Digital Commons Network^™

Dendritic Cells As Shepherds Of T Cell Immunity In Cancer, Mikael J Pittet, Mauro Di Pilato, Christopher Garris, Thorsten R Mempel

Faculty, Staff and Student Publications

In cancer patients, dendritic cells (DCs) in tumor-draining lymph nodes can present antigens to naive T cells in ways that break immunological tolerance. The clonally expanded progeny of primed T cells are further regulated by DCs at tumor sites. Intratumoral DCs can both provide survival signals to and drive effector differentiation of incoming T cells, thereby locally enhancing antitumor immunity; however, the paucity of intratumoral DCs or their expression of immunoregulatory molecules often limits antitumor T cell responses. Here, we review the current understanding of DC-T cell interactions at both priming and effector sites of immune responses. We place emerging …

Mathematical Modeling Of Radiotherapy: Impact Of Model Selection On Estimating Minimum Radiation Dose For Tumor Control, Achyudhan R Kutuva, Jimmy J Caudell, Kosj Yamoah, Heiko Enderling, Mohammad U Zahid

Faculty, Staff and Student Publications

INTRODUCTION: Radiation therapy (RT) is one of the most common anticancer therapies. Yet, current radiation oncology practice does not adapt RT dose for individual patients, despite wide interpatient variability in radiosensitivity and accompanying treatment response. We have previously shown that mechanistic mathematical modeling of tumor volume dynamics can simulate volumetric response to RT for individual patients and estimation personalized RT dose for optimal tumor volume reduction. However, understanding the implications of the choice of the underlying RT response model is critical when calculating personalized RT dose.

METHODS: In this study, we evaluate the mathematical implications and biological effects of 2 …

Cancer Survivors’ Health Behaviors And Outcomes: A Population-Based Study Of Sexual And Gender Minorities, Ulrike Boehmer, Shine Chang, Nelson F Sanchez, Bill M Jesdale, Matthew B Schabath

Faculty, Staff and Student Publications

BACKGROUND: Most case-control studies compare cancer survivors with general population controls without considering sexual orientation or gender identity. This case-control analysis compared health risk behaviors and health outcomes among sexual and gender minority cancer survivors to those of matched sexual and gender minority participants without cancer (controls).

METHODS: Using data from the 2014-2021 Behavioral Risk Factor Surveillance System, a population-based sample of 4507 cancer survivors who self-identified as transgender, gay men, bisexual men, lesbian women, or bisexual women were 1:1 propensity score matched, using age at survey, race and ethnicity, marital status, education, access to health care, and US census …

Znf683 Marks A Cd8+ T Cell Population Associated With Anti-Tumor Immunity Following Anti-Pd-1 Therapy For Richter Syndrome, Erin M Parry, Camilla K Lemvigh, Stephanie Deng, Nathan Dangle, Neil Ruthen, Binyamin A Knisbacher, Julien Broséus, Sébastien Hergalant, Romain Guièze, Shuqiang Li, Wandi Zhang, Connor Johnson, Jaclyn M Long, Shanye Yin, Lillian Werner, Annabelle Anandappa, Noelia Purroy, Satyen Gohil, Giacomo Oliveira, Pavan Bachireddy, Sachet A Shukla, Teddy Huang, Joseph D Khoury, Beenu Thakral, Michael Dickinson, Constantine Tam, Kenneth J Livak, Gad Getz, Donna Neuberg, Pierre Feugier, Peter Kharchenko, William Wierda, Lars Rønn Olsen, Nitin Jain, Catherine J Wu

Faculty, Staff and Student Publications

Unlike many other hematologic malignancies, Richter syndrome (RS), an aggressive B cell lymphoma originating from indolent chronic lymphocytic leukemia, is responsive to PD-1 blockade. To discover the determinants of response, we analyze single-cell transcriptome data generated from 17 bone marrow samples longitudinally collected from 6 patients with RS. Response is associated with intermediate exhausted CD8 effector/effector memory T cells marked by high expression of the transcription factor ZNF683, determined to be evolving from stem-like memory cells and divergent from terminally exhausted cells. This signature overlaps with that of tumor-infiltrating populations from anti-PD-1 responsive solid tumors. ZNF683 is found to directly …

