Biomedical Informatics Commons^™

A Translational Blueprint For Developing Intraoperative Imaging Agents Via Radiopharmaceutical-Guided Drug Design, Teresa E Sullivan, Servando Hernandez Vargas, Sukhen C Ghosh, Solmaz Aghaamiri, Naruhiko Ikoma, Ali Azhdarinia

Faculty, Staff and Student Publications

Cancer imaging is a rapidly evolving field due to the discovery of novel molecular targets and the availability of corresponding techniques to detect them with high precision, accuracy, and sensitivity. Nuclear medicine is the most widely used molecular imaging modality and has a growing toolkit of clinically used radiopharmaceuticals that enable whole-body tumor visualization, staging, and treatment monitoring for a variety of tumors in a non-invasive manner. The need for similar imaging capabilities in the operating room has led to the emergence of fluorescence-guided surgery (FGS) as a powerful technique that gives surgeons unprecedented ability to distinguish tumors from healthy …

Quantitative Multiplexed Imaging Technologies For Single-Cell Analysis To Assess Predictive Markers For Immunotherapy In Thoracic Immuno-Oncology: Promises And Challenges, Edwin Roger Parra, Marius Ilié, Ignacio I Wistuba, Paul Hofman

Faculty, Staff and Student Publications

The past decade has witnessed a revolution in cancer treatment by the shift from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular the immune-checkpoint inhibitors (ICIs). These immunotherapies selectively release the host immune system against the tumour and have shown unprecedented durable remission for patients with cancers that were thought incurable such as advanced non-small cell lung cancer (aNSCLC). The prediction of therapy response is based since the first anti-PD-1/PD-L1 molecules FDA and EMA approvals on the level of PD-L1 tumour cells expression evaluated by immunohistochemistry, and recently more or less on tumour mutation burden in …

Peripheral Levels Of The Brain-Derived Neurotrophic Factor In Coronary Artery Disease: A Systematic Review And Meta-Analysis, Parnian Shobeiri, Amir Hossein Behnoush, Amirmohammad Khalaji, Antonio Lucio Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

BACKGROUND: Among its functions, brain-derived neurotrophic factor (BDNF) regulates endothelial and macrophage activation, possibly playing a role in atherosclerotic plaque pathophysiology. Given contradicting reports, this study sought to investigate whether blood levels of BDNF differed between patients with coronary heart disease (CHD) and controls.

METHODS: We explored PubMed, Embase, Web of Science, and Cochrane Library for studies comparing BDNF blood levels in patients with CHD and controls. Random-effect meta-analysis was conducted to calculate the standardized mean differences (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa scale was used to evaluate the quality of included articles, and statistical analyses were conducted …

Refphase: Multi-Sample Phasing Reveals Haplotype-Specific Copy Number Heterogeneity, Thomas B K Watkins, Emma C Colliver, Matthew R Huska, Tom L Kaufmann, Emilia L Lim, Cody B Duncan, Kerstin Haase, Peter Van Loo, Charles Swanton, Nicholas Mcgranahan, Roland F Schwarz

Faculty, Staff and Student Publications

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient's disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample phasing. We demonstrate Refphase's ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours.

Young-Onset Rectal Cancer: Unique Tumoral Microbiome And Correlation With Response To Neoadjuvant Therapy, Michael G White, Ashish Damania, Jumanah Alshenaifi, Pranoti Sahasrabhojane, Oliver Peacock, Jillian Losh, Matthew C Wong, Zuzana Lutter-Berkova, George J Chang, Andrew Futreal, Jennifer A Wargo, Nadim J Ajami, Scott Kopetz, Y Nancy You

Faculty, Staff and Student Publications

OBJECTIVE: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology.

BACKGROUND: YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown.

