Medical Specialties Commons^™

Surface-Doped Zinc Gallate Colloidal Nanoparticles Exhibit Ph-Dependent Radioluminescence With Enhancement In Acidic Media, Navadeep Shrivastava, Jessa Guffie, Tamela L Moore, Burak Guzelturk, Amar S Kumbhar, Jianguo Wen, Zhiping Luo

Faculty, Staff and Student Publications

As abnormal acidic pH symbolizes dysfunctions of cells, it is highly desirable to develop pH-sensitive luminescent materials for diagnosing disease and imaging-guided therapy using high-energy radiation. Herein, we explored near-infrared-emitting Cr-doped zinc gallate ZnGa2O4 nanoparticles (NPs) in colloidal solutions with different pH levels under X-ray excitation. Ultrasmall NPs were synthesized via a facile hydrothermal method by controlling the addition of ammonium hydroxide precursor and reaction time, and structural characterization revealed Cr dopants on the surface of NPs. The synthesized NPs exhibited different photoluminescence and radioluminescence mechanisms, confirming the surface distribution of activators. It was observed that the colloidal NPs emit …

Gender Differences In A Mouse Model Of Hepatocellular Carcinoma Revealed Using Multi-Modal Imaging, Brian J Engel, Vincenzo Paolillo, Md Nasir Uddin, Kristyn A Gonzales, Kathryn M Mcginnis, Margie N Sutton, Madhavi Patnana, Brian J Grindel, Gregory J Gores, David Piwnica-Worms, Laura Beretta, Federica Pisaneschi, Seth T Gammon, Steven W Millward

Faculty, Staff and Student Publications

The worldwide incidence of hepatocellular carcinoma (HCC) continues to rise, in part due to poor diet, limited exercise, and alcohol abuse. Numerous studies have suggested that the loss or mutation of PTEN plays a critical role in HCC tumorigenesis through the activation of the PI3K/Akt signaling axis. The homozygous knockout of PTEN in the livers of mice results in the accumulation of fat (steatosis), inflammation, fibrosis, and eventually progression to HCC. This phenotype bears a striking similarity to non-alcoholic steatohepatitis (NASH) which is thought to occupy an intermediate stage between non-alcoholic fatty liver disease (NAFLD), fibrosis, and HCC. The molecular …

Islet: Individual-Specific Reference Panel Recovery Improves Cell-Type-Specific Inference, Hao Feng, Guanqun Meng, Tong Lin, Hemang Parikh, Yue Pan, Ziyi Li, Jeffrey Krischer, Qian Li

Faculty, Staff and Student Publications

We propose a statistical framework ISLET to infer individual-specific and cell-type-specific transcriptome reference panels. ISLET models the repeatedly measured bulk gene expression data, to optimize the usage of shared information within each subject. ISLET is the first available method to achieve individual-specific reference estimation in repeated samples. Using simulation studies, we show outstanding performance of ISLET in the reference estimation and downstream cell-type-specific differentially expressed genes testing. We apply ISLET to longitudinal transcriptomes profiled from blood samples in a large observational study of young children and confirm the cell-type-specific gene signatures for pancreatic islet autoantibody. ISLET is available at https://bioconductor.org/packages/ISLET …

Clinical Evidence Of Human Pathogens Implicated In Alzheimer’S Disease Pathology And The Therapeutic Efficacy Of Antimicrobials: An Overview, Celso S G Catumbela, Vijayasree V Giridharan, Tatiana Barichello, Rodrigo Morales

Faculty, Staff and Student Publications

A wealth of pre-clinical reports and data derived from human subjects and brain autopsies suggest that microbial infections are relevant to Alzheimer's disease (AD). This has inspired the hypothesis that microbial infections increase the risk or even trigger the onset of AD. Multiple models have been developed to explain the increase in pathogenic microbes in AD patients. Although this hypothesis is well accepted in the field, it is not yet clear whether microbial neuroinvasion is a cause of AD or a consequence of the pathological changes experienced by the demented brain. Along the same line, the gut microbiome has also …

Telehealth Diagnosis Of Autism Spectrum Disorder Through Clinical Cases, Emmanuela Ojukwu, Eunice Bawafaa, Sara Afsah, Shivangi Singh, Harsimran Grewal, Zainab Raja, Emily Mckay