Ccdc50 Promotes Tumor Growth Through Regulation Of Lysosome Homeostasis, Penghui Jia, Tian Tian, Zibo Li, Yicheng Wang, Yuxin Lin, Weijie Zeng, Yu Ye, Miao He, Xiangrong Ni, Ji'an Pan, Xiaonan Dong, Jian Huang, Chun-Mei Li, Deyin Guo, Panpan Hou

Faculty, Staff and Student Publications

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 …

Impact Of Post-Pci Ffr Stratified By Coronary Artery, Carlos Collet, Nils P Johnson, Takuya Mizukami, William F Fearon, Colin Berry, Jeroen Sonck, Damien Collison, Bon-Kwon Koo, Nicolas Meneveau, Shiv Kumar Agarwal, Barry Uretsky, Abdul Hakeem, Joon-Hyung Doh, Bruno R Da Costa, Keith G Oldroyd, Jonathon A Leipsic, Umberto Morbiducci, Charles Taylor, Brian Ko, Pim A L Tonino, Divaka Perera, Toshiro Shinke, Claudio Chiastra, Andrei C Sposito, Antonio Maria Leone, Olivier Muller, Stephane Fournier, Hitoshi Matsuo, Julien Adjedj, Nicolas Amabile, Zsolt Piróth, Fernando Alfonso, Fernando Rivero, Jung-Min Ahn, Gabor G Toth, Abdul Ihdayhid, Nick E J West, Tetsuya Amano, Eric Wyffels, Daniel Munhoz, Marta Belmonte, Hirofumi Ohashi, Koshiro Sakai, Emanuele Gallinoro, Emanuele Barbato, Thomas Engstrøm, Javier Escaned, Ziad A Ali, Morton J Kern, Nico H J Pijls, Peter Jüni, Bernard De Bruyne

Faculty, Staff and Student Publications

Background: Low fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) has been associated with adverse clinical outcomes. Hitherto, this assessment has been independent of the epicardial vessel interrogated.

Objectives: This study sought to assess the predictive capacity of post-PCI FFR for target vessel failure (TVF) stratified by coronary artery.

Methods: We performed a systematic review and individual patient-level data meta-analysis of randomized clinical trials and observational studies with protocol-recommended post-PCI FFR assessment. The difference in post-PCI FFR between left anterior descending (LAD) and non-LAD arteries was assessed using a random-effect models meta-analysis of mean differences. TVF was defined as …

Enzyme-Mediated Depletion Of Methylthioadenosine Restores T Cell Function In Mtap-Deficient Tumors And Reverses Immunotherapy Resistance, Donjeta Gjuka, Elio Adib, Kendra Garrison, Jianfeng Chen, Yuxue Zhang, Wenjiao Li, Daniel Boutz, Candice Lamb, Yuri Tanno, Amin Nassar, Talal El Zarif, Neil Kale, Mehrdad Rakaee, Tarek H Mouhieddine, Sarah Abou Alaiwi, Alexander Gusev, Thomas Rogers, Jianjun Gao, George Georgiou, David J Kwiatkowski, Everett Stone

Faculty, Staff and Student Publications

Chromosomal region 9p21 containing tumor suppressors CDKN2A/B and methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic deletions in cancer. 9p21 loss is correlated with reduced tumor-infiltrating lymphocytes (TILs) and resistance to immune checkpoint inhibitor (ICI) therapy. Previously thought to be caused by CDKN2A/B loss, we now show that it is loss of MTAP that leads to poor outcomes on ICI therapy and reduced TIL density. MTAP loss causes accumulation of methylthioadenosine (MTA) both intracellularly and extracellularly and profoundly impairs T cell function via the inhibition of protein arginine methyltransferase 5 (PRMT5) and by adenosine receptor agonism. Administration of …

Social Determinants Of Health And Disparate Disability Accumulation In A Cohort Of Black, Hispanic, And White Patients With Multiple Sclerosis, Michael C Robertson, Brian Downer, Paul E Schulz, Rafael Samper-Ternent, Elizabeth J Lyons, Sadaf Arefi Milani

Faculty, Staff and Student Publications

OBJECTIVES: Mexico has a rapidly aging population at risk for cognitive impairment. Social and leisure activities may protect against cognitive decline in older adults. The benefits of these behaviors may vary by patterns of cognitive impairment. The objectives of this study were to identify latent states of cognitive functioning, model the incidence of transitions between these states, and investigate how social and leisure activities were associated with state transitions over a 6-year period in Mexican adults aged 60 and older.

