Medicine and Health Sciences Commons^™

Mixcan: A Framework For Cell-Type-Aware Transcriptome-Wide Association Studies With An Application To Breast Cancer, Xiaoyu Song, Jiayi Ji, Joseph H Rothstein, Stacey E Alexeeff, Lori C Sakoda, Adriana Sistig, Ninah Achacoso, Eric Jorgenson, Alice S Whittemore, Robert J Klein, Laurel A Habel, Pei Wang, Weiva Sieh

Faculty, Staff and Student Publications

Human bulk tissue samples comprise multiple cell types with diverse roles in disease etiology. Conventional transcriptome-wide association study approaches predict genetically regulated gene expression at the tissue level, without considering cell-type heterogeneity, and test associations of predicted tissue-level expression with disease. Here we develop MiXcan, a cell-type-aware transcriptome-wide association study approach that predicts cell-type-level expression, identifies disease-associated genes via combination of cell-type-level association signals for multiple cell types, and provides insight into the disease-critical cell type. As a proof of concept, we conducted cell-type-aware analyses of breast cancer in 58,648 women and identified 12 transcriptome-wide significant genes using MiXcan compared …

Association Between E-Cigarette Use Behaviors And Anxiety/Depression Among Black/African American Adults Based On Sexual Identity, David Adzrago, Melissa B Harrell, Kayo Fujimoto, Antwan Jones, J Michael Wilkerson

Faculty, Staff and Student Publications

Limited studies have examined disparities in e-cigarette use among Black/African American adults by sexual identity and whether the relationship between symptoms of anxiety/depression and e-cigarette use varies by sexual identity. We examined the association between e-cigarette use behaviors (never, former, and current use) and anxiety/depression among a nationally representative sample of Black/African American adults who identified as a sexual minority (lesbian/gay, bisexual, and others) or heterosexual individuals. We combined cross-sectional data from the 2011 to 2020 Health Information National Trends Survey (n = 6267), which is a nationally representative data set. We computed weighted e-cigarette use prevalence and multinomial logistic …

Digital Health Interventions To Improve Adolescent Hpv Vaccination: A Systematic Review, Jihye Choi, Irene Tamí-Maury, Paula Cuccaro, Sooyoun Kim, Christine Markham

Faculty, Staff and Student Publications

Digital technologies are being increasingly utilized in healthcare to provide pertinent and timely information for primary prevention, such as vaccination. This study aimed to conduct a systematic review to describe and assess current digital health interventions to promote HPV vaccination among adolescents and parents of adolescents, and to recommend directions for future interventions of this kind. Using appropriate medical subject headings and keywords, we searched multiple databases to identify relevant studies published in English between 1 January 2017 and 31 July 2022. We screened and selected eligible studies for inclusion in the final analysis. We reviewed a total of 24 …

Epigenomic Charting And Functional Annotation Of Risk Loci In Renal Cell Carcinomaepigenomic Charting And Functional Annotation Of Risk Loci In Renal Cell Carcinoma, Amin H Nassar, Sarah Abou Alaiwi, Sylvan C Baca, Elio Adib, Rosario I Corona, Ji-Heui Seo, Marcos A S Fonseca, Sandor Spisak, Talal El Zarif, Viktoria Tisza, David A Braun, Heng Du, Monica He, Abdallah Flaifel, Michel Alchoueiry, Thomas Denize, Sayed G Matar, Andres Acosta, Sachet Shukla, Yue Hou, John Steinharter, Gabrielle Bouchard, Jacob E Berchuck, Edward O'Connor, Connor Bell, Pier Vitale Nuzzo, Gwo-Shu Mary Lee, Sabina Signoretti, Michelle S Hirsch, Mark Pomerantz, Elizabeth Henske, Alexander Gusev, Kate Lawrenson, Toni K Choueiri, David J Kwiatkowski, Matthew L Freedman

Faculty, Staff and Student Publications

While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC. We confirm histology-specific MTFs via immunohistochemistry including a ccRCC-specific TF, BHLHE41. FOXI1 overexpression with knock-down of EPAS1 in the 786-O ccRCC cell line induces transcriptional …

