Genetic Phenomena Commons^™

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, Cem Dede, 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 …

Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat, Pradeep Shrestha, Prince Jeyabal, Zhanglong Peng, Stephanie S Watowich

Faculty, Staff and Student Publications

The mechanisms by which Doxorubicin (Dox) causes acute and late cardiotoxicity are not completely understood. One understudied area is the innate immune response, and in particular the role of neutrophils in Dox-induced cardiotoxicity. Here, using echocardiography, flow cytometry and immunofluorescence staining, we demonstrated increased infiltration of neutrophils that correlated with decreased heart function, disruption of vascular structures and increased collagen deposition in the heart after Dox treatment. Depleting neutrophils protected the heart from Dox-induced cardiotoxicity and changes in vascular structure. Furthermore, our data using neutrophil elastase (NE) knock-out mice and the NE inhibitor AZD9668 suggest that neutrophils cause this damage …

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

Faculty, Staff and Student Publications

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 …

Evaluating A Pilot Culturally Sensitive Psychosocial Intervention On Posttraumatic Growth For Chinese American Breast Cancer Survivors, Qiao Chu, Moni Tang, Lingjun Chen, Lucy Young, Alice Loh, Qian Lu

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This study investigated the potential benefit of a pilot culturally sensitive group support intervention, named Joy Luck Academy (JLA), in fostering posttraumatic growth among Chinese American breast cancer survivors. Eighty-six Chinese American breast cancer survivors participated in an eight-week single-arm pre-/post-test trial of an intervention program, which included educational lectures and peer mentor support. The JLA participants were compared with an independent sample of 109 Chinese American breast cancer survivors who went through routine care. Both groups completed baseline and eight-week follow-up assessments of the five facets of posttraumatic growth (meaningful interpersonal relationships, finding new possibilities in life, personal strength, …

Harmonization Of Multi-Scanner In Vivo Magnetic Resonance Spectroscopy: Enigma Consortium Task Group Considerations, Ashley D Harris, Houshang Amiri, Mariana Bento, Ronald Cohen, Christopher R K Ching, Emily L Dennis, Stefan Ehrlich, Ivan I Kirov, Ralf Mekle, Georg Oeltzschner, Eric Porges, Roberto Souza, Friederike I Tam, Brian Taylor, Paul M Thompson, Yann Quidé, Elisabeth A Wilde, John Williamson, Alexander P Lin, Brenda Bartnik-Olson

Faculty, Staff and Student Publications

Magnetic resonance spectroscopy is a powerful, non-invasive, quantitative imaging technique that allows for the measurement of brain metabolites that has demonstrated utility in diagnosing and characterizing a broad range of neurological diseases. Its impact, however, has been limited due to small sample sizes and methodological variability in addition to intrinsic limitations of the method itself such as its sensitivity to motion. The lack of standardization from a data acquisition and data processing perspective makes it difficult to pool multiple studies and/or conduct multisite studies that are necessary for supporting clinically relevant findings. Based on the experience of the ENIGMA MRS …

Immune Checkpoint Inhibitor-Related Gastrointestinal Toxicity In Patients With Malignancy Involving The Luminal Gastrointestinal Tract And Its Impact On Cancer Outcomes, Kevin Yu, Antony Mathew, Fiyinfoluwa Abraham, Rajan Amin, Miho Kono, Dan Zhao, Muhammad A Khan, Anusha S Thomas, Yinghong Wang

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICI) are known to cause immune-related adverse events (irAE) with the gastrointestinal (GI) tract among the most affected. Our knowledge of GI irAE in patients with luminal GI malignancies is poor. We aimed to characterize the incidence, clinical features, treatment, and outcomes of these GI irAEs.

Methods: This was a retrospective study of patients with malignancies involving the luminal GI tract and GI irAEs at MD Anderson Cancer Center from January 2010 to June 2020. Clinical data were collected and analyzed.

