Medical Sciences Commons^™

Chronic Circadian Misalignment Accelerates Sarcopenia Progression In Mice, Takashi Seya, Nobuya Koike, Naoki Okubo, Yasuhiro Umemura, Yoshiki Tsuchiya, Kazuya Yabumoto, Yasuhiro Endo, Kanako Iinuma, Akiyo Kakibuchi, Akira Sugimoto, Kenji Takahashi, Seung-Hee Yoo, Zheng Chen, Kazuhiro Yagita

Faculty, Staff and Student Publications

Introduction: In today's 24/7 society, circadian misalignment caused by environmental and lifestyle factors is associated with various adverse health consequences. Understanding tissue-specific pathology is required to counter this growing public health challenge. A potential association of environmental circadian misalignment with sarcopenia, or accelerated loss of skeletal muscle strength and mass, is poorly documented.

Methods: 14-week-old wild-type C57BL/6J male mice were exposed to a chronic jet lag (CJL) paradigm consisting of an 8-h phase advance every 4 days (the ADV group) or a fixed light-dark cycle (the LD group) for 64 weeks. Grip strength was measured during the experiment, and hindlimb …

Key Considerations For Combination Therapy In Alzheimer’S Clinical Trials: Perspectives From An Expert Advisory Board Convened By The Alzheimer’S Drug Discovery Foundation, Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew Von Eschenbach, Suzanne Hendrix, Donald Berry, Cristina Sampaio, Kaycee Sink, Jaren Landen, Miia Kivipelto, Michael Grundman, Steven E Arnold, Allan Green, Katherine Partrick, Laura Nisenbaum, Aaron Burstein, Howard Fillit

Faculty, Staff and Student Publications

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer's disease. Progress …

Case Report: Rare Intraventricular H3 K27-Altered Diffuse Midline Glioma In An Adult, Merari Jasso, Jay-Jiguang Zhu, Meenakshi B Bhattacharjee, Georgene W Hergenroeder

Faculty, Staff and Student Publications

H3 K27-Altered Diffuse Midline Gliomas are commonly found in children and adolescents in midline locations such as the thalamus, brain stem, and spinal cord. It is rare for these tumors to affect adults and to occur in locations like the lateral ventricles. Despite aggressive treatment methodologies, there is no cure for this disease. The median survival is between 8-12 months. A 24-year-old white male presented to the emergency department due to severe headache refractory to pain medications with a 2-month history of progressive headaches and eventual memory problems. Computed tomography (CT) and magnetic resonance imaging (MRI) showed an intraventricular enhancing …

Prenatal Alcohol Exposure Inhibits Transient Expression Of Autophagy And Synaptic Proteins In Developing Brain, Monica Hampe, Nune Darbinian, Nana Merabova, Armine Darbinyan, Jamal Hamze, Uday Bharai, Yuri Persidsky, Mary F Morrison, Shohreh Amini, Laura Goetzl, Michael E Selzer

Faculty, Staff and Student Publications

Introduction: Neuronal apoptosis and consequent inhibition of autophagy, with loss of synaptic connections are central events in the genesis of fetal alcohol spectrum disorders (FASD). However, studies of molecular mechanisms of autophagy in human fetal brain are limited. Recently, prenatal exposure to EtOH was associated with reduced miRNA-9 levels in fetal brain-derived exosomes (FB- Es) isolated from maternal plasma, which correlated with small eyes, an anatomical hallmark of fetal alcohol syndrome (FAS). Since miR-9 targets several genes that regulate synaptic plasticity, EtOH-induced inhibition of miR-9 could potentially result in dysregulation of genes involved in synaptogenesis/plasticity.

Methods: Rats were fed a …

An Evaluation Of Genetic Predisposition To Congenital Anomalies And Pediatric Cancer Supports, Hyunjung Gu, Yao Yu, Saumya Dushyant Sisoudiya, Pamela Mishra, He Li, Jeremy M Schraw, Michael E Scheurer, Donna M Muzny, Danielle Mitchell, Olga Taylor, Shalini N Jhangiani, Shannon Dugan-Perez, Yifan Wu, Harsha Doddapaneni, Sravya Venkata Bhamidipati, Marie-Claude Gingras, Jennifer E Posey, Richard A Gibbs, Chad D Huff, Sharon E Plon, Philip J Lupo, Aniko Sabo

Faculty, Staff and Students Publications

Purpose: Although congenital anomalies are among the strongest risk factors for developing pediatric cancer, the genetic underpinnings remain unclear. Therefore, we evaluated germline susceptibility in children with congenital anomalies and cancer.

Methods: Through the Genetic Overlap Between Anomalies and Cancer in Kids Study, we recruited 47 participants with anomalies and cancer, along with their biological families. Genome sequencing was performed, focusing on single-nucleotide variants, indels, and structural variants. Pathogenic or likely pathogenic variants were identified by the American College of Medical Genetics and Genomics classification.

Results: We identified pathogenic or likely pathogenic variants in 23.4% (11 of 47) of participants. …

Measurement Of Oxygen Consumption Rate In Mouse Aortic Tissue, Zhen Zhou, Ripon Sarkar, Jose Emiliano Esparza Pinelo, Alexis Richard, Jay Dunn, Zhao Ren, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

Thoracic aortic aneurysm and dissection (TAD) is a life-threatening vascular disorder, and smooth muscle cell mitochondrial dysfunction leads to cell death, contributing to TAD. Accurate measurements of metabolic processes are essential for understanding cellular homeostasis in both healthy and diseased states. While assays for evaluating mitochondrial respiration have been well established for cultured cells and isolated mitochondria, no optimized application has been developed for aortic tissue. In this study, we generate an optimized protocol using the Agilent Seahorse XFe24 analyzer to measure mitochondrial respiration in mouse aortic tissue. This method allows for precise measurement of mitochondrial oxygen consumption in mouse …

Changes In Functional Connectivity Are Associated With Functional Independence In The Early Postoperative Period Following Awake Surgical Resection Of Language-Eloquent Glioma, Kyle R Noll, Evan D Bander, Henry S Chen, Mariana Bradshaw, Jeffrey S Wefel, Vinodh A Kumar, Sujit S Prabhu, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Neurocognitive decline in patients with primary brain tumors is associated with alterations in the functional connectome and reduced independence in daily living. This study explores postoperative connectomic changes associated with functional independence outcomes in patients with eloquent glioma, and how these associations differ from neurocognitive-connetcomic relationships.

Methods: Fifteen patients with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological evaluation within 2 weeks before and on average 1 month after resection. Functional independence was measured with the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living scale (IADL). Graph theoretical analysis quantified functional brain …

Integrative Multi-Omics Approach For Improving Causal Gene Identification, Austin King, Chong Wu

Faculty, Staff and Student Publications

Transcriptome-wide association studies (TWAS) have been widely used to identify thousands of likely causal genes for diseases and complex traits using predicted expression models. However, most existing TWAS methods rely on gene expression alone and overlook other regulatory mechanisms of gene expression, including DNA methylation and splicing, that contribute to the genetic basis of these complex traits and diseases. Here we introduce a multi-omics method that integrates gene expression, DNA methylation, and splicing data to improve the identification of associated genes with our traits of interest. Through simulations and by analyzing genome-wide association study (GWAS) summary statistics for 24 complex …

Comparison Of Primary Care Experiences And Outpatient Health Service Utilization Among Black And Latino Homeless-Experienced Veterans: An Analysis Of Patient-Centered Medical Homes, Melissa Chinchilla, Audrey L Jones, Aerin Derussy, Michael F Green, Lillian Gelberg, Alexander S Young, Jack Tsai, Sonya E Gabrielian, Stefan G Kertesz

Faculty, Staff and Student Publications

Objectives: To examine whether, among persons with recent homeless experience, minoritized clients rate primary care differently from non-minoritized clients in Veterans Affairs (VA) mainstream and homeless tailored clinics, through the largest survey of homeless-experienced Black, White, and Latino Veterans to date.

