Medical Specialties Commons^™

Radiofrequency Ablation In Combination With Cd73 Inhibitor Ab680 Reduces Tumor Growth And Enhances Anti-Tumor Immunity In A Syngeneic Model Of Pancreatic Ductal Adenocarcinoma, Erika Y Faraoni, Lincoln N Strickland, Baylee J O'Brien, Joseph F Barraza, Nirav C Thosani, Curtis J Wray, Tingting W Mills, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma presents a 5-year overall survival rate of 11%, placing an imperative need for the discovery and application of innovative treatments. Radiofrequency ablation represents a promising therapy for PDA, as studies show it induces coagulative necrosis and a host adaptive immune response. In this work we evaluated the effects of RFA treatment in vivo by establishing a syngeneic mouse model of PDA and performing tumor ablation in one flank. Our studies revealed RFA acutely impaired PDA tumor growth; however, such effects were not sustained one week after treatment. Adenosine (ADO) pathway represents a strong immunosuppressive mechanism that was …

Biophysical Characterization Of Light-Gated Ion Channels Using Planar Automated Patch Clamp, Elena G Govorunova, Oleg A Sineshchekov, Leonid S Brown, John L Spudich

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Channelrhodopsins (ChRs) are proteins that guide phototaxis in protists and exhibit light-gated channel conductance when their genes are heterologously expressed in mammalian cells. ChRs are widely used as molecular tools to control neurons and cardiomyocytes with light (optogenetics). Cation- and anion-selective ChRs (CCRs and ACRs, respectively) enable stimulation and inhibition of neuronal activity by depolarization and hyperpolarization of the membrane, respectively. More than 400 natural ChR variants have been identified so far, and high-throughput polynucleotide sequencing projects add many more each year. However, electrophysiological characterization of new ChRs lags behind because it is mostly done by time-consuming manual patch clamp …

Single-Cell Rna Sequencing Reveals Intratumoral Heterogeneity And Potential Mechanisms Of Malignant Progression In Prostate Cancer With Perineural Invasion, Bao Zhang, Shenghan Wang, Zhichao Fu, Qiang Gao, Lin Yang, Zhentao Lei, Yuqiang Shi, Kai Le, Jie Xiong, Siyao Liu, Jiali Zhang, Junyan Su, Jing Chen, Mengyuan Liu, Beifang Niu

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Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.

Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition …

Progranulin Loss Results In Sex-Dependent Dysregulation Of The Peripheral And Central Immune System, Madelyn C Houser, Oihane Uriarte Huarte, Rebecca L Wallings, Cody E Keating, Kathryn P Macpherson, Mary K Herrick, George T Kannarkat, Sean D Kelly, Jianjun Chang, Nicholas H Varvel, Jessica E Rexach, Malú Gámez Tansey

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INTRODUCTION: Progranulin (PGRN) is a secreted glycoprotein, the expression of which is linked to several neurodegenerative diseases. Although its specific function is still unclear, several studies have linked it with lysosomal functions and immune system regulation. Here, we have explored the role of PGRN in peripheral and central immune system homeostasis by investigating the consequences of PGRN deficiency on adaptive and innate immune cell populations.

METHODS: First, we used gene co-expression network analysis of published data to test the hypothesis that

RESULTS: Male PGRN KO mice exhibited a lower abundance of microglial cells with higher MHC-II expression, increased CD44 expression …

Donor Selection For Kir Alloreactivity Is Associated With Superior Survival In Haploidentical Transplant With Ptcy, Jun Zou, Piyanuch Kongtim, Samer A Srour, Uri Greenbaum, Johannes Schetelig, Falk Heidenreich, Henning Baldauf, Brandt Moore, Supawee Saengboon, Yudith Carmazzi, Gabriela Rondon, Qing Ma, Katayoun Rezvani, Elizabeth J Shpall, Richard E Champlin, Stefan O Ciurea, Kai Cao

