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Technology Meets Tils: Deciphering T Cell Function In The -Omics Era Jan 2023

Technology Meets Tils: Deciphering T Cell Function In The -Omics Era

Faculty, Staff and Students Publications

T cells are at the centerstage of cancer immunology due to their ability to recognize mutations within tumor cells and directly mediate cancer cell killing. Immunotherapies to rejuvenate exhausted T cell responses have transformed the clinical management of several malignancies. In parallel, the development of novel multidimensional analysis platforms such as single-cell RNA-sequencing and high-dimensional flow cytometry has yielded unprecedented insights into immune cell biology. This convergence has revealed substantial heterogeneity of tumor-infiltrating immune cells, both within single tumors, across tumor types, and among cancer patients. Here, we discuss the opportunities and challenges of studying the complex tumor microenvironment with …


Trends And Racial/Ethnic Differences In Predictors Of Cervical Cancer Screening Among Us Women Ages 30-64 Years, Aaron P Thrift Jan 2023

Trends And Racial/Ethnic Differences In Predictors Of Cervical Cancer Screening Among Us Women Ages 30-64 Years, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Cervical cancer screening (CCS) participation has decreased in the United States over the last several decades, contributing to cervical cancer's sustained incidence and mortality. This study examined recent trends and racial/ethnic differences in predictors of CCS uptake among US women.

METHODS: We analyzed combined data from the 2016 to 2020 Behavioral Risk Factor Surveillance System (BRFSS) and included 235,713 women ages 30 to 64 years without a hysterectomy. We used simple linear regression to assess trends over time and multivariable logistic regression models to evaluate racial/ethnic differences in predictors of up-to-date CCS.

RESULTS: We found little change in CCS …


Silencing Mir-146a-5p Protects Against Injury-Induced Osteoarthritis In Mice, Haocheng Qin, Cuicui Wang, Yonghua He, Aiwu Lu, Tiandao Li, Bo Zhang, Jie Shen Jan 2023

Silencing Mir-146a-5p Protects Against Injury-Induced Osteoarthritis In Mice, Haocheng Qin, Cuicui Wang, Yonghua He, Aiwu Lu, Tiandao Li, Bo Zhang, Jie Shen

2020-Current year OA Pubs

Osteoarthritis (OA), the most prevalent joint disease and the leading cause of disability, remains an incurable disease largely because the etiology and pathogenesis underlying this degenerative process are poorly understood. Low-grade inflammation within joints is a well-established factor that disturbs joint homeostasis and leads to an imbalance between anabolic and catabolic processes in articular cartilage; however, the complexity of the network between inflammatory factors that often involves positive and negative feedback loops makes current anti-cytokine therapy ineffective. MicroRNAs (miRNAs) have emerged as key regulators to control inflammation, and aberrant miRNAs expression has recently been linked to OA pathophysiology. In the …


Graph Theoretical Measures Of Fast Ripple Networks Improve The Accuracy Of Post-Operative Seizure Outcome Prediction, Shennan A Weiss, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Daniel Y. Rubinstein, Jerome Engel, Michael R Sperling, Richard J Staba Jan 2023

Graph Theoretical Measures Of Fast Ripple Networks Improve The Accuracy Of Post-Operative Seizure Outcome Prediction, Shennan A Weiss, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Daniel Y. Rubinstein, Jerome Engel, Michael R Sperling, Richard J Staba

Department of Neurosurgery Faculty Papers

Fast ripples (FR) are a biomarker of epileptogenic brain, but when larger portions of FR generating regions are resected seizure freedom is not always achieved. To evaluate and improve the diagnostic accuracy of FR resection for predicting seizure freedom we compared the FR resection ratio (RR) with FR network graph theoretical measures. In 23 patients FR were semi-automatically detected and quantified in stereo EEG recordings during sleep. MRI normalization and co-registration localized contacts and relation to resection margins. The number of FR, and graph theoretical measures, which were spatial (i.e., FR rate-distance radius) or temporal correlational (i.e., FR mutual information), …


Predicting The Risk Of A Clinical Event Using Longitudinal Data: The Generalized Landmark Analysis, Yi Yao, Liang Li, Brad Astor, Wei Yang, Tom Greene Jan 2023

Predicting The Risk Of A Clinical Event Using Longitudinal Data: The Generalized Landmark Analysis, Yi Yao, Liang Li, Brad Astor, Wei Yang, Tom Greene

Faculty, Staff and Student Publications

Background: In the development of prediction models for a clinical event, it is common to use the static prediction modeling (SPM), a regression model that relates baseline predictors to the time to event. In many situations, the data used in training and validation are from longitudinal studies, where predictor variables are time-varying and measured at clinical visits. But these data are not used in SPM. The landmark analysis (LA), previously proposed for dynamic prediction with longitudinal data, has interpretational difficulty when the baseline is not a risk-changing clinical milestone, as is often the case in observational studies of chronic disease …