Results: Eighteen patients with luminal GI tract malignancies treated with ICIs had evidence of GI …

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, Rosha P Chittuluru, Margarita Martinez-Moczygemba, Jonathan T Lei, David P Huston, Michael J Tuvim, Burton F Dickey, Scott E Evans

Faculty, Staff and Student Publications

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 …

Progression Free Survival Prediction For Head And Neck Cancer Using Deep Learning Based On Clinical And Pet/Ct Imaging Data, Mohamed A Naser, Kareem A Wahid, Abdallah S R Mohamed, Moamen Abobakr Abdelaal, Renjie He, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Determining progression-free survival (PFS) for head and neck squamous cell carcinoma (HNSCC) patients is a challenging but pertinent task that could help stratify patients for improved overall outcomes. PET/CT images provide a rich source of anatomical and metabolic data for potential clinical biomarkers that would inform treatment decisions and could help improve PFS. In this study, we participate in the 2021 HECKTOR Challenge to predict PFS in a large dataset of HNSCC PET/CT images using deep learning approaches. We develop a series of deep learning models based on the DenseNet architecture using a negative log-likelihood loss function that utilizes PET/CT …

Highlights From The 7th Oncological Pathology Conference 'Pathological Anatomy In The Context Of The National Cancer Law: An Overview Of The Latin American Experience', 15, 22 And 23 July 2022, Trujillo, Peru, Caddie Laberiano-Fernández, Joan Moreno Luján, Bruno De Carvalho Dornelas, Magali Franco Benites, Patricia Gutiérrez Quispe, Andric Guerrero Espinoza, Gabriela Gil-Arroyo Álvarez, Juan Astigueta-Pérez, Maria Teresa Garcia De Dávila, Sandro Casavilca Zambrano, Tatiana Vidaurre Rojas, Alejandro Mariños, Emmanuel S González, Rossana Lazcano, Ricardo R Lastra, Isabel Alvarado-Cabrero, Henry Guerra Miller, Ricardo H Bardales, Milagros Abad-Licham

Faculty, Staff and Student Publications

The seventh session of the Oncological Pathology Conference (JoPaO) entitled 'Pathological Anatomy in the context of the National Cancer Law: An overview of the Latin American experience', was held virtually on July 15, 22 and 23. Peru was the headquarters for this event, where 17 national and international professors of high academic standing participated. They interacted in a multidisciplinary context through talks with national panellists and the general public. The recent promulgation of the 'National Cancer Law' fosters the development of discussion forums to analyse the national realities and uphold continuous learning about experiences in other Latin American countries with …

Elastic Shape Analysis Of Brain Structures For Predictive Modeling Of Ptsd, Yuexuan Wu, Suprateek Kundu, Jennifer S Stevens, Negar Fani, Anuj Srivastava

Faculty, Staff and Student Publications

It is well-known that morphological features in the brain undergo changes due to traumatic events and associated disorders such as post-traumatic stress disorder (PTSD). However, existing approaches typically offer group-level comparisons, and there are limited predictive approaches for modeling behavioral outcomes based on brain shape features that can account for heterogeneity in PTSD, which is of paramount interest. We propose a comprehensive shape analysis framework representing brain sub-structures, such as the hippocampus, amygdala, and putamen, as parameterized surfaces and quantifying their shape differences using an elastic shape metric. Under this metric, we compute shape summaries (mean, covariance, PCA) of brain …

Proton Image-Guided Radiation Assignment For Therapeutic Escalation Via Selection Of Locally Advanced Head And Neck Cancer Patients [Pirates]: A Phase I Safety And Feasibility Trial Of Mri-Guided Adaptive Particle Radiotherapy, Lisanne V Van Dijk, Steven J Frank, Ying Yuan, Brandon Gunn, Amy C Moreno, Kathryn E Preston, Michael T Spiotto, William H Morrison, Anna Lee, Jack Phan, Adam S Garden, David I Rosenthal, Johannes A Langendijk, Clifton D Fuller

Faculty, Staff and Student Publications

Introduction: Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With "Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients" (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach.