Faculty, Staff and Student Publications

With the continuous increase in the use of haploidentical donors for transplantation, the selection of donors becomes increasingly important. Haploidentical donors have been selected primarily based on clinical characteristics, while the effects of killer cell immunoglobulin-like receptors (KIRs) on outcomes of haploidentical-hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCy) remain inconclusive. The present study aimed to thoroughly evaluate the effect of KIRs and binding ligands assessed by various models, in addition to other patient/donor variables, on clinical outcomes in haplo-HSCT. In a cohort of 354 patients undergoing their first haplo-HSCT, we found that a higher Count Functional inhibitory KIR …

Neoadjuvant Checkpoint Inhibitor Immunotherapy For Resectable Mucosal Melanoma, Joel Ho, Jane Mattei, Michael Tetzlaff, Michelle D Williams, Michael A Davies, Adi Diab, Isabella C Glitza Oliva, Jennifer Mcquade, Sapna P Patel, Hussein Tawbi, Michael K Wong, Sarah B Fisher, Ehab Hanna, Emily Z Keung, Merrick Ross, Roi Weiser, Shirley Y Su, Michael Frumovitz, Larissa A Meyer, Amir Jazaeri, Curtis A Pettaway, B Ashleigh Guadagnolo, Andrew J Bishop, Devarati Mitra, Ahsan Farooqi, Roland Bassett, Silvana Faria, Priyadharsini Nagarajan, Rodabe N Amaria

Faculty, Staff and Student Publications

BACKGROUND: Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM.

METHOD: Under an institutionally approved protocol, we identified adult …

Distal-Less Homeobox Genes Dlx5/6 Regulate Müllerian Duct Regression, Rachel D Mullen, Brice Bellessort, Giovanni Levi, Richard R Behringer

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Dlx5 and Dlx6 encode distal-less homeodomain transcription factors that are present in the genome as a linked pair at a single locus. Dlx5 and Dlx6 have redundant roles in craniofacial, skeletal, and uterine development. Previously, we performed a transcriptome comparison for anti-Müllerian hormone (AMH)-induced genes expressed in the Müllerian duct mesenchyme of male and female mouse embryos. In that study, we found that Dlx5 transcripts were nearly seven-fold higher in males compared to females and Dlx6 transcripts were found only in males, suggesting they may be AMH-induced genes. Therefore, we investigated the role of Dlx5 and Dlx6 during AMH-induced Müllerian …

Evaluation Of Medical Services From The Perspective Of Covid-19 Vaccine Demand Satisfaction In Hangzhou, China, Mingjun Cheng, Yunchen Zhu, Peili Cen, Shan Huang

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The outbreak of COVID-19 has had a huge global impact, and it continues to test the resilience of medical services to emergencies worldwide. In the current post-epidemic era, vaccination has become a highly effective strategy to prevent the spread of COVID-19. However, using conventional mathematical models to evaluate the spatial distribution of medical resources, including vaccination, ignore people's behaviors and choices and make simplifications to the real world. In this study, we use an enhanced model based on the Theory of People Behavior (TPB) to perform a macro analysis of the satisfaction ability of medical resources for vaccination in Hangzhou, …

Trigger Related Outcomes Of Takotsubo Syndrome In A Cancer Population, Ayesha Safdar, Talha Ahmed, Victor Y Liu, Antoine Addoumieh, Ali M Agha, Dana E Giza, Dinu V Balanescu, Teodora Donisan, Tariq Dayah, Juan C Lopez-Mattei, Peter Y Kim, Saamir Hassan, Kaveh Karimzad, Nicolas Palaskas, January Y Tsai, Gloria D Iliescu, Eric H Yang, Joerg Herrmann, Konstantinos Marmagkiolis, Paolo Angelini, Cezar A Iliescu

Faculty, Staff and Student Publications

BACKGROUND: Takotsubo syndrome (TTS) occurs more frequently in cancer patients than in the general population, but the effect of specific TTS triggers on outcomes in cancer patients is not well studied.

OBJECTIVES: The study sought to determine whether triggering event (chemotherapy, immune-modulators vs. procedural or emotional stress) modifies outcomes in a cancer patient population with TTS.