Plasma Cytokines/Chemokines As Predictive Biomarkers For Lymphedema In Breast Cancer Patients, Anna R Vang, Simona F Shaitelman, John C Rasmussen, Wenyaw Chan, Eva M Sevick-Muraca, Melissa B Aldrich

Faculty, Staff and Student Publications

Breast cancer-related lymphedema (BCRL) occurs in ~ 40% of patients after axillary lymph node dissection (ALND), radiation therapy (RT), or chemotherapy. First-line palliative treatment utilizes compression garments and specialized massage. Reparative microsurgeries have emerged as a second-line treatment, yet both compression and surgical therapy are most effective at early stages of LE development. Identifying patients at the highest risk for BCRL would allow earlier, more effective treatment. Perometric arm volume measurements, near-infrared fluorescent lymphatic imaging (NIRF-LI) data, and blood were collected between 2016 and 2021 for 40 study subjects undergoing treatment for breast cancer. Plasma samples were evaluated using MILLIPLEX …

Cost-Effectiveness Analysis Of Overground Robotic Training Versus Conventional Locomotor Training In People With Spinal Cord Injury, Daniel Pinto, Allen W Heinemann, Shuo-Hsiu Chang, Susan Charlifue, Edelle C Field-Fote, Catherine L Furbish, Arun Jayaraman, Candace Tefertiller, Heather B Taylor, Dustin D French

Faculty, Staff and Student Publications

BACKGROUND: Few, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort.

METHODS: A probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight …

Synthesize Heterogeneous Biological Knowledge Via Representation Learning For Alzheimer’S Disease Drug Repurposing, Kang-Lin Hsieh, German Plascencia-Villa, Ko-Hong Lin, George Perry, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Developing drugs for treating Alzheimer's disease has been extremely challenging and costly due to limited knowledge of underlying mechanisms and therapeutic targets. To address the challenge in AD drug development, we developed a multi-task deep learning pipeline that learns biological interactions and AD risk genes, then utilizes multi-level evidence on drug efficacy to identify repurposable drug candidates. Using the embedding derived from the model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, efficacy in preclinical models, population-based treatment effects, and clinical trials. We mechanistically validated the top-ranked candidates in neuronal cells, identifying drug combinations with efficacy in …

A Simple Seir-V Model To Estimate Covid-19 Prevalence And Predict Sars-Cov-2 Transmission Using Wastewater-Based Surveillance Data, Tin Phan, Samantha Brozak, Bruce Pell, Anna Gitter, Amy Xiao, Kristina D Mena, Yang Kuang, Fuqing Wu

Faculty, Staff and Student Publications

Wastewater-based surveillance (WBS) has been widely used as a public health tool to monitor SARS-CoV-2 transmission. However, epidemiological inference from WBS data remains understudied and limits its application. In this study, we have established a quantitative framework to estimate COVID-19 prevalence and predict SARS-CoV-2 transmission through integrating WBS data into an SEIR-V model. We conceptually divide the individual-level viral shedding course into exposed, infectious, and recovery phases as an analogy to the compartments in a population-level SEIR model. We demonstrated that the effect of temperature on viral losses in the sewer can be straightforwardly incorporated in our framework. Using WBS …

Outcomes Of Surgical Treatment For Extradural Benign Primary Spinal Tumors In Patients Younger Than 25 Years: An Ambispective International Multicenter Study, Alexander C Disch, Stefano Boriani, Aron Lazary, Laurence D Rhines, Alessandro Luzzati, Ziya L Gokaslan, Charles G Fisher, Michael G Fehlings, Michelle J Clarke, Dean Chou, Nicole M Germscheid, Klaus-Dieter Schaser, Jeremy J Reynolds, The Ao Spine Knowledge Forum Tumor