Multimodal Brain Age Estimates Relate To Alzheimer Disease Biomarkers And Cognition In Early Stages: A Cross-Sectional Observational Study, Peter R Millar, Brian A Gordon, Patrick H Luckett, Tammie L S Benzinger, Carlos Cruchaga, Anne M Fagan, Jason J Hassenstab, Richard J Perrin, Suzanne E Schindler, Randall J Bateman, John C Morris, Beau M Ances, Et Al. Jan 2023

Multimodal Brain Age Estimates Relate To Alzheimer Disease Biomarkers And Cognition In Early Stages: A Cross-Sectional Observational Study, Peter R Millar, Brian A Gordon, Patrick H Luckett, Tammie L S Benzinger, Carlos Cruchaga, Anne M Fagan, Jason J Hassenstab, Richard J Perrin, Suzanne E Schindler, Randall J Bateman, John C Morris, Beau M Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Estimates of 'brain-predicted age' quantify apparent brain age compared to normative trajectories of neuroimaging features. The brain age gap (BAG) between predicted and chronological age is elevated in symptomatic Alzheimer disease (AD) but has not been well explored in presymptomatic AD. Prior studies have typically modeled BAG with structural MRI, but more recently other modalities, including functional connectivity (FC) and multimodal MRI, have been explored.

METHODS: We trained three models to predict age from FC, structural (S), or multimodal MRI (S+FC) in 390 amyloid-negative cognitively normal (CN/A-) participants (18-89 years old). In independent samples of 144 CN/A-, 154 CN/A+, …


Protocol For The Phase 2 Edelife Trial Investigating The Efficacy And Safety Of Intra-Amniotic Er004 Administration To Male Subjects With X-Linked Hypohidrotic Ectodermal Dysplasia, Holm Schneider, Smail Hadj-Rabia, Florian Faschingbauer, Christine Bodemer, Dorothy K Grange, Mary E Norton, Riccardo Cavalli, Gianluca Tadini, Holger Stepan, Angus Clarke, Encarna Guillén-Navarro, Sigrun Maier-Wohlfart, Athmane Bouroubi, Florence Porte Jan 2023

Protocol For The Phase 2 Edelife Trial Investigating The Efficacy And Safety Of Intra-Amniotic Er004 Administration To Male Subjects With X-Linked Hypohidrotic Ectodermal Dysplasia, Holm Schneider, Smail Hadj-Rabia, Florian Faschingbauer, Christine Bodemer, Dorothy K Grange, Mary E Norton, Riccardo Cavalli, Gianluca Tadini, Holger Stepan, Angus Clarke, Encarna Guillén-Navarro, Sigrun Maier-Wohlfart, Athmane Bouroubi, Florence Porte

2020-Current year OA Pubs

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder characte-rised by abnormal development of the skin and its appendages, such as hair and sweat glands, the teeth, and mucous glands of the airways, resulting in serious, sometimes life-threatening complications like hyperthermia or recurrent respiratory infections. It is caused by pathogenic variants of the ectodysplasin A gene (


Pickles V3: The Updated Database Of Pooled In Vitro Crispr Knockout Library Essentiality Screens, Lance C Novak, Juihsuan Chou, Medina Colic, Christopher A Bristow, Traver Hart Jan 2023

Pickles V3: The Updated Database Of Pooled In Vitro Crispr Knockout Library Essentiality Screens, Lance C Novak, Juihsuan Chou, Medina Colic, Christopher A Bristow, Traver Hart

Faculty, Staff and Student Publications

PICKLES (https://pickles.hart-lab.org) is an updated web interface to a freely available database of genome-scale CRISPR knockout fitness screens in human cell lines. Using a completely rewritten interface, researchers can explore gene knockout fitness phenotypes across cell lines and tissue types and compare fitness profiles with fitness, expression, or mutation profiles of other genes. The database has been updated to include data from three CRISPR libraries (Avana, Score, and TKOv3), and includes information from 1162 whole-genome screens probing the knockout fitness phenotype of 18 959 genes. Source code for the interface and the integrated database are available for download.


Immune Environment And Antigen Specificity Of The T Cell Receptor Repertoire Of Malignant Ascites In Ovarian Cancer, Kyoko Yoshida-Court, Tatiana V Karpinets, Aparna Mitra, Travis N Solley, Stephanie Dorta-Estremera, Andrea Y Delgado Medrano, Mustapha Ahmed-Kaddar, Erica J Lynn, K Jagannadha Sastry, Jianhua Zhang, Andrew Futreal, Alpa Nick, Karen Lu, Lauren E Colbert, Ann H Klopp Jan 2023

Immune Environment And Antigen Specificity Of The T Cell Receptor Repertoire Of Malignant Ascites In Ovarian Cancer, Kyoko Yoshida-Court, Tatiana V Karpinets, Aparna Mitra, Travis N Solley, Stephanie Dorta-Estremera, Andrea Y Delgado Medrano, Mustapha Ahmed-Kaddar, Erica J Lynn, K Jagannadha Sastry, Jianhua Zhang, Andrew Futreal, Alpa Nick, Karen Lu, Lauren E Colbert, Ann H Klopp

