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Computational Sensitivity Evaluation Of Ultrasound Neuromodulation Resolution To Brain Tissue Sound Speed With Robust Beamforming, Boqiang Fan, Wayne Goodman, Sameer A Sheth, Richard R Bouchard, Behnaam Aazhang Apr 2025

Computational Sensitivity Evaluation Of Ultrasound Neuromodulation Resolution To Brain Tissue Sound Speed With Robust Beamforming, Boqiang Fan, Wayne Goodman, Sameer A Sheth, Richard R Bouchard, Behnaam Aazhang

Faculty, Staff and Student Publications

Low-intensity focused ultrasound (LIFU) neuromodulation requires precise targeting and high resolution enabled by phased array transducers and beamforming. However, focusing optimization usually relies on phantom measurements or simulations with inaccurate acoustic properties to degrade neuromodulation resolution. Therefore, this work analyzes the sensitivity of neuromodulation resolution, measured by off-target activation area (OTAA), to brain tissue sound speed. A Robust Optimal Resolution (ROR) beamforming method is proposed to minimize the worst-case OTAA with restricted sound speed inaccuracy and propagation information estimated with deviated sound speed. The propagation estimation model utilizes equivalent source method (ESM) to map sound field between different acoustic parameter …


Identifiability And Model Selection Frameworks For Models Of High-Grade Glioma Response To Chemoradiation, Khushi C Hiremath, Kenan Atakishi, Ernesto A B F Lima, Maguy Farhat, Bikash Panthi, Mihir D Shanker, Sara Thrower, Jodi Goldman, Caroline Chung, Thomas E Yankeelov, David A Hormuth Ii Apr 2025

Identifiability And Model Selection Frameworks For Models Of High-Grade Glioma Response To Chemoradiation, Khushi C Hiremath, Kenan Atakishi, Ernesto A B F Lima, Maguy Farhat, Bikash Panthi, Mihir D Shanker, Sara Thrower, Jodi Goldman, Caroline Chung, Thomas E Yankeelov, David A Hormuth Ii

Faculty, Staff and Student Publications

We have developed a family of biology-based mathematical models of high-grade glioma (HGG), capturing the key features of tumour growth and response to chemoradiation. We now seek to quantify the accuracy of parameter estimation and determine, when given a virtual patient cohort, which model was used to generate the tumours. In this way, we systematically test both the parameter and model identifiability. Virtual patients are generated from unique growth parameters whose growth dynamics are determined by the model family. We then assessed the ability to recover model parameters and select the model used to generate the tumour. We then evaluated …


Analyzing Social Media Trends In Cosmeceuticals: Insights From Google Trends And Tiktok Analytics, E. Correia, Jenna Mandel, Stephanie R. Jackson Cullison Apr 2025

Analyzing Social Media Trends In Cosmeceuticals: Insights From Google Trends And Tiktok Analytics, E. Correia, Jenna Mandel, Stephanie R. Jackson Cullison

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Social media usage has surged, particularly since the COVID-19 pandemic. Dermatology invokes intense interest on social media, and cosmeceuticals are among the most trending topics, offering a unique space for dermatologists to share their expertise. By using tools like Google Trends and TikTok viewership, we aim to capture cosmeceutical trends to guide dermatologists' educational efforts.

METHODS: A Google Trends search from January 2004 to December 2023 was performed on retinol, bakuchiol, salicylic acid, glycolic acid, azelaic acid, hydroquinone, niacinamide, vitamin C serum, and hyaluronic acid. Trend lines were created for each term, and yearly percent differences in relative search …


Evaluating The Human Abuse Potential Of Concurrent Use Of Electronic Cigarettes And Low Nicotine Cigarettes Among Adults Who Smoke, Jason D Robinson, Yong Cui, George Kypriotakis, Jeffrey M Engelmann, Maher Karam-Hage, Jennifer A Minnix, Charles E Green, Sanjay Shete, Dorothy K Hatsukami, Eric C Donny, Sharon E Murphy, Stephen S Hecht, Thomas Eissenberg, David W Wetter, Paul M Cinciripini Apr 2025

Evaluating The Human Abuse Potential Of Concurrent Use Of Electronic Cigarettes And Low Nicotine Cigarettes Among Adults Who Smoke, Jason D Robinson, Yong Cui, George Kypriotakis, Jeffrey M Engelmann, Maher Karam-Hage, Jennifer A Minnix, Charles E Green, Sanjay Shete, Dorothy K Hatsukami, Eric C Donny, Sharon E Murphy, Stephen S Hecht, Thomas Eissenberg, David W Wetter, Paul M Cinciripini

Faculty, Staff and Student Publications

The U.S. Food and Drug Administration has stated its intention to reduce the nicotine content of combustible cigarettes to render them less addictive. This study evaluated the impact of providing adults who smoke with both very low nicotine content cigarettes (VLNCCs) and electronic cigarettes (ECs) of varying nicotine content on measures of human abuse potential. Participants (