Faculty, Staff and Student Publications

Extradural primary spinal tumors were retrospectively analyzed from a prospective database of 1495 cases. All subjects with benign primary tumors under the age of 25 years, who were enrolled between 1990 and 2012 (Median FU was 2.4 years), were identified. Patient- and case-related characteristics were collected and statistically analyzed. Results: 161 patients (66f;95m; age 17.0 ± 4.7 years at time of diagnosis) were identified. The most common tumors were osteoblastomas n = 53 (32.9%), osteoid osteomas n = 45 (28.0%), and aneurysmal bone cysts n = 32 (19.9%). The tumor grade, according to the Enneking Classification S1/S2/S3, was 14/73/74 (8.7/45.3/46.0%), …

Acquired Genomic Alterations On First-Line Chemotherapy With Cetuximab In Advanced Colorectal Cancer: Circulating Tumor Dna Analysis Of The Calgb/Swog-80405 Trial (Alliance), Kanwal Raghav, Fang-Shu Ou, Alan P Venook, Federico Innocenti, Ryan Sun, Heinz-Josef Lenz, Scott Kopetz

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Acquired genomic alterations (Acq-GAs), specifically RAS, BRAF, and EGFR-ectodomain mutations and ERBB2 and MET amplifications, are recognized as major mechanisms of resistance to later-line anti-EGFR-antibody therapy in metastatic colorectal cancer (mCRC). However, data regarding …

Resistance Mechanisms To Anti–Epidermal Growth Factor Receptor Therapy In Ras/Raf Wild-Type Colorectal Cancer Vary By Regimen And Line Of Therapy, Christine M Parseghian, Ryan Sun, Melanie Woods, Stefania Napolitano, Hey Min Lee, Jumanah Alshenaifi, Jason Willis, Shakayla Nunez, Kanwal P Raghav, Van K Morris, John P Shen, Madhulika Eluri, Alexey Sorokin, Preeti Kanikarla, Eduardo Vilar, Marko Rehn, Agnes Ang, Teresa Troiani, Scott Kopetz

Faculty, Staff and Student Publications

Purpose: Acquired resistance to anti-epidermal growth factor receptor (EGFR) inhibitor (EGFRi) therapy in colorectal cancer (CRC) has previously been explained by the model of acquiring new mutations in KRAS/NRAS/EGFR, among other MAPK-pathway members. However, this was primarily on the basis of single-agent EGFRi trials and little is known about the resistance mechanisms of EGFRi combined with effective cytotoxic chemotherapy in previously untreated patients.

Methods: We analyzed paired plasma samples from patients with RAS/BRAF/EGFR wild-type metastatic CRC enrolled in three large randomized trials evaluating EGFRi in the first line in combination with chemotherapy and as a single agent in third …

Substrate Electronics Dominate The Rate Of Reductive Dehalogenation Promoted By The Flavin-Dependent Iodotyrosine Deiodinase, Jeffrey M Carlson, Ayzsa Tannis, Kate R Woodworth, Megan R Reynolds, Neha Shinde, Breanne Anderson, Keivon Hobeheidar, Aisha Praag, Kristen Campbell, Cynthia Carpentieri, Teri Willabus, Elizabeth Burkhardt, Elizabeth Torrone, Kevin P O'Callaghan, Kathryn Miele, Dana Meaney-Delman, Suzanne M Gilboa, Emily O'Malley Olsen, Van T Tong

Faculty, Staff and Student Publications

Despite universal prenatal syphilis screening recommendations and availability of effective antibiotic treatment, syphilis prevalence during pregnancy and the incidence of congenital syphilis have continued to increase in the United States (1,2). Concurrent increases in methamphetamine, injection drug, and heroin use have been described in women with syphilis (3). CDC used data on births that occurred during January 1, 2018-December 31, 2021, from two states (Arizona and Georgia) that participate in the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET) to describe the prevalence of substance use among pregnant persons with syphilis by congenital syphilis pregnancy outcome (defined …

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 …

Hypoxia Truncates And Constitutively Activates The Key Cholesterol Synthesis Enzyme Squalene Monooxygenase, Hudson W Coates, Isabelle M Capell-Hattam, Ellen M Olzomer, Ximing Du, Rhonda Farrell, Hongyuan Yang, Frances L Byrne, Andrew J Brown