Faculty, Staff and Student Publications

We evaluated the association of disease outcome with T cell immune-related characteristics and T cell receptor (TCR) repertoire in malignant ascites from patients with high-grade epithelial ovarian cancer. Ascitic fluid samples were collected from 47 high-grade epithelial ovarian cancer patients and analyzed using flow cytometry and TCR sequencing to characterize the complementarity determining region 3 TCR β-chain. TCR functions were analyzed using the McPAS-TCR and VDJ databases. TCR clustering was implemented using Grouping of Lymphocyte Interactions by Paratope Hotspots software. Patients with poor prognosis had ascites characterized by an increased ratio of CD8+ T cells to regulatory T cells, which …


Alcohol Consumption And Epigenetic Age Acceleration In Young Adults, Drew R Nannini, Lei Liu, Et Al. Jan 2023

Alcohol Consumption And Epigenetic Age Acceleration In Young Adults, Drew R Nannini, Lei Liu, Et Al.

2020-Current year OA Pubs

Alcohol is a widely consumed substance in the United States, however its effect on aging remains understudied. In this study of young adults, we examined whether cumulative alcohol consumption, i.e., alcohol years of beer, liquor, wine, and total alcohol, and recent binge drinking, were associated with four measures of age-related epigenetic changes via blood DNA methylation. A random subset of study participants in the Coronary Artery Risk Development in Young Adults Study underwent DNA methylation profiling using the Illumina MethylationEPIC Beadchip. Participants with alcohol consumption and methylation data at examination years 15 (


Agreement Between Patient’S Description Of Abdominal Symptoms Of Possible Upper Gastrointestinal Cancer And General Practitioner Consultation Notes: A Qualitative Analysis Of Video-Recorded Uk Primary Care Consultation Data, Rebecca Barnes, John Lancaster, Margaret Johnson, Matthew Thompson, Jon Emery, Hardeep Singh, Fiona M Walter Jan 2023

Agreement Between Patient’S Description Of Abdominal Symptoms Of Possible Upper Gastrointestinal Cancer And General Practitioner Consultation Notes: A Qualitative Analysis Of Video-Recorded Uk Primary Care Consultation Data, Rebecca Barnes, John Lancaster, Margaret Johnson, Matthew Thompson, Jon Emery, Hardeep Singh, Fiona M Walter

Faculty, Staff and Students Publications

Introduction: Abdominal symptoms are common in primary care but infrequently might be due to an upper gastrointestinal (UGI) cancer. Patients' descriptions may differ from medical terminology used by general practitioners (GPs). This may affect how information about abdominal symptoms possibly due to an UGI cancer are documented, creating potential missed opportunities for timely investigation.

Objectives: To explore how abdominal symptoms are communicated during primary care consultations, and identify characteristics of patients' descriptions that underpin variation in the accuracy and completeness with which they are documented in medical records.

Methods and analysis: Primary care consultation video recordings, transcripts and medical records …


Single-Cell Multi-Omics Integration For Unpaired Data By A Siamese Network With Graph-Based Contrastive Loss Jan 2023

Single-Cell Multi-Omics Integration For Unpaired Data By A Siamese Network With Graph-Based Contrastive Loss

Faculty, Staff and Students Publications

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

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


Obesity Is Associated With Altered Tumor Metabolism In Metastatic Melanoma, Andrew W Hahn, Ashley V Menk, Dayana B Rivadeneira, Ryan C Augustin, Mingchu Xu, Xiaogang Wu, Tuba N Gide, Camelia Quek, Yan Zang, Christine N Spencer, Alexander M Menzies, Carrie R Daniel, Courtney W Hudgens, Theodore Nowicki, Lauren E Haydu, M A Wadud Khan, Vancheswaran Gopalakrishnan, Elizabeth M Burton, Jared Malke, Julie M Simon, Chantale Bernatchez, Nagireddy Putluri, Scott E Woodman, Y N Vashisht Gopal, Renato Guerrieri, Grant M Fischer, Jian Wang, Khalida M Wani, John F Thompson, Jeffrey E Lee, Patrick Hwu, Nadim Ajami, Jeffrey E Gershenwald, Georgina V Long, Richard A Scolyer, Michael T Tetzlaff, Alexander J Lazar, Dirk Schadendorf, Jennifer A Wargo, John M Kirkwood, Ralph J Deberardinis, Han Liang, Andrew Futreal, Jianhua Zhang, James S Wilmott, Weiyi Peng, Michael A Davies, Greg M Delgoffe, Yana G Najjar, Jennifer L Mcquade Jan 2023