METHODS: YORC (old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to …

Phenotype And Fate Of Liver-Resident Cd8 T Cells During Acute And Chronic Hepacivirus Infection, Piyush Dravid, Satyapramod Murthy, Zayed Attia, Cole Cassady, Rahul Chandra, Sheetal Trivedi, Ashish Vyas, John Gridley, Brantley Holland, Anuradha Kumari, Arash Grakoui, John M Cullen, Christopher M Walker, Himanshu Sharma, Amit Kapoor

Faculty, Staff and Student Publications

Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and chronic rodent HCV-like virus (RHV) infections in lab mice. Here, we developed MHC class I and class II tetramers to characterize the serial changes in RHV-specific CD8 and CD4 T cells during acute and chronic infection in C57BL/6J mice. RHV infection induced rapid expansion of T cells targeting viral structural and nonstructural proteins. After virus clearance, the virus-specific T cells transitioned from effectors to long-lived liver-resident memory T cells (TRM). The effector and …

Emphasizing Others’ Persistence Can Promote Unwarranted Social Inferences In Children And Adults, Jamie Amemiya, Gail D Heyman, Caren M Walker

Faculty, Staff and Student Publications

People often hear stories about individuals who persist to overcome their constraints. While these stories can be motivating, emphasizing others’ persistence may promote unwarranted judgments about constrained individuals who do not persist. Using a developmental social inference task (Study 1a: n = 124 U.S. children, 5 to 12 years of age; Study 1b [n = 135] and Study 2 [n = 120]: U.S. adults), the present research tested whether persistence stories lead people to infer that a constrained individual who does not persist, and instead accepts the lower-quality option that is available to them, prefers it over a …

Prevalence Of Pituitary Hormone Dysfunction Following Radiotherapy For Sinonasal And Nasopharyngeal Malignancies, Kevin J Contrera, Jack Phan, Steven G Waguespack, Mohammed Aldehaim, Xin Wang, Tze Yee Lim, Dianna B Roberts, C David Fuller, Michael T Spiotto, Shaan M Raza, Franco Demonte, Ehab Y Hanna, Shirley Y Su

Faculty, Staff and Student Publications

BACKGROUND: There are limited studies and no surveillance protocols on pituitary dysfunction for adults who underwent anterior skull base radiation.

METHODS: Cross-sectional study of 50 consecutive patients with sinonasal or nasopharyngeal cancer who underwent definitive radiotherapy. The mean radiation doses, prevalence of pituitary dysfunction, and associated factors were calculated.

RESULTS: Pituitary hormone levels were abnormal in 23 (46%) patients, including 6 (12%) with symptomatic abnormalities requiring treatment. The most common hormonal abnormality was hyperprolactinemia (30%), central hypothyroidism (8%) and central hypogonadism (6%). Patients with abnormal pituitary hormone values received higher mean radiation doses to the pituitary gland (1143 cGy, P …

An Efficient Strategy For Evaluating New Non-Invasive Screening Tests For Colorectal Cancer: The Guiding Principles, Robert S Bresalier, Carlo Senore, Graeme P Young, James Allison, Robert Benamouzig, Sally Benton, Patrick M M Bossuyt, Luis Caro, Beatriz Carvalho, Han-Mo Chiu, Veerle M H Coupé, Willemijn De Klaver, Clasine Maria De Klerk, Evelien Dekker, Sunil Dolwani, Callum G Fraser, William Grady, Lydia Guittet, Samir Gupta, Stephen P Halloran, Ulrike Haug, Geir Hoff, Steven Itzkowitz, Tim Kortlever, Anastasios Koulaouzidis, Uri Ladabaum, Beatrice Lauby-Secretan, Mārcis Leja, Bernard Levin, Theodore Robert Levin, Finlay Macrae, Gerrit A Meijer, Joshua Melson, Colm O'Morain, Susan Parry, Linda Rabeneck, David F Ransohoff, Roque Sáenz, Hiroshi Saito, Silvia Sanduleanu-Dascalescu, Robert E Schoen, Kevin Selby, Harminder Singh, Robert J C Steele, Joseph J Y Sung, Erin Leigh Symonds, Sidney J Winawer, Members Of The World Endoscopy Colorectal Cancer Screening New Test Evaluation Expert Working Group

Faculty, Staff and Student Publications

OBJECTIVE: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers.

DESIGN: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles.