Faculty, Staff and Student Publications

Cholesterol synthesis is both energy- and oxygen-intensive, yet relatively little is known of the regulatory effects of hypoxia on pathway enzymes. We previously showed that the rate-limiting and first oxygen-dependent enzyme of the committed cholesterol synthesis pathway, squalene monooxygenase (SM), can undergo partial proteasomal degradation that renders it constitutively active. Here, we show hypoxia is a physiological trigger for this truncation, which occurs through a two-part mechanism: (1) increased targeting of SM to the proteasome via stabilization of the E3 ubiquitin ligase MARCHF6 and (2) accumulation of the SM substrate, squalene, which impedes the complete degradation of SM and liberates …

Integrated Mrna Sequence Optimization Using Deep Learning, Haoran Gong, Jianguo Wen, Ruihan Luo, Yuzhou Feng, Jingjing Guo, Hongguang Fu, Xiaobo Zhou

Faculty, Staff and Student Publications

The coronavirus disease of 2019 pandemic has catalyzed the rapid development of mRNA vaccines, whereas, how to optimize the mRNA sequence of exogenous gene such as severe acute respiratory syndrome coronavirus 2 spike to fit human cells remains a critical challenge. A new algorithm, iDRO (integrated deep-learning-based mRNA optimization), is developed to optimize multiple components of mRNA sequences based on given amino acid sequences of target protein. Considering the biological constraints, we divided iDRO into two steps: open reading frame (ORF) optimization and 5' untranslated region (UTR) and 3'UTR generation. In ORF optimization, BiLSTM-CRF (bidirectional long-short-term memory with conditional random …

Ontologies Applied In Clinical Decision Support System Rules: Systematic Review, Xia Jing, Hua Min, Yang Gong, Paul Biondich, David Robinson, Timothy Law, Christian Nohr, Arild Faxvaag, Lior Rennert, Nina Hubig, Ronald Gimbel

Faculty, Staff and Student Publications

BACKGROUND: Clinical decision support systems (CDSSs) are important for the quality and safety of health care delivery. Although CDSS rules guide CDSS behavior, they are not routinely shared and reused.

OBJECTIVE: Ontologies have the potential to promote the reuse of CDSS rules. Therefore, we systematically screened the literature to elaborate on the current status of ontologies applied in CDSS rules, such as rule management, which uses captured CDSS rule usage data and user feedback data to tailor CDSS services to be more accurate, and maintenance, which updates CDSS rules. Through this systematic literature review, we aim to identify the frontiers …

Impact Of Adherence To Procalcitonin Antibiotic Prescribing Guideline Recommendations For Low Procalcitonin Levels On Antibiotic Use, Brian E Malley, Jonathan G Yabes, Elizabeth Gimbel, Chung-Chou H Chang, Donald M Yealy, Michael J Fine, Derek C Angus, David T Huang, Proact Investigators

Faculty, Staff and Student Publications

BACKGROUND: The Procalcitonin Antibiotic Consensus Trial (ProACT) found provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians did not reduce antibiotic use. Possible reasons include clinician reluctance to follow the guideline, with an observed 64.8% adherence rate. In this study we sought to determine the threshold adherence rate for reduction in antibiotic use, and to explore opportunities to increase adherence.

METHODS: This study is a retrospective analysis of ProACT data. ProACT randomized 1656 patients presenting to 14 U.S. hospitals with suspected lower respiratory tract infection to usual care or provision of procalcitonin assay results and an antibiotic prescribing guideline …

Control Of Craniofacial Development By The Collagen Receptor, Discoidin Domain Receptor 2, Fatma F Mohamed, Chunxi Ge, Shawn A Hallett, Alec C Bancroft, Randy T Cowling, Noriaki Ono, Abdul-Aziz Binrayes, Barry Greenberg, Benjamin Levi, Vesa M Kaartinen, Renny T Franceschi