Methods: The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk …

Pld1 Promotes Reactive Oxygen Species Production In Vascular Smooth Muscle Cells And Injury-Induced Neointima Formation, Ming Cai, Ziqing Wang, Thi Thu Trang Luu, Dakai Zhang, Brian Finke, Li Wei Rachel Tay, Guangwei Du

Faculty, Staff and Student Publications

Phospholipase D (PLD) generates the signaling lipid phosphatidic acid (PA) and has been known to mediate proliferation signal in vascular smooth muscle cells (VSMCs). However, it remains unclear how PLD contributes to vascular diseases. VSMC proliferation directly contributes to the development and progression of cardiovascular disease, such as atherosclerosis and restenosis after angioplasty. Using the mouse carotid artery ligation model, we find that deletion of Pld1 gene inhibits neointima formation of the injuried blood vessels. PLD1 deficiency reduces the proliferation of VSMCs in both injured artery and primary cultures through the inhibition of ERK1/2 and AKT signals. Immunohistochemical staining of …

Recurrent Hgnet-Mn1 Altered (Astroblastoma Mn1-Altered) Of The Foramen Magnum: Case Report And Molecular Classification, Sricharan Gopakumar, Malcolm F Mcdonald, Himanshu Sharma, Claudio E Tatsui, Gregory N Fuller

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Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity.

Case description: Here, we present the case of …

Targetable Vulnerability Of Deregulated Foxm1/Plk1 Signaling Axis In Diffuse Large B Cell Lymphoma, Fang Yu, Hua He, Loretta J Nastoupil, Zijun Y Xu-Monette, Ky Pham, Guang Chen, C Cameron Yin, Dongfeng Tan, Yaling Yang, Shimin Hu, Ken H Young, Lan V Pham, M James You

Faculty, Staff and Student Publications

FOXM1 is a transcription factor that controls cell cycle regulation, cell proliferation, and differentiation. Overexpression of FOXM1 has been implicated in various cancer types. However, the activation status and functional significance of FOXM1 in diffuse large B cell lymphoma (DLBCL) have not been well investigated. Using proteomic approaches, we discovered that the protein expression levels of FOXM1 and PLK1 were positively correlated in DLBCL cell lines and primary DLBCL. Expression levels of FOXM1 and PLK1 mRNAs were also significantly higher in DLBCL than in normal human B cells and could predict poor prognosis of DLBCL, particularly in patients with germinal …

A Narrative Review On Invasive Brain Stimulation For Treatment-Resistant Depression, Manoj P Dandekar, Alexandre P Diaz, Ziaur Rahman, Ritele H Silva, Ziad Nahas, Sudhakar Selvaraj, Marsal Sanches, Jair C Soares, Patricio Riva-Posse, Joao Quevedo

Faculty, Staff and Student Publications

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic …

Head-Mounted Digital Metamorphopsia Suppression As A Countermeasure For Macular-Related Visual Distortions For Prolonged Spaceflight Missions And Terrestrial Health, Joshua Ong, Nasif Zaman, Ethan Waisberg, Sharif Amit Kamran, Andrew G Lee

Faculty, Staff and Student Publications

During long-duration spaceflight, astronauts are exposed to various risks including spaceflight-associated neuro-ocular syndrome, which serves as a risk to astronaut vision and a potential physiological barrier to future spaceflight. When considering exploration missions that may expose astronauts to longer periods of microgravity, radiation exposure, and natural aging processes during spaceflight, more severe changes to functional vision may occur. The macula plays a critical role in central vision and disruptions to this key area in the eye may compromise functional vision and mission performance. In this article, we describe the development of a countermeasure technique to digitally suppress monocular central visual …

Quaking But Not Parkin Is The Major Tumor Suppressor In 6q Deleted Region In Glioblastoma, Fatma Betul Aksoy Yasar, Takashi Shingu, Daniel B Zamler, Mohammad Fayyad Zaman, Derek Lin Chien, Jiangong Ren

Faculty, Staff and Student Publications

Glioblastoma (GBM) is a high-grade, aggressive brain tumor with dismal median survival time of 15 months. Chromosome 6q (Ch6q) is a hotspot of genomic alterations, which is commonly deleted or hyper-methylated in GBM. Two neighboring genes in this region, QKI and PRKN have been appointed as tumor suppressors in GBM. While a genetically modified mouse model (GEMM) of GBM has been successfully generated with Qk deletion in the central nervous system (CNS), in vivo genetic evidence supporting the tumor suppressor function of Prkn has not been established. In the present study, we generated a mouse model with Prkn-null allele …

Editorial: The Role Of The Igf Axis In Tumorigenesis And Cancer Treatment: From Genes To Metabolites, Guo Mengzhe, Xie Shanshan, Zhao Di, Wu Shihua

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No abstract provided.

Prediction Of Early (4-Week) Mortality In Acute Myeloid Leukemia With Intensive Chemotherapy, Koji Sasaki, Tapan Kadia, Kebede Begna, Courtney D Dinardo, Gautam Borthakur, Nitin Jain, Elias Jabbour, Guillermo Garcia-Manero, Guillermo Montalban Bravo, Lucia Masarova, Sherry Pierce, Marina Konopleva, Farhad Ravandi, Ayalew Tefferi, Hagop Kantarjian

Faculty, Staff and Student Publications

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m2 during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was …

Disruption Of Growth Hormone Receptor Signaling Abrogates Hepatocellular Carcinoma Development, Abedul Haque, Vishal Sahu, Jamie Lynne Lombardo, Lianchun Xiao, Bhawana George, Jeffrey S Morris, John J Kopchick, Ahmed O Kaseb, Hesham M Amin

Faculty, Staff and Student Publications

Introduction: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancers. It is an aggressive neoplasm with dismal outcome because most of the patients present with an advanced-stage disease, which precludes curative surgical options. Therefore, these patients require systemic therapies that typically induce small improvements in overall survival. Hence, it is crucial to identify new and promising therapeutic targets for HCC to improve the current outcome. The liver is a key organ in the signaling cascade triggered by the growth hormone receptor (GHR). Previous studies have shown that GHR signaling stimulates the proliferation and regeneration of liver cells …

Electroacupuncture Ameliorates Inflammatory Response Induced By Retinal Ischemia-Reperfusion Injury And Protects The Retina Through The Dor-Bdnf/Trkb Pathway, Runjie Guo, Yongjie Zhang, Yue Geng, Ping Chen, Tiantian Fu, Ren Zhang, Jingling Jin, Nange Jin, Hong Xu, Xuesong Tian

Faculty, Staff and Student Publications

Objectives: Retinal ischemia-reperfusion injury (RIRI) is the common pathological basis of many ophthalmic diseases in the later stages, and inflammation is the primary damage mechanism of RIRI. Our study aimed to assess whether electroacupuncture (EA) has a protective effect against RIRI and to elucidate its related mechanisms.

Methods: A high-intraocular pressure (HIOP) model was used to simulate RIRI in Wistar rats. EA was applied to the EA1 group [Jingming (BL1) + Shuigou (GV26)] and the EA2 group [Jingming (BL1) + Hegu (LI4)] respectively for 30 min starting immediately after the onset of reperfusion and repeated (30 min/time) at 12 h …

A Multicenter Study Of Icu Resource Utilization In Pediatric, Adolescent And Young Adult Patients Post Car-T Therapy, Dristhi Ragoonanan, Saleh Bhar, Gopi Mohan, Fernando Beltramo, Sajad J Khazal, Clark Andersen, Sattva S Neelapu, Elizabeth Shpall, Cristina Gutierrez, Priti Tewari, Basirat Shoberu, Aimee Talleur, David Mccall, Cesar Nunez, Branko Cuglievan, Francesco Paolo Tambaro, Demetrios Petropoulos, Hisham Abdel-Azim, Kris M Mahadeo

Faculty, Staff and Student Publications

Tisagenlecleucel is associated with remarkable outcomes in treating patients up to the age of 25 years with refractory B-cell acute lymphoblastic leukemia (ALL). Yet, due to unique and potentially life-threatening complications, access remains limited to higher-resource and certified centers. Reports of inequity and related disparities in care are emerging. In this multicenter study of ALL patients admitted for anti-leukemia therapy, who required pediatric intensive care (ICU) support (n = 205), patients receiving tisagenlecleucel (n = 39) were compared to those receiving conventional chemotherapy (n = 166). The median time to ICU transfer was 6 (0-43) versus 1 (0-116) days, respectively …

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, Vivian Salama, Travis Salzillo, Cem Dede, Nicolette Taku, Stephen Y Lai, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

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, …

Anatomy And Function Of Ventral Tegmental Area Glutamate Neurons, Jing Cai, Qingchun Tong

Faculty, Staff and Student Publications

The ventral tegmental area (VTA) is well known for regulating reward consumption, learning, memory, and addiction behaviors through mediating dopamine (DA) release in downstream regions. Other than DA neurons, the VTA is known to be heterogeneous and contains other types of neurons, including glutamate neurons. In contrast to the well-studied and established functions of DA neurons, the role of VTA glutamate neurons is understudied, presumably due to their relatively small quantity and a lack of effective means to study them. Yet, emerging studies have begun to reveal the importance of glutamate release from VTA neurons in regulating diverse behavioral repertoire …

Granuloma Annulare: An Updated Review Of Epidemiology, Pathogenesis, And Treatment Options, Tejas P Joshi, Madeleine Duvic

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Granuloma annulare (GA) is an inflammatory granulomatous skin disease that can be localized (localized GA) or disseminated (generalized GA), with patch, perforating, and subcutaneous subtypes being less common variants of this benign condition. Recently, new research has emerged that further elucidates GA epidemiology and etiopathogenesis; importantly, new therapeutic options for GA have also been described, although there remains a paucity of randomized controlled studies. In this review, we summarize recent updates on GA epidemiology and etiopathogenesis and offer an updated review of the therapeutic options for GA currently reported in the literature. We hope that the current review galvanizes randomized …

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Siwen Hu-Lieskovan, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …

Deep-Learning-Based Generation Of Synthetic 6-Minute Mri From 2-Minute Mri For Use In Head And Neck Cancer Radiotherapy, Kareem A Wahid, Jiaofeng Xu, Dina El-Habashy, Yomna Khamis, Moamen Abobakr, Nicolette O' Connell, Sara Ahmed, Christina Setareh Sharafi, Kathryn Preston, Travis C Salzillo, Abdallah S R Mohamed, Renjie He, Nathan Cho, John Christodouleas, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

Background: Quick magnetic resonance imaging (MRI) scans with low contrast-to-noise ratio are typically acquired for daily MRI-guided radiotherapy setup. However, for patients with head and neck (HN) cancer, these images are often insufficient for discriminating target volumes and organs at risk (OARs). In this study, we investigated a deep learning (DL) approach to generate high-quality synthetic images from low-quality images.

Methods: We used 108 unique HN image sets of paired 2-minute T2-weighted scans (2mMRI) and 6-minute T2-weighted scans (6mMRI). 90 image sets (~20,000 slices) were used to train a 2-dimensional generative adversarial DL model that utilized 2mMRI as input and …

Head And Neck Cancer Primary Tumor Auto Segmentation Using Model Ensembling Of Deep Learning In Pet/Ct Images, Mohamed A Naser, Kareem A Wahid, Lisanne V Van Dijk, Renjie He, Moamen Abobakr Abdelaal, Abdallah S R Mohamed

Faculty, Staff and Student Publications

Auto-segmentation of primary tumors in oropharyngeal cancer using PET/CT images is an unmet need that has the potential to improve radiation oncology workflows. In this study, we develop a series of deep learning models based on a 3D Residual Unet (ResUnet) architecture that can segment oropharyngeal tumors with high performance as demonstrated through internal and external validation of large-scale datasets (training size = 224 patients, testing size = 101 patients) as part of the 2021 HECKTOR Challenge. Specifically, we leverage ResUNet models with either 256 or 512 bottleneck layer channels that demonstrate internal validation (10-fold cross-validation) mean Dice similarity coefficient …

A Yeast Model For Trichohepatoenteric Syndrome Suggests Strong Loss Of Ski2 Function In Most Causative Mutations, Luisa J Orlando, Matthew K Yim, Thomson Hallmark, Michael Cotner, Sean J Johnson

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The intestinal and immune disorder trichohepatoenteric syndrome (THES) is characterized by mutations in human Ski2 and Ski3, also known as SKIV2L and TTC37, respectively. The mechanism by which these mutations leads to the immunodeficiency, chronic diarrhea, failure to thrive and liver disease associated with THES is unknown. To what degree THES patient mutations in Ski2 affect Ski2 function and how the differences in Ski2 function could lead to varying patient outcomes has not been studied. Here, we assayed function of THES ski2 mutants in the yeast homolog. Our results show that most THES patient mutations cause severe dysfunction in Ski2. …

Cgas-Sting Pathway Targeted Therapies And Their Applications In The Treatment Of High-Grade Glioma, Shashwat Tripathi, Hinda Najem, Akanksha Sanjay Mahajan, Peng Zhang, Justin T Low, Michael A Curran, Charles David James, Amy B Heimberger

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Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches …