Medicine and Health Sciences Commons^™

Phosphorylation And Stabilization Of Pd-L1 By Ck2 Suppresses Dendritic Cell Function, Xixi Zhao, Yongkun Wei, Yu-Yi Chu, Yintao Li, Jung-Mao Hsu, Zhou Jiang, Chunxiao Liu, Jennifer L Hsu, Wei-Chao Chang, Riyao Yang, Li-Chuan Chan, Jingkun Qu, Shuqun Zhang, Haoqiang Ying, Dihua Yu, Mien-Chie Hung

Faculty, Staff and Student Publications

UNLABELLED: Targeting immune checkpoints such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has transformed cancer treatment, with durable clinical responses across a wide range of tumor types. However, a high percentage of patients fail to respond to anti-PD-1/PD-L1 treatment. A greater understanding of PD-L1 regulation is critical to improving the clinical response rate of PD-1/PD-L1 blockade. Here, we demonstrate that PD-L1 is phosphorylated and stabilized by casein kinase 2 (CK2) in cancer and dendritic cells (DC). Phosphorylation of PD-L1 at Thr285 and Thr290 by CK2 disrupted PD-L1 binding with speckle-type POZ protein, an adaptor …

Quantifying Concordant Genetic Effects Of De Novo Mutations On Multiple Disorders, Hanmin Guo, Lin Hou, Yu Shi, Sheng Chih Jin, Xue Zeng, Boyang Li, Richard P Lifton, Martina Brueckner, Hongyu Zhao, Qiongshi Lu

2020-Current year OA Pubs

Exome sequencing on tens of thousands of parent-proband trios has identified numerous deleterious de novo mutations (DNMs) and implicated risk genes for many disorders. Recent studies have suggested shared genes and pathways are enriched for DNMs across multiple disorders. However, existing analytic strategies only focus on genes that reach statistical significance for multiple disorders and require large trio samples in each study. As a result, these methods are not able to characterize the full landscape of genetic sharing due to polygenicity and incomplete penetrance. In this work, we introduce EncoreDNM, a novel statistical framework to quantify shared genetic effects between …

Prefrontal Cortex Supports Speech Perception In Listeners With Cochlear Implants, Arefeh Sherafati, Noel Dwyer, Aahana Bajracharya, Mahlega Samira Hassanpour, Adam T Eggebrecht, Jill B Firszt, Joseph P Culver, Jonathan E Peelle

2020-Current year OA Pubs

Cochlear implants are neuroprosthetic devices that can restore hearing in people with severe to profound hearing loss by electrically stimulating the auditory nerve. Because of physical limitations on the precision of this stimulation, the acoustic information delivered by a cochlear implant does not convey the same level of acoustic detail as that conveyed by normal hearing. As a result, speech understanding in listeners with cochlear implants is typically poorer and more effortful than in listeners with normal hearing. The brain networks supporting speech understanding in listeners with cochlear implants are not well understood, partly due to difficulties obtaining functional neuroimaging …

What Is The State Of Children's Participation In Qualitative Research On Health Interventions?: A Scoping Study, Jean M Hunleth, Julie S Spray, Corey Meehan, Colleen Walsh Lang, Janet Njelesani

2020-Current year OA Pubs

BACKGROUND: Children are the focus of numerous health interventions throughout the world, yet the extent of children's meaningful participation in research that informs the adaptation, implementation, and evaluation of health interventions is not known. We examine the type, extent, and meaningfulness of children's participation in research in qualitative health intervention research.

