Biomedical Informatics Commons^™

Prediction Of Pathologic Complete Response To Neoadjuvant Systemic Therapy In Triple Negative Breast Cancer Using Deep Learning On Multiparametric Mri, Zijian Zhou, Beatriz E Adrada, Rosalind P Candelaria, Nabil A Elshafeey, Medine Boge, Rania M Mohamed, Sanaz Pashapoor, Jia Sun, Zhan Xu, Bikash Panthi, Jong Bum Son, Mary S Guirguis, Miral M Patel, Gary J Whitman, Tanya W Moseley, Marion E Scoggins, Jason B White, Jennifer K Litton, Vicente Valero, Kelly K Hunt, Debu Tripathy, Wei Yang, Peng Wei, Clinton Yam, Mark D Pagel, Gaiane M Rauch, Jingfei Ma

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Neoadjuvant systemic therapy (NAST) followed by surgery are currently standard of care for TNBC with 50-60% of patients achieving pathologic complete response (pCR). We investigated ability of deep learning (DL) on dynamic contrast enhanced (DCE) MRI and diffusion weighted imaging acquired early during NAST to predict TNBC patients' pCR status in the breast. During the development phase using the images of 130 TNBC patients, the DL model achieved areas under the receiver operating characteristic curves (AUCs) of 0.97 ± 0.04 and 0.82 ± 0.10 for the training and the …

Adar1 Deletion Causes Degeneration Of The Exocrine Pancreas Via Mavs-Dependent Interferon Signaling, Dhwani N Rupani, Fredrik I Thege, Vidhi Chandra, Hajar Rajaei, Robert W Cowan, Sonja M Wörmann, Olivereen Le Roux, Prerna Malaney, Sara L Manning, Jack Hashem, Jennifer Bailey-Lundberg, Andrew D Rhim, Florencia Mcallister

Faculty, Staff and Student Publications

Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing alters post-transcriptional RNA processing, making ADAR1 a crucial regulator of gene expression. Consequently, Adar1 has been implicated in organogenesis. To determine the role of Adar1 in pancreatic development and homeostasis, we conditionally deleted Adar1 from the murine pancreas (Ptf1aCre/+; Adar1Fl/Fl). The resulting mice had stunted growth, likely due to malabsorption associated with exocrine pancreatic insufficiency. Analyses of pancreata revealed ductal cell expansion, heightened interferon-stimulated gene expression and an increased influx of immune cells. Concurrent deletion of Adar1 and Mavs, a …

A Gain-Of-Function Tpc2 Variant R210c Increases Affinity To Pi(3,5)P2 And Causes Lysosome Acidification And Hypopigmentation, Qiaochu Wang, Zengge Wang, Yizhen Wang, Zhan Qi, Dayong Bai, Chentong Wang, Yuanying Chen, Wenjian Xu, Xili Zhu, Jaepyo Jeon, Jian Xiong, Chanjuan Hao, Michael Xi Zhu, Aihua Wei, Wei Li

Faculty, Staff and Student Publications

Albinism is a group of inherited disorders mainly affecting skin, hair and eyes. Here we identify a de novo point mutation, p.R210C, in the TPCN2 gene which encodes Two Pore Channel 2 (TPC2) from a patient with albinism. TPC2 is an endolysosome and melanosome localized non-selective cation channel involved in regulating pigment production. Through inside-out recording of plasma membrane targeted TPC2 and direct recording of enlarged endolysosomal vacuoles, we reveal that the R210C mutant displays constitutive channel activation and markedly increased affinity to PI(3,5)P2. Mice harboring the homologous mutation, R194C, also exhibit hypopigmentation in the fur and skin, as well …

Antihuman T Lymphocyte Porcine Immunoglobulin Combined With Cyclosporine As First-Line Immunosuppressive Therapy For Severe Aplastic Anemia In China: A Large Single-Center, 10-Year Retrospective Study, Wenrui Yang, Xu Liu, Xin Zhao, Li Zhang, Guangxin Peng, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Liping Jing, Fengkui Zhang

Faculty, Staff and Student Publications

BACKGROUND: Antihuman T lymphocyte porcine immunoglobulin (p-ATG) has been the most common ATG preparation in immunosuppressive therapy (IST) in Chinese patients with severe aplastic anemia (SAA) since 2009.