Endogenous Dna Damage At Sites Of Terminated Transcripts, Sadeieh Nimer, Alice X Wen, Jennifer A Halliday, Devon M Fitzgerald, Qian Mei, Ralf B Nehring, Mary Crum, Stanislav G Kozmin, Jun Xia, Matthew B Cooke, Yin Zhai, David Bates, Lei Li, P J Hastings, Irina Artsimovitch, Christophe Herman, Patrick M Sung, Kyle M Miller, Susan M Rosenberg Apr 2025

Endogenous Dna Damage At Sites Of Terminated Transcripts, Sadeieh Nimer, Alice X Wen, Jennifer A Halliday, Devon M Fitzgerald, Qian Mei, Ralf B Nehring, Mary Crum, Stanislav G Kozmin, Jun Xia, Matthew B Cooke, Yin Zhai, David Bates, Lei Li, P J Hastings, Irina Artsimovitch, Christophe Herman, Patrick M Sung, Kyle M Miller, Susan M Rosenberg

Faculty, Staff and Students Publications

DNA damage promotes mutations that fuel cancer, aging, and neurodegenerative diseases1–3, but surprisingly, the causes and types of damage remain largely unknown. There are three identified mechanisms that damage DNA during transcription: RNA polymerase (RNAP) colliding with DNA-replication machinery head-on and co-directionally4–6, and R-loop-induced DNA breakage7–10. Here, we identify DNA-damage reaction intermediates11,12 uncharacterized previously in living cells, and uncover a surprising fourth transcription-related source: endogenous DNA damage at sites of terminated transcripts. We engineered proteins to capture single-stranded (ss)DNA ends with 3'-polarity, in both bacterial …


Factors Associated With Completeness Of Sex And Gender Fields In Electronic Health Records, Dinah Foer Apr 2025

Factors Associated With Completeness Of Sex And Gender Fields In Electronic Health Records, Dinah Foer

Faculty, Staff and Students Publications

Purpose: Our purpose was to understand the completeness of sex and gender fields in electronic health record (EHR) data and patient-level factors associated with completeness of those fields. In doing so, we aimed to inform approaches to EHR sex and gender data collection.

Methods: This was a retrospective observational study using 2016-2021 deidentified EHR data from a large health care system. Our sample included adults who had an encounter at any of three hospitals within the health care system or were enrolled in the health care system's Accountable Care Organization. The sex and gender fields of interest were gender identity, …


Intestinal Epithelial Serotonin As A Novel Target For Treating Disorders Of Gut-Brain Interaction And Mood, Ardesheer Talati, Sarah A Najjar, Virginie Bouchard, Virginie Gillet, Yan Tong, Zixing Huang, Kirsteen N Browning, Jialiang Hua, Ying Liu, James O Woodruff, Daniel Juarez, Melissa Medina, Jonathan Posner, Raquel Tonello, Nazli Yalcinkaya, Narek Israelyan, Roey Ringel, Letao Yang, Kam W Leong, Mu Yang, Ji Ying Sze, Tor Savidge, Jay Gingrich, Robert J Shulman, Michael D Gershon, Annie Ouellet, Larissa Takser, Mark S Ansorge, Kara Gross Margolis Apr 2025

Intestinal Epithelial Serotonin As A Novel Target For Treating Disorders Of Gut-Brain Interaction And Mood, Ardesheer Talati, Sarah A Najjar, Virginie Bouchard, Virginie Gillet, Yan Tong, Zixing Huang, Kirsteen N Browning, Jialiang Hua, Ying Liu, James O Woodruff, Daniel Juarez, Melissa Medina, Jonathan Posner, Raquel Tonello, Nazli Yalcinkaya, Narek Israelyan, Roey Ringel, Letao Yang, Kam W Leong, Mu Yang, Ji Ying Sze, Tor Savidge, Jay Gingrich, Robert J Shulman, Michael D Gershon, Annie Ouellet, Larissa Takser, Mark S Ansorge, Kara Gross Margolis

Faculty, Staff and Students Publications

Background & aims: Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly …


A Novel Method For Semi-Quantitative Detection Of Hpv16 And Hpv18 Mrna With A Low-Cost, Open-Source Fluorimeter, Kathryn A Kundrod, Mary E Natoli, Chelsey A Smith, Jackson B Coole, Megan M Chang, Emilie Newsham Novak, Elizabeth Chiao, Elizabeth A Stier, Jane R Montealegre, Michael E Scheurer, Philip E Castle, Kathleen M Schmeler, Rebecca R Richards-Kortum Apr 2025