Methods: Surveys were collected from HEVs in Homeless-tailored Patient-Aligned Care Teams (HPACTs) and mainstream Patient Aligned Care Teams (PACTs; n = 4894). We tested multivariable associations between race/ethnicity, clinic (HPACT vs mainstream-PACT), and their interaction, on care experience ratings and service utilization.

Results: There were no major differences in care ratings by race/ethnicity; medical and social vulnerability factors were …

Hydroxychloroquine-Induced Cardiomyopathy: A Case Report, Ahmed Hussein, Aya Salih, Tebyan Mohammedali, Yousif Mohamed, L Maximilian Buja

Faculty, Staff and Student Publications

Hydroxychloroquine (HCQ) is an immunomodulatory medication used for decades. HCQ is a weak base accumulating in acidic cytoplasmic vesicles, such as lysosomes. This accumulation raises the pH and interferes with the functions of the lysosomal enzymes, including α-galactosidase A, resulting in a unique clinical and pathologic feature. We present a case with severe HCQ-induced cardiomyopathy to show the pattern of cardiac involvement and available imaging and pathologic modalities. The case involves a 76-year-old woman with a history of Sjögren's disease who had been treated with HCQ for 13 years and presented with symptoms of heart failure. An echocardiogram showed thick …

Anti-Cd137 Agonist Antibody-Independent And Clinically Feasible Preparation Of Tumor-Infiltrating Lymphocytes From Soft Tissue Sarcoma And Osteosarcoma, Yining Jin, Zhiliang Jia, Xueqing Xia, Nancy B Gordon, Joseph A Ludwig, Neeta Somaiah, Shulin Li

Faculty, Staff and Student Publications

Background: Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors.

Methods: We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist …

Impact Of Active Surveillance On Nephrometric Scores Of Bosniak Iii And Iv Renal Cysts, Roberto Dias Machado, Leonardo Bernardes De Amaro, Alessandro Prudente, Eliney Ferreira Faria, Antonio Antunes Rodrigues Júnior, Aradhana M Venkatesan, Jose A Karam, Valdair F Muglia, Leonardo O Reis, Rodolfo Borges Dos Reis

Faculty, Staff and Student Publications

Purpose: Active surveillance (AS) has been widely explored for small renal masses, but its role in complex renal cysts (CRCs) categorized as Bosniak (Bk) III and IV remains unclear. This study aims to evaluate changes in nephrometry scores (s-RENAL and s-PADUA) during AS and their potential impact on surgical complexity.

Methods: A retrospective, multicentric, observational study was conducted, analyzing 101 CRCs from 95 patients across three institutions. Nephrometry scores were evaluated at baseline and after a minimum follow-up of two years using computed tomography (CT) and magnetic resonance imaging (MRI). Statistical analysis included chi-square and marginal homogeneity tests, with data …

Correspondence To Letter To The Editor On “Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial”, Sung Hwan Lee, Sun Young Yim, Ji Hoon Kim, Sunyoung S Lee, Ahmed O Kaseb, Peng Wei, Ju-Seog Lee

Faculty, Staff and Student Publications

No abstract provided.

Case Report: Fia Plus Venetoclax In A Patient On Hemodialysis, Jacob E Herstein, Kayleigh R Marx, J Michael Savoy, Wei Ying Jen, Musa Yilmaz, Nicholas J Short, Ghayas C Issa, Farhad Ravandi, Tapan M Kadia, Naval G Daver, Courtney D Dinardo

Faculty, Staff and Student Publications

The safe and effective delivery of curative cytotoxic chemotherapy for acute myeloid leukemia (AML) in patients receiving intermittent hemodialysis (IHD) for end-stage renal disease (ESRD) remains a clinical challenge; pharmacological and logistical barriers necessitate close interdisciplinary coordination. In this case, we report a 65-year-old female patient with chronic ESRD on IHD and newly diagnosed AML who achieved complete remission (CR) after treatment with fludarabine, idarubicin, and cytarabine plus venetoclax (i.e., FIA + venetoclax).

Neuroprotective Role Of Ding Protein In Fetal Alcohol Spectrum Disorders And Depression, Nune Darbinian, Monica Hampe, Nana Merabova, Tamara Tatevosian-Geller, Laura Goetzl, Mary F Morrison, Gabriel Tatevosian, Malgorzata Simm, Eric Chabriere, Huaqing Zhao, Shohreh Amini, Michael E Selzer

Faculty, Staff and Student Publications

Introduction: An estimated 20% of women consume alcohol during pregnancy, and 10% of women receive antidepressants during their pregnancy. Women with depression are more likely to use alcohol (EtOH) in early pregnancy and are more likely to have a child with one of the fetal alcohol spectrum disorders (FASD). Previously, we provided evidence in rat neurons in vitro that DING phosphatase (p38SJ, a member of the DINGGG family of proteins that has neuroprotective effects under conditions of cellular stress) was neuroprotective against EtOH-mediated toxicity. Now, we examine the effects of DING, alone or in combination with EtOH and serotonergic (5-HT) …

Racial And Ethnic Disparities In Longitudinal Trajectories Of Cardiovascular Risk Factors In Us Middle-Aged And Older Adults, Matthew E Dupre, Radha Dhingra, Hanzhang Xu, Scott M Lynch, Qing Yang, Cassie Ford, Michael D Green, Ying Xian, Ann Marie Navar, Eric D Peterson

Faculty, Staff and Student Publications

Background: Racial and ethnic disparities in cardiovascular disease (CVD) risk factors are well-documented. However, racial and ethnic differences in the longitudinal changes among multiple CVD risk factors are unknown.

Methods: We used prospective cohort data of U.S. adults aged ≥50 in the 2006-2016 Health and Retirement Study. Group-based multi-trajectory models characterized age-related trajectories of systolic blood pressure ([BP] mmHg), non-HDL cholesterol (mg/dL), diabetes mellitus (DM), and smoking. Racial and ethnic differences in the multi-trajectory profiles were examined using multinomial logistic regression. Karlson-Holm-Breen methods were used to assess factors contributing to these associations.

Results: Among 10,292 participants (median age: 61), approximately …

Real-World Outcomes Of Upfront Autologous Hematopoietic Stem Cell Transplantation In Patients With Newly Diagnosed Multiple Myeloma With Deletion 17p, Curtis Marcoux, Oren Pasvolsky, Denái R Milton, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Hans C Lee, Krina K Patel, Partow Kebriaei, Amna Ahmed, Yosra Aljawai, Sheeba K Thomas, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Despite tremendous advancements in multiple myeloma (MM) therapeutics, outcomes remain heterogeneous, heavily influenced by clinical and cytogenetic factors. Among these, deletion of the short arm of chromosome 17 (del(17p)) is a strong predictor of poor prognosis. The aim of this study was to evaluate real-world outcomes in patients with newly diagnosed MM (NDMM) with del(17p) undergoing upfront autologous hematopoietic stem cell transplantation (auto-HCT). We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-HCT at MD Anderson Cancer Center between 2008 and 2018. Primary endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints being …

A New, Early Cretaceous Carettochelyid Turtle From South Korea Provides Insights Into Softshell Evolution And Aquatic Ecology, Minguk Kim, Jongyun Jung, Walter G Joyce, Jae-Il Park, Hye-Yeon Jung, Hyemin Jo, Min Huh

Faculty, Staff and Student Publications

Here, we present a new Cretaceous carettochelyid turtle, Byeoljubuchelys yeosuensis gen. et sp. nov., from the Lower Cretaceous Hasandong Formation of Yeosu, Korea. A nearly complete shell and select elements of the girdles and limbs provide crucial insight into the evolution and aquatic adaptation of this family. Phylogenetic analyses place Byeoljubuchelys yeosuensis at the most basal position within Carettochelyidae. The mid-sized plastron of Byeoljubuchelys yeosuensis appears to be plesiomorphic for the group. The expansion of the plastron during carettochelyid evolution, especially during the Paleogene, may be an evolutionary response to increasing body size or the threat of mammalian predators. …

Development Of Microcystoid Macular Degeneration In The Retina Of Nonhuman Primates: Time-Course And Associated Pathologies, Thomas C M Lavery, Carol A Rasmussen, Alexander W Katz, Charlene B Y Kim, James N Ver Hoeve, Paul E Miller, Peter J Sonnentag, Brian J Christian, Christopher J Murphy, David R Piwnica-Worms, Seth T Gammon, Xudong Qiu, Paul L Kaufman, T Michael Nork

Faculty, Staff and Student Publications

Purpose: Microcystoid macular degeneration (MMD) is a condition where cystoid vacuoles develop within the inner nuclear layer of the retina in humans in a variety of disorders. Here we report the occurrence of MMD in non-human primates (NHPs) with various retinal ganglion cell (RGC) pathologies and evaluate the hypothesis that MMD does not precede RGC loss but follows it.

Methods: Morphological studies were performed of the retinas of NHPs, specifically both rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis), in which MMD was identified after induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and spontaneous …

Optimization Of Proximity Labeling In Endothelial Cells: Overcoming Endogenous Biotin Interference And Cost Barriers, Ying Jiang, Kuizhi Qu, Mengjun Dai, Yan-Ning Rui, Zhen Xu

Faculty, Staff and Student Publications

Proximity labeling has become a powerful technique for mapping protein-protein interactions under physiologically relevant conditions, with TurboID offering high enzymatic activity and rapid labeling. However, its application in endothelial systems has been limited, partly due to the presence of endogenous biotin in specialized media, which reduces labeling specificity. Here, we optimized TurboID-mediated proximity labeling in brain microvascular endothelial cells by addressing two key challenges: endogenous biotin interference and cost-effective depletion. We discovered that endothelial cell medium contains substantial biotin levels, which saturate TurboID labeling and obscure the effects of exogenous biotin. Using High Capacity NeutrAvidin

Topss: Tolerability Of Transcranial Direct Current Stimulation In Pediatric Stroke Survivors, Stuart Fraser, Anna Clearman, Melika Abrahams, Bernadette Gillick, Tia Lal, Sean Savitz, Nuray Yozbatiran

Faculty, Staff and Student Publications

Background: Transcranial direct current stimulation is a non-invasive neuromodulation technique with emerging therapeutic potential in neurodevelopmental conditions. While childhood-onset stroke survivors frequently experience long-term motor impairment, there are very few studies examining the safety and feasibility of transcranial direct current stimulation in this population.

Objective: To evaluate the safety, feasibility, and tolerability of bihemispheric transcranial direct current stimulation paired with occupational therapy in children and adolescents with chronic hemiparesis following childhood-onset arterial ischemic stroke or intracranial hemorrhage.

Methods: In this single-arm, open-label pilot study, five participants aged 6-19 years of age received five daily sessions of transcranial direct current stimulation …

Rethinking Parkinson's Disease Genetics In The Precision Medicine Era: Why Genomic Diversity Matters?, Camilla Teixeira Pinheiro Gusmão, Giselli Scaini, Everton Ferreira De Souza, Rafael Antônio Vicente Lacerda, Matheus De Almeida Costa, Raja Mehanna, João Quevedo, Howard Lopes Ribeiro Junior

Faculty, Staff and Student Publications

No abstract provided.

Mechanisms Of How Sarcopenia Affects Functional Outcomes In Acute Ischaemic Stroke, Dong-Seok Gwak, Jinyong Chung, Dawid Schellingerhout, Hyerin Oh, Sang-Wuk Jeong, Ji Sung Lee, Dong-Eog Kim

Faculty, Staff and Student Publications

Sarcopenia, a common geriatric condition characterized by the loss of skeletal muscle mass and function, can negatively affect functional outcomes in acute ischaemic stroke; however, the underlying mechanisms remain unclear. We hypothesized that sarcopenia affects post-stroke outcomes, mediated through its impact on dysphagia, early neurological deterioration, or post-stroke recovery, particularly in patients with motor deficits. To explore this hypothesis, we included 600 consecutive elderly (≥65 years) patients with acute (< 1 week) ischaemic stroke and assessed: (i) the relationships sarcopenia has with dysphagia, early neurological deterioration and various phases of recovery after stroke (in-hospital, post-discharge [up to 3 months], and chronic [3 months to 1 year]) and (ii) whether either presenting symptoms or lesion locations modify the impact of sarcopenia on stroke outcomes. Temporal muscle thickness, a marker of sarcopenia, was measured by brain magnetic resonance imaging and dichotomized into low versus high temporal muscle thickness at the 25th percentile cut-off point. Logistic regression analysis, mediation analysis and statistical brain mapping were conducted. Mean age was 75.3 ± 6.1 years and 303 (50.5%) were male. Low temporal muscle thickness (< 5.1 mm) was independently associated with dysphagia (adjusted odds ratio 1.89 [95% confidence interval 1.06–3.37], P = 0.03), early neurological deterioration (adjusted odds ratio 2.75 [95% confidence interval 1.61–4.71], P < 0.001) and post-discharge recovery (adjusted odds ratio 0.56 [95% confidence interval 0.34–0.94], P = 0.03) but not with in-hospital or chronic recovery. In addition, dysphagia, early neurological …

Structured Personalized Oxygen And Supportive Therapies For Dyspnea In Oncology (Spot-On): A Personalized Randomized Clinical Trial Protocol, David Hui, Min Ji Kim, Saji Thomas, Gautam Sachdev, Sanjay Shete, Nisha Rathi, Nicole Hensch, Vera De La Cruz, Amy Ontai, Donald A Mahler, Jie Li, Eduardo Bruera

Faculty, Staff and Student Publications

Background: Low-flow supplemental oxygen (LFSO), high-flow nasal cannula (HFNC), and non-invasive ventilation (NIV) are often used for palliation of dyspnea in hospitalized patients. However, it is unclear how patients prefer to use these modalities and how they can be personalized for optimal dyspnea relief. The objective of this randomized clinical trial is to compare the effect of a personalized respiratory therapist (RT)-led intervention, termed SPOT-ON, and enhanced usual care on dyspnea intensity in both hypoxemic and non-hypoxemic hospitalized patients with cancer.

Methods: In this two-arm, parallel group, partially blinded, waitlist-controlled randomized clinical trial, hospitalized patients with advanced cancer and at …

Correlation Of Pancreatic Laminin Alpha 5 Expression With Clinical Outcomes In Total Pancreatectomy With Islet Autotransplantation, Jayachandra Kuncha, Carly M Darden, Yang Liu, Michael Lawrence, J Sebastian Danobeitia, Bashoo Naziruddin

Faculty, Staff and Student Publications

This study examines extracellular matrix (ECM) protein (ECM) expression in chronic pancreatitis (CP) patients and its correlation with graft function after total pancreatectomy with islet autologous transplantation (TPIAT). Pancreatic sections from 29 CP patients undergoing TPIAT were analyzed for ECM including pan-laminin, laminin alpha 5 (LAMA5), collagen IV, and Perlecan by immunohistochemistry and scored by the percentage positive staining area within the whole tissue area. Graft function was monitored by blood glucose and C-peptide levels. Laminin alpha 5 levels in blood plasma were greater in CP. Laminin alpha 5 expression was significantly higher in all CP patient etiological categories including …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Purpose

To combine deep learning and biology-based modeling to predict the response of locally advanced, triple-negative breast cancer before initiating neoadjuvant chemotherapy (NAC).

Materials and Methods

In this retrospective study, a biology-based mathematical model of tumor response to NAC was constructed and calibrated on a patient-specific basis using imaging data from patients enrolled in the MD Anderson A Robust TNBC Evaluation FraMework to Improve Survival trial (ARTEMIS; ClinicalTrials.gov registration no. NCT02276443) between April 2018 and May 2021. To relate the calibrated parameters in the biology-based model and pretreatment MRI data, a convolutional neural network (CNN) was employed. The CNN …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with limited targeted treatment options, heterogeneous treatment response, and high risk of early recurrence. Artificial intelligence (AI) has rapidly emerged as a powerful tool to address key clinical challenges in TNBC across diagnosis, treatment response assessment, and prognosis. Diagnostic and staging challenges persist due to variable imaging features in TNBC and limitations in conventional modalities, increasing the risk of delayed detection. Predicting response to neoadjuvant systemic therapy remains difficult, as patient responses are heterogeneous, and existing clinical markers provide limited early predictive value. Prognostication in TNBC is similarly constrained …

Inducing Hypertension In Myh11r247c/R247c Mice Triggers Aortic Dissections With Increased Focal Adhesion Kinase Signaling, Callie S Kwartler, Shanzhi Wang, Zhen Zhou, Pujun Guan, Yang Yu, Xue-Yan Duan, Theodore Zhang, Jiyuan Chen, Elaine C Davis, Dianna M Milewicz

Faculty, Staff and Student Publications

Objective: We sought to determine if hypertension in combination with a "variant of uncertain significance" that disrupts protein function, MYH11 p.Arg247Cys, would induce aortic dissections in a mouse model.

Approach and results: Administration of L-NAME via drinking water and a high salt diet increased blood pressure in WT and Myh11R247C/R247C mice and triggered type A dissections with cardiac tamponade in 20% of the Myh11R247C/R247C mice. Myh11R247C/R247C aortas have aberrant smooth muscle contractile unit-elastin connections by transmission electron microscopy, along with increased focal adhesion signaling at baseline, which further increases with hypertension.

Conclusion: Gene-environment interactions trigger aortic dissections in Myh11R247C/R247C mice.

Editorial: Immunoregulation By Adenosine Signaling In Infection And Inflammation, Xiangsheng Huang, Weidong Zhao, Tingting Mills, Lei Shi, Xiaoyi Yuan

Faculty, Staff and Student Publications

No abstract provided.

Dosimetric Evaluations Using Cycle-Consistent Generative Adversarial Network Synthetic Ct For Mr-Guided Adaptive Radiation Therapy, Gabriel L Asher, Shiru Wang, Bassem I Zaki, Gregory A Russo, Gobind S Gill, Charles R Thomas, Temiloluwa O Prioleau, Yuting Li, Rongxiao Zhang, Yue Yan, Brady Hunt

Faculty, Staff and Student Publications

Background: Magnetic resonance (MR) guided radiation therapy combines high-resolution image capabilities of MRI with the precise targeting of radiation therapy. However, MRI does not provide the essential electron density information for accurate dose calculation, which limit the application of MRI. In this presented work, we evaluated the potential for Deep Learning (DL) based synthetic CT (sCT) generation using 3D MRI setup scans acquired during real-time adaptive MRI-guided radiation therapy.

Methods: We trained and evaluated a Cycle-consistent Generative Adversarial Network (Cycle-GAN) using paired MRI and deformably registered CT scan slices (dCT) in the context of real-time adaptive MRI-guided radiation therapy. Synthetic …