Obesity Is Associated With Altered Tumor Metabolism In Metastatic Melanoma, Andrew W Hahn, Ashley V Menk, Dayana B Rivadeneira, Ryan C Augustin, Mingchu Xu, Xiaogang Wu, Tuba N Gide, Camelia Quek, Yan Zang, Christine N Spencer, Alexander M Menzies, Carrie R Daniel, Courtney W Hudgens, Theodore Nowicki, Lauren E Haydu, M A Wadud Khan, Vancheswaran Gopalakrishnan, Elizabeth M Burton, Jared Malke, Julie M Simon, Chantale Bernatchez, Nagireddy Putluri, Scott E Woodman, Y N Vashisht Gopal, Renato Guerrieri, Grant M Fischer, Jian Wang, Khalida M Wani, John F Thompson, Jeffrey E Lee, Patrick Hwu, Nadim Ajami, Jeffrey E Gershenwald, Georgina V Long, Richard A Scolyer, Michael T Tetzlaff, Alexander J Lazar, Dirk Schadendorf, Jennifer A Wargo, John M Kirkwood, Ralph J Deberardinis, Han Liang, Andrew Futreal, Jianhua Zhang, James S Wilmott, Weiyi Peng, Michael A Davies, Greg M Delgoffe, Yana G Najjar, Jennifer L Mcquade

Faculty, Staff and Student Publications

PURPOSE: Overweight/obese (OW/OB) patients with metastatic melanoma unexpectedly have improved outcomes with immune checkpoint inhibitors (ICI) and BRAF-targeted therapies. The mechanism(s) underlying this association remain unclear, thus we assessed the integrated molecular, metabolic, and immune profile of tumors, as well as gut microbiome features, for associations with patient body mass index (BMI).

EXPERIMENTAL DESIGN: Associations between BMI [normal (NL < 25) or OW/OB (BMI ≥ 25)] and tumor or microbiome characteristics were examined in specimens from 782 patients with metastatic melanoma across 7 cohorts. DNA associations were evaluated in The Cancer Genome Atlas cohort. RNA sequencing from 4 cohorts (n = 357) was batch corrected and gene set enrichment analysis (GSEA) by BMI category was performed. Metabolic profiling was conducted in a subset of patients (x = 36) by LC/MS, and in flow-sorted melanoma tumor cells (x = 37) and patient-derived melanoma cell lines (x = 17) using the Seahorse XF assay. Gut microbiome features were examined in an independent cohort (n = 371).

RESULTS: DNA mutations and copy number variations were not associated with BMI. GSEA demonstrated that tumors from OW/OB patients were metabolically quiescent, with downregulation of oxidative phosphorylation and multiple other metabolic pathways. Direct metabolite analysis and functional metabolic profiling confirmed decreased …


Phase I Dose Escalation Study Of Topical Bexarotene In Women At High Risk For Breast Cancer, Parijatham S Thomas, Anisha B Patel, J Jack Lee, Diane D Liu, Mike Hernandez, Alejandro Contreras, Carrie Mays, Diane Weber, Lana A Vornik, Seema A Khan, Eileen Dimond, Brandy M Heckman-Stoddard, Marjorie Perloff, Powel H Brown Jan 2023

Phase I Dose Escalation Study Of Topical Bexarotene In Women At High Risk For Breast Cancer, Parijatham S Thomas, Anisha B Patel, J Jack Lee, Diane D Liu, Mike Hernandez, Alejandro Contreras, Carrie Mays, Diane Weber, Lana A Vornik, Seema A Khan, Eileen Dimond, Brandy M Heckman-Stoddard, Marjorie Perloff, Powel H Brown

Faculty, Staff and Student Publications

Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.


Provider Beliefs In Effectiveness And Recommendations For Primary Hpv Testing In 3 Health-Care Systems, Gina R Kruse, Jacquelyn M Lykken, Eric J Kim, Jennifer S Haas, Robin T Higashi, Steven J Atlas, Anne Marie Mccarthy, Jasmin A Tiro, Michelle I Silver, Celette S Skinner, Aruna Kamineni Jan 2023

Provider Beliefs In Effectiveness And Recommendations For Primary Hpv Testing In 3 Health-Care Systems, Gina R Kruse, Jacquelyn M Lykken, Eric J Kim, Jennifer S Haas, Robin T Higashi, Steven J Atlas, Anne Marie Mccarthy, Jasmin A Tiro, Michelle I Silver, Celette S Skinner, Aruna Kamineni

2020-Current year OA Pubs

In 2018, the US Preventive Services Task Force endorsed primary human papillomavirus testing (pHPV) for cervical cancer screening. We aimed to describe providers' beliefs about pHPV testing effectiveness and which screening approach they regularly recommend. We invited providers who performed 10 or more cervical cancer screens in 2019 in 3 healthcare systems that had not adopted pHPV testing: Kaiser Permanente Washington, Mass General Brigham, and Parkland Health; 53.7% (501/933) completed the survey between October and December 2020. Response distributions varied across modalities (P < .001), with cytology alone or cotesting being more often viewed as somewhat or very effective for 30- to 65-year-olds compared with pHPV (cytology alone 94.1%, cotesting 96.1%, pHPV 66.0%). In 21- to 29-year-olds, the pattern was similar (cytology alone 92.2%, 64.7% cotesting, 50.8% pHPV). Most providers were either incorrect or unsure of the guideline-recommended screening interval for pHPV. Educational efforts are needed about the relative effectiveness and recommended use of pHPV to promote guideline-concordant care.


Silicone Gel Sheeting For Treating Keloid Scars, Fan Tian, Qingling Jiang, Junjie Chen, Zhenmi Liu Jan 2023

Silicone Gel Sheeting For Treating Keloid Scars, Fan Tian, Qingling Jiang, Junjie Chen, Zhenmi Liu

Faculty, Staff and Student Publications

BACKGROUND: Keloid scarring is one of the most common types of pathological scarring. Keloid scars that fail to heal can affect a person's physical and psychological function by causing pain, pruritus, contractures, and cosmetic disfigurement. Silicone gel sheeting (SGS) is made from medical-grade silicone reinforced with a silicone membrane backing and is one of the most commonly used treatments for keloid scars. However, there is no up-to-date systematic review assessing the effectiveness of SGS for keloid scars. A clear and rigorous review of current evidence is required to guide clinicians, healthcare managers and people with keloid scarring.

OBJECTIVES: To assess …


Subtype And Site Specific-Induced Metabolic Vulnerabilities In Prostate Cancer, Federica Mossa, Daniele Robesti, Ramachandran Sumankalai, Eva Corey, Mark Titus, Jianhua Zhang, Francesco Montorsi, Christopher P Vellano, Joseph R Marszalek, Daniel E Frigo, Christopher J Logothetis, Taranjit S Gujral, Eleonora Dondossola Jan 2023

Subtype And Site Specific-Induced Metabolic Vulnerabilities In Prostate Cancer, Federica Mossa, Daniele Robesti, Ramachandran Sumankalai, Eva Corey, Mark Titus, Jianhua Zhang, Francesco Montorsi, Christopher P Vellano, Joseph R Marszalek, Daniel E Frigo, Christopher J Logothetis, Taranjit S Gujral, Eleonora Dondossola

Faculty, Staff and Student Publications

Aberrant metabolic functions play a crucial role in prostate cancer progression and lethality. Currently, limited knowledge is available on subtype-specific metabolic features and their implications for treatment. We therefore investigated the metabolic determinants of the two major subtypes of castration-resistant prostate cancer [androgen receptor-expressing prostate cancer (ARPC) and aggressive variant prostate cancer (AVPC)]. Transcriptomic analyses revealed enrichment of gene sets involved in oxidative phosphorylation (OXPHOS) in ARPC tumor samples compared with AVPC. Unbiased screening of metabolic signaling pathways in patient-derived xenograft models by proteomic analyses further supported an enrichment of OXPHOS in ARPC compared with AVPC, and a skewing toward …


Psychotic Symptom, Mood, And Cognition-Associated Multimodal Mri Reveal Shared Links To The Salience Network Within The Psychosis Spectrum Disorders, Jessica A Turner, Xiao Zhang, Kaicheng Li, Xijia Xu, Daoqiang Zhang, Shile Qi, Vince D Calhoun Jan 2023

Psychotic Symptom, Mood, And Cognition-Associated Multimodal Mri Reveal Shared Links To The Salience Network Within The Psychosis Spectrum Disorders, Jessica A Turner, Xiao Zhang, Kaicheng Li, Xijia Xu, Daoqiang Zhang, Shile Qi, Vince D Calhoun

Faculty, Staff and Student Publications

Schizophrenia (SZ), schizoaffective disorder (SAD), and psychotic bipolar disorder share substantial overlap in clinical phenotypes, associated brain abnormalities and risk genes, making reliable diagnosis among the three illness challenging, especially in the absence of distinguishing biomarkers. This investigation aims to identify multimodal brain networks related to psychotic symptom, mood, and cognition through reference-guided fusion to discriminate among SZ, SAD, and BP. Psychotic symptom, mood, and cognition were used as references to supervise functional and structural magnetic resonance imaging (MRI) fusion to identify multimodal brain networks for SZ, SAD, and BP individually. These features were then used to assess the ability …


Vista Targeting Of T-Cell Quiescence And Myeloid Suppression Overcomes Adaptive Resistance, Elizabeth C Nowak, Nicole C Smits, Jie Deng, Aurelien Sarde, Cecilia A Webber, Dina Rabadi, Chao Cheng, Randolph Noelle, J Louise Lines Jan 2023

Vista Targeting Of T-Cell Quiescence And Myeloid Suppression Overcomes Adaptive Resistance, Elizabeth C Nowak, Nicole C Smits, Jie Deng, Aurelien Sarde, Cecilia A Webber, Dina Rabadi, Chao Cheng, Randolph Noelle, J Louise Lines

Faculty, Staff and Students Publications

VISTA is a premier target for cancer treatment due to its broad expression in many cancer types and enhanced expression upon development of adaptive immune checkpoint resistance. In the CT26 colorectal cancer model, monotherapy of small tumors with anti-VISTA resulted in slowed tumor growth. In a combination therapy setting, large CT26 tumors showed complete adaptive resistance to anti-PD-1/CTLA-4, but inclusion of anti-VISTA led to rejection of half the tumors. Mechanisms of enhanced anti-tumor immunity were investigated using scRNA-seq, multiplex image analysis and flow cytometry of the tumor immune infiltrate. In both treatment models, anti-VISTA upregulated stimulated antigen-presentation pathways and reduced …


Phenopacket-Tools: Building And Validating Ga4gh Phenopackets., Daniel Danis, Julius O B Jacobsen, Alex H Wagner, Tudor Groza, Martha A Beckwith, Lauren Rekerle, Leigh Carmody, Justin Reese, Harshad Hegde, Markus S Ladewig, Berthold Seitz, Monica Munoz-Torres, Nomi L Harris, Jordi Rambla, Michael Baudis, Christopher J Mungall, Melissa A Haendel, Peter N Robinson Jan 2023

Phenopacket-Tools: Building And Validating Ga4gh Phenopackets., Daniel Danis, Julius O B Jacobsen, Alex H Wagner, Tudor Groza, Martha A Beckwith, Lauren Rekerle, Leigh Carmody, Justin Reese, Harshad Hegde, Markus S Ladewig, Berthold Seitz, Monica Munoz-Torres, Nomi L Harris, Jordi Rambla, Michael Baudis, Christopher J Mungall, Melissa A Haendel, Peter N Robinson

Faculty Research 2023

The Global Alliance for Genomics and Health (GA4GH) is a standards-setting organization that is developing a suite of coordinated standards for genomics. The GA4GH Phenopacket Schema is a standard for sharing disease and phenotype information that characterizes an individual person or biosample. The Phenopacket Schema is flexible and can represent clinical data for any kind of human disease including rare disease, complex disease, and cancer. It also allows consortia or databases to apply additional constraints to ensure uniform data collection for specific goals. We present phenopacket-tools, an open-source Java library and command-line application for construction, conversion, and validation of phenopackets. …


Lipid Alternations In The Plasma Of Covid-19 Patients With Various Clinical Presentations., Xiao Liang, Xin Qi, Jin Yang, Xiaorui Wang, Hongyu Qin, Fang Hu, Han Bai, Yixin Li, Chengsheng Zhang, Bingyin Shi Jan 2023

Lipid Alternations In The Plasma Of Covid-19 Patients With Various Clinical Presentations., Xiao Liang, Xin Qi, Jin Yang, Xiaorui Wang, Hongyu Qin, Fang Hu, Han Bai, Yixin Li, Chengsheng Zhang, Bingyin Shi

Faculty Research 2023

BACKGROUND: COVID-19 is a highly infectious respiratory disease that can manifest in various clinical presentations. Although many studies have reported the lipidomic signature of COVID-19, the molecular changes in asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain elusive.

METHODS: This study combined a comprehensive lipidomic analysis of 220 plasma samples from 166 subjects: 62 healthy controls, 16 asymptomatic infections, and 88 COVID-19 patients. We quantified 732 lipids separately in this cohort. We performed a difference analysis, validated with machine learning models, and also performed GO and KEGG pathway enrichment analysis using differential lipids from different control groups.

RESULTS: …


An Intravenous Pancreatic Cancer Therapeutic: Characterization Of Crispr/Cas9n-Modified Clostridium Novyi-Non Toxic, Kaitlin M. Dailey, James M. Small, Jessica E. Pullan, Seth Winfree, Krysten E. Vance, Megan Orr, Sanku Mallik, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E Brooks Jan 2023

An Intravenous Pancreatic Cancer Therapeutic: Characterization Of Crispr/Cas9n-Modified Clostridium Novyi-Non Toxic, Kaitlin M. Dailey, James M. Small, Jessica E. Pullan, Seth Winfree, Krysten E. Vance, Megan Orr, Sanku Mallik, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E Brooks

Journal Articles: Pathology and Microbiology

Clostridium novyi has demonstrated selective efficacy against solid tumors largely due to the microenvironment contained within dense tumor cores. The core of a solid tumor is typically hypoxic, acidic, and necrotic-impeding the penetration of current therapeutics. C. novyi is attracted to the tumor microenvironment and once there, can both lyse and proliferate while simultaneously re-activating the suppressed immune system. C. novyi systemic toxicity is easily mitigated by knocking out the phage DNA plasmid encoded alpha toxin resulting in C. novyi-NT; but, after intravenous injection spores are quickly cleared by phagocytosis before accomplishing significant tumor localization. C. novyi-NT could be designed …


Association Between Prenatal Antimicrobial Use And Offspring Attention Deficit Hyperactivity Disorder, Jennifer K. Straughen, Alexandra R. Sitarik, Ganesa Wegienka, Christine C. Johnson, Tisa Johnson-Hooper, Andrea E. Cassidy-Bushrow Jan 2023

Association Between Prenatal Antimicrobial Use And Offspring Attention Deficit Hyperactivity Disorder, Jennifer K. Straughen, Alexandra R. Sitarik, Ganesa Wegienka, Christine C. Johnson, Tisa Johnson-Hooper, Andrea E. Cassidy-Bushrow

Public Health Sciences Articles

BACKGROUND: Gut-brain cross-talk may play an important role in modulating neurodevelopment. Few studies have examined the association between antimicrobials that influence infant gut microbiota assemblage and attention deficit hyperactivity disorder (ADHD).

OBJECTIVE: To examine the association between maternal prenatal antimicrobial use and ADHD in offspring at 10 years of age.

METHODS: Data are from the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, a racially and socioeconomically diverse birth cohort in metropolitan Detroit, Michigan. Maternal antimicrobial use was extracted from the medical record. ADHD diagnoses were based on parental report at the 10-year study visit. Poisson regression models with …


Contraception And Healthcare Utilization By Reproductive-Age Women Who Use Drugs In Rural Communities: A Cross-Sectional Survey., Ximena A. Levander, Canyon A. Foot, Sara L. Magnusson, Ryan R. Cook, Jerel M. Ezell, Judith Feinberg, Vivian F. Go, Kathryn E. Lancaster, Elizabeth Salisbury-Afshar, Gordon S. Smith, Ryan P. Westergaard, April M. Young, Judith I. Tsui, P. Todd Korthuis Jan 2023

Contraception And Healthcare Utilization By Reproductive-Age Women Who Use Drugs In Rural Communities: A Cross-Sectional Survey., Ximena A. Levander, Canyon A. Foot, Sara L. Magnusson, Ryan R. Cook, Jerel M. Ezell, Judith Feinberg, Vivian F. Go, Kathryn E. Lancaster, Elizabeth Salisbury-Afshar, Gordon S. Smith, Ryan P. Westergaard, April M. Young, Judith I. Tsui, P. Todd Korthuis

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: Women who use drugs (WWUD) have low rates of contraceptive use and high rates of unintended pregnancy. Drug use is common among women in rural U.S. communities, with limited data on how they utilize reproductive, substance use disorder (SUD), and healthcare services.

OBJECTIVE: We determined contraceptive use prevalence among WWUD in rural communities then compared estimates to women from similar rural areas. We investigated characteristics of those using contraceptives, and associations between contraceptive use and SUD treatment, healthcare utilization, and substance use.

DESIGN: Rural Opioids Initiative (ROI) - cross-sectional survey using respondent-driven sampling (RDS) involving eight rural U.S. regions …


Robotic-Arm Assisted Lateral Unicompartmental Knee Arthroplasty: 5-Year Outcomes & Survivorship, Michael A. Gaudiani, Linsen T. Samuel, John N. Diana, Jennifer L. Debattista, Thomas M. Coon, Ryan E. Moore, Atul F. Kamath Jan 2023

Robotic-Arm Assisted Lateral Unicompartmental Knee Arthroplasty: 5-Year Outcomes & Survivorship, Michael A. Gaudiani, Linsen T. Samuel, John N. Diana, Jennifer L. Debattista, Thomas M. Coon, Ryan E. Moore, Atul F. Kamath

Orthopedics Articles

INTRODUCTION: Robotic-arm assisted unicompartmental knee arthroplasty (RA-UKA) has demonstrated accurate component positioning and excellent outcomes for medial components. However, there is a paucity of literature on lateral compartment RA-UKA. The purpose of our study was to assess the midterm clinical outcomes and survivorship of lateral RA-UKA.

METHODS: This study was a retrospective review of a single-center prospectively maintained cohort of 33 patients (36 knees) indicated for lateral UKA. Perioperative, and postoperative two- and five-year Knee injury Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Score (WOMAC), and Forgotten Joint Score (FJS) patient reported outcome measures were collected. Five-year …


Safely Correct Hyponatremia With Continuous Renal Replacement Therapy: A Flexible, All-Purpose Method Based On The Mixing Paradigm, Sheldon Chen, Jerry Yee, Robert Chiaramonte Jan 2023

Safely Correct Hyponatremia With Continuous Renal Replacement Therapy: A Flexible, All-Purpose Method Based On The Mixing Paradigm, Sheldon Chen, Jerry Yee, Robert Chiaramonte

Nephrology Articles

Treating chronic hyponatremia by continuous renal replacement therapy (CRRT) is challenging because the gradient between a replacement fluid's [sodium] and a patient's serum sodium can be steep, risking too rapid of a correction rate with possible consequences. Besides CRRT, other gains and losses of sodium- and potassium-containing solutions, like intravenous fluid and urine output, affect the correction of serum sodium over time, known as osmotherapy. The way these fluids interact and contribute to the sodium/potassium/water balance can be parsed as a mixing problem. As Na/K/H(2) O are added, mixed in the body, and drained via CRRT, the net balance of …