A Novel Method For Semi-Quantitative Detection Of Hpv16 And Hpv18 Mrna With A Low-Cost, Open-Source Fluorimeter, Kathryn A Kundrod, Mary E Natoli, Chelsey A Smith, Jackson B Coole, Megan M Chang, Emilie Newsham Novak, Elizabeth Chiao, Elizabeth A Stier, Jane R Montealegre, Michael E Scheurer, Philip E Castle, Kathleen M Schmeler, Rebecca R Richards-Kortum

Center for Medical Ethics and Health Policy Staff Publications

Despite global calls to eliminate cervical cancer, rates of cervical cancer incidence and mortality remain high in resource-limited settings, where it is challenging to implement and sustain screening, diagnosis, and treatment programs. The presence of high-risk HPV mRNA in cervical cells is a sensitive and specific biomarker of cervical precancer. Yet, current testing methods are too costly and complex for use in resource-limited settings. Here, we present a novel method for semi-quantitative detection of HPV16 and HPV18 mRNA with minimal infrastructure requirements. The assay relies on isothermal reverse transcription recombinase polymerase amplification (RT-RPA) with real-time fluorescence readout, demonstrated on rugged, …


Il-12-Producing Cytokine Factories Induce Precursor Exhausted T Cells And Elimination Of Primary And Metastatic Tumors, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh Apr 2025

Il-12-Producing Cytokine Factories Induce Precursor Exhausted T Cells And Elimination Of Primary And Metastatic Tumors, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh

Faculty, Staff and Students Publications

Background: Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable responses.

Methods: In this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (NCT05538624) to identify …


Environmental Health Disparities In Pediatric Cancer: A Report From The Fourth Symposium On Childhood Cancer Health Disparities, Manish Arora, Stephen H Linder, Leticia M Nogueira, Amy E Hughes, Lindsay A Williams, Jeremy M Schraw, Michael E Scheurer, Philip J Lupo Apr 2025

Environmental Health Disparities In Pediatric Cancer: A Report From The Fourth Symposium On Childhood Cancer Health Disparities, Manish Arora, Stephen H Linder, Leticia M Nogueira, Amy E Hughes, Lindsay A Williams, Jeremy M Schraw, Michael E Scheurer, Philip J Lupo

Faculty, Staff and Student Publications

The 4th Symposium on Childhood Cancer Health Disparities was held at Texas Children's Hospital in Houston, Texas, on September 26, 2023. The symposium registered 94 attendees from different backgrounds (e.g. clinicians, epidemiologists, exposure assessment scientists, geospatial experts) with an interest in environmental health disparities of pediatric cancer susceptibility and treatment outcomes. The focus of the symposium was to provide an overview of the role of environmental risk factors in studies of pediatric cancer, introduce novel exposure assessment tools that can be applied to the field, and highlight opportunities to study the impact of environmental health disparities in pediatric cancer susceptibility …


Symptom Documentation In Unstructured Palliative Care Notes Of Children And Adolescents With Cancer., Katherine Bernier Carney, Jacob Wilkes, Tumilara Aderibigbe, Kristin Stegenga, Holly Spraker-Perlman, Lauri A. Linder Apr 2025

Symptom Documentation In Unstructured Palliative Care Notes Of Children And Adolescents With Cancer., Katherine Bernier Carney, Jacob Wilkes, Tumilara Aderibigbe, Kristin Stegenga, Holly Spraker-Perlman, Lauri A. Linder

Manuscripts, Articles, Book Chapters and Other Papers

CONTEXT: Children and adolescents with cancer experiencing complex symptoms can benefit from subspeciality palliative care. However, standardized methods of symptom documentation by pediatric palliative care teams are lacking. Understanding current approaches to symptom documentation will inform next steps to optimize symptom support.

OBJECTIVE: To explore the documentation of symptom prevalence and characteristics in unstructured clinical notes by pediatric palliative care clinicians caring for children and adolescents with cancer.

METHODS: We reviewed unstructured clinical notes documented by the pediatric palliative care team for 115 children and adolescents with cancer. Symptom-related data were abstracted and evaluated using content analysis based on the …


Acute Trem2 Inhibition Depletes Mafb-High Microglia And Hinders Remyelination, Jinchao Hou, Roberta Magliozzi, Yun Chen, Junjie Wu, John Wulf Ii, Gregory Strout, Xiangming Fang, Marco Colonna Apr 2025

Acute Trem2 Inhibition Depletes Mafb-High Microglia And Hinders Remyelination, Jinchao Hou, Roberta Magliozzi, Yun Chen, Junjie Wu, John Wulf Ii, Gregory Strout, Xiangming Fang, Marco Colonna

2020-Current year OA Pubs

We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting the


Lyset Facilitates Integration Of Both The N- And C-Terminal Transmembrane Helices/Cytoplasmic Domains Of Glcnac-1-Phosphotransferase, Baraj Doray, Benjamin C Jennings, Xi Yang, Lin Liu, Varsha Venkatarangan, Stuart Kornfeld, Ming Li Apr 2025