Faculty, Staff and Student Publications

Development of the craniofacial skeleton requires interactions between progenitor cells and the collagen-rich extracellular matrix (ECM). The mediators of these interactions are not well-defined. Mutations in the discoidin domain receptor 2 gene (DDR2), which encodes a non-integrin collagen receptor, are associated with human craniofacial abnormalities, such as midface hypoplasia and open fontanels. However, the exact role of this gene in craniofacial morphogenesis is not known. As will be shown, Ddr2-deficient mice exhibit defects in craniofacial bones including impaired calvarial growth and frontal suture formation, cranial base hypoplasia due to aberrant chondrogenesis and delayed ossification at growth plate …

Ultrasound Assessment Of Spastic Muscles In Ambulatory Chronic Stroke Survivors Reveals Function-Dependent Changes, Javier González-Buonomo, Alexander H Pham, Jaskiran Ghuman, Aila Malik, Nuray Yozbatiran, Gerard E Francisco, Walter R Frontera, Sheng Li

Faculty, Staff and Student Publications

OBJECTIVE: To correlate ultrasound characteristics of spastic muscles with clinical and functional measurements in chronic stroke survivors.

METHODS: Ultrasound assessment and clinical and functional assessments were performed in 28 ambulatory stroke survivors (12 females, mean age 57.8 ± 11.8 years, 76 ± 45 months after stroke).

RESULTS: Muscle thickness in the affected side was decreased compared with the contralateral side (p < 0.001). The decrease was more evident in the upper limb muscles. On the affected side, the modified Heckmatt scale score was lowest (closer to normal) in the rectus femoris (RF) muscle compared with other muscles (biceps brachii (BB), flexor carpi ulnaris (FCU) and medial gastrocnemius (MG)). Muscle thickness and echogenicity of spastic muscles did not correlate with spasticity, as measured with the modified Ashworth scale (MAS), Fugl-Meyer motor assessment scores, age, or time since stroke. There was a significant negative correlation between grip strength and percentage decrease in muscle thickness for the spastic FCU muscle (r = -0.49, p = 0.008). RF muscle thickness correlated with ambulatory function (Timed Up and Go test (r = 0.44, p = 0.021) and 6-metre walk test (r = 0.41, p = 0.032)). There was no significant correlation between echogenicity and functional assessments Conclusion: Ambulatory chronic stroke survivors had function-dependent changes in muscle thickness on the affected side. Muscle thickness and echogenicity of spastic muscles did not correlate with spasticity, Fugl-Meyer motor assessment scores, age, or time since stroke.

Cortical Connectomic Mediations On Gamma Band Synchronization In Schizophrenia, Xiaoming Du, Stephanie Hare, Ann Summerfelt, Bhim M Adhikari, Laura Garcia, Wyatt Marshall, Peng Zan, Mark Kvarta, Eric Goldwaser, Heather Bruce, Si Gao, Hemalatha Sampath, Peter Kochunov, Jonathan Z Simon, L Elliot Hong

Faculty, Staff and Student Publications

Aberrant gamma frequency neural oscillations in schizophrenia have been well demonstrated using auditory steady-state responses (ASSR). However, the neural circuits underlying 40 Hz ASSR deficits in schizophrenia remain poorly understood. Sixty-six patients with schizophrenia spectrum disorders and 85 age- and gender-matched healthy controls completed one electroencephalography session measuring 40 Hz ASSR and one imaging session for resting-state functional connectivity (rsFC) assessments. The associations between the normalized power of 40 Hz ASSR and rsFC were assessed via linear regression and mediation models. We found that rsFC among auditory, precentral, postcentral, and prefrontal cortices were positively associated with 40 Hz ASSR in …

Circadian Rhythms As Modulators Of Brain Health During Development And Throughout Aging, Rachel Van Drunen, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

The circadian clock plays a prominent role in neurons during development and throughout aging. This review covers topics pertinent to the role of 24-h rhythms in neuronal development and function, and their tendency to decline with aging. Pharmacological or behavioral modification that augment the function of our internal clock may be central to decline of cognitive disease and to future chronotherapy for aging-related diseases of the central nervous system.

