriptomics Data With Gsdensity, Qingnan Liang, Yuefan Huang, Shan He, Ken Chen

Faculty, Staff and Student Publications

Advances in single-cell technology have enabled molecular dissection of heterogeneous biospecimens at unprecedented scales and resolutions. Cluster-centric approaches are widely applied in analyzing single-cell data, however they have limited power in dissecting and interpreting highly heterogenous, dynamically evolving data. Here, we present GSDensity, a graph-modeling approach that allows users to obtain pathway-centric interpretation and dissection of single-cell and spatial transcriptomics (ST) data without performing clustering. Using pathway gene sets, we show that GSDensity can accurately detect biologically distinct cells and reveal novel cell-pathway associations ignored by existing methods. Moreover, GSDensity, combined with trajectory analysis can identify curated pathways that are …

Lesion Detection In Women Breast’S Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using Deep Learning, Saurav Mallik, Ujjwal Maulik, Zhongming Zhao

Faculty, Staff and Student Publications

Breast cancer is one of the most common cancers in women and the second foremost cause of cancer death in women after lung cancer. Recent technological advances in breast cancer treatment offer hope to millions of women in the world. Segmentation of the breast's Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) is one of the necessary tasks in the diagnosis and detection of breast cancer. Currently, a popular deep learning model, U-Net is extensively used in biomedical image segmentation. This article aims to advance the state of the art and conduct a more in-depth analysis with a focus on the use …

Combining The Tyrosine Kinase Inhibitor Cabozantinib And The Mtorc1/2 Inhibitor Sapanisertib Blocks Erk Pathway Activity And Suppresses Tumor Growth In Renal Cell Carcinoma., Yige Wu, Siqi Chen, Xiaolu Yang, Kazuhito Sato, Preet Lal, Yuefan Wang, Andrew T Shinkle, Michael C Wendl, Tina M Primeau, Yanyan Zhao, Alanna Gould, Hua Sun, Jacqueline L Mudd, Jeremy Hoog, R Jay Mashl, Matthew A Wyczalkowski, Chia-Kuei Mo, Ruiyang Liu, John M Herndon, Sherri R Davies, Di Liu, Xi Ding, Yvonne A Evrard, Bryan E Welm, David Lum, Mei Yee Koh, Alana L Welm, Jeffrey Chuang, Jeffrey A Moscow, Funda Meric-Bernstam, Ramaswamy Govindan, Shunqiang Li, James Hsieh, Ryan C Fields, Kian-Huat Lim, Cynthia X Ma, Hui Zhang, Li Ding, Feng Chen

Faculty Research 2023

UNLABELLED: Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced …

Diversity And Dissemination Of Viruses In Pathogenic Protozoa, Senne Heeren, Ilse Maes, Mandy Sanders, Lon-Fye Lye, Vanessa Adaui, Jorge Arevalo, Alejandro Llanos-Cuentas, Lineth Garcia, Philippe Lemey, Stephen M Beverley, James A Cotton, Jean-Claude Dujardin, Frederik Van Den Broeck

2020-Current year OA Pubs

Viruses are the most abundant biological entities on Earth and play a significant role in the evolution of many organisms and ecosystems. In pathogenic protozoa, the presence of viruses has been linked to an increased risk of treatment failure and severe clinical outcome. Here, we studied the molecular epidemiology of the zoonotic disease cutaneous leishmaniasis in Peru and Bolivia through a joint evolutionary analysis of Leishmania braziliensis and their dsRNA Leishmania virus 1. We show that parasite populations circulate in tropical rainforests and are associated with single viral lineages that appear in low prevalence. In contrast, groups of hybrid parasites …

Timigp: An R Package To Depict The Tumor Microenvironment From Bulk Transcriptomics

Faculty, Staff and Students Publications

Exploring the clinical relevance of diverse immune cell types within the tumor microenvironment is pivotal for unraveling cancer intricacies and developing treatments. Here, we present a protocol for using tumor immune microenvironment illustration based on gene pairs, an R package to deduce cell-cell interactions, unveiling the association between immune cell relative abundance and patient prognoses from bulk gene expression and survival data. We describe steps for harnessing cell-type markers derived from single-cell RNA sequencing data to map the tumor immune microenvironment across a spectrum of cancer types. For complete details on the use and execution of this protocol, please refer …