METHOD: A scoping study was conducted of qualitative published research with children (ages 6-11 years) carried out as part of health intervention research. Following Arksey and O'Malley's scoping study methodology and aligned with the PRISMA-ScR guidelines on the reporting of scoping reviews, the authors searched, charted, collated, and summarized …

De Novo Fzr1 Loss-Of-Function Variants Cause Developmental And Epileptic Encephalopathies, Sathiya N Manivannan, Jolien Roovers, Noor Smal, Candace T Myers, Dilsad Turkdogan, Filip Roelens, Oguz Kanca, Hyung-Lok Chung, Tasja Scholz, Katharina Hermann, Tatjana Bierhals, Hande S Caglayan, Hannah Stamberger, Mae Working Group Of Euroepinomics Res Consortium, Heather Mefford, Peter De Jonghe, Shinya Yamamoto, Sarah Weckhuysen, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

FZR1, which encodes the Cdh1 subunit of the anaphase-promoting complex, plays an important role in neurodevelopment by regulating the cell cycle and by its multiple post-mitotic functions in neurons. In this study, evaluation of 250 unrelated patients with developmental and epileptic encephalopathies and a connection on GeneMatcher led to the identification of three de novo missense variants in FZR1. Whole-exome sequencing in 39 patient-parent trios and subsequent targeted sequencing in an additional cohort of 211 patients was performed to identify novel genes involved in developmental and epileptic encephalopathy. Functional studies in Drosophila were performed using three different mutant alleles of …

Molecular Imaging Phenotyping For Selecting And Monitoring Radioligand Therapy Of Neuroendocrine Neoplasms, Amir Iravani, Ashwin Singh Parihar, Timothy Akhurst, Rodney J Hicks

2020-Current year OA Pubs

Neuroendocrine neoplasia (NEN) is an umbrella term that includes a widely heterogeneous disease group including well-differentiated neuroendocrine tumours (NETs), and aggressive neuroendocrine carcinomas (NECs). The site of origin of the NENs is linked to the intrinsic tumour biology and is predictive of the disease course. It is understood that NENs demonstrate significant biologic heterogeneity which ultimately translates to widely varying clinical presentations, disease course and prognosis. Thus, significant emphasis is laid on the pre-therapy evaluation of markers that can help predict tumour behavior and dynamically monitors the response during and after treatment. Most well-differentiated NENs express somatostatin receptors (SSTRs) which …

Top-Ld: A Tool To Explore Linkage Disequilibrium With Topmed Whole-Genome Sequence Data, Le Huang, Jonathan D Rosen, Quan Sun, Jiawen Chen, Marsha M Wheeler, Ying Zhou, Yuan-I Min, Charles Kooperberg, Matthew P Conomos, Adrienne M Stilp, Stephen S Rich, Jerome I Rotter, Ani Manichaikul, Ruth J F Loos, Eimear E Kenny, Thomas W Blackwell, Albert V Smith, Goo Jun, Fritz J Sedlazeck, Ginger Metcalf, Eric Boerwinkle, Laura M Raffield, Alex P Reiner, Paul L Auer, Yun Li

Faculty, Staff and Student Publications

Current publicly available tools that allow rapid exploration of linkage disequilibrium (LD) between markers (e.g., HaploReg and LDlink) are based on whole-genome sequence (WGS) data from 2,504 individuals in the 1000 Genomes Project. Here, we present toP-LD, an online tool to explore LD inferred with high-coverage (∼30×) WGS data from 15,578 individuals in the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. toP-LD provides a significant upgrade compared to current LD tools, as the toPMed WGS data provide a more comprehensive representation of genetic variation than the 1000 Genomes data, particularly for rare variants and in the specific populations that we …

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 …

Identification Of Functional Heterogeneity Of Carcinoma-Associated Fibroblasts With Distinct Il6-Mediated Therapy Resistance In Pancreatic Cancer, Kathleen M Mcandrews, Yang Chen, J Kebbeh Darpolor, Xiaofeng Zheng, Sujuan Yang, Julienne L Carstens, Bingrui Li, Huamin Wang, Toru Miyake, Pedro Correa De Sampaio, Michelle L Kirtley, Mariangela Natale, Chia-Chin Wu, Hikaru Sugimoto, Valerie S Lebleu, Raghu Kalluri