METHODS: All cancer patients presenting with acute coronary syndrome (ACS) between December 2008 and December 2020 at our institution were enrolled in the catheterization laboratory registry. Demographic and clinical data of the identified patients with TTS were retrospective collected and further classified according to …

Case Report: Successful Treatment Of Late-Onset Immune Checkpoint Inhibitor-Associated Membranous Nephropathy In A Patient With Advanced Renal Cell Carcinoma, Praveen Ratanasrimetha, Vikas D Reddy, Jaya Kala, Amanda Tchakarov, William F Glass, Pavlos Msaouel, Jamie S Lin

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BACKGROUND: Diagnosing immune checkpoint inhibitor (ICI)-associated nephritis can be challenging since it is a rare complication of therapy, associated with a spectrum of immune-mediated pathologies, and can present months after ICI therapy discontinuation (i.e., late-onset). ICIs are increasingly administered in combination with other cancer therapies with associated nephrotoxicity, further obfuscating the diagnosis of ICI-associated nephritis. In this report, we describe the first suspected case of late-onset ICI-associated membranous nephropathy (MN) in a patient with metastatic clear cell renal cell carcinoma (RCC) who had discontinued ICI therapy 6 months prior to presentation. Prompt recognition of the suspected late-onset immune-related adverse event …

Emerging Current Trends And Research Focus Related To Pancreatic Cancer Metabolism: A Bibliometric And Visualized Analysis, Qian Shen, Chuanlong Zhang, Xiaochen Jiang, Junchen Li, Fudong Liu, Xiyuan Zhang, Ge'er En, Bo Pang

Faculty, Staff and Student Publications

BACKGROUND: As a malignant digestive system tumor, pancreatic cancer has unique metabolic characteristics. In recent years, the study of pancreatic cancer metabolism is in full swing, which provides a new direction for the treatment of pancreatic cancer patients. However, there is no systematic report of pancreatic cancer metabolism. In this paper, bibliometrics and visualization methods were used to analyze the number of publications, countries/regions, authors, institutions, journals, co-cited references, and keywords of pancreatic cancer metabolism articles, to summarize the research trends and predict research hotspots.

METHODS: We searched, screened and downloaded articles on pancreatic cancer metabolism through the Web of …

Treatment And Management Of Xiphoidalgia, Nazir Noor, Ariunzaya Amgalan, Neeraj Vij, Kelly Habib, Lekha Anantuni, Daniel An, Hisham Kassem, Antonella Paladini, Giustino Varrassi, Alan D Kaye

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Xiphodynia is a rare but debilitating condition that can be described as a form of pain on the xiphisternal joint or any related structures that are anchored to the xiphoid process. Although xiphodynia is a musculoskeletal pain in nature, the pain located in the anterior chest can commonly mislead physicians into pursuing other diagnoses such as cardiac diseases. This leads to a prolonged duration of pain before receiving treatment. In the attempt to alleviate pain resulting from this condition, physicians have previously utilized a range of treatment options, including conservative management, injections, or in severe cases, xiphoidectomy. In this review, …

Oral Administration Of A Dual Eta/Etb Receptor Antagonist Promotes Neuroprotection In A Rodent Model Of Glaucoma, Bindu Kodati, Nolan R Mcgrady, Hayden B Jefferies, Dorota L Stankowska, Raghu R Krishnamoorthy

Faculty, Staff and Student Publications

PURPOSE: Glaucoma is a neurodegenerative disease associated with elevated intraocular pressure and characterized by optic nerve axonal degeneration, cupping of the optic disc, and loss of retinal ganglion cells (RGCs). The endothelin (ET) system of vasoactive peptides (ET-1, ET-2, ET-3) and their G-protein coupled receptors (ET

METHODS: Male and female Brown Norway rats were subjected to the Morrison model of ocular hypertension by injection of hypertonic saline through the episcleral veins. Following IOP elevation, macitentan (5 mg/kg body wt) was administered orally 3 days per week, and rats with IOP elevation were maintained for 4 weeks. RGC function was determined …

Clinical Implementation And Initial Experience With A 15 Tesla Mr-Linac For Mr-Guided Radiation Therapy For Gynecologic Cancer: An R-Ideal Stage 1 And 2a First In Humans Feasibility Study Of New Technology Implementation, David S Lakomy, Jinzhong Yang, Sastry Vedam, Jihong Wang, Belinda Lee, Angela Sobremonte, Pamela Castillo, Neil Hughes, Mustefa Mohammedsaid, Anuja Jhingran, Ann H Klopp, Seungtaek Choi, C David Fuller, Lilie L Lin

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PURPOSE: Magnetic resonance imaging-guided linear accelerator systems (MR-linacs) can facilitate the daily adaptation of radiation therapy plans. Here, we report our early clinical experience using a MR-linac for adaptive radiation therapy of gynecologic malignancies.

METHODS AND MATERIALS: Treatments were planned with an Elekta Monaco v5.4.01 and delivered by a 1.5 Tesla Elekta Unity MR-linac. The system offers a choice of daily adaptation based on either position (ATP) or shape (ATS) of the tumor and surrounding normal structures. The ATS approach has the option of manually editing the contours of tumors and surrounding normal structures before the plan is adapted. Here, …

Glioma And The Gut-Brain Axis: Opportunities And Future Perspectives, Antonio Dono, Jack Nickles, Ana G Rodriguez-Armendariz, Braden C Mcfarland, Nadim J Ajami, Leomar Y Ballester, Jennifer A Wargo, Yoshua Esquenazi

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The gut-brain axis has presented a valuable new dynamic in the treatment of cancer and central nervous system (CNS) diseases. However, little is known about the potential role of this axis in neuro-oncology. The goal of this review is to highlight potential implications of the gut-brain axis in neuro-oncology, in particular gliomas, and future areas of research. The gut-brain axis is a well-established biochemical signaling axis that has been associated with various CNS diseases. In neuro-oncology, recent studies have described gut microbiome differences in tumor-bearing mice and glioma patients compared to controls. These differences in the composition of the microbiome …

A Novel Group Of Genes That Cause Endocrine Resistance In Breast Cancer Identified By Dynamic Gene Expression Analysis, Arvand Asghari, Katherine Wall, Michael Gill, Natascha Del Vecchio, Farnaz Allahbakhsh, Jacky Wu, Nan Deng, W Jim Zheng, Hulin Wu, Michihisa Umetani, Vahed Maroufy

Faculty, Staff and Student Publications

Breast cancer (BC) is the most common type of cancer diagnosed in women. Among female cancer deaths, BC is the second leading cause of death worldwide. For estrogen receptor-positive (ER-positive) breast cancers, endocrine therapy is an effective therapeutic approach. However, in many cases, an ER-positive tumor becomes unresponsive to endocrine therapy, and tumor regrowth occurs after treatment. While some genetic mutations contribute to resistance in some patients, the underlying causes of resistance to endocrine therapy are mostly undetermined. In this study, we utilized a recently developed statistical approach to investigate the dynamic behavior of gene expression during the development of …

Effects Of Tamoxifen Inducible Mercremer On Gene Expression In Cardiac Myocytes In Mice, Leila Rouhi, Siyang Fan, Sirisha M Cheedipudi, Melis Olcum, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

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The Cre-LoxP technology, including the tamoxifen (TAM) inducible MerCreMer (MCM), is increasingly used to delineate gene function, understand the disease mechanisms, and test therapeutic interventions. We set to determine the effects of TAM-MCM on cardiac myocyte transcriptome. Expression of the MCM was induced specifically in cardiac myocytes upon injection of TAM to myosin heavy chain 6-MCM (Myh6-Mcm) mice for 5 consecutive days. Cardiac function, myocardial histology, and gene expression (RNA-sequencing) were analyzed 2 weeks after TAM injection. A total of 346 protein coding genes (168 up- and 178 down-regulated) were differentially expressed. Transcript levels of 85 genes, analyzed …