METHODS: We performed latent transition analyses to identify distinct cognitive statuses in the 2012 and 2018 waves of the Mexican …

Blood-Based Transcriptomic Biomarkers Are Predictive Of Neurodegeneration Rather Than Alzheimer's Disease, Artur Shvetcov, Shannon Thomson, Jessica Spathos, Ann-Na Cho, Heather M Wilkins, Shea J Andrews, Fabien Delerue, Timothy A Couttas, Jasmeen Kaur Issar, Finula Isik, Simranpreet Kaur, Eleanor Drummond, Carol Dobson-Stone, Shantel L Duffy, Natasha M Rogers, Daniel Catchpoole, Wendy A Gold, Russell H Swerdlow, David A Brown, Caitlin A Finney

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a growing global health crisis affecting millions and incurring substantial economic costs. However, clinical diagnosis remains challenging, with misdiagnoses and underdiagnoses being prevalent. There is an increased focus on putative, blood-based biomarkers that may be useful for the diagnosis as well as early detection of AD. In the present study, we used an unbiased combination of machine learning and functional network analyses to identify blood gene biomarker candidates in AD. Using supervised machine learning, we also determined whether these candidates were indeed unique to AD or whether they were indicative of other neurodegenerative diseases, such as …

Influence Of Macrophages On Vascular Invasion Of Inflammatory Breast Cancer Emboli Measured Using An In Vitro Microfluidic Multi-Cellular Platform, Manasa Gadde, Melika Mehrabi-Dehdezi, Bisrat G Debeb, Wendy A Woodward, Marissa Nichole Rylander

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC) is an aggressive disease with a poor prognosis and a lack of effective treatments. It is widely established that understanding the interactions between tumor-associated macrophages (TAMs) and the tumor microenvironment is essential for identifying distinct targeting markers that help with prognosis and subsequent development of effective treatments. In this study, we present a 3D in vitro microfluidic IBC platform consisting of THP1 M0, M1, or M2 macrophages, IBC cells, and endothelial cells. The platform comprises a collagen matrix that includes an endothelialized vessel, creating a physiologically relevant environment for cellular interactions. Through the utilization of this …

The Neuroimmune Regulation And Potential Therapeutic Strategies Of Optic Pathway Glioma, Khushboo Irshad, Yu-Kai Huang, Paul Rodriguez, Jung Lo, Benjamin E Aghoghovwia, Yuan Pan, Kun-Che Chang

Faculty, Staff and Student Publications

Optic pathway glioma (OPG) is one of the causes of pediatric visual impairment. Unfortunately, there is as yet no cure for such a disease. Understanding the underlying mechanisms and the potential therapeutic strategies may help to delay the progression of OPG and rescue the visual morbidities. Here, we provide an overview of preclinical OPG studies and the regulatory pathways controlling OPG pathophysiology. We next discuss the role of microenvironmental cells (neurons, T cells, and tumor-associated microglia and macrophages) in OPG development. Last, we provide insight into potential therapeutic strategies for treating OPG and promoting axon regeneration.

Early Season Monitoring Of Tarnished Plant Bug, Lygus Lineolaris, In Wild Hosts Using Pheromone Traps, Justin George, James P Glover, Gadi V P Reddy, Chris Johnson, David R Hall

Faculty, Staff and Student Publications

Simple Summary

The tarnished plant bug, Lygus lineolaris (Hemiptera: Miridae), is a polyphagous pest and causes severe economic damage to cotton crops. Managing the weedy field edges is important in preventing early-season infestations of L. lineolaris in cotton to prevent damage to the squares and other fruiting structures. Scouting fields for L. lineolaris is time- and labor-intensive, and end-user variability associated with field sampling can lead to inaccuracies. Insect traps that combine visual cues and pheromones are more accurate, sustainable, and economically feasible in contrast to traditional insect detection methods. In this study, we investigated the application of red or …

Stabilizing Peri-Stent Restenosis Using A Novel Therapeutic Carrier, Maria P Blasco Conesa, Frank W Blixt, Pedram Peesh, Romeesa Khan, Janelle Korf, Juneyoung Lee, Gayathri Jagadeesan, Alexander Andersohn, Tushar K Das, Chunfeng Tan, Claudia Di Gesu, Gabriela Delevati Colpo, Jose Félix Moruno-Manchón, Louise D Mccullough, Robert Bryan, Bhanu P Ganesh

Faculty, Staff and Student Publications

Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely determined by the extent of ischemic injury, however, there is growing recognition that systemic inflammatory responses also contribute to outcomes. Mast cells (MCs) rapidly respond to injury and release histamine (HA), a pro-inflammatory neurotransmitter that enhances inflammation. The gut serves as a major reservoir of HA. We hypothesized that cromolyn, a mast cell stabilizer that prevents the release of inflammatory mediators, would decrease peripheral and central inflammation, reduce MC trafficking to the brain, and …

The Gut Microbiome As A Biomarker And Therapeutic Target In Hepatocellular Carcinoma, Betul Gok Yavuz, Saumil Datar, Shadi Chamseddine, Yehia I Mohamed, Michael Lapelusa, Sunyoung S Lee, Zishuo Ian Hu, Eugene J Koay, Hop S Tran Cao, Prasun Kumar Jalal, Carrie Daniel-Macdougall, Manal Hassan, Dan G Duda, Hesham M Amin, Ahmed O Kaseb

Faculty, Staff and Student Publications

The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer; thus, …

Medical Imaging Applications Of Federated Learning, Sukhveer Singh Sandhu, Hamed Taheri Gorji, Pantea Tavakolian, Kouhyar Tavakolian, Alireza Akhbardeh

Faculty, Staff and Student Publications

Since its introduction in 2016, researchers have applied the idea of Federated Learning (FL) to several domains ranging from edge computing to banking. The technique's inherent security benefits, privacy-preserving capabilities, ease of scalability, and ability to transcend data biases have motivated researchers to use this tool on healthcare datasets. While several reviews exist detailing FL and its applications, this review focuses solely on the different applications of FL to medical imaging datasets, grouping applications by diseases, modality, and/or part of the body. This Systematic Literature review was conducted by querying and consolidating results from ArXiv, IEEE Xplorer, and PubMed. Furthermore, …

Multiphoton In Vivo Microscopy Of Embryonic Thrombopoiesis Reveals The Generation Of Platelets Through Budding, Huan Liu, Hellen Ishikawa-Ankerhold, Julia Winterhalter, Michael Lorenz, Mykhailo Vladymyrov, Steffen Massberg, Christian Schulz, Mathias Orban

Faculty, Staff and Student Publications

Platelets are generated by specialized cells called megakaryocytes (MKs). However, MK's origin and platelet release mode have remained incompletely understood. Here, we established direct visualization of embryonic thrombopoiesis in vivo by combining multiphoton intravital microscopy (MP-IVM) with a fluorescence switch reporter mouse model under control of the platelet factor 4 promoter (Pf4CreRosa26mTmG). Using this microscopy tool, we discovered that fetal liver MKs provide higher thrombopoietic activity than yolk sac MKs. Mechanistically, fetal platelets were released from MKs either by membrane buds or the formation of proplatelets, with the former constituting the key process. In E14.5 c-Myb-deficient …

High-Fat Diet, But Not Duration Of Lactation, Increases Mammary Gland Lymphatic Vessel Function And Subsequent Growth Of Inflammatory Breast Cancer Cells, Wintana Balema, Janelle Morton, Richard A Larson, Li Li, Fred Christian Velasquez, Natalie W Fowlkes, Savitri Krishnamurthy, Bisrat G Debeb, Eva Sevick-Muraca, Wendy A Woodward