RESULTS: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a …

Zyxin Inhibits The Epithelial-Mesenchymal Transition Process In Gastric Cancer By Upregulating Sirt1, Jing Lou, Sha Geng, Wei He, Song-Bai Liu, Xinghong Shi, Ying Chang, Shiyuan Han, Panting Qian, Hesham M Amin, Yao-Hua Song, Yangxin Li, Jin Zhou

Faculty, Staff and Student Publications

Tumor development relies on the stemness of cancer stem cells, which is regulated by environmental cues. Previous studies have shown that zyxin can inhibit the expression of genes for embryonic stem cell status. In the present study, the expression levels of zyxin protein in cancer tissues and adjacent noncancerous tissues from 73 gastric cancer patients with different clinical stages were analyzed by Western blot. We showed that the relative expression levels of zyxin in gastric cancer tissues (cancer tissues/adjacent tissues) were significantly downregulated in advanced clinical stages. Overexpression of zyxin inhibited the stemness and epithelial-mesenchymal transition (EMT) processes in gastric …

Therapeutic Effects Of Combining Curcumin And Swimming In Osteoarthritis Using A Rat Model, Mona M Saber, Manal Moustafa Mahmoud, Hesham M Amin, Reham M Essam

Faculty, Staff and Student Publications

Osteoarthritis (OA) is a common debilitating degenerative disease of the elderly. We aimed to study the therapeutic effects of combining curcumin and swimming in monosodium iodoacetate (MIA)-induced OA in a rat model. The rats were divided into 5 groups (n = 9). Group 1 received saline and served as a control group. Groups 2-5 were injected intra-articularly in the right knee with 100 μL MIA. One week later, groups 3 and 5 were started on daily swimming sessions that gradually increased to 20-mins per session, and for groups 4 and 5, oral curcumin was administered at a dose of 200 …

Co-Targeting Bcl-Xl And Bcl-2 By Protac 753b Eliminates Leukemia Cells And Enhances Efficacy Of Chemotherapy By Targeting Senescent Cells, Yannan Jia, Lina Han, Cassandra L Ramage, Zhe Wang, Connie C Weng, Lei Yang, Simona Colla, Helen Ma, Weiguo Zhang, Michael Andreeff, Naval Daver, Nitin Jain, Naveen Pemmaraju, Kapil Bhalla, Satu Mustjoki, Peiyi Zhang, Guangrong Zheng, Daohong Zhou, Qi Zhang, Marina Konopleva

Faculty, Staff and Student Publications

BCL-XL and BCL-2 are key anti-apoptotic proteins and validated cancer targets. 753B is a novel BCL-XL/BCL-2 proteolysis targeting chimera (PROTAC) that targets both BCL-XL and BCL-2 to the von Hippel-Lindau (VHL) E3 ligase, leading to BCLX L/BCL-2 ubiquitination and degradation selectively in cells expressing VHL. Because platelets lack VHL expression, 753B spares on-target platelet toxicity caused by the first-generation dual BCL-XL/BCL-2 inhibitor navitoclax (ABT-263). Here, we report pre-clinical single-agent activity of 753B against different leukemia subsets. 753B effectively reduced cell viability and induced dose-dependent degradation of BCL-XL and BCL-2 in a subset of hematopoietic cell lines, acute myeloid leukemia (AML) …

Combining Clinical And Biological Data To Predict Progressive Pulmonary Fibrosis In Patients With Systemic Sclerosis Despite Immunomodulatory Therapy, Elizabeth R Volkmann, Holly Wilhalme, Shervin Assassi, Grace Hyun J Kim, Jonathan Goldin, Masataka Kuwana, Donald P Tashkin, Michael D Roth

Faculty, Staff and Student Publications

OBJECTIVE: Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc-related interstitial lung disease (SSc-ILD).

METHODS: Patients with SSc-ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC). Clinical and biological parameters were analyzed using univariable and multivariable logistic regression, and a nomogram was created to assess the risk of PPF and validated by bootstrap resampling.