An Ensemble-Based Deep Convolutional Neural Network For Computer-Aided Polyps Identification From Colonoscopy, Pallabi Sharma, Bunil Kumar Balabantaray, Kangkana Bora, Saurav Mallik, Kunio Kasugai, Zhongming Zhao

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Colorectal cancer (CRC) is the third leading cause of cancer death globally. Early detection and removal of precancerous polyps can significantly reduce the chance of CRC patient death. Currently, the polyp detection rate mainly depends on the skill and expertise of gastroenterologists. Over time, unidentified polyps can develop into cancer. Machine learning has recently emerged as a powerful method in assisting clinical diagnosis. Several classification models have been proposed to identify polyps, but their performance has not been comparable to an expert endoscopist yet. Here, we propose a multiple classifier consultation strategy to create an effective and powerful classifier for …

A Deep Learning-Based Framework For Supporting Clinical Diagnosis Of Glioblastoma Subtypes, Sana Munquad, Tapas Si, Saurav Mallik, Asim Bikas Das, Zhongming Zhao

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Understanding molecular features that facilitate aggressive phenotypes in glioblastoma multiforme (GBM) remains a major clinical challenge. Accurate diagnosis of GBM subtypes, namely classical, proneural, and mesenchymal, and identification of specific molecular features are crucial for clinicians for systematic treatment. We develop a biologically interpretable and highly efficient deep learning framework based on a convolutional neural network for subtype identification. The classifiers were generated from high-throughput data of different molecular levels, i.e., transcriptome and methylome. Furthermore, an integrated subsystem of transcriptome and methylome data was also used to build the biologically relevant model. Our results show that deep learning model outperforms …

Sulfhemoglobinemia And Methemoglobinemia Following Acetaminophen Overdose, Justin A Seltzer, Irvan Bubic, Garret A Winkler, Nathan A Friedman, Jessica Bagby, Christian A Tomaszewski, Richard F Clark, Allyson Kreshak, Daniel R Lasoff

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INTRODUCTION: Though acetaminophen overdoses are common, acetaminophen induced methemoglobinemia is rare and it is thought to be due to oxidative stress from reactive metabolites. However, few prior cases of sulfhemoglobinemia in the setting of acetaminophen overdose have been reported. We report a case of mixed methemoglobinemia and sulfhemoglobinemia in the setting of a large, isolated acetaminophen ingestion.

CASE REPORT: A 30-year-old African American male presented after intentionally ingesting 50 tablets of 500 mg acetaminophen two days prior. He was cyanotic and tachypneic. Peripheral oxygen saturation was 78 % on room air and minimally improved with high-flow oxygen. He was noted …

The Wnt/Β-Catenin Pathway Regulates Expression Of The Genes Involved In Cell Cycle Progression And Mitochondrial Oxidative Phosphorylation In The Postmitotic Cardiac Myocytes, Melis Olcum, Sirisha M Cheedipudi, Leila Rouhi, Siyang Fan, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

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INTRODUCTION: Aging is associated with cardiac myocyte loss, sarcopenia, and cardiac dysfunction. Adult cardiac myocytes are postmitotic cells with an insufficient proliferative capacity to compensate for myocyte loss. The canonical WNT (cWNT) pathway is involved in the regulation of cell cycle reentry in various cell types. The effects of the cWNT pathway on the expression of genes involved in cell cycle reentry in the postmitotic cardiac myocytes are unknown.

AIM: The aim of the study was to identify genes whose expression is regulated by the β-catenin, the indispensable component to the cWNT signaling, in the postmitotic myocytes.

METHODS AND RESULTS: …

Distinguish Bipolar And Major Depressive Disorder In Adolescents Based On Multimodal Neuroimaging: Results From The Adolescent Brain Cognitive Development Stud, Yujun Liu, Kai Chen, Yangyang Luo, Jiqiu Wu, Qu Xiang, Li Peng, Jian Zhang, Weiling Zhao, Mingliang Li, Xiaobo Zhou

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BACKGROUND: Major depressive disorder and bipolar disorder in adolescents are prevalent and are associated with cognitive impairment, executive dysfunction, and increased mortality. Early intervention in the initial stages of major depressive disorder and bipolar disorder can significantly improve personal health.