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC) presents as rapid-onset swelling and breast skin changes caused by tumor emboli in the breast and breast skin lymphatics. IBC has been linked with obesity and duration of breastfeeding, but how these factors affect IBC tumor progression is not clear. We modeled the simultaneous effects of diet and weaning in mice on in vivo lymphatic function; on IBC tumor growth; and on aspects of the mammary gland microenvironment before and after IBC (SUM149) xenograft inoculation. We hypothesized that weaning status and diet would have synergistic effects on lymphatic function and the breast microenvironment to enhance IBC …

Müllerian-Type Clear Cell Carcinoma Of Donor Origin In A Male Patient With A Kidney Transplant: Ascertained By Molecular Testing, J Bryan Iorgulescu, Leah K Shaw, Asif Rashid, Priya Rao, Sreedhar Mandayam, Keyur P Patel, Kathleen M Schmeler, Richard K Yang, Pavlos Msaouel

Faculty, Staff and Student Publications

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem …

In-Utero Exposure To Antibiotics And Risk Of Colorectal Cancer In A Prospective Cohort Of 18 000 Adult Offspring, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Dean P Jones, Timothy Zaki, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring.

METHODS: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides …

Pls3 Missense Variants Affecting The Actin-Binding Domains Cause X-Linked Congenital Diaphragmatic Hernia And Body-Wall Defects, Florence Petit, Mauro Longoni, Julie Wells, Richard S Maser, Eric L Bogenschutz, Matthew J Dysart, Hannah T M Contreras, Frederic Frénois, Barbara R Pober, Robin D Clark, Philip F Giampietro, Hilger H Ropers, Hao Hu, Maria Loscertales, Richard Wagner, Xingbin Ai, Harrison Brand, Anne-Sophie Jourdain, Marie-Ange Delrue, Brigitte Gilbert-Dussardier, Louise Devisme, Boris Keren, David J Mcculley, Lu Qiao, Rebecca Hernan, Julia Wynn, Tiana M Scott, Daniel G Calame, Zeynep Coban-Akdemir, Patricia Hernandez, Andres Hernandez-Garcia, Hagith Yonath, James R Lupski, Yufeng Shen, Wendy K Chung, Daryl A Scott, Carol J Bult, Patricia K Donahoe, Frances A High

Faculty, Staff and Student Publications

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical …

Rare Variants In Long Non-Coding Rnas Are Associated With Blood Lipid Levels In The Topmed Whole-Genome Sequencing Study, Yuxuan Wang, Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Jacob A Holdcraft, Donna K Arnett, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Brian E Cade, Jenna C Carlson, April P Carson, Yii-Der Ida Chen, Joanne E Curran, Paul S De Vries, Susan K Dutcher, Patrick T Ellinor, James S Floyd, Myriam Fornage, Barry I Freedman, Stacey Gabriel, Soren Germer, Richard A Gibbs, Xiuqing Guo, Jiang He, Nancy Heard-Costa, Bertha Hildalgo, Lifang Hou, Marguerite R Irvin, Roby Joehanes, Robert C Kaplan, Sharon Lr Kardia, Tanika N Kelly, Ryan Kim, Charles Kooperberg, Brian G Kral, Daniel Levy, Changwei Li, Chunyu Liu, Don Lloyd-Jone, Ruth Jf Loos, Michael C Mahaney, Lisa W Martin, Rasika A Mathias, Ryan L Minster, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Joanne M Murabito, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Michael H Preuss, Bruce M Psaty, Laura M Raffield, Dabeeru C Rao, Susan Redline, Alexander P Reiner, Stephen S Rich, Muagututi'a Sefuiva Ruepena, Wayne H-H Sheu, Jennifer A Smith, Albert Smith, Hemant K Tiwari, Michael Y Tsai, Karine A Viaud-Martinez, Zhe Wang, Lisa R Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Jerome I Rotter, Xihong Lin, Pradeep Natarajan, Gina M Peloso

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants …

Analysis And Prediction Of Liver Volume Change Maps Derived From Computational Tomography Scans Acquired Pre- And Post-Radiation Therapy, Guillaume Cazoulat, Aashish C Gupta, Mais M Al Taie, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