RESULTS: Among …

Recent Insights Into The Pathogenesis And Therapeutic Targets Of Chronic Liver Diseases, Yankai Wen, Lichun Ma, Cynthia Ju

Faculty, Staff and Student Publications

Viral hepatitis, alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the three major causes of chronic liver diseases, which account for approximately 2 million deaths per year worldwide. The current direct-acting antiviral drugs and vaccinations have effectively reduced and ameliorated viral hepatitis infection, but there are still no effective drug treatments for ALD, NAFLD and liver cancer due to the poor understanding of their pathogenesis. To better understand the pathogenesis, the fifth Chinese American Liver Society/Society of Chinese Bioscientists in America Hepatology Division Annual Symposium, which was held virtually on 21-22 October 2022, focused on the topics …

A Ck2 And Sumo-Dependent, Pml Nb-Involved Regulatory Mechanism Controlling Blm Ubiquitination And G-Quadruplex Resolution, Shichang Liu, Erin Atkinson, Adriana Paulucci-Holthauzen, Bin Wang

Faculty, Staff and Student Publications

The Boom syndrome helicase (BLM) unwinds a variety of DNA structures such as Guanine (G)-quadruplex. Here we reveal a role of RNF111/Arkadia and its paralog ARKL1, as well as Promyelocytic Leukemia Nuclear Bodies (PML NBs), in the regulation of ubiquitination and control of BLM protein levels. RNF111 exhibits a non-canonical SUMO targeted E3 ligase (STUBL) activity targeting BLM ubiquitination in PML NBs. ARKL1 promotes RNF111 localization to PML NBs through SUMO-interacting motif (SIM) interaction with SUMOylated RNF111, which is regulated by casein kinase 2 (CK2) phosphorylation of ARKL1 at a serine residue near the ARKL1 SIM domain. Upregulated BLM in …

A Case Report: A Patient Rescued By Va-Ecmo After Cardiac Arrest Triggered By Trigeminocardiac Reflex After Nasal Surgery, Xu Zhang, Bin Sun, Chen Pac-Soo, Daqing Ma, Liwei Wang

Faculty, Staff and Student Publications

Rationale:

Cardiac arrest (CA) caused by trigeminocardiac reflex (TCR) after endoscopic nasal surgery is rare. Hence, when a patient suffers from TCR induced CA in the recovery room, most doctors may not be able to find the cause in a short time, and standard cardiopulmonary resuscitation and resuscitation measures may not be effective. Providing circulatory assistance through venous-arterial extracorporeal membrane oxygenation (VA-ECMO) can help healthcare providers gain time to identify the etiology and initiate symptom-specific treatment.

Patient concerns:

We report a rare case of CA after endoscopic nasal surgery treated with VA-ECMO.

Diagnoses:

We excluded myocardial infarction, pulmonary embolism, allergies, …

New Jak3-Insl3 Fusion Transcript-An Oncogenic Event In Cutaneous T-Cell Lymphoma, Loka Reddy Velatooru, Cheng Hui Hu, Pedram Bijani, Xiaohong Wang, Pierr Bojaxhi, Hao Chen, Madeleine Duvic, Xiao Ni

Faculty, Staff and Student Publications

Constitutively activated tyrosine kinase JAK3 is implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCL). The mechanisms of constitutive JAK3 activation are unknown although a JAK3 mutation was reported in a small portion of CTCL patients. In this study, we assessed the oncogenic roles of a newly identified JAK3-INSL3 fusion transcript in CTCL. Total RNA from malignant T-cells in 33 patients with Sézary syndrome (SS), a leukemic form of CTCL, was examined for the new JAK3-INSL3 fusion transcript by RT-PCR followed by Sanger sequencing. The expression levels were assessed by qPCR and correlated with patient survivals. Knockdown and/or knockout assays …

Heterogenous Lung Inflammation Ct Patterns Distinguish Pneumonia And Immune Checkpoint Inhibitor Pneumonitis And Complement Blood Biomarkers In Acute Myeloid Leukemia: Proof Of Concept, Muhammad Aminu, Naval Daver, Myrna C B Godoy, Girish Shroff, Carol Wu, Luis F Torre-Sada, Alberto Goizueta, Vickie R Shannon, Saadia A Faiz, Mehmet Altan, Guillermo Garcia-Manero, Hagop Kantarjian, Farhad Ravandi-Kashani, Tapan Kadia, Marina Konopleva, Courtney Dinardo, Sherry Pierce, Aung Naing, Sang T Kim, Dimitrios P Kontoyiannis, Fareed Khawaja, Caroline Chung, Jia Wu, Ajay Sheshadri

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is time-consuming and challenging. To fill this gap, we build an image-based tool, and further evaluate it clinically alongside relevant blood biomarkers.