Long-Term Bidirectional Association Between Asthma And Attention Deficit Hyperactivity Disorder: A Big Data Cohort Study, Hye Jin Park, Young Hyeon Kim, Da Ye Na, Seong Won Jeong, Min Gyu Lee, Jong-Hwan Lee, Yun Na Yang, Min Gu Kang, Sang Woo Yeom, Jong Seung Kim

Faculty, Staff and Student Publications

BACKGROUND: Previous studies have argued that attention deficit hyperactivity disorder (ADHD) is associated with asthma. However, reliable evidence to verify this association has not yet been reported.

OBJECTIVES: To investigate the bidirectional association between asthma and ADHD through a 12-year big data cohort study.

METHODS: The independent variable group was extracted from 3.5 million individuals randomly sampled by the National Health Insurance Service (NHIS). In Study 1, the incidence of ADHD according to asthma was evaluated, while in Study 2, the incidence of asthma according to ADHD was analyzed. Propensity score (PS) matching with several variables was used to obtain …

A Comprehensive Assessment Of Cell Type-Specific Differential Expression Methods In Bulk Data, Guanqun Meng, Wen Tang, Emina Huang, Ziyi Li, Hao Feng

Faculty, Staff and Student Publications

Accounting for cell type compositions has been very successful at analyzing high-throughput data from heterogeneous tissues. Differential gene expression analysis at cell type level is becoming increasingly popular, yielding biomarker discovery in a finer granularity within a particular cell type. Although several computational methods have been developed to identify cell type-specific differentially expressed genes (csDEG) from RNA-seq data, a systematic evaluation is yet to be performed. Here, we thoroughly benchmark six recently published methods: CellDMC, CARseq, TOAST, LRCDE, CeDAR and TCA, together with two classical methods, csSAM and DESeq2, for a comprehensive comparison. We aim to systematically evaluate the performance …

Ccsynergy: An Integrative Deep-Learning Framework Enabling Context-Aware Prediction Of Anti-Cancer Drug Synergy, Sayed-Rzgar Hosseini, Xiaobo Zhou

Faculty, Staff and Student Publications

Combination therapy is a promising strategy for confronting the complexity of cancer. However, experimental exploration of the vast space of potential drug combinations is costly and unfeasible. Therefore, computational methods for predicting drug synergy are much needed for narrowing down this space, especially when examining new cellular contexts. Here, we thus introduce CCSynergy, a flexible, context aware and integrative deep-learning framework that we have established to unleash the potential of the Chemical Checker extended drug bioactivity profiles for the purpose of drug synergy prediction. We have shown that CCSynergy enables predictions of superior accuracy, remarkable robustness and improved context generalizability …

Dynamic Imine Bonding Facilitates Mannan Release From A Nanofibrous Peptide Hydrogel, Brett H Pogostin, Gabriel Saenz, Carson C Cole, Erin M Euliano, Jeffrey D Hartgerink, Kevin J Mchugh

Faculty, Staff and Student Publications

Recently, there has been increased interest in using mannan as an immunomodulatory bioconjugate. Despite notable immunological and functional differences between the reduced (R-Man) and oxidized (O-Man) forms of mannan, little is known about the impact of mannan oxidation state on its in vivo persistence or its potential controlled release from biomaterials that may improve immunotherapeutic or prophylactic efficacy. Here, we investigate the impact of oxidation state on the in vitro and in vivo release of mannan from a biocompatible and immunostimulatory multidomain peptide hydrogel, K2(SL)6K2 (abbreviated as K2), that has been previously used for the controlled release of protein and …

Multisite Evaluation Of Prediction Models For Emergency Department Crowding Before And During The Covid-19 Pandemic, Ari J Smith, Brian W Patterson, Michael S Pulia, John Mayer, Rebecca J Schwei, Radha Nagarajan, Frank Liao, Manish N Shah, Justin J Boutilier

Faculty, Staff and Student Publications

OBJECTIVE: To develop a machine learning framework to forecast emergency department (ED) crowding and to evaluate model performance under spatial and temporal data drift.

MATERIALS AND METHODS: We obtained 4 datasets, identified by the location: 1-large academic hospital and 2-rural hospital, and time period: pre-coronavirus disease (COVID) (January 1, 2019-February 1, 2020) and COVID-era (May 15, 2020-February 1, 2021). Our primary target was a binary outcome that is equal to 1 if the number of patients with acute respiratory illness that were ED boarding for more than 4 h was above a prescribed historical percentile. We trained a random forest …

Multimodality Annotated Hepatocellular Carcinoma Data Set Including Pre- And Post-Tace With Imaging Segmentation, Ahmed W Moawad, Ali Morshid, Ahmed M Khalaf, Mohab M Elmohr, John D Hazle, David Fuentes, Mohamed Badawy, Ahmed O Kaseb, Manal Hassan, Armeen Mahvash, Janio Szklaruk, Aliyya Qayyum, Abdelrahman Abusaif, William C Bennett, Tracy S Nolan, Brittney Camp, Khaled M Elsayes

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm, and its incidence has doubled over the past two decades owing to increasing risk factors. Despite surveillance, most HCC cases are diagnosed at advanced stages and can only be treated using transarterial chemo-embolization (TACE) or systemic therapy. TACE failure may occur with incidence reaching up to 60% of cases, leaving patients with a financial and emotional burden. Radiomics has emerged as a new tool capable of predicting tumor response to TACE from pre-procedural computed tomography (CT) studies. This data report defines the HCC-TACE data collection of confirmed HCC patients who …

The Safety Of Appropriate Use Of Over-The-Counter Proton Pump Inhibitors: An Evidence-Based Review And Delphi Consensus, Wilfredo De Jesús-Rojas, Jesús Meléndez-Montañez, José Muñiz-Hernández, André Marra-Nazario, Francisco Alvarado-Huerta, Arnaldo Santos-López, Marcos J Ramos-Benitez, Ricardo A Mosquera

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The radial spoke head protein 4 homolog A (RSPH4A) gene is one of more than 50 genes that cause Primary ciliary dyskinesia (PCD), a rare genetic ciliopathy. Genetic mutations in the RSPH4A gene alter an important protein structure involved in ciliary pathogenesis. Radial spoke proteins, such as RSPH4A, have been conserved across multiple species. In humans, ciliary function deficiency caused by RSPH4A pathogenic variants results in a clinical phenotype characterized by recurrent oto-sino-pulmonary infections. More than 30 pathogenic RSPH4A genetic variants have been associated with PCD. In Puerto Rican Hispanics, a founder mutation (RSPH4A (c.921+3_921+6delAAGT (intronic)) has …

Met Amplification As A Resistance Driver To Tki Therapies In Lung Cancer: Clinical Challenges And Opportunities, Kang Qin, Lingzhi Hong, Jianjun Zhang, Xiuning Le

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Targeted therapy has emerged as an important pillar for the standard of care in oncogene-driven non-small cell lung cancer (NSCLC), which significantly improved outcomes of patients whose tumors harbor oncogenic driver mutations. However, tumors eventually develop resistance to targeted drugs, and mechanisms of resistance can be diverse.

Wrapper-Based Deep Feature Optimization For Activity Recognition In The Wearable Sensor Networks Of Healthcare Systems, Karam Kumar Sahoo, Raghunath Ghosh, Saurav Mallik, Arup Roy, Pawan Kumar Singh, Zhongming Zhao

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The Human Activity Recognition (HAR) problem leverages pattern recognition to classify physical human activities as they are captured by several sensor modalities. Remote monitoring of an individual's activities has gained importance due to the reduction in travel and physical activities during the pandemic. Research on HAR enables one person to either remotely monitor or recognize another person's activity via the ubiquitous mobile device or by using sensor-based Internet of Things (IoT). Our proposed work focuses on the accurate classification of daily human activities from both accelerometer and gyroscope sensor data after converting into spectrogram images. The feature extraction process follows …