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Prediction Accuracy Of Soil Chemical Parameters By Field- And Laboratory-Obtained Vis-Nir Spectra After External Parameter Orthogonalization, Konrad Metzger, Frank Liebisch, Juan M Herrera, Thomas Guillaume, Luca Bragazza

Faculty, Staff and Student Publications

One challenge in predicting soil parameters using in situ visible and near infrared spectroscopy is the distortion of the spectra due to soil moisture. External parameter orthogonalization (EPO) is a mathematical method to remove unwanted variability from spectra. We created two different EPO correction matrices based on the difference between spectra collected in situ and, respectively, spectra collected from the same soil samples after drying and sieving and after drying, sieving and finely grinding. Spectra from 134 soil samples recorded with two different spectrometers were split into calibration and validation sets and the two EPO corrections were applied. Clay, organic …

Correction: Ver-Net: A Hybrid Transfer Learning Model For Lung Cancer Detection Using Ct Scan Images, Anindita Saha, Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Rakesh Kumar Yadav, Saurav Mallik, Zhongming Zhao

Faculty, Staff and Student Publications

No abstract provided.

Using Patient-Specific 3d Modeling And Simulations To Optimize Microwave Ablation Therapy For Liver Cancer, Amirreza Heshmat, Caleb S O'Connor, Jessica Albuquerque Marques Silva, Iwan Paolucci, Aaron Kyle Jones, Bruno C Odisio, Kristy K Brock

Faculty, Staff and Student Publications

Microwave ablation (MWA) of liver tumors presents challenges like under- and over-ablation, potentially leading to inadequate tumor destruction and damage to healthy tissue. This study aims to develop personalized three-dimensional (3D) models to simulate MWA for liver tumors, incorporating patient-specific characteristics. The primary objective is to validate the predicted ablation zones compared to clinical outcomes, offering insights into MWA before therapy to facilitate accurate treatment planning. Contrast-enhanced CT images from three patients were used to create 3D models. The simulations used coupled electromagnetic wave propagation and bioheat transfer to estimate the temperature distribution, predicting tumor destruction and ablation margins. The …

Multiomics Analysis Of The Phlda Gene Family In Different Cancers And Their Clinical Prognostic Value, Safia Iqbal, Md Rezaul Karim, Shahnawaz Mohammad, Ramya Mathiyalagan, Md Niaj Morshed, Deok-Chun Yang, Hyocheol Bae, Esrat Jahan Rupa, Dong Uk Yang

Faculty, Staff and Student Publications

The PHLDA (pleckstrin homology-like domain family) gene family is popularly known as a potential biomarker for cancer identification, and members of the PHLDA family have become considered potentially viable targets for cancer treatments. The PHLDA gene family consists of PHLDA1, PHLDA2, and PHLDA3. The predictive significance of PHLDA genes in cancer remains unclear. To determine the role of pleckstrin as a prognostic biomarker in human cancers, we conducted a systematic multiomics investigation. Through various survival analyses, pleckstrin expression was evaluated, and their predictive significance in human tumors was discovered using a variety of online platforms. By analyzing the protein-protein interactions, …

An International Phantom Study Of Inter-Site Variability In Technetium-99m Image Quantification: Analyses From The Target Radioembolization Study, Grace Keane, Rob Van Rooij, Marnix Lam, S Cheenu Kappadath, Bilal Kovan, Stephanie Leon, Matthew Dreher, Kirk Fowers, Hugo De Jong

Faculty, Staff and Student Publications

BACKGROUND: Personalised multi-compartment dosimetry based on [

RESULTS: Regarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6-10.1%). A standardised protocol did not improve variation (interquartile range 8.4-9.0%) but did improve mean accuracy compared to the site-specific protocols (5.0% error for standardised protocol vs 8.8% error for site-specific protocols). Regarding the CRC, inter-system variation was notable for site-specific SPECT protocols and could not be improved by the standardised protocol (CRC interquartile range for 37 mm sphere 0.5-0.7 and 0.6-0.8 respectively), however the standardised protocol did improve accuracy of …

Plasmonic Nano-Aperture Label-Free Imaging Of Single Small Extracellular Vesicles For Cancer Detection, Nareg Ohannesian, Mohammad Sadman Mallick, Jianzhong He, Yawei Qiao, Nan Li, Simona F Shaitelman, Chad Tang, Eileen H Shinn, Wayne L Hofstetter, Alexei Goltsov, Manal M Hassan, Kelly K Hunt, Steven H Lin, Wei-Chuan Shih

Faculty, Staff and Student Publications

BACKGROUND: Small extracellular vesicle (sEV) analysis can potentially improve cancer detection and diagnostics. However, this potential has been constrained by insufficient sensitivity, dynamic range, and the need for complex labeling.