Lyset Facilitates Integration Of Both The N- And C-Terminal Transmembrane Helices/Cytoplasmic Domains Of Glcnac-1-Phosphotransferase, Baraj Doray, Benjamin C Jennings, Xi Yang, Lin Liu, Varsha Venkatarangan, Stuart Kornfeld, Ming Li

2020-Current year OA Pubs

LYSET is a recently identified Golgi transmembrane (TM) protein, and inactivating mutations in the


Model For End Stage Liver Disease Excluding International Normalized Ratio Predicts Severe Right Ventricular Failure After Heartmate 3 Implantation In A Contemporary Cohort, David S Lambert, Ana María Picó, Justin D Vincent, Elena Deych, Erin Coglianese, Joel D Schilling, Justin M Vader, Bin Q Yang Apr 2025

Model For End Stage Liver Disease Excluding International Normalized Ratio Predicts Severe Right Ventricular Failure After Heartmate 3 Implantation In A Contemporary Cohort, David S Lambert, Ana María Picó, Justin D Vincent, Elena Deych, Erin Coglianese, Joel D Schilling, Justin M Vader, Bin Q Yang

2020-Current year OA Pubs

BACKGROUND: Right ventricular failure (RVF) after left ventricular assist devices is associated with significant morbidity and mortality. Therefore, identifying patients at risk for severe RVF is important for clinical decision-making. Current risk prediction models were not developed in contemporary populations with left ventricular assist devices and have limited clinical applicability. In this study, we sought to evaluate whether the Model for End Stage Liver Disease Excluding International Normalized Ratio (MELD-XI) can predict severe RVF after HeartMate 3 implantation.

METHODS: We retrospectively analyzed all adult patients who received HeartMate 3 left ventricular assist devices as initial implantation at 2 academic medical …


Microvascular Aberrations Found In Human Polycystic Kidneys Are An Early Feature In A Pkd1 Mutant Mouse Model, Daniyal J Jafree, Yoshiharu Muto, Benjamin D Humphreys, Et Al. Apr 2025

Microvascular Aberrations Found In Human Polycystic Kidneys Are An Early Feature In A Pkd1 Mutant Mouse Model, Daniyal J Jafree, Yoshiharu Muto, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Therapies targeting blood vessels hold promise for autosomal dominant polycystic kidney disease (ADPKD), the most common inherited disorder causing kidney failure. However, the onset and nature of kidney vascular abnormalities in ADPKD are poorly defined. Accordingly, we employed a combination of single-cell transcriptomics; three-dimensional imaging with geometric, topological and fractal analyses; and multimodal magnetic resonance imaging with arterial spin labelling to investigate aberrant microvasculature in ADPKD kidneys. Within human ADPKD kidneys with advanced cystic pathology and excretory failure, we identified a molecularly distinct blood microvascular subpopulation, characterised by impaired angiogenic signalling and metabolic dysfunction, differing from endothelial injury profiles observed …


Ethical Considerations For Sharing Aggregate Results From Pragmatic Clinical Trials, Stephanie R Morain, Abigail Brickler, Joseph Ali, Patricia Pearl O'Rourke, Kayte Spector-Bagdady, Benjamin Wilfond, Vasiliki Rahimzadeh, Caleigh Propes, Kayla Mehl, David Wendler Apr 2025

Ethical Considerations For Sharing Aggregate Results From Pragmatic Clinical Trials, Stephanie R Morain, Abigail Brickler, Joseph Ali, Patricia Pearl O'Rourke, Kayte Spector-Bagdady, Benjamin Wilfond, Vasiliki Rahimzadeh, Caleigh Propes, Kayla Mehl, David Wendler

Center for Medical Ethics and Health Policy Staff Publications

A growing literature has explored the ethical obligations and current practices related to sharing aggregate results with research participants. However, no prior work has examined these issues in the context of pragmatic clinical trials. Several characteristics of pragmatic clinical trials may complicate both the ethics and the logistics of sharing aggregate results. Among these characteristics include that pragmatic clinical trials may affect the rights, welfare, and interests of not only patient-subjects but also clinicians, meaning that results may be owed to a broader range of groups than typically considered in other research contexts. In addition, some pragmatic clinical trials are …


Cytokine Storms In Covid-19, Hemophagocytic Lymphohistiocytosis, And Car-T Therapy, James P Long, Rishab Prakash, Paul Edelkamp, Mark Knafl, Anath C Lionel, Sairah Ahmed, Luis E Malpica Castillo, Ajlan Al-Zaki, Kelly Chien, Dai Chihara, Jason Westin, Fareed Khawaja, Loretta J Nastoupil, Victor Mulanovich, Andrew Futreal, Scott E Woodman, Naval G Daver, Christopher R Flowers, Sattva Neelapu, Joanna-Grace Manzano, Swaminathan P Iyer Apr 2025