Faculty, Staff and Student Publications

The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of fibroblasts as part of the host response to cancer. Employing single-cell RNA-sequencing, multiplex immunostaining, and several genetic mouse models, we identify carcinoma-associated fibroblasts (CAFs) with opposing functions in PDAC progression. Depletion of fibroblast activation protein (FAP)+ CAFs results in increased survival, in contrast to depletion of alpha smooth muscle actin (αSMA)+ CAFs that leads to decreased survival. Tumor-promoting FAP+ CAFs (TP-CAFs) and tumor-restraining αSMA+ CAFs (TR-CAFs) differentially regulate cancer-associated pathways and accumulation of Tregs. Improved efficacy of gemcitabine is observed when IL-6 is deleted from αSMA+ CAFs …

Macrophages Disseminate Pathogen Associated Molecular Patterns Through The Direct Extracellular Release Of The Soluble Content Of Their Phagolysosomes, Catherine J Greene, Jenny A Nguyen, Samuel M Cheung, Corey R Arnold, Dale R Balce, Ya Ting Wang, Adrian Soderholm, Neil Mckenna, Devin Aggarwal, Rhiannon I Campden, Benjamin W Ewanchuk, Herbert W Virgin, Robin M Yates

2020-Current year OA Pubs

Recognition of pathogen-or-damage-associated molecular patterns is critical to inflammation. However, most pathogen-or-damage-associated molecular patterns exist within intact microbes/cells and are typically part of non-diffusible, stable macromolecules that are not optimally immunostimulatory or available for immune detection. Partial digestion of microbes/cells following phagocytosis potentially generates new diffusible pathogen-or-damage-associated molecular patterns, however, our current understanding of phagosomal biology would have these molecules sequestered and destroyed within phagolysosomes. Here, we show the controlled release of partially-digested, soluble material from phagolysosomes of macrophages through transient, iterative fusion-fission events between mature phagolysosomes and the plasma membrane, a process we term eructophagy. Eructophagy is most active …

Optimizing Allocation Of Curricular Content Across The Undergraduate & Graduate Medical Education Continuum, Samara B Ginzburg, Margaret M Hayes, Brittany L Ranchoff, Eva Aagaard, Katharyn M Atkins, Michelle Barnes, Jennifer B Soep, Andrew C Yacht, Erik K Alexander, Richard M Schwartzstein

2020-Current year OA Pubs

BACKGROUND: Medical educators struggle to incorporate socio-cultural topics into crowded curricula. The "continuum of learning" includes undergraduate and graduate medical education. Utilizing an exemplar socio-cultural topic, we studied the feasibility of achieving expert consensus among two groups of faculty (experts in medical education and experts in social determinants of health) on which aspects of the topic could be taught during undergraduate versus graduate medical education.

METHODS: A modified Delphi method was used to generate expert consensus on which learning objectives of social determinants of health are best taught at each stage of medical education. Delphi respondents included experts in medical …

Synchronized Diaphragmatic Stimulation: A Case Report Of A Novel Extra-Cardiac Intervention For Chronic Heart Failure., Lee R Goldberg, Ana Jorbenadze, Tamaz Shaburishvilli, Michael Mirro Md, Marat Fudim, Michel Zuber, Simon F Stämpfli, Felix C Tanner, Paul Erne, John G Cleland

Parkview Heart Institute

Synchronized diaphragmatic stimulation (SDS) is a novel extra-cardiac device-based therapy for symptomatic heart failure with reduced ejection fraction. SDS provides imperceptible chronic stimulation of the diaphragm through a laparoscopically implanted system consisting of an implantable pulse generator and two sensing/stimulating leads affixed to the inferior surface of the diaphragm delivering imperceptible R-wave gaited pulses that alter intrathoracic pressure improving ventricular filling and cardiac output. We describe, in a man with a history of myocardial infarctions resulting in heart failure and persistent New York Heart Association Class III symptoms despite standard therapies, the successful implantation of SDS resulting in improved quality …