METHODS: We collected 309 samples from the Adolescent Brain Cognitive Development study, including 116 adolescents with bipolar disorder, 64 adolescents with major depressive disorder, and 129 healthy adolescents, and employed a support vector machine to develop classification models for identification. We developed a multimodal model, which combined functional connectivity of resting-state functional magnetic resonance imaging and four anatomical measures of …

Multiplexed Engineering And Precision Gene Editing In Cellular Immunotherapy, Alexander Biederstädt, Gohar Shahwar Manzar, May Daher

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The advent of cellular immunotherapy in the clinic has entirely redrawn the treatment landscape for a growing number of human cancers. Genetically reprogrammed immune cells, including chimeric antigen receptor (CAR)-modified immune effector cells as well as T cell receptor (TCR) therapy, have demonstrated remarkable responses across different hard-to-treat patient populations. While these novel treatment options have had tremendous success in providing long-term remissions for a considerable fraction of treated patients, a number of challenges remain. Limited

Re-Thinking Therapeutic Development For Cns Metastatic Disease, Chantal Saberian, Michael A Davies

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There has been unprecedented progress in the development of systemic therapies for patients with metastatic melanoma over the last decade. There is now tremendous potential and momentum to further and markedly reduce the impact of this disease. However, developing more effective treatments for metastases to the CNS remains a critical challenge for patients with melanoma. Melanoma patients with active CNS metastases have largely been excluded from both early-phase and registration trials for all currently approved targeted and immune therapies for this disease. While this exclusion has generally been justified in clinical research due to concerns about poor prognosis, lack of …

Deep Learning Auto-Segmentation Of Cervical Skeletal Muscle For Sarcopenia Analysis In Patients With Head And Neck Cancer, Mohamed A Naser, Kareem A Wahid, Aaron J Grossberg, Brennan Olson, Rishab Jain, Dina El-Habashy, Cem Dede, Vivian Salama, Moamen Abobakr, Abdallah S R Mohamed, Renjie He, Joel Jaskari, Jaakko Sahlsten, Kimmo Kaski, Clifton D Fuller

Faculty, Staff and Student Publications

Background/purpose: Sarcopenia is a prognostic factor in patients with head and neck cancer (HNC). Sarcopenia can be determined using the skeletal muscle index (SMI) calculated from cervical neck skeletal muscle (SM) segmentations. However, SM segmentation requires manual input, which is time-consuming and variable. Therefore, we developed a fully-automated approach to segment cervical vertebra SM.

Materials/methods: 390 HNC patients with contrast-enhanced CT scans were utilized (300-training, 90-testing). Ground-truth single-slice SM segmentations at the C3 vertebra were manually generated. A multi-stage deep learning pipeline was developed, where a 3D ResUNet auto-segmented the C3 section (33 mm window), the middle slice of the …

Evaluation Of Deep Learning-Based Multiparametric Mri Oropharyngeal Primary Tumor Auto-Segmentation And Investigation Of Input Channel Effects: Results From A Prospective Imaging Registry, Kareem A Wahid, Sara Ahmed, Renjie He, Lisanne V Van Dijk, Jonas Teuwen, Brigid A Mcdonald, Vivian Salama, Abdallah S R Mohamed, Travis Salzillo, Cem Dede, Nicolette Taku, Stephen Y Lai, Clifton D Fuller, Mohamed A Naser

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Background/purpose: Oropharyngeal cancer (OPC) primary gross tumor volume (GTVp) segmentation is crucial for radiotherapy. Multiparametric MRI (mpMRI) is increasingly used for OPC adaptive radiotherapy but relies on manual segmentation. Therefore, we constructed mpMRI deep learning (DL) OPC GTVp auto-segmentation models and determined the impact of input channels on segmentation performance.