Cytokine Storms In Covid-19, Hemophagocytic Lymphohistiocytosis, And Car-T Therapy, James P Long, Rishab Prakash, Paul Edelkamp, Mark Knafl, Anath C Lionel, Sairah Ahmed, Luis E Malpica Castillo, Ajlan Al-Zaki, Kelly Chien, Dai Chihara, Jason Westin, Fareed Khawaja, Loretta J Nastoupil, Victor Mulanovich, Andrew Futreal, Scott E Woodman, Naval G Daver, Christopher R Flowers, Sattva Neelapu, Joanna-Grace Manzano, Swaminathan P Iyer

Faculty, Staff and Student Publications

Importance: Cytokine storm (CS) is a hyperinflammatory syndrome causing multiorgan dysfunction and high mortality, especially in patients with malignant hematologic neoplasms. Triggers include malignant neoplasm-associated hemophagocytic lymphohistiocytosis (MN-HLH), cytokine release syndrome from chimeric antigen receptor T-cell therapy (CAR-T CRS), and COVID-19, but the underlying mechanisms of inflammation and their impact on outcomes are poorly understood.

Objective: To delineate the inflammatory patterns characterizing different CS etiologies and their association with clinical outcomes.

Design, setting, and participants: This retrospective cohort study was conducted at the MD Anderson Cancer Center in Houston, Texas, between March 1, 2020, and November 20, 2022, using the …


American College Of Radiology Manual On Mr Safety: 2024 Update And Revisions, Ivan Pedrosa, David A Altman, Jonathan R Dillman, Michael N Hoff, Alexander M Mckinney, Jeffrey M Rogg, James A Webb, Dina L Hernandez, Robert E Watson Apr 2025

American College Of Radiology Manual On Mr Safety: 2024 Update And Revisions, Ivan Pedrosa, David A Altman, Jonathan R Dillman, Michael N Hoff, Alexander M Mckinney, Jeffrey M Rogg, James A Webb, Dina L Hernandez, Robert E Watson

Faculty, Staff and Student Publications

Since the introduction of the American College of Radiology (ACR) MRI safety guidelines in 2002, the indications for use of MRI in clinical care and research have continued to expand. Similarly, MRI technologies have evolved, with multiple field strengths now available for human imaging. While several publications have updated the ACR recommendations since the first guidelines, a single source in a structured format was lacking. Accordingly, the ACR Committee on MR Safety recently updated the online ACR Manual on MR Safety that compiles ACR recommendations for safe use of MRI equipment in humans into a single document. This review describes …


Lysyl Hydroxylase 2 Glucosylates Collagen Vi To Drive Lung Cancer Progression, Shike Wang, Houfu Guo, Reo Fukushima, Masahiko Terajima, Min Liu, Lenka Koudelková, Xin Liu, Jiang Yu, Emma Burris, Jun Xu, Alvise Schiavinato, William K Russell, Mitsuo Yamauchi, Xiaochao Tan, Jonathan M Kurie Apr 2025

Lysyl Hydroxylase 2 Glucosylates Collagen Vi To Drive Lung Cancer Progression, Shike Wang, Houfu Guo, Reo Fukushima, Masahiko Terajima, Min Liu, Lenka Koudelková, Xin Liu, Jiang Yu, Emma Burris, Jun Xu, Alvise Schiavinato, William K Russell, Mitsuo Yamauchi, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

Lysyl hydroxylase 2 (LH2) is highly expressed in multiple tumor types and accelerates disease progression by hydroxylating lysine residues on fibrillar collagen telopeptides to generate stable collagen cross links in tumor stroma. Here, we show that a galactosylhydroxylysyl glucosyltransferase (GGT) domain on LH2-modified type-VI collagen (Col6) to promote lung adenocarcinoma (LUAD) growth and metastasis. In tumors generated by LUAD cells lacking LH2 GGT domain activity, stroma was less stiff, and stable types of collagen cross links were reduced. Mass spectrometric analysis of total and glycosylated peptides in parental and GGT-inactive tumor samples identified Col6 chain α3 (Col6a3), a component of …


Defining A 'Cells To Society' Research Framework For Appendiceal Tumours, Andreana N Holowatyj, Michael J Overman, Konstantinos I Votanopoulos, Andrew M Lowy, Patrick Wagner, Cathy Eng, Richard M Goldberg, Mojgan Hosseini, Kamran Idrees, Douglas B Johnson, Ardaman Shergill, Erin Ward, Nicholas C Zachos, Deborah Shelton Apr 2025

Defining A 'Cells To Society' Research Framework For Appendiceal Tumours, Andreana N Holowatyj, Michael J Overman, Konstantinos I Votanopoulos, Andrew M Lowy, Patrick Wagner, Cathy Eng, Richard M Goldberg, Mojgan Hosseini, Kamran Idrees, Douglas B Johnson, Ardaman Shergill, Erin Ward, Nicholas C Zachos, Deborah Shelton