The Rd-Connect Genome-Phenome Analysis Platform: Accelerating Diagnosis, Research, And Gene Discovery For Rare Diseases., Steven Laurie, Davide Piscia, Leslie Matalonga, Alberto Corvó, Marcos Fernández-Callejo, Carles Garcia-Linares, Carles Hernandez-Ferrer, Cristina Luengo, Inés Martínez, Anastasios Papakonstantinou, Daniel Picó-Amador, Joan Protasio, Rachel Thompson, Raul Tonda, Mònica Bayés, Gemma Bullich, Jordi Camps-Puchadas, Ida Paramonov, Jean-Rémi Trotta, Angel Alonso, Marcella Attimonelli, Christophe Béroud, Virginie Bros-Facer, Orion J Buske, Andrés Cañada-Pallarés, José M Fernández, Mats G Hansson, Rita Horvath, Julius O B Jacobsen, Rajaram Kaliyaperumal, Séverine Lair-Préterre, Luana Licata, Pedro Lopes, Estrella López-Martín, Deborah Mascalzoni, Lucia Monaco, Luis A Pérez-Jurado, Manuel Posada De La Paz, Jordi Rambla, Ana Rath, Olaf Riess, Peter N Robinson, David Salgado, Damian Smedley, Dylan Spalding, Peter A C 'T Hoen, Ana Töpf, Irina Zaharieva, Holm Graessner, Ivo G Gut, Hanns Lochmüller, Sergi Beltran

Faculty Research 2022

Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is …

Prenatal Phenotyping: A Community Effort To Enhance The Human Phenotype Ontology., Ferdinand Dhombres, Patricia Morgan, Bimal P Chaudhari, Isabel Filges, Teresa N Sparks, Pablo Lapunzina, Tony Roscioli, Umber Agarwal, Shagun Aggarwal, Claire Beneteau, Pilar Cacheiro, Leigh Carmody, Sophie Collardeau-Frachon, Esther A Dempsey, Andreas Dufke, Michael Henri Duyzend, Mirna El Ghosh, Jessica L Giordano, Ragnhild Glad, Ieva Grinfelde, Dominic G Iliescu, Markus S Ladewig, Monica C Munoz-Torres, Marzia Pollazzon, Francesca Clementina Radio, Carlota Rodo, Raquel Gouveia Silva, Damian Smedley, Jagadish Chandrabose Sundaramurthi, Sabrina Toro, Irene Valenzuela, Nicole A Vasilevsky, Ronald J Wapner, Roni Zemet, Melissa A Haendel, Peter N Robinson

Faculty Research 2022

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and …

Analysis Of Blood Type For Sars-Cov-2 And Correlation For Disease Acquisition In Various Sociodemographic Groups Including Women Of Childbearing Age., Maria L. Vacca, Nikunj Vyas, Joshua Banks, Elaine Joyce, Cindy Hou, Benjamin E. Leiby, Stefanie Deangelo, Todd P. Levin, Autum Shingler-Nace, Marilyn Mapp, Ashlee Hiester, Jonathan H. Coughenour

Division of Infectious Diseases and Environmental Medicine Faculty Papers

BACKGROUND: Multiple studies have occurred to determine if a patient's blood type, Rhesus factor (Rh), and sociodemographic attributes contribute to contracting SARS-CoV-2. True association remains unknown.

METHODS: Inclusion criteria included in-patients who were tested for SARS-CoV-2 with blood type assessed. Study endpoints combined ABO, Rh and all-cause inpatient mortality (ACIM) with testing positivity. Pregnancy status was one of several secondary endpoints evaluated. A logistic regression analysis was used to estimate association.