MATERIALS AND METHODS: We studied CT images from 97 patients with pneumonia and 29 patients with pneumonitis from acute myeloid leukemia treated with ICIs. We developed a CT-derived signature using a habitat imaging algorithm, whereby infected lungs are segregated into clusters ("habitats"). We validated the model and compared it with a clinical-blood model to determine whether imaging can add …

Elastic Stable Intramedullary Nail Fixation Versus Submuscular Plate Fixation Of Pediatric Femur Shaft Fractures In School Age Patients: A Prisma-Compliant Systematic Review And Meta-Analysis, Donglai Hu, Zihang Xu, Tao Shi, Hui Zhong, Yuting Xie, Junjie Chen

Faculty, Staff and Student Publications

BACKGROUND: Studies of clinical outcomes that compare the elastic stable intramedullary nail (ESIN) with the submuscular plate (SMP) were controversial. The meta-analysis was performed to summarize existing evidence, aiming to determine whether ESIN was superior to SMP in pediatric femur shaft fractures.

METHODS: Search strategies followed the recommendations of the Cochrane collaboration. Electronic searches such as PubMed, Embase, Web of Science, Cochrane were systematically searched for publications concerning ESIN and SMP from the inception date to March 2023. Two investigators independently searched, screened, and reviewed the full text of the article. Disagreements generated throughout the process were resolved by consensus, …

Integrated Molecular And Multiparametric Mri Mapping Of High-Grade Glioma Identifies Regional Biologic Signatures, Leland S Hu, Fulvio D'Angelo, Taylor M Weiskittel, Francesca P Caruso, Shannon P Fortin Ensign, Mylan R Blomquist, Matthew J Flick, Lujia Wang, Christopher P Sereduk, Kevin Meng-Lin, Gustavo De Leon, Ashley Nespodzany, Javier C Urcuyo, Ashlyn C Gonzales, Lee Curtin, Erika M Lewis, Kyle W Singleton, Timothy Dondlinger, Aliya Anil, Natenael B Semmineh, Teresa Noviello, Reyna A Patel, Panwen Wang, Junwen Wang, Jennifer M Eschbacher, Andrea Hawkins-Daarud, Pamela R Jackson, Itamar S Grunfeld, Christian Elrod, Gina L Mazza, Sam C Mcgee, Lisa Paulson, Kamala Clark-Swanson, Yvette Lassiter-Morris, Kris A Smith, Peter Nakaji, Bernard R Bendok, Richard S Zimmerman, Chandan Krishna, Devi P Patra, Naresh P Patel, Mark Lyons, Matthew Neal, Kliment Donev, Maciej M Mrugala, Alyx B Porter, Scott C Beeman, Todd R Jensen, Kathleen M Schmainda, Yuxiang Zhou, Leslie C Baxter, Christopher L Plaisier, Jing Li, Hu Li, Anna Lasorella, C Chad Quarles, Kristin R Swanson, Michele Ceccarelli, Antonio Iavarone, Nhan L Tran

Faculty, Staff and Student Publications

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate …

National Survey On The Availability Of Oncology Palliative Care Services At Tertiary General And Cancer Hospitals In China, Xiaomei Li, Xin Shelley Wang, Haili Huang, Miao Liu, Yinan Wu, Jiaojiao Qiu, Boran Zhang, Linhong Cui, David Hui

Faculty, Staff and Student Publications

Background: This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China.

Methods: Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service.