External beam radiation therapy (EBRT) of liver cancers can cause local liver atrophy as a result of tissue damage or hypertrophy as a result of liver regeneration. Predicting those volumetric changes would enable new strategies for liver function preservation during treatment planning. However, understanding of the spatial dose/volume relationship is still limited. This study leverages the use of deep learning-based segmentation and biomechanical deformable image registration (DIR) to analyze and predict this relationship. Pre- and Post-EBRT imaging data were collected for 100 patients treated for hepatocellular carcinomas, cholangiocarcinoma or CRC with intensity-modulated radiotherapy (IMRT) with prescription doses ranging from 50 …

Detection Of Early Myocardial Dysfunction By Imaging Biomarkers In Cancer Patients Undergoing Photon Beam Vs Proton Beam Radiotherapy: A Prospective Study, Muhannad Aboud Abbasi, Giulia Bruno, Cristina Di Stefano, Laura Garcia Bello, Nadia N Laack, Kimberly S Corbin, Thomas J Whitaker, Patricia A Pellikka, Robert W Mutter, Hector R Villarraga

Faculty, Staff and Student Publications

1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) …

The Use Of Electronic Health Record Data To Identify Variation In Referral, Consent, And Engagement In A Pediatric Intervention For Overweight And Obesity: A Cross-Sectional Study, Joshua S Yudkin, Marlyn A Allicock, Folefac D Atem, Carol A Galeener, Sarah E Messiah, Sarah E Barlow

Faculty, Staff and Student Publications

Clinical weight management programs face low participation. The authors assessed whether using electronic health record (EHR) data can identify variation in referral, consent, and engagement in a pediatric overweight and obesity (OW/OB) intervention. Using Epic EHR data collected between August 2020 and April 2021, sociodemographic and clinical diagnostic data (ie, International Classification of Disease [ICD] codes from visit and problem list [PL]) were analyzed to determine their association with referral, consent, and engagement in an OW/OB intervention. Bivariate analyses and multivariable logistic regression modeling were performed, with Bayesian inclusion criterion score used for model selection. Compared with the 581 eligible …

Disrupted Stiffness Ratio Alters Nuclear Mechanosensing, Brandon K Walther, Adam P Sears, Anahita Mojiri, Reza Avazmohammadi, Jianhua Gu, Olga V Chumakova, Navaneeth Krishna Rajeeva Pandian, Abishai Dominic, Jean-Louis Martiel, Saami K Yazdani, John P Cooke, Jacques Ohayon, Roderic I Pettigrew

Faculty, Staff and Student Publications

The ability of endothelial cells to sense and respond to dynamic changes in blood flow is critical for vascular homeostasis and cardiovascular health. The mechanical and geometric properties of the nuclear and cytoplasmic compartments affect mechanotransduction. We hypothesized that alterations to these parameters have resulting mechanosensory consequences. Using atomic force microscopy and mathematical modeling, we assessed how the nuclear and cytoplasmic compartment stiffnesses modulate shear stress transfer to the nucleus within aging endothelial cells. Our computational studies revealed that the critical parameter controlling shear transfer is not the individual mechanics of these compartments, but the stiffness ratio between them. Replicatively …

Index Of Consciousness Monitoring During General Anesthesia May Effectively Enhance Rehabilitation In Elderly Patients Undergoing Laparoscopic Urological Surgery: A Randomized Controlled Clinical Trial, Fengling Qi, Long Fan, Chunxiu Wang, Yang Liu, Shuyi Yang, Zhen Fan, Fangfang Miao, Minhui Kan, Kunpeng Feng, Tianlong Wang

Faculty, Staff and Student Publications

Background: Based on electroencephalogram (EEG) analysis, index of consciousness (IoC) monitoring is a new technique for monitoring anesthesia depth. IoC is divided into IoC1 (depth of sedation) and IoC2 (depth of analgesia). The potential for concurrent monitoring of IoC1 and IoC2 to expedite postoperative convalescence remains to be elucidated. We investigated whether combined monitoring of IoC1 and IoC2 can effectively enhances postoperative recovery compared with bispectral index (BIS) in elderly patients undergoing laparoscopic urological surgery under general anesthesia.