OBJECTIVES: This study aimed to evaluate the early hematologic response and long-term outcomes of a large cohort of patients with SAA who received p-ATG plus cyclosporine (CsA) as first-line therapy from 2010 to 2019.

DESIGN: This is a single-center retrospective study of medical records.

METHODS: We analyzed the data of 1023 consecutive patients with acquired aplastic anemia (AA) who underwent p-ATG combined with CsA as a first-line IST treatment from 2010 to …

Efficacy Of Eltrombopag With Immunosuppressive Therapy For Children With Acquired Aplastic Anemia, Yufei Zhao, Wenrui Yang, Xin Zhao, Xiangrong Hu, Jing Hu, Xu Liu, Jianping Li, Lei Ye, Youzhen Xiong, Yang Yang, Baohang Zhang, Xiaoxia Li, Xiawan Yang, Yimeng Shi, Guangxin Peng, Yuan Li, Huihui Fan, Kang Zhou, Liping Jing, Li Zhang, Fengkui Zhang

Faculty, Staff and Student Publications

BACKGROUND: Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial.

METHODS: We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) …

Many People With Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma Benefit From Ibrutinib Treatment Up To 8 Years: A Plain Language Summary, Paul M Barr, Carolyn Owen, Tadeusz Robak, Alessandra Tedeschi, Osnat Bairey, Jan A Burger, Peter Hillmen, Claire Dearden, Sebastian Grosicki, Helen Mccarthy, Jian Yong Li, Fritz Offner, Carol Moreno, Mandy Jermain, Cathy Zhou, Emily Hsu, Anita Szoke, Thomas J Kipps, Paolo Ghia

Faculty, Staff and Student Publications

What is this summary about?: This is a plain language summary of a publication describing long-term results from the RESONATE-2 study with up to 8 years of follow-up. The original paper was published in Blood Advances in June 2022.

What were the results?: Researchers looked at 269 adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had not received any treatment for their CLL/SLL. Study participants were randomly divided into two groups: 136 participants received treatment with a drug called ibrutinib, and 133 participants received treatment with a drug called chlorambucil. Participants in the study were treated …

Histopathologic And Proteogenomic Heterogeneity Reveals Features Of Clear Cell Renal Cell Carcinoma Aggressiveness, Yize Li, Tung-Shing M Lih, Saravana M Dhanasekaran, Rahul Mannan, Lijun Chen, Marcin Cieslik, Yige Wu, Rita Jiu-Hsien Lu, David J Clark, Iga Kołodziejczak, Runyu Hong, Siqi Chen, Yanyan Zhao, Seema Chugh, Wagma Caravan, Nataly Naser Al Deen, Noshad Hosseini, Chelsea J Newton, Karsten Krug, Yuanwei Xu, Kyung-Cho Cho, Yingwei Hu, Yuping Zhang, Chandan Kumar-Sinha, Weiping Ma, Anna Calinawan, Matthew A Wyczalkowski, Michael C Wendl, Yuefan Wang, Shenghao Guo, Cissy Zhang, Anne Le, Aniket Dagar, Alex Hopkins, Hanbyul Cho, Felipe Da Veiga Leprevost, Xiaojun Jing, Guo Ci Teo, Wenke Liu, Melissa A Reimers, Russell Pachynski, Alexander J Lazar, Arul M Chinnaiyan, Brian A Van Tine, Bing Zhang, Karin D Rodland, Gad Getz, D R Mani, Pei Wang, Feng Chen, Galen Hostetter, Mathangi Thiagarajan, W Marston Linehan, David Fenyö, Scott D Jewell, Gilbert S Omenn, Rohit Mehra, Maciej Wiznerowicz, Ana I Robles, Mehdi Mesri, Tara Hiltke, Eunkyung An, Henry Rodriguez, Daniel W Chan, Christopher J Ricketts, Alexey I Nesvizhskii, Hui Zhang, Li Ding, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 …