Results: Most responders …

Comparative Study Of Guanidine-, Acetamidine- And Urea-Based Chloroaluminate Electrolytes For An Aluminum Battery, Iwan Sumarlan, Anand Kunverji, Anthony J Lucio, A Robert Hillman, Karl S Ryder

Faculty, Staff and Student Publications

Aluminum-based batteries are a promising alternative to lithium-ion as they are considered to be low-cost and more friendly to the environment. In addition, aluminum is abundant and evenly distributed across the globe. Many studies and Al battery prototypes use imidazolium chloroaluminate electrolytes because of their good rheological and electrochemical performance. However, these electrolytes are very expensive, and so cost is a barrier to industrial scale-up. A urea-based electrolyte, AlCl3:Urea, has been proposed as an alternative, but its performance is relatively poor because of its high viscosity and low conductivity. This type of electrolyte has become known as an ionic liquid …

Development Of A Xylose-Inducible Promoter And Riboswitch Combination System For Manipulating Gene Expression In Fusobacterium Nucleatum, Bibek G C, Peng Zhou, Arindam Naha, Jianhua Gu, Chenggang Wu

Faculty, Staff and Student Publications

Inducible gene expression systems are important for studying bacterial gene function, yet most exhibit leakage. In this study, we engineered a leakage-free hybrid system for precise gene expression controls in Fusobacterium nucleatum by integrating the xylose-inducible expression system with the theophylline-responsive riboswitch. This innovative method enables concurrent control of target gene expression at both transcription and translation initiation levels. Using luciferase and the indole-producing enzyme tryptophanase (TnaA) as reporters, we demonstrated that the hybrid system displays virtually no observable signal in the absence of inducers. We employed this system to express FtsX, a protein related to fusobacterial cytokinesis, in an …

Author Correction: Synthetic Oct-A Blood Vessel Maps Using Fundus Images And Generative Adversarial Networks, Ivan Coronado, Samiksha Pachade, Emanuele Trucco, Rania Abdelkhaleq, Juntao Yan, Sergio Salazar-Marioni, Amanda Jagolino-Cole, Mozhdeh Bahrainian, Roomasa Channa, Sunil A Sheth, Luca Giancardo

Faculty, Staff and Student Publications

No abstract provided.

Antibodies To Coagulase Of Staphylococcus Aureus Crossreact To Efb And Reveal Different Binding Of Shared Fibrinogen Binding Repeats, Federico Bertoglio, Ya-Ping Ko, Sheila Thomas, Liliana Giordano, Francesca Romana Scommegna, Doris Meier, Saskia Polten, Marlies Becker, Srishtee Arora, Michael Hust, Magnus Höök, Livia Visai

Faculty, Staff and Student Publications

Staphylococcus aureus pathology is caused by a plethora of virulence factors able to combat multiple host defence mechanisms. Fibrinogen (Fg), a critical component in the host coagulation cascade, plays an important role in the pathogenesis of this bacterium, as it is the target of numerous staphylococcal virulence proteins. Amongst its secreted virulence factors, coagulase (Coa) and Extracellular fibrinogen-binding protein (Efb) share common Fg binding motives and have been described to form a Fg shield around staphylococcal cells, thereby allowing efficient bacterial spreading, phagocytosis escape and evasion of host immune system responses. Targeting these proteins with monoclonal antibodies thus represents a …

Differential Effects Of Pancreatic Cancer-Derived Extracellular Vesicles Driving A Suppressive Environment, Anurag Purushothaman, Jacqueline Oliva-Ramírez, Warapen Treekitkarnmongkol, Deivendran Sankaran, Mark W Hurd, Nagireddy Putluri, Anirban Maitra, Cara Haymaker, Subrata Sen

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) cells display extensive crosstalk with their surrounding environment to regulate tumor growth, immune evasion, and metastasis. Recent advances have attributed many of these interactions to intercellular communication mediated by small extracellular vesicles (sEVs), involving cancer-associated fibroblasts (CAF). To explore the impact of sEVs on monocyte lineage transition as well as the expression of checkpoint receptors and activation markers, peripheral blood monocytes from healthy subjects were exposed to PDAC-derived sEVs. Additionally, to analyze the role of sEV-associated HA in immune regulation and tissue-resident fibroblasts, monocytes and pancreatic stellate cells were cultured in the presence of PDAC sEVs …

A Peptide-Binding Domain Shared With An Antarctic Bacterium Facilitates, Cameron J Lloyd, Shuaiqi Guo, Brett Kinrade, Hossein Zahiri, Robert Eves, Syed Khalid Ali, Fitnat Yildiz, Ilja K Voets, Peter L Davies, Karl E Klose

Faculty, Staff and Student Publications

No abstract provided.