Faculty, Staff and Student Publications

INTRODUCTION: African, Caribbean and Black (ACB) adolescents are disproportionately affected by teen pregnancy in North America. Teen pregnancy poses risks to the quality of life of adolescent boys and girls, including physical, psychosocial and socioeconomic risks. Our review aims to explore this public health concern for ACB adolescents within North America. We aim to identify and analyse available evidence on the incidence and prevalence of, associated factors of and interventions to curtail teen pregnancy involvement (TPI) among ACB adolescent boys and girls in North America. This review will explore TPI, rather than teen pregnancy, to ensure a review of men' …

Tissue-Specific Features Of The T Cell Repertoire After Allogeneic Hematopoietic Cell Transplantation In Human And Mouse, Susan Dewolf, Yuval Elhanati, Katherine Nichols, Nicholas R Waters, Chi L Nguyen, John B Slingerland, Natasia Rodriguez, Olga Lyudovyk, Paul A Giardina, Anastasia I Kousa, Hana Andrlová, Nick Ceglia, Teng Fei, Rajya Kappagantula, Yanyun Li, Nathan Aleynick, Priscilla Baez, Rajmohan Murali, Akimasa Hayashi, Nicole Lee, Brianna Gipson, Madhumitha Rangesa, Zoe Katsamakis, Anqi Dai, Amanda G Blouin, Maria Arcila, Ignas Masilionis, Ronan Chaligne, Doris M Ponce, Heather J Landau, Ioannis Politikos, Roni Tamari, Alan M Hanash, Robert R Jenq, Sergio A Giralt, Kate A Markey, Yanming Zhang, Miguel-Angel Perales, Nicholas D Socci, Benjamin D Greenbaum, Christine A Iacobuzio-Donahue, Travis J Hollmann, Marcel R M Van Den Brink, Jonathan U Peled

Faculty, Staff and Student Publications

T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood …

Comprehensive Analysis Of The Prognostic Significance Of The Trim Family In The Context Of Tp53 Mutations In Cancers, Trung Vu, Annaliese Fowler, Nami Mccarty

Faculty, Staff and Student Publications

The p53 protein is an important tumor suppressor, and TP53 mutations are frequently associated with poor prognosis in various cancers. Mutations in TP53 result in a loss of p53 function and enhanced expression of cell cycle genes, contributing to the development and progression of cancer. Meanwhile, several tripartite motif (TRIM) proteins are known to regulate cell growth and cell cycle transition. However, the prognostic values between TP53 and TRIM family genes in cancer are unknown. In this study, we analyzed the relationship between the

Prescribing Patterns Of Fall Risk-Increasing Drugs In Older Adults Hospitalized For Heart Failure, Esther Liu, Musarrat Nahid, Mahad Musse, Ligong Chen, Sarah N Hilmer, Andrew Zullo, Min Ji Kwak, Mark Lachs, Emily B Levitan, Monika M Safford, Parag Goyal

Faculty, Staff and Student Publications

BACKGROUND: Older adults hospitalized for heart failure (HF) are at risk for falls after discharge. One modifiable contributor to falls is fall risk-increasing drugs (FRIDs). However, the prevalence of FRIDs among older adults hospitalized for HF is unknown. We describe patterns of FRIDs use and examine predictors of a high FRID burden.

METHODS: We used the national biracial REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective cohort recruited from 2003-2007. We included REGARDS participants aged ≥ 65 years discharged alive after a HF hospitalization from 2003-2017. We determined FRIDs -cardiovascular (CV) and non-cardiovascular (non-CV) medications - …

Impact Of Type Of Induction Therapy On Outcomes In Older Adults With Aml After Allogeneic Stem Cell Transplantation, Nicholas J Short, Faustine Ong, Farhad Ravandi, Graciela Nogueras-Gonzalez, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Marina Konopleva, Gautam Borthakur, Betul Oran, Gheath Al-Atrash, Rohtesh Mehta, Elias J Jabbour, Musa Yilmaz, Ghayas C Issa, Abhishek Maiti, Richard E Champlin, Hagop Kantarjian, Elizabeth J Shpall, Uday Popat

Faculty, Staff and Student Publications

Although venetoclax-based lower-intensity regimens have greatly improved outcomes for older adults with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, the optimal induction for older patients with newly diagnosed AML who are suitable candidates for hematopoietic stem cell transplant (HSCT) is controversial. We retrospectively analyzed the post HSCT outcomes of 127 patients ≥60 years of age who received induction therapy at our institution with intensive chemotherapy (IC; n = 44), lower-intensity therapy (LIT) without venetoclax (n = 29), or LIT with venetoclax (n = 54) and who underwent allogeneic HSCT in the first remission. The 2-year relapse-free survival …

Agrp Neurons Are Not Indispensable For Body Weight Maintenance In Adult Mice, Jing Cai, Jing Chen, Joshua Ortiz-Guzman, Jessica Huang, Benjamin R Arenkiel, Yuchen Wang, Yan Zhang, Yuyan Shi, Qingchun Tong, Cheng Zhan

Faculty, Staff and Student Publications

In addition to their role in promoting feeding and obesity development, hypothalamic arcuate agouti-related protein/neuropeptide Y (AgRP/NPY) neurons are widely perceived to be indispensable for maintaining normal feeding and body weight in adults, and consistently, acute inhibition of AgRP neurons is known to reduce short-term food intake. Here, we adopted complementary methods to achieve nearly complete ablation of arcuate AgRP/NPY neurons in adult mice and report that lesioning arcuate AgRP/NPY neurons in adult mice causes no apparent alterations in ad libitum feeding or body weight. Consistent with previous studies, loss of AgRP/NPY neurons blunts fasting refeeding. Thus, our studies show …

Dual Targeting Of Cdk4/6 And Bcl-2 Exhibits A Potent Antitumor Effect On Mantle Cell Lymphoma, Yuxuan Che, Yang Liu, Yijing Li, Joseph M Mcintosh, Alexa Jordan, Fangfang Yan, Wei Wang, Lei Nie, Heng-Huan Lee, Jingling Jin, Yixin Yao, Zhongming Zhao, Vivian Changying Jiang, Michael Wang

Faculty, Staff and Student Publications

No abstract provided.

The Mastery Lifestyle Intervention To Reduce Biopsychosocial Risks For Pregnant Latinas And African Americans And Their Infants: Protocol For A Randomized Controlled Trial, Berta H Ganizada, Koen D Reesink, Shaiv Parikh, Mitch J F G Ramaekers, Asim C Akbulut, Pepijn J M H Saraber, Gijs P Debeij, Mumc-Taa Student Team, Armand M Jaminon, Ehsan Natour, Roberto Lorusso, Joachim E Wildberger, Barend Mees, Geert Willem Schurink, Michael J Jacobs, Jack Cleutjens, Ingrid Krapels, Alexander Gombert, Jos G Maessen, Ryan Accord, Tammo Delhaas, Simon Schalla, Leon J Schurgers, Elham Bidar

Faculty, Staff and Student Publications

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5-5.5 cm or shows a growth rate of >0.5 cm/year estimated from echo/CT/MRI. However, many aTAA dissections (aTAAD) occur in vessels with diameters below the surgical intervention threshold ofMoreover, during aTAA repair surgeons observe and experience considerable variations in tissue strength, thickness, and stiffness that appear not fully explained by patient risk factors. To improve the understanding of aTAA pathophysiology, we established a multi-disciplinary research infrastructure: The Maastricht acquisition platform for studying mechanisms of tissue-cell crosstalk (MAPEX). The explicit scientific focus of the …

Deep Learning-Based Tem Image Analysis For Fully Automated Detection Of Gold Nanoparticles Internalized Within Tumor Cell, Amrit Kaphle, Sandun Jayarathna, Hem Moktan, Maureen Aliru, Subhiksha Raghuram, Sunil Krishnan, Sang Hyun Cho

Faculty, Staff and Student Publications

Transmission electron microscopy (TEM) imaging can be used for detection/localization of gold nanoparticles (GNPs) within tumor cells. However, quantitative analysis of GNP-containing cellular TEM images typically relies on conventional/thresholding-based methods, which are manual, time-consuming, and prone to human errors. In this study, therefore, deep learning (DL)-based methods were developed for fully automated detection of GNPs from cellular TEM images. Several models of "you only look once (YOLO)" v5 were implemented, with a few adjustments to enhance the model's performance by applying the transfer learning approach, adjusting the size of the input image, and choosing the best optimization algorithm. Seventy-eight original …

Abatacept, Cenicriviroc, Or Infliximab For Treatment Of Adults Hospitalized With Covid-19 Pneumonia: A Randomized Clinical Trial, Jane A O'Halloran, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W Mccarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M Lachiewicz, Cynthia Gonzalez, P Brian Smith, Sabina Mendivil-Tuchia De Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M Rauseo, Cameron R Wolfe, Britta Witting, Jennifer P Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M O'Brien, Hussein R Al-Khalidi, Michael A Maldonado, Richard Melsheimer, William G Ferguson, Steven E Mcnulty, Pearl Zakroysky, Susan Halabi, Daniel K Benjamin, Sandra Butler, Jane C Atkinson, Stacey J Adam, Soju Chang, Lisa Lavange, Michael Proschan, Samuel A Bozzette, William G Powderly, Activ-1 Im Study Group Members

Faculty, Staff and Student Publications

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19.

OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and …

Simplified And Highly-Reliable Automated Production Of [8f]Fspg For Clinical Studies, Mai Lin, Robert T Ta, H Charles Manning

Faculty, Staff and Student Publications

Background: (S)-4-(3-18F-Fluoropropyl)-L-Glutamic Acid ([18F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc-), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of [18F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [18F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [18F]FSPG production are still lacking to further increase the utility and …

Rad51c-Xrcc3 Structure And Cancer Patient Mutations Define Dna Replication Roles, Michael A Longo, Sunetra Roy, Yue Chen, Karl-Heinz Tomaszowski, Andrew S Arvai, Jordan T Pepper, Rebecca A Boisvert, Selvi Kunnimalaiyaan, Caezanne Keshvani, David Schild, Albino Bacolla, Gareth J Williams, John A Tainer, Katharina Schlacher

Faculty, Staff and Student Publications

RAD51C is an enigmatic predisposition gene for breast, ovarian, and prostate cancer. Currently, missing structural and related functional understanding limits patient mutation interpretation to homology-directed repair (HDR) function analysis. Here we report the RAD51C-XRCC3 (CX3) X-ray co-crystal structure with bound ATP analog and define separable RAD51C replication stability roles informed by its three-dimensional structure, assembly, and unappreciated polymerization motif. Mapping of cancer patient mutations as a functional guide confirms ATP-binding matching RAD51 recombinase, yet highlights distinct CX3 interfaces. Analyses of CRISPR/Cas9-edited human cells with RAD51C mutations combined with single-molecule, single-cell and biophysics measurements uncover discrete CX3 regions for DNA replication …

Longitudinal Diffusion And Volumetric Kinetics Of Head And Neck Cancer Magnetic Resonance On A 15 T Mr-Linear Accelerator Hybrid System: A Prospective R-Ideal Stage 2a Imaging Biomarker Characterization/Pre-Qualification Study, Joint Head And Neck Radiation Therapy-Mri Development Cooperative, Mr-Linac Consortium Head And Neck Tumor Site Group

Faculty, Staff and Student Publications

Objectives: We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5 T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort.

Methods:Thirty patients with HNSCC who received curative-intent RT at MD Anderson Cancer Center, were included. Baseline and weekly MRI were obtained, and various ADC parameters were extracted from the regions of interest (ROIs). Baseline and weekly ADC parameters were …

Clinical And Functional Correlates Of Parkinsonism In A Population-Based Sample Of Individuals Aged 75 +: The Pietà Study, Thiago Cardoso Vale, Francisco Eduardo Costa Cardoso, Danilo Jorge Da Silva, Elisa De Paula Franca Resende, Débora Palma Maia, Mauro César Quintão Cunningham, Henrique Cerqueira Guimarães, João Carlos Barbosa Machado, Antônio Lúcio Teixeira, Paulo Caramelli, Maira Tonidandel Barbosa

Faculty, Staff and Student Publications

BACKGROUND: Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG].

METHODS: The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG …

Targeting Polyploid Giant Cancer Cells Potentiates A Therapeutic Response And Overcomes Resistance To Parp Inhibitors In Ovarian Cancer, Xudong Zhang, Jun Yao, Xiaoran Li, Na Niu, Yan Liu, Richard A Hajek, Guang Peng, Shannon Westin, Anil K Sood, Jinsong Liu

Faculty, Staff and Student Publications

To understand the mechanism of acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) olaparib, we induced the formation of polyploid giant cancer cells (PGCCs) in ovarian and breast cancer cell lines, high-grade serous cancer (HGSC)-derived organoids, and patient-derived xenografts (PDXs). Time-lapse tracking of ovarian cancer cells revealed that PGCCs primarily developed from endoreplication after exposure to sublethal concentrations of olaparib. PGCCs exhibited features of senescent cells but, after olaparib withdrawal, can escape senescence via restitutional multipolar endomitosis and other noncanonical modes of cell division to generate mitotically competent resistant daughter cells. The contraceptive drug mifepristone blocked PGCC formation and daughter cell …

Intraoperative Cortical Localization Of Music And Language Reveals Signatures Of Structural Complexity In Posterior Temporal Cortex, Meredith J Mccarty, Elliot Murphy, Xavier Scherschligt, Oscar Woolnough, Cale W Morse, Kathryn Snyder, Bradford Z Mahon, Nitin Tandon

Faculty, Staff and Student Publications

Language and music involve the productive combination of basic units into structures. It remains unclear whether brain regions sensitive to linguistic and musical structure are co-localized. We report an intraoperative awake craniotomy in which a left-hemispheric language-dominant professional musician underwent cortical stimulation mapping (CSM) and electrocorticography of music and language perception and production during repetition tasks. Musical sequences were melodic or amelodic, and differed in algorithmic compressibility (Lempel-Ziv complexity). Auditory recordings of sentences differed in syntactic complexity (single vs. multiple phrasal embeddings). CSM of posterior superior temporal gyrus (pSTG) disrupted music perception and production, along with speech production. pSTG and …

Pragmatic, Randomized, Blinded Trial To Shorten Pharmacologic Treatment Of Newborns With Neonatal Opioid Withdrawal Syndrome (Nows), Adam Czynski, Abbot Laptook, Abhik Das, Brian Smith, Alan Simon, Rachel Greenberg, Robert Annett, Jeannette Lee, Jessica Snowden, Claudia Pedroza, Barry Lester, Barry Eggleston, Drew Bremer, Elisabeth Mcgowan

Faculty, Staff and Student Publications

BACKGROUND: The incidence of maternal opioid use in the USA has increased substantially since 2000. As a consequence of opioid use during pregnancy, the incidence of neonatal opioid withdrawal syndrome (NOWS) has increased fivefold between 2002 and 2012. Pharmacological therapy is indicated when signs of NOWS cannot be controlled, and the objective of pharmacological therapy is to control NOWS signs. Once pharmacologic therapy has started, there is great variability in strategies to wean infants. An important rationale for studying weaning of pharmacological treatment for NOWS is that weaning represents the longest time interval of drug treatment. Stopping medications too early …

Single-Cell Chromatin Accessibility Profiling Of Acute Myeloid Leukemia Reveals Heterogeneous Lineage Composition Upon Therapy-Resistance, Huihui Fan, Feng Wang, Andy Zeng, Alex Murison, Katarzyna Tomczak, Dapeng Hao, Fatima Zahra Jelloul, Bofei Wang, Praveen Barrodia, Shaoheng Liang, Ken Chen, Linghua Wang, Zhongming Zhao, Kunal Rai, Abhinav K Jain, John Dick, Naval Daver, Andy Futreal, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by high rate of therapy resistance. Since the cell of origin can impact response to therapy, it is crucial to understand the lineage composition of AML cells at time of therapy resistance. Here we leverage single-cell chromatin accessibility profiling of 22 AML bone marrow aspirates from eight patients at time of therapy resistance and following subsequent therapy to characterize their lineage landscape. Our findings reveal a complex lineage architecture of therapy-resistant AML cells that are primed for stem and progenitor lineages and spanning quiescent, activated and late stem cell/progenitor states. Remarkably, …

Genome-Wide Crispr-Cas9 Screen Analyzed By Slider Identifies Network Of Repressor Complexes That Regulate Trim24, Lalit R Patel, Sabrina A Stratton, Megan Mclaughlin, Patrick Krause, Kendra Allton, Andrés López Rivas, Daniela Barbosa, Traver Hart, Michelle C Barton

Faculty, Staff and Student Publications

TRIM24 is an oncogenic chromatin reader that is frequently overexpressed in human tumors and associated with poor prognosis. However, TRIM24 is rarely mutated, duplicated, or rearranged in cancer. This raises questions about how TRIM24 is regulated and what changes in its regulation are responsible for its overexpression. Here, we perform a genome-wide CRISPR-Cas9 screen by fluorescence-activated cell sorting (FACS) that nominated 220 negative regulators and elucidated a regulatory network that includes the KAP1 corepressor, CNOT deadenylase, and GID/CTLH E3 ligase. Knocking out required components of these three complexes caused TRIM24 overexpression, confirming their negative regulation of TRIM24. Our findings …

Single-Cell Sequencing Reveals The Landscape Of The Human Brain Metastatic Microenvironment, Qianqian Song, Jimmy Ruiz, Fei Xing, Hui-Wen Lo, Lou Craddock, Ashok K Pullikuth, Lance D Miller, Michael H Soike, Stacey S O'Neill, Kounosuke Watabe, Michael D Chan, Jing Su

Faculty, Staff and Student Publications

Brain metastases is the most common intracranial tumor and account for approximately 20% of all systematic cancer cases. It is a leading cause of death in advanced-stage cancer, resulting in a five-year overall survival rate below 10%. Therefore, there is a critical need to identify effective biomarkers that can support frequent surveillance and promote efficient drug guidance in brain metastasis. Recently, the remarkable breakthroughs in single-cell RNA-sequencing (scRNA-seq) technology have advanced our insights into the tumor microenvironment (TME) at single-cell resolution, which offers the potential to unravel the metastasis-related cellular crosstalk and provides the potential for improving therapeutic effects mediated …

Differential Effects Of Bariatric Surgery And Caloric Restriction On Hepatic One-Carbon And Fatty Acid Metabolism, Arnon Haran, Michael Bergel, Doron Kleiman, Liron Hefetz, Hadar Israeli, Sarah Weksler-Zangen, Bella Agranovich, Ifat Abramovich, Rachel Ben-Haroush Schyr, Eyal Gottlieb, Danny Ben-Zvi

Faculty, Staff and Student Publications

Weight loss interventions, including dietary changes, pharmacotherapy, or bariatric surgery, prevent many of the adverse consequences of obesity, and may also confer intervention-specific benefits beyond those seen with decreased weight alone. We compared the molecular effects of different interventions on liver metabolism to understand the mechanisms underlying these benefits. Male rats on a high-fat, high-sucrose diet underwent sleeve gastrectomy (SG) or intermittent fasting with caloric restriction (IF-CR), achieving equivalent weight loss. The interventions were compared to

Gold Nanoparticles For Monitoring Of Mesenchymal Stem-Cell-Loaded Bioresorbable Polymeric Wraps For Arteriovenous Fistula Maturation, Allan John R Barcena, Joy Vanessa D Perez, Jossana A Damasco, Marvin R Bernardino, Erin Marie D San Valentin, Carleigh Klusman, Benjamin Martin, Andrea Cortes, Gino Martin Canlas, Huckie C Del Mundo, Francisco M Heralde, Rony Avritscher, Natalie Fowlkes, Richard R Bouchard, Jizhong Cheng, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

Mesenchymal stem cell (MSC)-seeded polymeric perivascular wraps have been shown to enhance arteriovenous fistula (AVF) maturation. However, the wraps' radiolucency makes their placement and integrity difficult to monitor. Through electrospinning, we infused gold nanoparticles (AuNPs) into polycaprolactone (PCL) wraps to improve their radiopacity and tested whether infusion affects the previously reported beneficial effects of the wraps on the AVF's outflow vein. Sprague Dawley rat MSCs were seeded on the surface of the wraps. We then compared the effects of five AVF treatments-no perivascular wrap (i.e., control), PCL wrap, PCL + MSC wrap, PCL-Au wrap, and PCL-Au + MSC wrap-on AVF …