Methods: In this prospective, controlled, double-blinded trail, 120 patients aged 65 years or older were arbitrarily assigned to either the IoC group …

Influence Of Sex On Meat And Fat Quality From Heavy Alentejano Pigs Finished Outdoors On Commercial And High Fiber Diets, José Manuel Martins, Rui Charneca, Nicolás Garrido, André Albuquerque, Eliana Jerónimo, Olinda Guerreiro, Patrícia Lage, Carla Marmelo, Filipa Costa, Amélia Ramos, Luísa Martin

Faculty, Staff and Student Publications

This work aimed to examine the effects of sex on meat and fat quality traits from thirty Portuguese Alentejano (AL) pigs reared in outdoor conditions. These pigs were divided into three groups and fed ad libitum. From ~40 to 130 kg LW, castrated (C group) and intact animals (I and IExp) consumed commercial diets. Until slaughter (~160 kg), C and I pigs remained on commercial diets, and IExp changed to a more sustainable experimental diet with locally produced pulses and byproducts. Samples were collected from the Longissimus lumborum (LL), Psoas major (PM), and dorsal subcutaneous fat (DSF). At ~160 …

Gut Microbiota Aggravates Neutrophil Extracellular Traps-Induced Pancreatic Injury In Hypertriglyceridemic Pancreatitis, Guanqun Li, Liwei Liu, Tianqi Lu, Yuhang Sui, Can Zhang, Yongwei Wang, Tao Zhang, Yu Xie, Peng Xiao, Zhongjie Zhao, Chundong Cheng, Jisheng Hu, Hongze Chen, Dongbo Xue, Hua Chen, Gang Wang, Rui Kong, Hongtao Tan, Xuewei Bai, Zhibo Li, Florencia Mcallister, Le Li, Bei Sun

Faculty, Staff and Student Publications

Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. …

High-Level Ceftazidime/Avibactam Resistance In Escherichia Coli Conferred By The Novel Plasmid-Mediated Β-Lactamase Cmy-185 Variant, William C Shropshire, Bradley T Endres, Jovan Borjan, Samuel L Aitken, William C Bachman, Christi L Mcelheny, Chin-Ting Wu, Stephanie L Egge, Ayesha Khan, William R Miller, Micah M Bhatti, Pranoti Saharasbhojane, Akito Kawai, Ryan K Shields, Samuel A Shelburne, Yohei Doi

Faculty, Staff and Student Publications

OBJECTIVES: To characterize a blaCMY variant associated with ceftazidime/avibactam resistance from a serially collected Escherichia coli isolate.

METHODS: A patient with an intra-abdominal infection due to recurrent E. coli was treated with ceftazidime/avibactam. On Day 48 of ceftazidime/avibactam therapy, E. coli with a ceftazidime/avibactam MIC of >256 mg/L was identified from abdominal drainage. Illumina and Oxford Nanopore Technologies WGS was performed on serial isolates to identify potential resistance mechanisms. Site-directed mutants of CMY β-lactamase were constructed to identify amino acid residues responsible for ceftazidime/avibactam resistance.

RESULTS: WGS revealed that all three isolates were E. coli ST410. The ceftazidime/avibactam-resistant strain uniquely …

Privacy-Preserving Federated Genome-Wide Association Studies Via Dynamic Sampling, Xinyue Wang, Leonard Dervishi, Wentao Li, Erman Ayday, Xiaoqian Jiang, Jaideep Vaidya

Faculty, Staff and Student Publications

MOTIVATION: Genome-wide association studies (GWAS) benefit from the increasing availability of genomic data and cross-institution collaborations. However, sharing data across institutional boundaries jeopardizes medical data confidentiality and patient privacy. While modern cryptographic techniques provide formal secure guarantees, the substantial communication and computational overheads hinder the practical application of large-scale collaborative GWAS.

RESULTS: This work introduces an efficient framework for conducting collaborative GWAS on distributed datasets, maintaining data privacy without compromising the accuracy of the results. We propose a novel two-step strategy aimed at reducing communication and computational overheads, and we employ iterative and sampling techniques to ensure accurate results. We …