Digital Commons Network^™

Challenges And Opportunities For Advancing Patient-Centered Clinical Decision Support: Findings From A Horizon Scan, Prashila Dullabh, Shana F Sandberg, Krysta Heaney-Huls, Lauren S Hovey, David F Lobach, Aziz Boxwala, Priyanka J Desai, Elise Berliner, Chris Dymek, Michael I Harrison, James Swiger, Dean F Sittig

Faculty, Staff and Student Publications

OBJECTIVE: We conducted a horizon scan to (1) identify challenges in patient-centered clinical decision support (PC CDS) and (2) identify future directions for PC CDS.

MATERIALS AND METHODS: We engaged a technical expert panel, conducted a scoping literature review, and interviewed key informants. We qualitatively analyzed literature and interview transcripts, mapping findings to the 4 phases for translating evidence into PC CDS interventions (Prioritizing, Authoring, Implementing, and Measuring) and to external factors.

RESULTS: We identified 12 challenges for PC CDS development. Lack of patient input was identified as a critical challenge. The key informants noted that patient input is critical …

A Peptide Blocking The Adora1-Neurabin Interaction Is Anticonvulsant And Inhibits Epilepsy In An Alzheimer's Model, Shalini Saggu, Yunjia Chen, Liping Chen, Diana Pizarro, Sandipan Pati, Wen Jing Law, Lori Mcmahon, Kai Jiao, Qin Wang

Faculty, Staff and Student Publications

Epileptic seizures are common sequelae of stroke, acute brain injury, and chronic neurodegenerative diseases, including Alzheimer's disease (AD), and cannot be effectively controlled in approximately 40% of patients, necessitating the development of novel therapeutic agents. Activation of the A1 receptor (A1R) by endogenous adenosine is an intrinsic mechanism to self-terminate seizures and protect neurons from excitotoxicity. However, targeting A1R for neurological disorders has been hindered by side effects associated with its broad expression outside the nervous system. Here we aim to target the neural-specific A1R/neurabin/regulator of G protein signaling 4 (A1R/neurabin/RGS4) complex that dictates A1R signaling strength and response outcome …

Latent Linguistic Motifs In Social Media Postings Resisting Covid-19 Misinformation, Tavleen Singh, Sofia Olivares, Sahiti Myneni

Faculty, Staff and Student Publications

Social media has become a predominant source of information for many health care consumers. However, false and misleading information is a pervasive problem in this context. Specifically, health-related misinformation has become a significant public health challenge, impeding the effectiveness of public health awareness campaigns and resulting in suboptimal responsiveness to the communication of legitimate risk-related information. Little is known about the mechanisms driving the seeding and spreading of such information. In this paper, we specifically examine COVID-19 tweets which attempt to correct misinformation. We employ a mixed-methods approach comprising qualitative coding, deep learning classification, and computerized text analysis to understand …

Structural Characterization Of Dicyanopyridine Containing Dnmt1-Selective, Non-Nucleoside Inhibitors, John R Horton, Sarath Pathuri, Kristen Wong, Ren Ren, Lourdes Rueda, David T Fosbenner, Dirk A Heerding, Michael T Mccabe, Melissa B Pappalardi, Xing Zhang, Bryan W King, Xiaodong Cheng

Faculty, Staff and Student Publications

DNMT1 maintains the parental DNA methylation pattern on newly replicated hemimethylated DNA. The failure of this maintenance process causes aberrant DNA methylation that affects transcription and contributes to the development and progression of cancers such as acute myeloid leukemia. Here, we structurally characterized a set of newly discovered DNMT1-selective, reversible, non-nucleoside inhibitors that bear a core 3,5-dicyanopyridine moiety, as exemplified by GSK3735967, to better understand their mechanism of inhibition. All of the dicyanopydridine-containing inhibitors examined intercalate into the hemimethylated DNA between two CpG base pairs through the DNA minor groove, resulting in conformational movement of the DNMT1 active-site loop. In …