Adaptation And Formative Evaluation Of Online Decision Support To Implement Evidence-Based Strategies To Increase Hpv Vaccination Rates In Pediatric Clinics, Ross Shegog, Lara S Savas, Erica L Frost, Laura C Thormaehlen, Travis Teague, Jack Steffy, Catherine Mary Healy, Laura Aubree Shay, Sharice Preston, Sally W Vernon

Faculty, Staff and Student Publications

Human papilloma virus (HPV) vaccination rates remain below national goals in the United States despite the availability of evidence-based strategies to increase rates. The Adolescent Vaccination Program (AVP) is a multi-component intervention demonstrated to increase HPV vaccination rates in pediatric clinics through the implementation of six evidence-based strategies. The purpose of this study, conducted in Houston, Texas, from 2019-2021, was to adapt the AVP into an online decision support implementation tool for standalone use and to evaluate its feasibility for use in community clinics. Phase 1 (Adaptation) comprised clinic interviews (

Study Of Polytopic Membrane Protein Topological Organization As A Function Of Membrane Lipid Composition, Takefumi Morizumi, Kyumhyuk Kim, Hai Li, Elena G Govorunova, Oleg A Sineshchekov, Yumei Wang, Lei Zheng, Éva Bertalan, Ana-Nicoleta Bondar, Azam Askari, Leonid S Brown, John L Spudich, Oliver P Ernst

Faculty, Staff and Student Publications

Kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) is a light-gated channel used for optogenetic silencing of mammalian neurons. It selects K+ over Na+ in the absence of the canonical tetrameric K+ selectivity filter found universally in voltage- and ligand-gated channels. The genome of H. catenoides also encodes a highly homologous cation channelrhodopsin (HcCCR), a Na+ channel with >100-fold larger Na+ to K+ permeability ratio. Here, we use cryo-electron microscopy to determine atomic structures of these two channels embedded in peptidiscs to elucidate structural foundations of their dramatically different cation selectivity. Together with structure-guided mutagenesis, we show that K+ versus Na+ …

Measuring And Enhancing The Ionic Conductivity Of Chloroaluminate Electrolytes For Al-Ion Batteries, Anthony J Lucio, Iwan Sumarlan, Elena Bulmer, Igor Efimov, Stephen Viles, A Robert Hillman, Christopher J Zaleski, Karl S Ryder

Faculty, Staff and Student Publications

At the core of the aluminum (Al) ion battery is the liquid electrolyte, which governs the underlying chemistry. Optimizing the rheological properties of the electrolyte is critical to advance the state of the art. In the present work, the chloroaluminate electrolyte is made by reacting AlCl3 with a recently reported acetamidinium chloride (Acet-Cl) salt in an effort to make a more performant liquid electrolyte. Using AlCl3:Acet-Cl as a model electrolyte, we build on our previous work, which established a new method for extracting the ionic conductivity from fitting voltammetric data, and in this contribution, we validate the method across a …

A Novel Statistical Method For Decontaminating T-Cell Receptor Sequencing Data, Ruoxing Li, Mehmet Altan, Alexandre Reuben, Ruitao Lin, John V Heymach, Hai Tran, Runzhe Chen, Latasha Little, Shawna Hubert, Jianjun Zhang, Ziyi Li

Faculty, Staff and Student Publications

The T-cell receptor (TCR) repertoire is highly diverse among the population and plays an essential role in initiating multiple immune processes. TCR sequencing (TCR-seq) has been developed to profile the T cell repertoire. Similar to other high-throughput experiments, contamination can happen during several steps of TCR-seq, including sample collection, preparation and sequencing. Such contamination creates artifacts in the data, leading to inaccurate or even biased results. Most existing methods assume 'clean' TCR-seq data as the starting point with no ability to handle data contamination. Here, we develop a novel statistical model to systematically detect and remove contamination in TCR-seq data. …