RESULTS: Of the 27,662 patients who met inclusion criteria, Type A blood was associated with increased positivity [1.01 (1.0-1.21), P = .03]. Type B [1.10 (0.99-1.23), P = .08] …

Pediatric Nemaline Myopathy: A Systematic Review Using Individual Patient Data, Briana Christophers, Michael A Lopez, Vandana A Gupta, Hannes Vogel, Mary Baylies

Faculty, Staff and Student Publications

Nemaline myopathy is a skeletal muscle disease that affects 1 in 50 000 live births. The objective of this study was to develop a narrative synthesis of the findings of a systematic review of the latest case descriptions of patients with NM. A systematic search of MEDLINE, Embase, CINAHL, Web of Science, and Scopus was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the keywords pediatric, child, NM, nemaline rod, and rod myopathy. Case studies focused on pediatric NM and published in English between January 1, 2010, and December 31, …

Use Of Physiologically-Based Pharmacokinetic Modeling To Inform Dosing Of The Opioid Analgesics Fentanyl And Methadone In Children With Obesity, Jacqueline G. Gerhart, Fernando O. Carreño, Jennifer L. Ford, Andrea N. Edginton, Eliana M. Perrin, Kevin M. Watt, William J. Muller, Andrew M. Atz, Amira Al-Uzri, Paula Delmore, Daniel Gonzalez, Catherine Sherwin

Pediatrics Faculty Publications

Obesity is an increasingly alarming public health threat, with nearly 20% of children classified as obese in the United States today. Children with obesity are commonly prescribed the opioids fentanyl and methadone, and accurate dosing is critical to reducing the risk of serious adverse events associated with overexposure. However, pharmacokinetic studies in children with obesity are challenging to conduct, so there is limited information to guide fentanyl and methadone dosing in these children. To address this clinical knowledge gap, physiologically-based pharmacokinetic models of fentanyl and methadone were developed in adults and scaled to children with and without obesity to explore …

Analysis Of Lung Cancer Screening By Race After Uspstf Expansion Of Screening Eligibility In 2021., Christine S Shusted, Nathaniel R Evans, Gregory C Kane, Hee-Soon Juon, Julie A Barta

Department of Medicine Faculty Papers

This cross-sectional study examines differences among individuals deemed eligible for lung cancer screening under USPSTF 2013 vs under USPTSF 2021 guidelines.

Prescriptions For Potentially Inappropriate Medications From The Beers Criteria Among Older Adults Hospitalized For Heart Failure, Diana Jaber, Fabian Vargas, Linh Nguyen, Joanna Ringel, Kate Zarzuela, Mahad Musse, Min Ji Kwak, Emily B Levitan, Mathew S Maurer, Mark S Lachs, Monika M Safford, Parag Goyal

Faculty, Staff and Student Publications

BACKGROUND: We sought to better understand patterns of potentially inappropriate medications (PIMs) from the Beers criteria among older adults hospitalized with heart failure (HF). This observational study of hospitalizations was derived from the geographically diverse REasons for Geographic and Racial Differences in Stroke cohort.

METHODS AND RESULTS: We examined participants aged 65 years and older with an expert-adjudicated hospitalization for HF. The Beers criteria medications were abstracted from medical records. The prevalence of PIMs was 61.1% at admission and 64.0% at discharge. Participants were taking a median of 1 PIM (interquartile range [IQR] 0-1 PIM) at hospital admission and a …

Recurrent Neural Network Models (Covrnn) For Predicting Outcomes Of Patients With Covid-19 On Admission To Hospital: Model Development And Validation Using Electronic Health Record Data, Laila Rasmy, Masayuki Nigo, Bijun Sai Kannadath, Ziqian Xie, Bingyu Mao, Khush Patel, Yujia Zhou, Wanheng Zhang, Angela Ross, Hua Xu, Degui Zhi

Faculty, Staff and Student Publications

BACKGROUND: Predicting outcomes of patients with COVID-19 at an early stage is crucial for optimised clinical care and resource management, especially during a pandemic. Although multiple machine learning models have been proposed to address this issue, because of their requirements for extensive data preprocessing and feature engineering, they have not been validated or implemented outside of their original study site. Therefore, we aimed to develop accurate and transferrable predictive models of outcomes on hospital admission for patients with COVID-19.