Multicenter International Study Of The Consensus Immunoscore For The Prediction Of Relapse And Survival In Early-Stage Colon Cancer, Bernhard Mlecnik, Alessandro Lugli, Gabriela Bindea, Florence Marliot, Carlo Bifulco, Jiun-Kae Jack Lee, Inti Zlobec, Tilman T Rau, Martin D Berger, Iris D Nagtegaal, Elisa Vink-Börger, Arndt Hartmann, Carol I Geppert, Julie Kolwelter, Susanne Merkel, Robert Grützmann, Marc Van Den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Léonard, Christophe Remue, Julia Wang, Prashant Bavi, Michael H A Roehrl, Pamela S Ohashi, Linh T Nguyen, Seongjun Han, Heather L Macgregor, Sara Hafezi-Bakhtiari, Bradly G Wouters, Giuseppe V Masucci, Emilia K Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Tessa Fredriksen, Bénédicte Buttard, Lucie Lafontaine, Pauline Maby, Amine Majdi, Assia Hijazi, Carine El Sissy, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn Van De Water, Shannon Van Lent-Van Vliet, Nikki Knijn, Ana-Maria Mușină, Dragos-Viorel Scripcariu, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Prabhu Patel, Hemangini H Vora, Birva Shah, Jayendrakumar B Patel, Kruti N Rajvik, Shashank J Pandya, Shilin N Shukla, Yili Wang, Guanjun Zhang, Yutaka Kawakami, Francesco M Marincola, Paolo A Ascierto, Bernard A Fox, Franck Pagès, Jérôme Galon

Faculty, Staff and Student Publications

Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival …

Bcl2l11 Induction Mediates Sensitivity To Src And Mek1/2 Inhibition In Thyroid Cancer, Madison M Rose, Veronica L Espinoza, Katelyn J Hoff, Laura A Pike, Vibha Sharma, Marie-Claude Hofmann, Aik Choon Tan, Nikita Pozdeyev, Rebecca E Schweppe

Faculty, Staff and Student Publications

Patients with advanced thyroid cancer, including advanced papillary thyroid cancer and anaplastic thyroid cancer (ATC), have low survival rates because of the lack of efficient therapies available that can combat their aggressiveness. A total of 90% of thyroid cancers have identifiable driver mutations, which often are components of the MAPK pathway, including BRAF, RAS, and RET-fusions. In addition, Src is a non-receptor tyrosine kinase that is overexpressed and activated in thyroid cancer, which we and others have shown is a clinically relevant target. We have previously demonstrated that combined inhibition of Src with dasatinib and the MAPK …

Single-Cell Multi-Omics Integration For Unpaired Data By A Siamese Network With Graph-Based Contrastive Loss, Chaozhong Liu, Linhua Wang, Zhandong Liu

Faculty, Staff and Students Publications

BACKGROUND: Single-cell omics technology is rapidly developing to measure the epigenome, genome, and transcriptome across a range of cell types. However, it is still challenging to integrate omics data from different modalities. Here, we propose a variation of the Siamese neural network framework called MinNet, which is trained to integrate multi-omics data on the single-cell resolution by using graph-based contrastive loss.

RESULTS: By training the model and testing it on several benchmark datasets, we showed its accuracy and generalizability in integrating scRNA-seq with scATAC-seq, and scRNA-seq with epitope data. Further evaluation demonstrated our model's unique ability to remove the batch …

Radiation Therapy For Retroperitoneal Sarcomas: A Strass-Ful Situation, Ahsan S Farooqi, B Ashleigh Guadagnolo, Devarati Mitra, Andrew J Bishop

Faculty, Staff and Student Publications

Locoregional recurrence (LRR) is the predominant pattern of relapse and often the cause of death in patients with retroperitoneal sarcomas (RPS). As a result, reducing LRR is a critical objective for RPS patients. However, unlike soft tissue sarcomas (STS) of the superficial trunk and extremity where the benefits of radiation therapy (RT) are well-established, the role of RT in the retroperitoneum remains controversial. Historically, preoperative or postoperative RT, either alone or in combination with intraoperative radiation (IORT), was commonly justified for RPS based on extrapolation from the superficial trunk and extremity STS literature. However, long-awaited results were recently published from …