METHODS: In this study, we demonstrate the combination of PANORAMA and fluorescence imaging for single sEV analysis. The co-acquisition of PANORAMA and fluorescence images enables label-free visualization, enumeration, size determination, and enables detection of cargo microRNAs (miRs).

RESULTS: An increased sEV count is observed in human plasma samples from patients with cancer, regardless of cancer type. The cargo miR-21 provides molecular specificity within the same sEV population at the single …

Ver-Net: A Hybrid Transfer Learning Model For Lung Cancer Detection Using Ct Scan Images, Anindita Saha, Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Rakesh Kumar Yadav, Saurav Mallik, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: Lung cancer is the second most common cancer worldwide, with over two million new cases per year. Early identification would allow healthcare practitioners to handle it more effectively. The advancement of computer-aided detection systems significantly impacted clinical analysis and decision-making on human disease. Towards this, machine learning and deep learning techniques are successfully being applied. Due to several advantages, transfer learning has become popular for disease detection based on image data.

METHODS: In this work, we build a novel transfer learning model (VER-Net) by stacking three different transfer learning models to detect lung cancer using lung CT scan images. …

Evaluating Performance And Applications Of Sample-Wise Cell Deconvolution Methods On Human Brain Transcriptomic Data, Rujia Dai, Tianyao Chu, Ming Zhang, Xuan Wang, Alexandre Jourdon, Feinan Wu, Jessica Mariani, Flora M Vaccarino, Donghoon Lee, John F Fullard, Gabriel E Hoffman, Panos Roussos, Yue Wang, Xusheng Wang, Dalila Pinto, Sidney H Wang, Chunling Zhang, Psychencode Consortium, Chao Chen, Chunyu Liu

Faculty, Staff and Student Publications

Sample-wise deconvolution methods estimate cell-type proportions and gene expressions in bulk tissue samples, yet their performance and biological applications remain unexplored, particularly in human brain transcriptomic data. Here, nine deconvolution methods were evaluated with sample-matched data from bulk tissue RNA sequencing (RNA-seq), single-cell/nuclei (sc/sn) RNA-seq, and immunohistochemistry. A total of 1,130,767 nuclei per cells from 149 adult postmortem brains and 72 organoid samples were used. The results showed the best performance of dtangle for estimating cell proportions and bMIND for estimating sample-wise cell-type gene expressions. For eight brain cell types, 25,273 cell-type eQTLs were identified with deconvoluted expressions (decon-eQTLs). The …