METHODS: In this study, we developed recurrent neural network-based models (CovRNN) to predict the outcomes of patients with COVID-19 by use …

Gdf5+ Chondroprogenitors Derived From Human Pluripotent Stem Cells Preferentially Form Permanent Chondrocytes, Azim Pothiawala, Berke E Sahbazoglu, Bryan K Ang, Nadine Matthias, Guangsheng Pei, Qing Yan, Brian R Davis, Johnny Huard, Zhongming Zhao, Naoki Nakayama

Faculty, Staff and Student Publications

It has been established in the mouse model that during embryogenesis joint cartilage is generated from a specialized progenitor cell type, distinct from that responsible for the formation of growth plate cartilage. We recently found that mesodermal progeny of human pluripotent stem cells gave rise to two types of chondrogenic mesenchymal cells in culture: SOX9+ and GDF5+ cells. The fast-growing SOX9+ cells formed in vitro cartilage that expressed chondrocyte hypertrophy markers and readily underwent mineralization after ectopic transplantation. In contrast, the slowly growing GDF5+ cells derived from SOX9+ cells formed cartilage that tended to express low to undetectable levels of …

External Validation Of A Laboratory Prediction Algorithm For The Reduction Of Unnecessary Labs In The Critical Care Setting, Linda T Li, Tongtong Huang, Elmer V Bernstam, Xiaoqian Jiang

Faculty, Staff and Student Publications

BACKGROUND: Unnecessary laboratory tests contribute to iatrogenic harm and are a major source of waste in the health care system. We previously developed a machine learning algorithm to help clinicians identify unnecessary laboratory tests, but it has not been externally validated. In this study, we externally validate our machine learning algorithm.

METHODS: To externally validate the machine learning algorithm that was originally trained on the Medical Information Mart for Intensive Care (MIMIC) III database, we tested the algorithm in a separate institution. We identified and abstracted data for all patients older than 18 years admitted to the intensive care unit …

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 …

Adopting Clinical Practice Guidelines For Pharmacologic Management Of Acute Spinal Cord Injury From A Developed World Context To A Developing Global Region, Seyed Behnam Jazayeri, Seyed Farzad Maroufi, Zahra Ghodsi, Heshmatollah Ghawami, Ahmad Pourrashidi, Abbas Amirjamshidi, Mojtaba Mojtahedzadeh, Jalil Arabkheradmand, Farzin Farahbakhsh, Maryam Shabany, Morteza Faghih-Jouibari, Michael G Fehlings, Brian K Kwon, James Harrop, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

Background: Proper utilization of high-quality clinical practice guidelines (CPGs) eliminates the dependence of patients' outcomes on the ability and knowledge of "individual" health care providers and reduces unwarranted variation in care. The aim of this study was to adapt/adopt two CPGs for pharmacologic management of acute spinal cord injury (SCI) using guideline adaptation methods.

Methods: This study was conducted based on the ADAPTE process. Following establishment of an organizing committee and choosing the health topics, we appraised the quality of the CPGs using the Appraisal of Clinical Guidelines for Research & Evaluation II (AGREE II). Then, the authors extracted and …

Mutation Spectrum Of Congenital Heart Disease In A Consanguineous Turkish Population, Weilai Dong, Hande Kaymakcalan, Sheng Chih Jin, Nicholas S Diab, Cansaran Tanıdır, Ali Seyfi Yalim Yalcin, A Gulhan Ercan-Sencicek, Shrikant Mane, Murat Gunel, Richard P Lifton, Kaya Bilguvar, Martina Brueckner

2020-Current year OA Pubs

BACKGROUNDS: While many studies agree that consanguinity increases the rate of congenital heart disease (CHD), few genome analyses have been conducted with consanguineous CHD cohorts.