Faculty, Staff and Student Publications

Tumours of the appendix — a vestigial digestive organ attached to the colon — are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity — wherein the potential misclassification of appendiceal tumours as …


Adoptively Transferred Tumor-Specific Il-9-Producing Cytotoxic Cd8+ T Cells Activate Host Cd4+ T Cells To Control Tumors With Antigen Loss, Xingzhe Ma, Miao Xian, Qiang Wang, Qi Guo, Wei Xiong, Pan Su, Lingqun Ye, Yabo Li, Ling Zhong, Jianfei Qian, Yong Lu, Zhongming Zhao, Qing Yi Apr 2025

Adoptively Transferred Tumor-Specific Il-9-Producing Cytotoxic Cd8+ T Cells Activate Host Cd4+ T Cells To Control Tumors With Antigen Loss, Xingzhe Ma, Miao Xian, Qiang Wang, Qi Guo, Wei Xiong, Pan Su, Lingqun Ye, Yabo Li, Ling Zhong, Jianfei Qian, Yong Lu, Zhongming Zhao, Qing Yi

Faculty, Staff and Student Publications

Host effector CD4+ T cells emerge as critical mediators for tumor regression but whether they can be activated by adoptively transferred CD8+ T cells remains unknown. We previously reported that adoptive transfer of interleukin 9 (IL-9)-producing cytotoxic CD8+ T (Tc9) cells achieved long-term control of tumor growth. Here, we demonstrate that murine tumor-specific Tc9 cells control the outgrowth of antigen-loss relapsed tumors by recruiting and activating host effector CD4+ T cells. Tc9 cells secreted IL-24 and recruited CCR7-expressing conventional type 2 dendritic cells (cDC2 cells) into tumor-draining lymph nodes to prime host CD4+ T cells against relapsed tumors. Host CD4+ …


Immunotherapy Targeting A Leader Sequence Cathepsin G-Derived Peptide, Chunhua Shi, Ze Tian, Jun Yan, Mao Zhang, Pariya Sukhumalchandra, Guojun Yang, Meng Cui, Qing Shi, Celine Kerros, Anne Philips, Na Qiao, Hiroki Torikai, Sathvik Patchametla, Anna Sergeeva, Lisa St John, Helen He, Dmitri Wiederschain, Benjamin H Lee, Geraldine L C Paulus, Dongxing Zha, Jeffrey Molldrem, Gheath Alatrash Apr 2025

Immunotherapy Targeting A Leader Sequence Cathepsin G-Derived Peptide, Chunhua Shi, Ze Tian, Jun Yan, Mao Zhang, Pariya Sukhumalchandra, Guojun Yang, Meng Cui, Qing Shi, Celine Kerros, Anne Philips, Na Qiao, Hiroki Torikai, Sathvik Patchametla, Anna Sergeeva, Lisa St John, Helen He, Dmitri Wiederschain, Benjamin H Lee, Geraldine L C Paulus, Dongxing Zha, Jeffrey Molldrem, Gheath Alatrash

Faculty, Staff and Student Publications

Myeloid azurophil granules provide a rich source of intracellular leukemia antigens. Cathepsin G (CG) is a serine protease that has higher expression in acute myeloid leukemia (AML) blasts in comparison to normal myeloid progenitors. Based on the unique biology of HLA-A*0201 (HLA-A2), in which presentation of leader sequence (LS)-derived peptides is favored, we focused on the LS-CG-derived peptide CG1 (FLLPTGAEA). We previously detected CG1/HLA-A2 complexes on the surface of primary HLA-A2+ AML blasts and cell lines, and immunity targeting CG1/HLA-A2 in leukemia patients. T cell receptor (TCR)-mimic (m) antibodies are immunotherapeutic antibodies that target peptide-HLA (pHLA) complexes. Here we report …


Il13rα2-Targeting Antibodies For Immuno-Pet In Solid Malignancies, Leah Gajecki, Irina V Lebedeva, Yu-Rou Liao, Daisy Ambriz, Lukas M Carter, Samantha Lovibond, Maya S Graham, Michael Postow, Jason S Lewis, David P Andrew, Manuel Baca, Heiko Schöder, Steven M Larson, Darren R Veach, Simone Krebs Apr 2025

Il13rα2-Targeting Antibodies For Immuno-Pet In Solid Malignancies, Leah Gajecki, Irina V Lebedeva, Yu-Rou Liao, Daisy Ambriz, Lukas M Carter, Samantha Lovibond, Maya S Graham, Michael Postow, Jason S Lewis, David P Andrew, Manuel Baca, Heiko Schöder, Steven M Larson, Darren R Veach, Simone Krebs

Faculty, Staff and Student Publications

Interleukin-13 receptor α-2 (IL13Rα2) is a cell surface receptor frequently expressed in solid malignancies, such as glioblastoma and melanoma, with limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor delineation. In this study, we report the development of 5 novel IL13Rα2-targeted human monoclonal antibodies (mAbs) KLG-1-5; in subsequent in vitro and in vivo studies after radiolabeling with 89Zr, we evaluate their performance to identify a lead candidate.