Validation Of Human Telomere Length Multi-Ancestry Meta-Analysis Association Signals Identifies Pop5 And Kbtbd6 As Human Telomere Length Regulation Genes, Rebecca Keener, Surya B Chhetri, Carla J Connelly, Margaret A Taub, Matthew P Conomos, Joshua Weinstock, Bohan Ni, Benjamin Strober, Stella Aslibekyan, Paul L Auer, Lucas Barwick, Lewis C Becker, John Blangero, Eugene R Bleecker, Jennifer A Brody, Brian E Cade, Juan C Celedon, Yi-Cheng Chang, L Adrienne Cupples, Brian Custer, Barry I Freedman, Mark T Gladwin, Susan R Heckbert, Lifang Hou, Marguerite R Irvin, Carmen R Isasi, Jill M Johnsen, Eimear E Kenny, Charles Kooperberg, Ryan L Minster, Take Naseri, Satupa'itea Viali, Sergei Nekhai, Nathan Pankratz, Patricia A Peyser, Kent D Taylor, Marilyn J Telen, Baojun Wu, Lisa R Yanek, Ivana V Yang, Christine Albert, Donna K Arnett, Allison E Ashley-Koch, Kathleen C Barnes, Joshua C Bis, Thomas W Blackwell, Eric Boerwinkle, Esteban G Burchard, April P Carson, Zhanghua Chen, Yii-Der Ida Chen, Dawood Darbar, Mariza De Andrade, Patrick T Ellinor, Myriam Fornage, Bruce D Gelb, Frank D Gilliland, Jiang He, Talat Islam, Stefan Kaab, Sharon L R Kardia, Shannon Kelly, Barbara A Konkle, Rajesh Kumar, Ruth J F Loos, Fernando D Martinez, Stephen T Mcgarvey, Deborah A Meyers, Braxton D Mitchell, Courtney G Montgomery, Kari E North, Nicholette D Palmer, Juan M Peralta, Benjamin A Raby, Susan Redline, Stephen S Rich, Dan Roden, Jerome I Rotter, Ingo Ruczinski, David Schwartz, Frank Sciurba, M Benjamin Shoemaker, Edwin K Silverman, Moritz F Sinner, Nicholas L Smith, Albert V Smith, Hemant K Tiwari, Ramachandran S Vasan, Scott T Weiss, L Keoki Williams, Yingze Zhang, Elad Ziv, Laura M Raffield, Alexander P Reiner, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Hematology And Hemostasis Working Group, Topmed Structural Variation Working Group, Marios Arvanitis, Carol W Greider, Rasika A Mathias, Alexis Battle

Faculty, Staff and Student Publications

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of …

Brain Cell-Type Shifts In Alzheimer’S Disease, Autism, And Schizophrenia Interrogated Using Methylomics And Genetics, Chloe X Yap, Daniel D Vo, Matthew G Heffel, Arjun Bhattacharya, Cindy Wen, Yuanhao Yang, Kathryn E Kemper, Jian Zeng, Zhili Zheng, Zhihong Zhu, Eilis Hannon, Dorothea Seiler Vellame, Alice Franklin, Christa Caggiano, Brie Wamsley, Daniel H Geschwind, Noah Zaitlen, Alexander Gusev, Bogdan Pasaniuc, Jonathan Mill, Chongyuan Luo, Michael J Gandal

Faculty, Staff and Student Publications

Few neuropsychiatric disorders have replicable biomarkers, prompting high-resolution and large-scale molecular studies. However, we still lack consensus on a more foundational question: whether quantitative shifts in cell types-the functional unit of life-contribute to neuropsychiatric disorders. Leveraging advances in human brain single-cell methylomics, we deconvolve seven major cell types using bulk DNA methylation profiling across 1270 postmortem brains, including from individuals diagnosed with Alzheimer's disease, schizophrenia, and autism. We observe and replicate cell-type compositional shifts for Alzheimer's disease (endothelial cell loss), autism (increased microglia), and schizophrenia (decreased oligodendrocytes), and find age- and sex-related changes. Multiple layers of evidence indicate that endothelial …

Dynamic Cbct Imaging Using Prior Model-Free Spatiotemporal Implicit Neural Representation (Pmf-Stinr), Hua-Chieh Shao, Tielige Mengke, Tinsu Pan, You Zhang

Faculty, Staff and Student Publications

Objective. Dynamic cone-beam computed tomography (CBCT) can capture high-spatial-resolution, time-varying images for motion monitoring, patient setup, and adaptive planning of radiotherapy. However, dynamic CBCT reconstruction is an extremely ill-posed spatiotemporal inverse problem, as each CBCT volume in the dynamic sequence is only captured by one or a few x-ray projections, due to the slow gantry rotation speed and the fast anatomical motion (e.g. breathing).Approach. We developed a machine learning-based technique, prior-model-free spatiotemporal implicit neural representation (PMF-STINR), to reconstruct dynamic CBCTs from sequentially acquired x-ray projections. PMF-STINR employs a joint image reconstruction and registration approach to address the …

Gte: A Graph Learning Framework For Prediction Of T-Cell Receptors And Epitopes Binding Specificity, Feng Jiang, Yuzhi Guo, Hehuan Ma, Saiyang Na, Wenliang Zhong, Yi Han, Tao Wang, Junzhou Huang