Axl-Initiated Paracrine Activation Of Pstat3 Enhances Mesenchymal And Vasculogenic Supportive Features Of Tumor-Associated Macrophages, Chia-Nung Hung, Meizhen Chen, Daniel T Dearmond, Cheryl H-L Chiu, Catherine A Limboy, Xi Tan, Meena Kusi, Chih-Wei Chou, Li-Ling Lin, Zhao Zhang, Chiou-Miin Wang, Chun-Liang Chen, Kohzoh Mitsuya, Pawel A Osmulski, Maria E Gaczynska, Nameer B Kirma, Ratna K Vadlamudi, Don L Gibbons, Steve Warner, Andrew J Brenner, Daruka Mahadevan, Joel E Michalek, Tim H-M Huang, Josephine A Taverna

Faculty, Staff and Student Publications

Tumor-associated macrophages (TAMs) are integral to the development of complex tumor microenvironments (TMEs) and can execute disparate cellular programs in response to extracellular cues. However, upstream signaling processes underpinning this phenotypic plasticity remain to be elucidated. Here, we report that concordant AXL-STAT3 signaling in TAMs is triggered by lung cancer cells or cancer-associated fibroblasts in the cytokine milieu. This paracrine action drives TAM differentiation toward a tumor-promoting "M2-like" phenotype with upregulation of CD163 and putative mesenchymal markers, contributing to TAM heterogeneity and diverse cellular functions. One of the upregulated markers, CD44, mediated by AXL-IL-11-pSTAT3 signaling cascade, enhances macrophage ability to …

Using Artificial Intelligence To Learn Optimal Regimen Plan For Alzheimer’S Disease, Kritib Bhattarai, Sivaraman Rajaganapathy, Trisha Das, Yejin Kim, Yongbin Chen, Alzheimer’S Disease Neuroimaging Initiative, Australian Imaging Biomarkers And Lifestyle Flagship Study Of Ageing, Qiying Dai, Xiaoyang Li, Xiaoqian Jiang, Nansu Zong

Faculty, Staff and Student Publications

BACKGROUND: Alzheimer's disease (AD) is a progressive neurological disorder with no specific curative medications. Sophisticated clinical skills are crucial to optimize treatment regimens given the multiple coexisting comorbidities in the patient population.

OBJECTIVE: Here, we propose a study to leverage reinforcement learning (RL) to learn the clinicians' decisions for AD patients based on the longitude data from electronic health records.

METHODS: In this study, we selected 1736 patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We focused on the two most frequent concomitant diseases-depression, and hypertension, thus creating 5 data cohorts (ie, Whole Data, AD, AD-Hypertension, AD-Depression, and AD-Depression-Hypertension). …

Mapping The Delineation Of Practice To The Amia Foundational Domains For Applied Health Informatics, Todd R Johnson, Eta S Berner, Sue S Feldman, Josette Jones, Annette L Valenta, Damian Borbolla, Gloria Deckard, Laverne Manos

Faculty, Staff and Student Publications

OBJECTIVE: This article reports on the alignment between the foundational domains and the delineation of practice (DoP) for health informatics, both developed by the American Medical Informatics Association (AMIA). Whereas the foundational domains guide graduate-level curriculum development and accreditation assessment, providing an educational pathway to the minimum competencies needed as a health informatician, the DoP defines the domains, tasks, knowledge, and skills that a professional needs to competently perform in the discipline of health informatics. The purpose of this article is to determine whether the foundational domains need modification to better reflect applied practice.

MATERIALS AND METHODS: Using an iterative …