Methods: Five novel human anti-IL13Rα2 mAbs KLG-1-5 were developed and in vitro binding properties and target specificity assessed. In vivo 89Zr-immuno-PET using KLG-1-5 was conducted in a …


The Effect Of Alzheimer's Disease Genetic Factors On Limbic White Matter Microstructure, Anna Lorenz, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Chenyu Gao, Karthik Ramadass, Praitayini Kanakaraj, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Niranjana Shashikumar, Kimberly R Pechman, Trevor Bryan Jackson, Abigail W Workmeister, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Mohamad Habes, Di Wang, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Barbara Bendlin, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer Apr 2025

The Effect Of Alzheimer's Disease Genetic Factors On Limbic White Matter Microstructure, Anna Lorenz, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Chenyu Gao, Karthik Ramadass, Praitayini Kanakaraj, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Niranjana Shashikumar, Kimberly R Pechman, Trevor Bryan Jackson, Abigail W Workmeister, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Mohamad Habes, Di Wang, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Barbara Bendlin, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

Faculty, Staff and Student Publications

Introduction: White matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences.

Methods: To evaluate how AD genetic risk factors affect limbic WM microstructure - crucial for memory and early impacted in disease - we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores …


A New Multiple Imputation Method For High-Dimensional Neuroimaging Data, Tong Lu, Peter Kochunov, Chixiang Chen, Hsin-Hsiung Huang, L Elliot Hong, Shuo Chen Apr 2025

A New Multiple Imputation Method For High-Dimensional Neuroimaging Data, Tong Lu, Peter Kochunov, Chixiang Chen, Hsin-Hsiung Huang, L Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Missing data are a prevalent challenge in neuroimaging, with significant implications for downstream statistical analysis. Neglecting this issue can introduce bias and lead to erroneous inferential conclusions, making it crucial to employ appropriate statistical methods for handling missing data. Although the multiple imputation is a widely used technique, its application in neuroimaging is severely hindered by the high dimensionality of neuroimaging data, and the substantial computational demands. To tackle the critical computational challenges, we propose a novel approach, High dimensional Multiple Imputation (HIMA), based on Bayesian models specifically designed for large-scale neuroimaging datasets. HIMA introduces a new computational strategy to …


Limosilactobacillus Reuteri Promotes The Expression And Secretion Of Enteroendocrine- And Enterocyte-Derived Hormones, Ari Roberts, Robert A Britton Mar 2025

Limosilactobacillus Reuteri Promotes The Expression And Secretion Of Enteroendocrine- And Enterocyte-Derived Hormones, Ari Roberts, Robert A Britton

Faculty, Staff and Students Publications

Intestinal microbes can beneficially impact host physiology, prompting investigations into the therapeutic usage of such microbes in a range of diseases. For example, human intestinal microbe Limosilactobacillus reuteri strains ATCC PTA 6475 and DSM 17938 are being considered for use for intestinal ailments, including colic, infection, and inflammation, as well as for non-intestinal ailments, including osteoporosis, wound healing, and autism spectrum disorder. While many of their beneficial properties are attributed to suppressing inflammatory responses, we postulated that L. reuteri may also regulate intestinal hormones to affect physiology within and outside of the gut. To determine if L. reuteri secreted factors …


Cytosimplex: Visualizing Single-Cell Fates And Transitions On A Simplex Mar 2025

Cytosimplex: Visualizing Single-Cell Fates And Transitions On A Simplex

Faculty, Staff and Student Publications

Summary: Cells differentiate to their final fates along unique trajectories, often involving multi-potent progenitors that can produce multiple terminally differentiated cell types. Recent developments in single-cell transcriptomic and epigenomic measurement provide tremendous opportunities for mapping these trajectories. The visualization of single-cell data often relies on dimension reduction methods such as UMAP to simplify high-dimensional single-cell data down to an understandable 2D form. However, these dimension reduction methods are not constructed to allow direct interpretation of the reduced dimensions in terms of cell differentiation. To address these limitations, we developed a new approach that places each cell from a single-cell dataset …


Bridging Gaps In Cancer Care: Utilizing Large Language Models For Accessible Dietary Recommendations, Julia A. Logan, Sriya Sadhu, Cameo Hazlewood, Melissa Denton, Sara Burke, Christina A. Simone-Soule, Caroline Black, Corey Ciaverelli, Jacqueline Stulb, Hamidreza Nourzadeh, Yevgeniy Vinogradskiy, Amy Leader, Adam Dicker, Wookjin Choi, Nicole L Simone Mar 2025