Development And Validation Of A Questionnaire To Assess Awareness And Knowledge Of Nonalcoholic Fatty Liver Disease, A Liver Cancer Etiological Factor, Among Chinese Young Adults, Yi Du, Fedja A. Rochling, Dejun Su, Kendra Ratnapradipa, Jianghu James Dong, Evi A. Farazi Jan 2023

Development And Validation Of A Questionnaire To Assess Awareness And Knowledge Of Nonalcoholic Fatty Liver Disease, A Liver Cancer Etiological Factor, Among Chinese Young Adults, Yi Du, Fedja A. Rochling, Dejun Su, Kendra Ratnapradipa, Jianghu James Dong, Evi A. Farazi

Journal Articles: Epidemiology

PURPOSE: Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), a liver cancer etiological factor, among Chinese young adults (CYA), there is a lack of valid, reliable, ready-to-use survey instruments for assessing awareness and knowledge of NAFLD in this population. The aims of this study were to develop, validate, and assess the reliability of a web-based, self-administered questionnaire evaluating awareness and knowledge of NAFLD among CYA.

METHODS: Based on review of relevant literature, a draft questionnaire was initially developed. Face and content validity of the questionnaire was evaluated by an expert panel of seven gastroenterologists. The construct validity was …


Hiv Associated Cell Death: Peptide-Induced Apoptosis Restricts Viral Transmission., Qiongyu Chen, Yan Zhao, Yonghong Zhang, Jianbo Zhang, Wenshu Lu, Chih-Hao Chang, Shisong Jiang Jan 2023

Hiv Associated Cell Death: Peptide-Induced Apoptosis Restricts Viral Transmission., Qiongyu Chen, Yan Zhao, Yonghong Zhang, Jianbo Zhang, Wenshu Lu, Chih-Hao Chang, Shisong Jiang

Faculty Research 2023

The human immunodeficiency virus (HIV) is still a global pandemic and despite the successful use of anti-retroviral therapy, a well-established cure remains to be identified. Viral modulation of cell death has a significant role in HIV pathogenesis. Here we sought to understand the major mechanisms of HIV- induced death of lymphocytes and the effects on viral transmission. Flow cytometry analysis of lymphocytes from five latent HIV-infected patients, and HIV IIIB-infected MT2 cells demonstrated both necrosis and apoptosis to be the major mechanisms of cell death in CD4+ and CD4-/CD8- lymphocytes. Significantly, pro-apoptotic tumor necrosis factor (TNF) peptide (P13) was found …


Nonsystematic Reporting Biases Of The Sars-Cov-2 Variant Mu Could Impact Our Understanding Of The Epidemiological Dynamics Of Emerging Variants, Mary E. Petrone, Carolina Lucas, Bridget Menasche, Mallery I. Breban, Inci Yildirim, Melissa Campbell, Saad B. Omer, Edward C. Holmes, Albert I. Ko, Nathan D. Grubaugh, Akiko Iwasaki, Craig B. Wilen, Chantal B. F. Vogels, Joseph R. Fauver Jan 2023

Nonsystematic Reporting Biases Of The Sars-Cov-2 Variant Mu Could Impact Our Understanding Of The Epidemiological Dynamics Of Emerging Variants, Mary E. Petrone, Carolina Lucas, Bridget Menasche, Mallery I. Breban, Inci Yildirim, Melissa Campbell, Saad B. Omer, Edward C. Holmes, Albert I. Ko, Nathan D. Grubaugh, Akiko Iwasaki, Craig B. Wilen, Chantal B. F. Vogels, Joseph R. Fauver

Journal Articles: Epidemiology

Developing a timely and effective response to emerging SARS-CoV-2 variants of concern (VOCs) is of paramount public health importance. Global health surveillance does not rely on genomic data alone to identify concerning variants when they emerge. Instead, methods that utilize genomic data to estimate the epidemiological dynamics of emerging lineages have the potential to serve as an early warning system. However, these methods assume that genomic data are uniformly reported across circulating lineages. In this study, we analyze differences in reporting delays among SARS-CoV-2 VOCs as a plausible explanation for the timing of the global response to the former VOC …


Protecting Low-Income Consumers In The Era Of Digital Grocery Shopping: Implications For Wic Online Ordering, Qi Zhang, Priyanka Patel, Caitlin M. Lowery Jan 2023

Protecting Low-Income Consumers In The Era Of Digital Grocery Shopping: Implications For Wic Online Ordering, Qi Zhang, Priyanka Patel, Caitlin M. Lowery

Community & Environmental Health Faculty Publications

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is now expected to allow participants to redeem their food benefits online, i.e., via online ordering, rather than only in-store. However, it is unclear how this new benefit redemption model may impact participants’ welfare since vendors may have an asymmetric information advantage compared with WIC customers. The WIC online ordering environment may also change the landscape for WIC vendors, which will eventually affect WIC participants. To protect WIC consumers’ rights in the new online ordering model, policymakers need an appropriate legal and regulatory framework. This narrative review provides that …