High Body Mass Index Changes Peri-Tumor Adipose Tissue Which In Turn Promotes Triple Negative Breast Cancer, Cora Elizabeth Miracle

Theses, Dissertations and Capstones

Cancer is one of the leading causes of death worldwide, responsible for over half a million deaths each year. There are multiple risk factors associated with the development of cancer. Some of these risks include genetics, smoking, and most recently, obesity (Lewandowska et al., 2019) (De Pergola & Silvestris, 2013). Research has shown that obesity is linked to the promotion of fourteen different cancers, including aggressive triple negative breast cancer (TNBC). Patients that are obese are more likely to develop cancer (Park et al., 2014). In addition, if the patient is obese at the time of a cancer diagnosis, they …

The Short- And Long-Term Readmission Of Four Major Categories Of Digestive System Cancers: Does Obesity Or Metabolic Disorder Matter?, Yan Li, Xiaoqin Wu, Yongfeng Song, Peipei Wang, Bofei Zhang, Bingzhou Guo, Ziwei Liu, Yafei Wu, Shanshan Shao, Yiping Cheng, Honglin Guo, Xiude Fan, Jiajun Zhao

Faculty, Staff and Student Publications

Purpose: Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC.

Experimental design: A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox …

Receptor-Interacting Protein 1 And 3 Kinase Activity Are Required For High-Fat Diet Induced Liver Injury In Mice, Xiaoqin Wu, Rakesh K Arya, Emily Huang, Megan R Mcmullen, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND: The RIP1-RIP3-MLKL-mediated cell death pathway is associated with progression of non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Previous work identified a critical role for MLKL, the key effector regulating necroptosis, but not RIP3, in mediating high fat diet-induced liver injury in mice. RIP1 and RIP3 have active N-terminus kinase domains essential for activation of MLKL and subsequent necroptosis. However, little is known regarding domain-specific roles of RIP1/RIP3 kinase in liver diseases. Here, we hypothesized that RIP1/RIP3 kinase activity are required for the development of high fat diet-induced liver injury.

METHODS:Rip1K45A/K45A and Rip3K51A/K51A kinase-dead mice on a C57BL/6J background and their littermate …

Acute Myeloid Leukemia With Concurrent Npm1 And Runx1 Mutations, Zhuang Zuo, L Jeffrey Medeiros, C Cameron Yin

Faculty, Staff and Student Publications

NPM1 mutation, as a founding genetic event, cooperates with other gene mutations, such as DNMT3A and FLT3, to promote the development of acute myeloid leukemia. NPM1 mutation, however, has been reported to be mutually exclusive with RUNX1 mutation in acute myeloid leukemia cases. In this study, we analyzed mutation panel testing data from a relatively large cohort of rare AML cases with both NPM1 and RUNX1 mutations. We describe the dynamic process of the emergence of these mutations, as well as molecular genetic features and clinical outcome of these patients. We show that concurrence of both mutations in acute …

Integrated Clinical Genotype-Phenotype Characteristics Of Early T-Cell Precursor Acute Lymphoblastic Leukemia, Matthew T Ye, Yi Wang, Zhuang Zuo, Steliana Calin, Hua He, Zhenya Tang, Elias J Jabbour, Gautam Borthakur, Yizhuo Zhang, Yaling Yang, M James You

Faculty, Staff and Student Publications

Background: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a unique immunophenotype and high treatment failure rate. The molecular genetic abnormalities and their prognostic impact in ETP-ALL patients are poorly understood.

Methods: The authors performed systematic analyses of the clinicopathologic features with an emphasis on molecular genetic aspects of 32 patients with ETP-ALL.

Results: The median age was 43 years (range, 16-71). The blasts were positive for cytoplasmic CD3 and CD7 and negative for CD1a and CD8. Other markers expressed included CD34 (88%), CD33 (72%), CD117 (68%), CD13 (58%), CD5 (partial, 56%), CD2 (38%), …

Revolutionizing Bone Regeneration: Advanced Biomaterials For Healing Compromised Bone Defects, Kamal Awad, Neelam Ahuja, Ahmed S Yacoub, Leticia Brotto, Simon Young, Antonios Mikos, Pranesh Aswath, Venu Varanasi

Faculty, Staff and Student Publications

In this review, we explore the application of novel biomaterial-based therapies specifically targeted towards craniofacial bone defects. The repair and regeneration of critical sized bone defects in the craniofacial region requires the use of bioactive materials to stabilize and expedite the healing process. However, the existing clinical approaches face challenges in effectively treating complex craniofacial bone defects, including issues such as oxidative stress, inflammation, and soft tissue loss. Given that a significant portion of individuals affected by traumatic bone defects in the craniofacial area belong to the aging population, there is an urgent need for innovative biomaterials to address the …

Membranous Nephropathy In Chronic Lymphocytic Leukemia Responsive To Ibrutinib: A Case Report, Anna-Eve Turcotte, William F Glass, Jamie S Lin, Jan A Burger

Faculty, Staff and Student Publications

Membranous nephropathy (MN) is an uncommon renal presentation in patients with chronic lymphocytic leukemia (CLL), and as such, there is no standard therapy for these patients. A few cases of MN in CLL have been described with varying success in MN treatment involving alkylating agents and fludarabine. Here we report the first case of MN in a patient with CLL treated with ibrutinib with complete renal response. This presentation underlines the importance of recognizing rare glomerular diseases that may occur with CLL and offers a new therapeutic avenue to the treatment of CLL-associated MN.

Machine Learning-Based Prediction Of Acute Mortality In Emergency Department Patients Using Twelve-Lead Electrocardiogram, Po-Cheng Chang, Zhi-Yong Liu, Yu-Chang Huang, Yu-Chun Hsu, Jung-Sheng Chen, Ching-Heng Lin, Richard Tsai, Chung-Chuan Chou, Ming-Shien Wen, Hung-Ta Wo, Wen-Chen Lee, Hao-Tien Liu, Chun-Chieh Wang, Chang-Fu Kuo

Faculty, Staff and Student Publications

BACKGROUND: The risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients.

METHODS: The database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were …

Artificial Intelligence-Enabled Electrocardiographic Screening For Left Ventricular Systolic Dysfunction And Mortality Risk Prediction, Yu-Chang Huang, Yu-Chun Hsu, Zhi-Yong Liu, Ching-Heng Lin, Richard Tsai, Jung-Sheng Chen, Po-Cheng Chang, Hao-Tien Liu, Wen-Chen Lee, Hung-Ta Wo, Chung-Chuan Chou, Chun-Chieh Wang, Ming-Shien Wen, Chang-Fu Kuo

Faculty, Staff and Student Publications

BACKGROUND: Left ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis.

METHODS: This retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF

RESULTS: The mean age of patients in the testing dataset was 63.7 ± 16.3 years (46.3% …

School-Based Intervention Impacts Availability Of Vegetables And Beverages In Participants’ Homes, Erin A Hudson, Marissa Burgermaster, Sophia M Isis, Matthew R Jeans, Sarvenaz Vandyousefi, Matthew J Landry, Rebecca Seguin-Fowler, Joya Chandra, Jaimie Davis

Faculty, Staff and Student Publications

As rates of metabolic syndrome rise, children consume too few vegetables and too much added sugar. Because children tend to eat what is available at home, the home environment plays a key role in shaping dietary habits. This secondary analysis evaluated the effects of a school-based gardening, cooking, and nutrition education intervention (TX Sprouts) compared to control on the availability of vegetables, fruit juice, and sugar-sweetened beverages (SSBs) at home. In the TX Sprouts cluster-randomized trial, 16 schools were randomized to TX Sprouts (

Immune Checkpoint Inhibitors In Advanced Cutaneous Squamous Cell Carcinoma: A Systemic Review And Meta-Analysis, Haoran Zhang, Ai Zhong, Junjie Chen

Faculty, Staff and Student Publications

BACKGROUND: To evaluate the immune checkpoint inhibitors (CPI) for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC).

MATERIALS AND METHODS: A meta-analysis was conducted, and the efficacy and safety of CPI were assessed.

RESULTS: A total of 13 studies with 980 patients were included. The pooled objective response rate (ORR) and disease control rate were 47.2% and 64.4%, separately. In addition, patients with primary tumor located in head and neck (odds ratio [OR]: 0.374, 95% confidence interval [CI]: 0.219-0.640, p < 0.001) and positive expression of programmed death ligand 1 (OR: 0.364, 95% CI: 0.158-0.842, P = 0.018) had superior ORR during CPI treatment. The incidence of progression free survival at 6 and 12 months was 59.3% and 52.8%, and 80.6% and 76.4% for overall survival. As for safety, the overall incidence of adverse events with all grades and 3-4 grade was 76.9% and 20.2%.

CONCLUSIONS: Our systematic review confirmed the satisfying efficacy and acceptable toxicity of CPI for advanced CSCC.

Endothelial Activation And Fibrotic Changes Are Impeded By Laminar Flow-Induced Chk1-Senp2 Activity Through Mechanisms Distinct From Endothelial-To-Mesenchymal Cell Transition, Minh T H Nguyen, Masaki Imanishi, Shengyu Li, Khanh Chau, Priyanka Banerjee, Loka Reddy Velatooru, Kyung Ae Ko, Venkata S K Samanthapudi, Young J Gi, Ling-Ling Lee, Rei J Abe, Elena Mcbeath, Anita Deswal, Steven H Lin, Nicolas L Palaskas, Robert Dantzer, Keigi Fujiwara, Mae K Borchrdt, Estefani Berrios Turcios, Elizabeth A Olmsted-Davis, Sivareddy Kotla, John P Cooke, Guangyu Wang, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

BACKGROUND: The deSUMOylase sentrin-specific isopeptidase 2 (SENP2) plays a crucial role in atheroprotection. However, the phosphorylation of SENP2 at T368 under disturbed flow (D-flow) conditions hinders its nuclear function and promotes endothelial cell (EC) activation. SUMOylation has been implicated in D-flow-induced endothelial-to-mesenchymal transition (endoMT), but the precise role of SENP2 in counteracting this process remains unclear.

METHOD: We developed a phospho-specific SENP2 S344 antibody and generated knock-in (KI) mice with a phospho-site mutation of SENP2 S344A using CRISPR/Cas9 technology. We then investigated the effects of SENP2 S344 phosphorylation under two distinct flow patterns and during hypercholesteremia (HC)-mediated EC activation.

RESULT: …

The Health-Promoting Effects And The Mechanism Of Intermittent Fasting, Simin Liu, Min Zeng, Weixi Wan, Ming Huang, Xiang Li, Zixian Xie, Shang Wang, Yu Cai

Faculty, Staff and Student Publications

Intermittent fasting (IF) is an eating pattern in which individuals go extended periods with little or no energy intake after consuming regular food in intervening periods. IF has several health-promoting effects. It can effectively reduce weight, fasting insulin levels, and blood glucose levels. It can also increase the antitumor activity of medicines and cause improvement in the case of neurological diseases, such as memory deficit, to achieve enhanced metabolic function and prolonged longevity. Additionally, IF activates several biological pathways to induce autophagy, encourages cell renewal, prevents cancer cells from multiplying and spreading, and delays senescence. However, IF has specific adverse …

Survey Of West Nile And Banzi Viruses In Mosquitoes, South Africa, 2011-2018, Caitlin Macintyre, Milehna Mara Guarido, Megan Amy Riddin, Todd Johnson, Leo Braack, Maarten Schrama, Erin Gorsich, Antonio Paulo Gouveia Almeida, Marietjie Venter

Faculty, Staff and Student Publications

We collected >40,000 mosquitoes from 5 provinces in South Africa during 2011-2018 and screened for zoonotic flaviviruses. We detected West Nile virus in mosquitoes from conservation and periurban sites and potential new mosquito vectors; Banzi virus was rare. Our results suggest flavivirus transmission risks are increasing in South Africa.

Induction Of Thrombotic Thrombocytopenic Purpura By Dengue Virus Infection In A Critical Patient: Role Of Therapeutic Plasma Exchange, Rathindra Nath Biswas, Sudipta Sekhar Das, Anupam Chakrapani, Subrata Sen

Faculty, Staff and Student Publications

Thrombotic thrombocytopenic purpura (TTP) secondary to dengue fever is a very unusual occurrence. Both conditions are fatal and can result in significant mortality and morbidity if left untreated. In this case, we present a young lady who suffered dengue fever followed by microangiopathic anemia, thrombocytopenic purpura, and altered sensorium. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. As soon as, we diagnosed the patient as having TTP, we treated her with serial plasma exchange therapy, steroids, and monoclonal antibodies such as rituximab. The patient responded very well to the treatment and completely recovered from neurological symptoms …

View-Sharing For 4d Magnetic Resonance Imaging With Randomized Projection-Encoding Enables Improvements Of Respiratory Motion Imaging For Treatment Planning In Abdominothoracic Radiotherapy, Ergys Subashi, Li Feng, Yilin Liu, Scott Robertson, Paul Segars, Bastiaan Driehuys, Christopher R Kelsey, Fang-Fang Yin, Ricardo Otazo, Jing Cai

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The accuracy and precision of radiation therapy are dependent on the characterization of organ-at-risk and target motion. This work aims to demonstrate a 4D magnetic resonance imaging (MRI) method for improving spatial and temporal resolution in respiratory motion imaging for treatment planning in abdominothoracic radiotherapy.

MATERIALS AND METHODS: The spatial and temporal resolution of phase-resolved respiratory imaging is improved by considering a novel sampling function based on quasi-random projection-encoding and peripheral k-space view-sharing. The respiratory signal is determined directly from k-space, obviating the need for an external surrogate marker. The average breathing curve is used to optimize …

Pyrolyzed Deketene Curcumin Controls Regulatory T Cell Generation And Gastric Cancer Metabolism Cooperate With 2-Deoxy-D-Glucose, Takashi Maruyama, Hirofumi Miyazaki, Yun-Ji Lim, Jian Gu, Masaki Ishikawa, Taichi Yoshida, Wanjun Chen, Yuji Owada, Hiroyuki Shibata

Faculty, Staff and Student Publications

Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-β). However, GO-Y022 showed less impact on Foxp3+ Tregs in the gastric tumor microenvironment. Gastric tumor cells produce a large amount of L-lactate in the presence of GO-Y022 and diminish the inhibitory role of GO-Y022 against Treg generation in response to TGF-β. Therefore, naïve CD4+ T cells co-cultured with GO-Y022 treated gastric tumor cells increased Treg generation. …

Cytosolic Dna Sensing Protein Pathway Is Activated In Human Hearts With Dilated Cardiomyopathy, Leila Rouhi, Sirisha M Cheedipudi, Benjamin Cathcart, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: The genome is constantly exposed to numerous stressors, which induce DNA lesions, including double-stranded DNA breaks (DSBs). DSBs are the most dangerous, as they induce genomic instability. In response to DNA damage, the cell activates nuclear DNA damage response (DDR) and the cytosolic DNA sensing protein (CDSP) pathways, the latter upon release of the DSBs to the cytosol. The CDSP pathway activates NFκB and IRF3, which induce the expression of the pro-inflammatory genes. There is scant data on the activation of the CDSP pathway in human hearts with dilated cardiomyopathy (DCM).

AIM: We aimed to determine expression levels of …

Review Article: New Treatments For Advanced Differentiated Thyroid Cancers And Potential Mechanisms Of Drug Resistance, Sarah Hamidi, Marie-Claude Hofmann, Priyanka C Iyer, Maria E Cabanillas, Mimi I Hu, Naifa L Busaidy, Ramona Dadu

Faculty, Staff and Student Publications

The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in …