Bridging Gaps In Cancer Care: Utilizing Large Language Models For Accessible Dietary Recommendations, Julia A. Logan, Sriya Sadhu, Cameo Hazlewood, Melissa Denton, Sara Burke, Christina A. Simone-Soule, Caroline Black, Corey Ciaverelli, Jacqueline Stulb, Hamidreza Nourzadeh, Yevgeniy Vinogradskiy, Amy Leader, Adam Dicker, Wookjin Choi, Nicole L Simone

Department of Radiation Oncology Faculty Papers

Background/Objectives: Weight management is directly linked to cancer recurrence and survival, but unfortunately, nutritional oncology counseling is not typically covered by insurance, creating a disparity for patients without nutritional education and food access. Novel ways of imparting personalized nutrition advice are needed to address this issue. Large language models (LLMs) offer a promising path toward tailoring dietary advice to individual patients. This study aimed to assess the capacity of LLMs to offer personalized dietary advice to patients with breast cancer. Methods: Thirty-one prompt templates were designed to evaluate dietary recommendations generated by ChatGPT and Gemini with variations within …


Assessing Cancer Therapeutic Efficacy In Vivo Using [2h7]Glucose Deuterium Metabolic Imaging, Mario C Chang, Vinay R Malut, Rohit Mahar, Anna Rushin, Marc A Mcleod, Indu R Malut, Max E Glanz, Mukundan Ragavan, Gaurav Sharma, Manoj Madheswaran, Arshee Badar, Aparna D Rao, Brian K Law, Michael S Kilberg, James H P Collins, Vikram D Kodibagkar, James A Bankson, Ralph J Deberardinis, Matthew E Merritt Mar 2025

Assessing Cancer Therapeutic Efficacy In Vivo Using [2h7]Glucose Deuterium Metabolic Imaging, Mario C Chang, Vinay R Malut, Rohit Mahar, Anna Rushin, Marc A Mcleod, Indu R Malut, Max E Glanz, Mukundan Ragavan, Gaurav Sharma, Manoj Madheswaran, Arshee Badar, Aparna D Rao, Brian K Law, Michael S Kilberg, James H P Collins, Vikram D Kodibagkar, James A Bankson, Ralph J Deberardinis, Matthew E Merritt

Faculty, Staff and Student Publications

Metabolic imaging produces powerful visual assessments of organ function in vivo. Current techniques can be improved by safely increasing metabolic contrast. The gold standard, 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, is limited by radioactive exposure and sparse assessment of metabolism beyond glucose uptake and retention. Deuterium magnetic resonance imaging (DMRI) with [6,6-2H2]glucose is nonradioactive, achieves tumor metabolic contrast, but can be improved by enriched contrast from deuterated water (HDO) based imaging. Here, we developed a DMRI protocol employing [2H7]glucose. Imaging 2H-signal and measuring HDO production in tumor-bearing mice detected differential glucose utilization across baseline tumors, tumors treated with vehicle control or …


Haploinsufficiency Of Itsn1 Is Associated With A Substantial Increased Risk Of Parkinson’S Disease, Jonathan Mitchell, Vida Ravanmehr, Jessica C Butts, Ruth B De-Paula, Youngdoo Kim, Fengyuan Hu, Quanli Wang, Dimitrios Vitsios, Manik Garg, Lawrence Middleton, Michal Tyrlik, Mirko Messa, Guillermo Del Angel, Daniel G Calame, Hiba Saade, Laurie Robak, Ben Hollis, Vishnu A Cuddapah, Huda Y Zoghbi, Joshua M Shulman, Slavé Petrovski, Ismael Al-Ramahi, Ioanna Tachmazidou, Ryan S Dhindsa Mar 2025

Haploinsufficiency Of Itsn1 Is Associated With A Substantial Increased Risk Of Parkinson’S Disease, Jonathan Mitchell, Vida Ravanmehr, Jessica C Butts, Ruth B De-Paula, Youngdoo Kim, Fengyuan Hu, Quanli Wang, Dimitrios Vitsios, Manik Garg, Lawrence Middleton, Michal Tyrlik, Mirko Messa, Guillermo Del Angel, Daniel G Calame, Hiba Saade, Laurie Robak, Ben Hollis, Vishnu A Cuddapah, Huda Y Zoghbi, Joshua M Shulman, Slavé Petrovski, Ismael Al-Ramahi, Ioanna Tachmazidou, Ryan S Dhindsa

Faculty, Staff and Students Publications

Despite its significant heritability, the genetic basis of Parkinson's disease (PD) remains incompletely understood. Here, in analyzing whole-genome sequence data from 3,809 PD cases and 247,101 controls in the UK Biobank, we discover that protein-truncating variants in ITSN1 confer a substantially increased risk of PD (p = 6.1 × 10