METHODS: We recruited 73 CHD probands from consanguineous families in Turkey and used whole-exome sequencing (WES) to identify genetic lesions in these patients.

RESULTS: On average, each patient had 6.95 rare damaging homozygous variants, 0.68 of which are loss-of-function (LoF) variants. Seven patients (9.6%) carried damaging homozygous variants in five causal CHD genes. Six of those patients exhibited laterality defects (six HTX and one D-TGA). Three additional patients (4.1%) harbored other types of CHD-associated genomic …

Fibroblast Growth Factor-9 Expression In Airway Epithelial Cells Amplifies The Type I Interferon Response And Alters Influenza A Virus Pathogenesis, Bradley E. Hiller, Yongjun Yin, Yi-Chieh Perng, Ítalo De Araujo Castro, Lindsey E. Fox, Marissa C. Locke, Kristen J. Monte, Carolina B. López, David M. Ornitz, Deborah J. Lenschow

2020-Current year OA Pubs

Influenza A virus (IAV) preferentially infects conducting airway and alveolar epithelial cells in the lung. The outcome of these infections is impacted by the host response, including the production of various cytokines, chemokines, and growth factors. Fibroblast growth factor-9 (FGF9) is required for lung development, can display antiviral activity in vitro, and is upregulated in asymptomatic patients during early IAV infection. We therefore hypothesized that FGF9 would protect the lungs from respiratory virus infection and evaluated IAV pathogenesis in mice that overexpress FGF9 in club cells in the conducting airway epithelium (FGF9-OE mice). However, we found that FGF9-OE mice were …

Rationale Of Using The Dual Chemokine Receptor Ccr2/Ccr5 Inhibitor Cenicriviroc For The Treatment Of Covid-19, Daniel Clark Files, Frank Tacke, Alexandra O'Sullivan, Patrick Dorr, William G. Ferguson, William G. Powderly

2020-Current year OA Pubs

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created a global pandemic infecting over 230 million people and costing millions of lives. Therapies to attenuate severe disease are desperately needed. Cenicriviroc (CVC), a C-C chemokine receptor type 5 (CCR5) and C-C chemokine receptor type 2 (CCR2) antagonist, an agent previously studied in advanced clinical trials for patients with HIV or nonalcoholic steatohepatitis (NASH), may have the potential to reduce respiratory and cardiovascular organ failures related to COVID-19. Inhibiting the CCR2 and CCR5 pathways could attenuate or prevent inflammation or fibrosis in both early and …

Accuracy Of Chest Computed Tomography In Distinguishing Cystic Pleuropulmonary Blastoma From Benign Congenital Lung Malformations In Children, Abigail J Engwall-Gill, Jacqueline M Saito, Rebecca L Hulett Bowling, Et Al.

2020-Current year OA Pubs

Importance: The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear.

Objective: To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children.

Design, Setting, and Participants: This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed …

Associations Between Adherence To The Dietary Approaches To Stop Hypertension (Dash) Diet And Six Glucose Homeostasis Traits In The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Gautam Ramesh, Alexis C Wood, Matthew A Allison, Stephen S Rich, Elizabeth T Jensen, Yii-Der I Chen, Jerome I Rotter, Alain G Bertoni, Mark O Goodarzi

Children’s Nutrition Research Center Staff Publications

Background and aims: The DASH diet conveys protection against type 2 diabetes mellitus (T2D) Via plant-based and non-plant-based recommendations. Research has not identified which glucose homeostasis pathways are improved. We examined associations between adherence to a DASH diet and six glucose homeostasis traits, probing whether associations could be attributed to the plant-based (DASH-P) and/or non-plant based (DASH-NP) components.

Methods and results: We included data from 295 adults without T2D (age 59.3 ± 9.00 years; 63.46% non-Hispanic White and 36.54% African American, self-reported race ancestry) participating in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). An oral glucose tolerance test (OGTT) …