Faculty, Staff and Student Publications

The interaction between T-cell receptors (TCRs) and peptides (epitopes) presented by major histocompatibility complex molecules (MHC) is fundamental to the immune response. Accurate prediction of TCR–epitope interactions is crucial for advancing the understanding of various diseases and their prevention and treatment. Existing methods primarily rely on sequence-based approaches, overlooking the inherent topology structure of TCR–epitope interaction networks. In this study, we present , a novel heterogeneous Graph neural network model based on inductive learning to capture the topological structure between TCRs and Epitopes. Furthermore, we address the challenge of constructing negative samples within the graph by proposing a dynamic edge …

The Macrophage Landscape Across The Lifespan Of A Human Cardiac Allograft, Xiao Li, Diwakar Turaga, Rich G Li, Chang-Ru Tsai, Julianna N Quinn, Yi Zhao, Ruby Wilson, Katherine Carlson, Jun Wang, Joseph A Spinner, Edward J Hickey, Iki Adachi, James F Martin

Faculty, Staff and Student Publications

Background: Much of our knowledge of organ rejection after transplantation is derived from rodent models.

Methods: We used single-nucleus RNA sequencing to investigate the inflammatory myocardial microenvironment in human pediatric cardiac allografts at different stages after transplantation. We distinguished donor- from recipient-derived cells using naturally occurring genetic variants embedded in single-nucleus RNA sequencing data.

Results: Donor-derived tissue resident macrophages, which accompany the allograft into the recipient, are lost over time after transplantation. In contrast, monocyte-derived macrophages from the recipient populate the heart within days after transplantation and form 2 macrophage populations: recipient MP1 and recipient MP2. Recipient MP2s have cell …

Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids: The Alps Follow-Up Study, Cynthia Gyamfi-Bannerman, Rebecca G Clifton, Alan T N Tita, Sean C Blackwell, Monica Longo, Jessica A De Voest, T Michael O'Shea, Sabine Z Bousleiman, Felecia Ortiz, Dwight J Rouse, Torri D Metz, George R Saade, Kara M Rood, Kent D Heyborne, John M Thorp, Geeta K Swamy, William A Grobman, Kelly S Gibson, Yasser Y El-Sayed, George A Macones, Eunice Kennedy Shriver Maternal-Fetal Medicine Units Network

Faculty, Staff and Student Publications

Importance: The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United States by finding that antenatal betamethasone at 34 to 36 weeks decreased short-term neonatal respiratory morbidity. However, the trial also found increased risk of neonatal hypoglycemia after betamethasone. This follow-up study focused on long-term neurodevelopmental outcomes after late preterm steroids.

Objective: To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes.

Design, setting, and participants: Prospective follow-up study of children aged 6 years or older whose birthing parent had enrolled in the multicenter randomized clinical trial, conducted at 13 centers that …

Tumor Niche Network-Defined Subtypes Predict Immunotherapy Response Of Esophageal Squamous Cell Cancer, Kyung-Pil Ko, Shengzhe Zhang, Yuanjian Huang, Bongjun Kim, Gengyi Zou, Sohee Jun, Jie Zhang, Yahui Zhao, Cecilia Martin, Karen J Dunbar, Gizem Efe, Anil K Rustgi, Hiroshi Nakagawa, Haiyang Zhang, Zhihua Liu, Jae-Il Park

Faculty, Staff and Student Publications

Despite the promising outcomes of immune checkpoint inhibitors (ICIs), resistance to ICI presents a new challenge. Therefore, selecting patients for specific ICI applications is crucial for maximizing therapeutic efficacy. Herein, we curated 69 human esophageal squamous cell cancer (ESCC) patients' tumor microenvironment (TME) single-cell transcriptomic datasets to subtype ESCC. Integrative analyses of the cellular network and transcriptional signatures of T cells and myeloid cells define distinct ESCC subtypes characterized by T cell exhaustion, and interleukin (IL) and interferon (IFN) signaling. Furthermore, this approach classifies ESCC patients into ICI responders and non-responders, as validated by whole tumor transcriptomes and liquid biopsy-based …

Changes In Walking Function And Neural Control Following Pelvic Cancer Surgery With Reconstruction, Geng Li, Di Ao, Marleny M Vega, Payam Zandiyeh, Shuo-Hsiu Chang, Alexander N Penny, Valerae O Lewis, Benjamin J Fregly

Faculty, Staff and Student Publications

Introduction: Surgical planning and custom prosthesis design for pelvic cancer patients are challenging due to the unique clinical characteristics of each patient and the significant amount of pelvic bone and hip musculature often removed. Limb-sparing internal hemipelvectomy surgery with custom prosthesis reconstruction has become a viable option for this patient population. However, little is known about how post-surgery walking function and neural control change from pre-surgery conditions.

Methods: This case study combined comprehensive walking data (video motion capture, ground reaction, and electromyography) with personalized neuromusculoskeletal computer models to provide a thorough assessment of pre- to post-surgery changes in walking function …

Dynamic Visual Acuity, Vestibulo-Ocular Reflex, And Visual Field In National Football League (Nfl) Officiating: Physiology And Visualization Engineering For 3d Virtual On-Field Training, Joshua Ong, Nicole V Carrabba, Ethan Waisberg, Nasif Zaman, Hamza Memon, Nicholas Panzo, Virginia A Lee, Prithul Sarker, Ashtyn Z Vogt, Noor Laylani, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

The ability to make on-field, split-second decisions is critical for National Football League (NFL) game officials. Multiple principles in visual function are critical for accuracy and precision of these play calls, including foveation time and unobstructed line of sight, static visual acuity, dynamic visual acuity, vestibulo-ocular reflex, and sufficient visual field. Prior research has shown that a standardized curriculum in these neuro-ophthalmic principles have demonstrated validity and self-rated improvements in understanding, confidence, and likelihood of future utilization by NFL game officials to maximize visual performance during officiating. Virtual reality technology may also be able to help optimize understandings of specific …

Transcriptomic Profiling Of Plasma Extracellular Vesicles Enables Reliable Annotation Of The Cancer-Specific Transcriptome And Molecular Subtype, Vahid Bahrambeigi, Jaewon J Lee, Vittorio Branchi, Kimal I Rajapakshe, Zhichao Xu, Naishu Kui, Jason T Henry, Wang Kun, Bret M Stephens, Sarah Dhebat, Mark W Hurd, Ryan Sun, Peng Yang, Eytan Ruppin, Wenyi Wang, Scott Kopetz, Anirban Maitra, Paola A Guerrero

Faculty, Staff and Student Publications

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predicted consensus molecular subtypes in patients with metastatic colorectal cancer. Analysis of plasma evRNA also enabled monitoring of changes in transcriptomic subtype under treatment selection pressure and identification of molecular pathways associated with recurrence. This approach …

Ataxia-Telangiectasia Mutated Loss-Of-Function Displays Variant And Tissue-Specific Differences Across Tumor Types, Patrick G Pilié, Virginia Giuliani, Wei-Lien Wang, Daniel J Mcgrail, Christopher A Bristow, Natalie Y L Ngoi, Keith Kyewalabye, Khalida M Wani, Hung Le, Erick Campbell, Nora S Sanchez, Dong Yang, Jinesh S Gheeya, Rohit Vivek Goswamy, Vijaykumar Holla, Kenna Rael Shaw, Funda Meric-Bernstam, Chiu-Yi Liu, Xiaoyan Ma, Ningping Feng, Annette A Machado, Jennifer P Bardenhagen, Christopher P Vellano, Joseph R Marszalek, Eeson Rajendra, Desiree Piscitello, Timothy I Johnson, Maria Likhatcheva, Elias Elinati, Jayesh Majithiya, Joana Neves, Vera Grinkevich, Marco Ranzani, Marina Roy Luzarraga, Marie Boursier, Lucy Armstrong, Lerin Geo, Giorgia Lillo, Wai Yiu Tse, Alexander J Lazar, Scott E Kopetz, Mary K Geck Do, Sarah Lively, Michael G Johnson, Helen M R Robinson, Graeme C M Smith, Christopher L Carroll, M Emilia Di Francesco, Philip Jones, Timothy P Heffernan, Timothy A Yap

Faculty, Staff and Student Publications

PURPOSE: Mutations in the ATM gene are common in multiple cancers, but clinical studies of therapies targeting ATM-aberrant cancers have yielded mixed results. Refinement of ATM loss of function (LOF) as a predictive biomarker of response is urgently needed.

EXPERIMENTAL DESIGN: We present the first disclosure and preclinical development of a novel, selective ATR inhibitor, ART0380, and test its antitumor activity in multiple preclinical cancer models. To refine ATM LOF as a predictive biomarker, we performed a comprehensive pan-cancer analysis of ATM variants in patient tumors and then assessed the ATM variant-to-protein relationship. Finally, we assessed a novel ATM LOF …

Targeting Ccl2/Ccr2 Signaling Overcomes Mek Inhibitor Resistance In Acute Myeloid Leukemia, Rucha V Modak, Katia G De Oliveira Rebola, John Mcclatchy, Mona Mohammadhosseini, Alisa Damnernsawad, Stephen E Kurtz, Christopher A Eide, Guanming Wu, Ted Laderas, Tamilla Nechiporuk, Marina A Gritsenko, Joshua R Hansen, Chelsea Hutchinson, Sara J C Gosline, Paul Piehowski, Daniel Bottomly, Nicholas Short, Karin Rodland, Shannon K Mcweeney, Jeffrey W Tyner, Anupriya Agarwal

Faculty, Staff and Student Publications

Purpose: Emerging evidence underscores the critical role of extrinsic factors within the microenvironment in protecting leukemia cells from therapeutic interventions, driving disease progression, and promoting drug resistance in acute myeloid leukemia (AML). This finding emphasizes the need for the identification of targeted therapies that inhibit intrinsic and extrinsic signaling to overcome drug resistance in AML.

Experimental design: We performed a comprehensive analysis utilizing a cohort of ∼300 AML patient samples. This analysis encompassed the evaluation of secreted cytokines/growth factors, gene expression, and ex vivo drug sensitivity to small molecules. Our investigation pinpointed a notable association between elevated levels of CCL2 …

Ire1Α Determines Ferroptosis Sensitivity Through Regulation Of Glutathione Synthesis, Dadi Jiang, Youming Guo, Tianyu Wang, Liang Wang, Yuelong Yan, Ling Xia, Rakesh Bam, Zhifen Yang, Hyemin Lee, Takao Iwawaki, Boyi Gan, Albert C Koong

Faculty, Staff and Student Publications

Cellular sensitivity to ferroptosis is primarily regulated by mechanisms mediating lipid hydroperoxide detoxification. We show that inositol-requiring enzyme 1 (IRE1α), an endoplasmic reticulum (ER) resident protein critical for the unfolded protein response (UPR), also determines cellular sensitivity to ferroptosis. Cancer and normal cells depleted of IRE1α gain resistance to ferroptosis, while enhanced IRE1α expression promotes sensitivity to ferroptosis. Mechanistically, IRE1α's endoribonuclease activity cleaves and down-regulates the mRNA of key glutathione biosynthesis regulators glutamate-cysteine ligase catalytic subunit (GCLC) and solute carrier family 7 member 11 (SLC7A11). This activity of IRE1α is independent of its role in regulating the UPR and is …

The Calcineurin-Nfatc Pathway Modulates The Lipid Mediators In Bal Fluid Extracellular Vesicles, Thereby Regulating Microvascular Endothelial Cell Barrier Function, Manjula Karpurapu, Yunjuan Nie, Sangwoon Chung, Jiasheng Yan, Patrick Dougherty, Sonal Pannu, Jon Wisler, Ryan Harkless, Narasimham Parinandi, Evgeny Berdyshev, Dehua Pei, John W Christman

Faculty, Staff and Student Publications

Extracellular vesicles mediate intercellular communication by transporting biologically active macromolecules. Our prior studies have demonstrated that the nuclear factor of activated T cell cytoplasmic member 3 (NFATc3) is activated in mouse pulmonary macrophages in response to lipopolysaccharide (LPS). Inhibition of NFATc3 activation by a novel cell-permeable calcineurin peptide inhibitor CNI103 mitigated the development of acute lung injury (ALI) in LPS-treated mice. Although pro-inflammatory lipid mediators are known contributors to lung inflammation and injury, it remains unclear whether the calcineurin-NFATc pathway regulates extracellular vesicle (EV) lipid content and if this content contributes to ALI pathogenesis. In this study, EVs from mouse …

Integrative Molecular Analyses Of The Md Anderson Prostate Cancer Patient-Derived Xenograft (Mda Pca Pdx) Series, Nicolas Anselmino, Estefania Labanca, Peter D A Shepherd, Jiabin Dong, Jun Yang, Xiaofei Song, Subhiksha Nandakumar, Ritika Kundra, Cindy Lee, Nikolaus Schultz, Jianhua Zhang, John C Araujo, Ana M Aparicio, Sumit K Subudhi, Paul G Corn, Louis L Pisters, John F Ward, John W Davis, Elba S Vazquez, Geraldine Gueron, Christopher J Logothetis, Andrew Futreal, Patricia Troncoso, Yu Chen, Nora M Navone

Faculty, Staff and Student Publications

PURPOSE: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer models. This initiative builds on the rich MD Anderson (MDA) prostate cancer (PCa) patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal prostate cancer.

EXPERIMENTAL DESIGN: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived …

Oncology Patients’ Willingness To Report Their Medication Safety Concerns From Home: A Qualitative Study, Deema Bunni, Grace Walters, Misun Hwang, Katie Gahn, Heidi Mason, Milisa Manojlovich, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Purpose: Oncology patients often struggle to manage their medications and related adverse events during transitions of care. They are expected to take an active role in self-monitoring and timely reporting of their medication safety events or concerns to clinicians. The purpose of this study was to explore the factors influencing oncology patients' willingness to report adverse events or concerns related to their medication after their transitions back home.

Methods: A qualitative interview study was conducted with adult patients with breast, prostate, lung, or colorectal cancer who experienced care transitions within the previous year. A semi-structured interview guide was developed to …

Third-Party Fecal Microbiota Transplantation For High-Risk Treatment-Naïve Acute Gvhd Of The Lower Gi Tract, Zachariah Defilipp, Ashish V Damania, Haesook T Kim, Chia-Chi Chang, Areej El-Jawahri, Steven L Mcafee, Aj S Bottoms, Vesselina Toncheva, Melissa M Smith, Maria Dolaher, Lindsey Perry, Meghan White, Brittany Diana, Sheila Connolly, Bimalangshu R Dey, Matthew J Frigault, Richard A Newcomb, Paul V O'Donnell, Thomas R Spitzer, Michael K Mansour, Daniela Weber, Nadim J Ajami, Elizabeth Hohmann, Robert R Jenq, Yi-Bin Chen

Faculty, Staff and Student Publications

Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% …

High All-Cause Mortality And Increasing Proportion Of Older Adults With Tuberculosis In Texas, 2008–2020, Belinda A Medrano, Miryoung Lee, Gretchen Gemeinhardt, Lana Yamba, Blanca I Restrepo

Faculty, Staff and Student Publications

Pulmonary tuberculosis (PTB) elimination efforts must consider the global growth of the ageing population. Here we used TB surveillance data from Texas, United States (2008-2020; total n = 10656) to identify unique characteristics and outcomes in older adults (OA, ≥65 years) with PTB, compared to young adults (YA, 18-39 years) or middle-aged adults (40-64 years). We found that the proportion of OA with PTB increased from 15% in 2008 to 24% in 2020 (trend p < 0.05). Diabetes was highly prevalent in OA (32%) but not associated with adverse outcomes. Death was 13-fold higher in OA compared to YA and was 7% at the time of diagnosis which suggests diagnostic delays. However, once TB was suspected, we found no differences in culture, smear, or nucleic acid detection of mycobacteria (although less lung cavitations) in OA. During treatment, OA had less drug-resistant TB, few adverse reactions and adhered with TB treatment. We recommend training healthcare workers to 'think TB' in OA, for prompt treatment initiation to diminish deaths. Furthermore, OA should be added as a priority group to the latent TB treatment guidelines by the World Health Organization, to prevent TB disease in this highly vulnerable group.