Predictive Performance Of Different Ntcp Techniques For Radiation-Induced Esophagitis In Nsclc Patients Receiving Proton Radiotherapy, Mei Chen, Zeming Wang, Shengpeng Jiang, Jian Sun, Li Wang, Narayan Sahoo, G Brandon Gunn, Steven J Frank, Cheng Xu, Jiayi Chen, Quynh-Nhu Nguyen, Joe Y Chang, Zhongxing Liao, X Ronald Zhu, Xiaodong Zhang

Faculty, Staff and Student Publications

This study aimed to compare the predictive performance of different modeling methods in developing normal tissue complication probability (NTCP) models for predicting radiation-induced esophagitis (RE) in non-small cell lung cancer (NSCLC) patients receiving proton radiotherapy. The dataset was composed of 328 NSCLC patients receiving passive-scattering proton therapy and 41.6% of the patients experienced ≥ grade 2 RE. Five modeling methods were used to build NTCP models: standard Lyman-Kutcher-Burman (sLKB), generalized LKB (gLKB), multivariable logistic regression using two variable selection procedures-stepwise forward selection (Stepwise-MLR), and least absolute shrinkage and selection operator (LASSO-MLR), and support vector machines (SVM). Predictive performance was internally …

Precision Combination Therapies Based On Recurrent Oncogenic Coalterations, Xubin Li, Elisabeth K Dowling, Gonghong Yan, Zeynep Dereli, Behnaz Bozorgui, Parisa Imanirad, Jacob H Elnaggar, Augustin Luna, David G Menter, Patrick G Pilié, Timothy A Yap, Scott Kopetz, Chris Sander, Anil Korkut

Faculty, Staff and Student Publications

UNLABELLED: Cancer cells depend on multiple driver alterations whose oncogenic effects can be suppressed by drug combinations. Here, we provide a comprehensive resource of precision combination therapies tailored to oncogenic coalterations that are recurrent across patient cohorts. To generate the resource, we developed Recurrent Features Leveraged for Combination Therapy (REFLECT), which integrates machine learning and cancer informatics algorithms. Using multiomic data, the method maps recurrent coalteration signatures in patient cohorts to combination therapies. We validated the REFLECT pipeline using data from patient-derived xenografts, in vitro drug screens, and a combination therapy clinical trial. These validations demonstrate that REFLECT-selected combination therapies …

Beyond The Backbone: The Next Generation Of Pathwalking Utilities For Model Building In Cryoem Density Maps, Corey F Hryc, Matthew L Baker

Faculty, Staff and Student Publications

Single-particle electron cryomicroscopy (cryoEM) has become an indispensable tool for studying structure and function in macromolecular assemblies. As an integral part of the cryoEM structure determination process, computational tools have been developed to build atomic models directly from a density map without structural templates. Nearly a decade ago, we created Pathwalking, a tool for de novo modeling of protein structure in near-atomic resolution cryoEM density maps. Here, we present the latest developments in Pathwalking, including the addition of probabilistic models, as well as a companion tool for modeling waters and ligands. This software was evaluated on the 2021 CryoEM Ligand …

A Multi-Task Gaussian Process Self-Attention Neural Network For Real-Time Prediction Of The Need For Mechanical Ventilators In Covid-19 Patients, Kai Zhang, Siddharth Karanth, Bela Patel, Robert Murphy, Xiaoqian Jiang

Faculty, Staff and Student Publications

OBJECTIVE: The Coronavirus Disease 2019 (COVID-19) pandemic has overwhelmed the capacity of healthcare resources and posed a challenge for worldwide hospitals. The ability to distinguish potentially deteriorating patients from the rest helps facilitate reasonable allocation of medical resources, such as ventilators, hospital beds, and human resources. The real-time accurate prediction of a patient's risk scores could also help physicians to provide earlier respiratory support for the patient and reduce the risk of mortality.

METHODS: We propose a robust real-time prediction model for the in-hospital COVID-19 patients' probability of requiring mechanical ventilation (MV). The end-to-end neural network model incorporates the Multi-task …

External Validation Of A Model Determining Risk Of Neoplastic Progression Of Barrett’S Esophagus In A Cohort Of Us Veterans, Theresa H Nguyen, Aaron P Thrift, Gyanprakash A Ketwaroo, Xianglin L Du, Luis Leon Novelo, Rollin George, Daniel G Rosen, Hashem B El-Serag

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Risk of esophageal adenocarcinoma (EAC) in those with Barrett's esophagus (BE) is 11-fold greater than the general population. It remains unclear which BE patients are at highest risk of progression to EAC. We aimed to validate a predictive model risk-stratifying BE patients.

METHODS: We conducted a retrospective cohort study at the Houston Veteran Affairs Medical Center of consecutive patients with a new diagnosis of BE from November 1990 to January 2019. Study follow-up was through February 2020. Patients were excluded if they had no follow-up EGD with esophageal biopsy sampling after the initial BE-diagnosing EGD or evidence …

External Validation Of A Model Determining Risk Of Neoplastic Progression Of Barrett's Esophagus In A Cohort Of Us Veterans, Theresa H Nguyen, Aaron P Thrift, Gyanprakash A Ketwaroo, Xianglin L Du, Luis Leon Novelo, Rollin George, Daniel G Rosen, Hashem B El-Serag

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Risk of esophageal adenocarcinoma (EAC) in those with Barrett's esophagus (BE) is 11-fold greater than the general population. It remains unclear which BE patients are at highest risk of progression to EAC. We aimed to validate a predictive model risk-stratifying BE patients.

METHODS: We conducted a retrospective cohort study at the Houston Veteran Affairs Medical Center of consecutive patients with a new diagnosis of BE from November 1990 to January 2019. Study follow-up was through February 2020. Patients were excluded if they had no follow-up EGD with esophageal biopsy sampling after the initial BE-diagnosing EGD or evidence …

Integrative Analysis Of Clinical And Epigenetic Biomarkers Of Mortality, Tianxiao Huan, Steve Nguyen, Elena Colicino, Carolina Ochoa-Rosales, W David Hill, Jennifer A Brody, Mette Soerensen, Yan Zhang, Antoine Baldassari, Mohamed Ahmed Elhadad, Tanaka Toshiko, Yinan Zheng, Arce Domingo-Relloso, Dong Heon Lee, Jiantao Ma, Chen Yao, Chunyu Liu, Shih-Jen Hwang, Roby Joehanes, Myriam Fornage, Jan Bressler, Joyce B J Van Meurs, Birgit Debrabant, Jonas Mengel-From, Jacob Hjelmborg, Kaare Christensen, Pantel Vokonas, Joel Schwartz, Sina A Gahrib, Nona Sotoodehnia, Colleen M Sitlani, Sonja Kunze, Christian Gieger, Annette Peters, Melanie Waldenberger, Ian J Deary, Luigi Ferrucci, Yishu Qu, Philip Greenland, Donald M Lloyd-Jones, Lifang Hou, Stefania Bandinelli, Trudy Voortman, Brenner Hermann, Andrea Baccarelli, Eric Whitsel, James S Pankow, Daniel Levy

Faculty, Staff and Student Publications

DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10

Regularized Regression On Compositional Trees With Application To Mri Analysis, Bingkai Wang, Brian S Caffo, Xi Luo, Chin-Fu Liu, Andreia V Faria, Michael I Miller, Yi Zhao

Faculty, Staff and Student Publications

A compositional tree refers to a tree structure on a set of random variables where each random variable is a node and composition occurs at each non-leaf node of the tree. As a generalization of compositional data, compositional trees handle more complex relationships among random variables and appear in many disciplines, such as brain imaging, genomics and finance. We consider the problem of sparse regression on data that are associated with a compositional tree and propose a transformation-free tree-based regularized regression method for component selection. The regularization penalty is designed based on the tree structure and encourages a sparse tree …

Gene-Lifestyle Interactions In The Genomics Of Human Complex Traits, Vincent Laville, Timothy Majarian, Yun J Sung, Karen Schwander, Mary F Feitosa, Daniel I Chasman, Amy R Bentley, Charles N Rotimi, L Adrienne Cupples, Paul S De Vries, Michael R Brown, Alanna C Morrison, Aldi T Kraja, Mike Province, C Charles Gu, W James Gauderman, Charge Gene-Lifestyle Interactions Working Group, D C Rao, Alisa K Manning, Hugues Aschard

Faculty, Staff and Student Publications

The role and biological significance of gene-environment interactions in human traits and diseases remain poorly understood. To address these questions, the CHARGE Gene-Lifestyle Interactions Working Group conducted series of genome-wide interaction studies (GWIS) involving up to 610,475 individuals across four ancestries for three lipids and four blood pressure traits, while accounting for interaction effects with drinking and smoking exposures. Here we used GWIS summary statistics from these studies to decipher potential differences in genetic associations and G×E interactions across phenotype-exposure-ancestry combinations, and to derive insights on the potential mechanistic underlying G×E through in-silico functional analyses. Our analyses show first that …

Multi-Phenotype Analyses Of Hemostatic Traits With Cardiovascular Events Reveal Novel Genetic Associations, Gerard Temprano-Sagrera, Colleen M Sitlani, William P Bone, Miguel Martin-Bornez, Benjamin F Voight, Alanna C Morrison, Scott M Damrauer, Paul S De Vries, Nicholas L Smith, Maria Sabater-Lleal

Faculty, Staff and Student Publications

BACKGROUND: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes.

OBJECTIVES: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events.

METHODS: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen …

Grief Symptoms Promote Inflammation During Acute Stress Among Bereaved Spouses, Ryan L Brown, Angie S Leroy, Michelle A Chen, Robert Suchting, Lisa M Jaremka, Jia Liu, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

The death of a spouse is associated with maladaptive immune alterations; grief severity may exacerbate this link. We investigated whether high grief symptoms were associated with an amplified inflammatory response to subsequent stress among 111 recently bereaved older adults. Participants completed a standardized psychological stressor and underwent a blood draw before, 45 min after, and 2 hr after the stressor. Those experiencing high grief symptoms (i.e., scoring > 25 on the Inventory of Complicated Grief) experienced a 45% increase in interleukin-6 (IL-6; a proinflammatory cytokine) per hour, whereas those experiencing low grief symptoms demonstrated a 26% increase. In other words, high …

Experimental Models Of Undifferentiated Pleomorphic Sarcoma And Malignant Peripheral Nerve Sheath Tumor, Angela D Bhalla, Sharon M Landers, Anand K Singh, Jace P Landry, Michelle G Yeagley, Gabryella S B Myerson, Cristian B Delgado-Baez, Stephanie Dunnand, Theresa Nguyen, Xiaoyan Ma, Svetlana Bolshakov, Brian A Menegaz, Salah-Eddine Lamhamedi-Cherradi, Xizeng Mao, Xingzhi Song, Alexander J Lazar, Ian E Mccutcheon, John M Slopis, Joseph A Ludwig, Dina C Lev, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models available, we generated additional cell lines to study these rare cancers. Patient-derived tumors were used to establish 4 new UPS models, including one radiation-associated UPS-UPS271.1, UPS511, UPS0103, and RIS620, one unclassified spindle cell sarcoma-USC060.1, and 3 new models of …

A Roadmap To Clinical Trials For Flash, Paige A Taylor, Jean M Moran, David A Jaffray, Jeffrey C Buchsbaum

Faculty, Staff and Student Publications

While FLASH radiation therapy is inspiring enthusiasm to transform the field, it is neither new nor well understood with respect to the radiobiological mechanisms. As FLASH clinical trials are designed, it will be important to ensure we can deliver dose consistently and safely to every patient. Much like hyperthermia and proton therapy, FLASH is a promising new technology that will be complex to implement in the clinic and similarly will require customized credentialing for multi-institutional clinical trials. There is no doubt that FLASH seems promising, but many technologies that we take for granted in conventional radiation oncology, such as rigorous …

Integrating Mechanism-Based Modeling With Biomedical Imaging To Build Practical Digital Twins For Clinical Oncology, Chengyue Wu, Guillermo Lorenzo, David A Hormuth, Ernesto A B F Lima, Kalina P Slavkova, Julie C Dicarlo, John Virostko, Caleb M Phillips, Debra Patt, Caroline Chung, Thomas E Yankeelov

Faculty, Staff and Student Publications

Digital twins employ mathematical and computational models to virtually represent a physical object (e.g., planes and human organs), predict the behavior of the object, and enable decision-making to optimize the future behavior of the object. While digital twins have been widely used in engineering for decades, their applications to oncology are only just emerging. Due to advances in experimental techniques quantitatively characterizing cancer, as well as advances in the mathematical and computational sciences, the notion of building and applying digital twins to understand tumor dynamics and personalize the care of cancer patients has been increasingly appreciated. In this review, we …

Distinct Immune Gene Programs Associated With Host Tumor Immunity, Neoadjuvant Chemotherapy, And Chemoimmunotherapy In Resectable Nsclc, Pedro Rocha, Jiexin Zhang, Raquel Laza-Briviesca, Alberto Cruz-Bermúdez, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridon, Katsuhiro Yoshimura, Carmen Behrens, Wei Lu, Ximing Tang, Apar Pataer, Edwin R Parra, Cara Haymaker, Junya Fujimoto, Stephen G Swisher, John V Heymach, Don L Gibbons, J Jack Lee, Boris Sepesi, Tina Cascone, Luisa M Solis, Mariano Provencio, Ignacio I Wistuba, Humam Kadara

Faculty, Staff and Student Publications

Purpose: Our understanding of the immunopathology of resectable non-small cell lung cancer (NSCLC) is still limited. Here, we explore immune programs that inform of tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in localized NSCLC.

Experimental design: Targeted immune gene sequencing using the HTG Precision Immuno-Oncology panel was performed in localized NSCLCs from three cohorts based on treatment: naïve (n = 190), neoadjuvant chemotherapy (n = 38), and neoadjuvant chemoimmunotherapy (n = 21). Tumor immune microenvironment (TIME) phenotypes were based on the location of CD8+ T cells (inflamed, cold, excluded), tumoral PD-L1 expression (<1% and ≥1%), and tumor-infiltrating lymphocytes (TIL). Immune programs and signatures were statistically analyzed on the basis of tumoral PD-L1 expression, immune phenotypes, and pathologic response and were cross-compared across the three cohorts.

Results: PD-L1-positive tumors exhibited increased …

Obif: An Omics-Based Interaction Framework To Reveal Molecular Drivers Of Synergy, Jezreel Pantaleón García, Vikram V Kulkarni, Tanner C Reese, Shradha Wali, Saima J Wase, Jiexin Zhang, Ratnakar Singh, Mauricio S Caetano, Humam Kadara, Seyed Javad Moghaddam, Faye M Johnson, Jing Wang, Yongxing Wang, Scott E Evans

Faculty, Staff and Student Publications

Bioactive molecule library screening may empirically identify effective combination therapies, but molecular mechanisms underlying favorable drug-drug interactions often remain unclear, precluding further rational design. In the absence of an accepted systems theory to interrogate synergistic responses, we introduce Omics-Based Interaction Framework (OBIF) to reveal molecular drivers of synergy through integration of statistical and biological interactions in synergistic biological responses. OBIF performs full factorial analysis of feature expression data from single versus dual exposures to identify molecular clusters that reveal synergy-mediating pathways, functions and regulators. As a practical demonstration, OBIF analyzed transcriptomic and proteomic data of a dyad of immunostimulatory molecules …

Comprehensive Characterization Of Tumor Immune Landscape Following Oncolytic Virotherapy By Single-Cell Rna Sequencing, Divya Ravirala, Guangsheng Pei, Zhongming Zhao, Xiaoliu Zhang

Faculty, Staff and Student Publications

An important mechanism of oncolytic virotherapy in ameliorating cancer immunotherapy is by inducing significant changes in the immune landscape in the tumor microenvironment (TME). Despite this notion and the potential therapeutic implications, a comprehensive analysis of the immune changes in carcinomas induced by virotherapy has not yet been elucidated. We conducted single-cell RNA sequencing analysis on carcinomas treated with an HSV-2-based oncolytic virus to characterize the immunogenic changes in the TME. We specifically analyzed and compared the immune cell composition between viral treated and untreated tumors. We also applied CellChat to analyze the complex interactions among the infiltrated immune cells. …

Peripheral Blood Gene Expression Profiling Shows Predictive Significance For Response To Mycophenolate In Systemic Sclerosis-Related Interstitial Lung Disease, Shervin Assassi, Elizabeth R Volkmann, W Jim Zheng, Xuan Wang, Holly Wilhalme, Marka A Lyons, Michael D Roth, Donald P Tashkin

Faculty, Staff and Student Publications

OBJECTIVES: To characterise the peripheral blood cell (PBC) gene expression changes ensuing from mycophenolate mofetil (MMF) or cyclophosphamide (CYC) treatment and to determine the predictive significance of baseline PBC transcript scores for response to immunosuppression in systemic sclerosis (SSc)-related interstitial lung disease (ILD).

METHODS: PBC RNA samples from baseline and 12-month visits, corresponding to the active treatment period of both arms in Scleroderma Lung Study II, were investigated by global RNA sequencing. Joint models were created to examine the predictive significance of

RESULTS: 134 patients with SSc-ILD (CYC=69 and MMF=65) were investigated. CYC led to an upregulation of erythropoiesis, inflammation …

Does Gender Impact A Diagnosis Of Ankylosing Spondylitis?, Mark C Hwang, Martin Rozycki, David Kauffman, Theresa Arndt, Esther Yi, Michael H Weisman

Faculty, Staff and Student Publications

Objective: The study objective was to explore differences in ankylosing spondylitis (AS) diagnosis experiences between men and women by examining the coding of health events over the 2 years preceding AS diagnosis.

Methods: Claims data (January 2006-April 2019) from the MarketScan databases were examined. Patients who had received two or more AS diagnoses at least 30 days apart and had at least 2 years of insurance enrollment before their first AS diagnosis were analyzed. Men were matched 1:1 to women by age, diagnosis date, insurance type, and enrollment duration. Health events (diagnosis and provider codes) were examined over 2 years …

Exploratory Investigation Of The Plasma Proteome Associated With The Endotheliopathy Of Trauma, Joseph D Krocker, Kyung Hyun Lee, Hanne H Henriksen, Yao-Wei Willa Wang, Erwin M Schoof, Sigurdur T Karvelsson, Óttar Rolfsson, Pär I Johansson, Claudia Pedroza, Charles E Wade

Faculty, Staff and Student Publications

Background: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma.

Methods: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry.

Results: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) …

Nexmif Pathogenic Variants In Individuals Of Korean, Vietnamese, And Mexican Descent, Elizabeth Langley, Laura S Farach, Mary K Koenig, Hope Northrup, David F Rodriguez-Buritica, Kate Mowrey

Faculty, Staff and Student Publications

NEXMIF pathogenic variants have been known to produce a wide spectrum of X-linked intellectual disability (ID) in both males and females. Thus far, few individuals from diverse populations have been described with NEXMIF-related disorders. Herein, we report three individuals with NEXMIF pathogenic variants, the first two are the only males of Korean and Vietnamese descent described with this disorder to our knowledge. The last patient is a Hispanic female who harbors the same pathogenic variant as a previously described Caucasian individual, but with differing clinical presentation. These patients present with many classic symptoms of NEXMIF-related disorders including ID, epilepsy, developmental …

Walking Improvement In Chronic Incomplete Spinal Cord Injury With Exoskeleton Robotic Training (Wise): A Randomized Controlled Trial, Dylan J Edwards, Gail Forrest, Mar Cortes, Margaret M Weightman, Cristina Sadowsky, Shuo-Hsiu Chang, Kimberly Furman, Amy Bialek, Sara Prokup, John Carlow, Leslie Vanhiel, Laura Kemp, Darrell Musick, Marc Campo, Arun Jayaraman

Faculty, Staff and Student Publications

Study design: Clinical trial.

Objective: To demonstrate that a 12-week exoskeleton-based robotic gait training regimen can lead to a clinically meaningful improvement in independent gait speed, in community-dwelling participants with chronic incomplete spinal cord injury (iSCI).