Materials/methods: GTVp ground truth segmentations were manually generated for 30 OPC patients from a clinical trial. We evaluated five mpMRI input channels (T2, T1, ADC, Ktrans, Ve). 3D Residual U-net models were developed and assessed using leave-one-out cross-validation. A baseline T2 model was compared to mpMRI models (T2 + T1, …

Epithelial Immunomodulation By Aerosolized Toll-Like Receptor Agonists Prevents Allergic Inflammation In Airway Mucosa In Mice, David L Goldblatt, Gabriella Valverde Ha, Shradha Wali, Vikram V Kulkarni, Michael K Longmire, Ana M Jaramillo, Rosha P Chittuluru, Adrienne Fouts, Margarita Martinez-Moczygemba, Jonathan T Lei, David P Huston, Michael J Tuvim, Burton F Dickey, Scott E Evans

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Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells …

Comparison Of Three Exercise Interventions With And Without Gemcitabine Treatment On Pancreatic Tumor Growth In Mice: No Impact On Tumor Infiltrating Lymphocytes, Priti Gupta, Charles F Hodgman, Claudia Alvarez-Florez, Keri L Schadler, Melissa M Markofski, Daniel P O'Connor, Emily C Lavoy

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Exercise has been shown to slow pancreatic tumor growth, but whether exercise interventions of differing volume or intensity yield differential effects on tumor outcomes is unknown. In this study, we compared three exercise training interventions implemented with and without chemotherapy on pancreatic tumor growth in mice. Methods: Male C57BL/6 mice (6-8 weeks old) were subcutaneously inoculated with pancreatic ductal adenocarcinoma tumor cells (PDAC 4662). Upon tumor detection, mice received gemcitabine 15 mg/kg intraperitoneally 3 days/week and were assigned to exercise: high volume continuous exercise (HVCE), low volume continuous exercise (LVCE), high intensity interval training (HIIT), or sedentary (SED). HVCE ran …

B Cells Are Required To Generate Optimal Anti-Melanoma Immunity In Response To Checkpoint Blockade, Shubhra Singh, Jason Roszik, Neeraj Saini, Vipul Kumar Singh, Karishma Bavisi, Zhiqiang Wang, Long T Vien, Zixi Yang, Suprateek Kundu, Richard E Davis, Laura Bover, Adi Diab, Sattva S Neelapu, Willem W Overwijk, Kunal Rai, Manisha Singh

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Immunotherapies such as checkpoint blockade therapies are known to enhance anti-melanoma CD8+ T cell immunity, but only a fraction of patients treated with these therapies achieve durable immune response and disease control. It may be that CD8+ T cells need help from other immune cells to generate effective and long-lasting anti-tumor immunity or that CD8+ T cells alone are insufficient for complete tumor regression and cure. Melanoma contains significant numbers of B cells; however, the role of B cells in anti-melanoma immunity is controversial. In this study, B16 melanoma mouse models were used to determine the role of B cells …

Automated Segmentation Of Colorectal Liver Metastasis And Liver Ablation On Contrast-Enhanced Ct Images, Brian M Anderson, Bastien Rigaud, Yuan-Mao Lin, A Kyle Jones, Hynseon Christine Kang, Bruno C Odisio, Kristy K Brock

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Objectives: Colorectal cancer (CRC), the third most common cancer in the USA, is a leading cause of cancer-related death worldwide. Up to 60% of patients develop liver metastasis (CRLM). Treatments like radiation and ablation therapies require disease segmentation for planning and therapy delivery. For ablation, ablation-zone segmentation is required to evaluate disease coverage. We hypothesize that fully convolutional (FC) neural networks, trained using novel methods, will provide rapid and accurate identification and segmentation of CRLM and ablation zones.

Methods: Four FC model styles were investigated: Standard 3D-UNet, Residual 3D-UNet, Dense 3D-UNet, and Hybrid-WNet. Models were trained on 92 patients from …