Mammographic Density Mediates The Protective Effect Of Early-Life Body Size On Breast Cancer Risk, Marina Vabistsevits, George Davey Smith, Tom G Richardson, Rebecca C Richmond, Weiva Sieh, Joseph H Rothstein, Laurel A Habel, Stacey E Alexeeff, Bethan Lloyd-Lewis, Eleanor Sanderson

Faculty, Staff and Student Publications

The unexplained protective effect of childhood adiposity on breast cancer risk may be mediated via mammographic density (MD). Here, we investigate a complex relationship between adiposity in childhood and adulthood, puberty onset, MD phenotypes (dense area (DA), non-dense area (NDA), percent density (PD)), and their effects on breast cancer. We use Mendelian randomization (MR) and multivariable MR to estimate the total and direct effects of adiposity and age at menarche on MD phenotypes. Childhood adiposity has a decreasing effect on DA, while adulthood adiposity increases NDA. Later menarche increases DA/PD, but when accounting for childhood adiposity, this effect is attenuated. …

Dataset Of Weekly Intra-Treatment Diffusion Weighted Imaging In Head And Neck Cancer Patients Treated With Mr-Linac, Dina M El-Habashy, Kareem A Wahid, Renjie He, Brigid Mcdonald, Samuel J Mulder, Yao Ding, Travis Salzillo, Stephen Y Lai, John Christodouleas, Alex Dresner, Jihong Wang, Mohamed A Naser, Clifton D Fuller, Abdallah Sherif Radwan Mohamed, Joint Head And Neck Radiation Therapy-Mri Development Cooperative

Faculty, Staff and Student Publications

Radiation therapy (RT) is a crucial treatment for head and neck squamous cell carcinoma (HNSCC); however, it can have adverse effects on patients' long-term function and quality of life. Biomarkers that can predict tumor response to RT are being explored to personalize treatment and improve outcomes. While tissue and blood biomarkers have limitations, imaging biomarkers derived from magnetic resonance imaging (MRI) offer detailed information. The integration of MRI and a linear accelerator in the MR-Linac system allows for MR-guided radiation therapy (MRgRT), offering precise visualization and treatment delivery. This data descriptor offers a valuable repository for weekly intra-treatment diffusion-weighted imaging …

Casi: A Framework For Cross-Timepoint Analysis Of Single-Cell Rna Sequencing Data, Yizhuo Wang, Christopher R Flowers, Michael Wang, Xuelin Huang, Ziyi Li

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) technology has been widely used to study the differences in gene expression at the single cell level, providing insights into the research of cell development, differentiation, and functional heterogeneity. Various pipelines and workflows of scRNA-seq analysis have been developed but few considered multi-timepoint data specifically. In this study, we develop CASi, a comprehensive framework for analyzing multiple timepoints' scRNA-seq data, which provides users with: (1) cross-timepoint cell annotation, (2) detection of potentially novel cell types emerged over time, (3) visualization of cell population evolution, and (4) identification of temporal differentially expressed genes (tDEGs). Through comprehensive simulation …

Adapting And Evaluating A Theory-Driven, Non-Pharmacological Intervention To Self-Manage Pain, Jennifer Kawi, Chao Hsing Yeh, Lauren Grant, Johannes Thrul, Hulin Wu, Paul J Christo, Lorraine S Evangelista

Faculty, Staff and Student Publications

BACKGROUND: The existing literature has limited detail on theory-driven interventions, particularly in pain studies. We adapted Bandura's self-efficacy framework toward a theory-driven, non-pharmacological intervention using auricular point acupressure (APA) and evaluated participants' perceptions of this intervention on their pain self-management. APA is a non-invasive modality based on auricular acupuncture principles.

METHODS: We mapped our study intervention components according to Bandura's key sources of self-efficacy (performance accomplishments, vicarious experience, verbal persuasion, and emotional arousal) to facilitate the self-management of pain. Through a qualitative study design, we conducted virtual interviews at one and three months after a 4-week APA intervention among 23 …