Setting: Outpatient rehabilitation or research institute.

Methods: Multi-site (United States), randomized, controlled trial, comparing exoskeleton gait training (12 weeks, 36 sessions) with standard gait training or no gait training (2:2:1 randomization) in chronic iSCI (>1 year post injury, AIS-C, and D), with residual stepping ability. The primary outcome measure was change in robot-independent gait speed (10-meter walk test, 10MWT) post 12-week intervention. Secondary …

Using Artificial Neural Networks To Predict Intra-Abdominal Abscess Risk Post-Appendectomy, Morouge M Alramadhan, Hassan S Al Khatib, James R Murphy, Kuojen Tsao, Michael L Chang

Faculty, Staff and Student Publications

OBJECTIVE: To determine if artificial neural networks (ANN) could predict the risk of intra-abdominal abscess (IAA) development post-appendectomy.

BACKGROUND: IAA formation occurs in 13.6% to 14.6% of appendicitis cases with "complicated" appendicitis as the most common cause of IAA. There remains inconsistency in describing the severity of appendicitis with variation in treatment with respect to perforated appendicitis.

METHODS: Two "reproducible" ANN with different architectures were developed on demographic, clinical, and surgical information from a retrospective surgical dataset of 1574 patients less than 19 years old classified as either negative (n = 1,328) or positive (n = 246) for IAA post-appendectomy …

Klif-Associated Cytoskeletal Proteins In Trypanosoma Brucei Regulate Cytokinesis By Promoting Cleavage Furrow Positioning And Ingression, Qing Zhou, Huiqing Hu, Ziyin Li

Faculty, Staff and Student Publications

Cytokinesis in the early divergent protozoan Trypanosoma brucei occurs from the anterior cell tip of the new-flagellum daughter toward the nascent posterior end of the old-flagellum daughter of a dividing biflagellated cell. The cleavage furrow ingresses unidirectionally along the preformed cell division fold and is regulated by an orphan kinesin named kinesin localized to the ingressing furrow (KLIF) that localizes to the leading edge of the ingressing furrow. Little is known about how furrow ingression is controlled by KLIF and whether KLIF interacts with and cooperates with other cytokinesis regulatory proteins to promote furrow ingression. Here, we investigated the roles …

A Wireless Millimetric Magnetoelectric Implant For The Endovascular Stimulation Of Peripheral Nerves, Joshua C Chen, Peter Kan, Zhanghao Yu, Fatima Alrashdan, Roberto Garcia, Amanda Singer, C S Edwin Lai, Ben Avants, Scott Crosby, Zhongxi Li, Boshuo Wang, Michelle M Felicella, Ariadna Robledo, Angel V Peterchev, Stefan M Goetz, Jeffrey D Hartgerink, Sunil A Sheth, Kaiyuan Yang, Jacob T Robinson

Faculty, Staff and Student Publications

Implantable bioelectronic devices for the simulation of peripheral nerves could be used to treat disorders that are resistant to traditional pharmacological therapies. However, for many nerve targets, this requires invasive surgeries and the implantation of bulky devices (about a few centimetres in at least one dimension). Here we report the design and in vivo proof-of-concept testing of an endovascular wireless and battery-free millimetric implant for the stimulation of specific peripheral nerves that are difficult to reach via traditional surgeries. The device can be delivered through a percutaneous catheter and leverages magnetoelectric materials to receive data and power through tissue via …

Care Levels For Fetal Therapy Centers, Ahmet A Baschat, Sean B Blackwell, Debnath Chatterjee, James J Cummings, Stephen P Emery, Shinjiro Hirose, Lisa M Hollier, Anthony Johnson, Sarah J Kilpatrick, Francois I Luks, M Kathryn Menard, Lawrence B Mccullough, Julie S Moldenhauer, Anita J Moon-Grady, George B Mychaliska, Michael Narvey, Mary E Norton, Mark D Rollins, Eric D Skarsgard, Kuojen Tsao, Barbara B Warner, Abigail Wilpers, Greg Ryan

Faculty, Staff and Student Publications

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels …