Digital Commons Network^™

Lineage Abundance Estimation For Sars-Cov-2 In Wastewater Using Transcriptome Quantification Techniques, Jasmijn A. Baaijens, Alessandro Zulli, Isabel M. Ott, Ioanna Nika, Mart J. Van Der Lugt, Mary E. Petrone, Tara Alpert, Joseph R. Fauver, Chaney C. Kalinich, Chantal B. F. Vogels, Mallery I. Breban, Claire Duvallet, Kyle A. Mcelroy, Newsha Ghaeli, Maxim Imakaev, Malaika F. Mckenzie-Bennett, Keith Robison, Alex Plocik, Rebecca Schilling, Martha Pierson, Rebecca Littlefield, Michelle L. Spencer, Birgitte B. Simen, Yale Sars-Cov-2 Genomic Surveillance Initiative, William P. Hanage, Nathan D. Grubaugh, Jordan Peccia, Michael Baym

Journal Articles: Epidemiology

Effectively monitoring the spread of SARS-CoV-2 mutants is essential to efforts to counter the ongoing pandemic. Predicting lineage abundance from wastewater, however, is technically challenging. We show that by sequencing SARS-CoV-2 RNA in wastewater and applying algorithms initially used for transcriptome quantification, we can estimate lineage abundance in wastewater samples. We find high variability in signal among individual samples, but the overall trends match those observed from sequencing clinical samples. Thus, while clinical sequencing remains a more sensitive technique for population surveillance, wastewater sequencing can be used to monitor trends in mutant prevalence in situations where clinical sequencing is unavailable.

Quantifying The Impact Of Immune History And Variant On Sars-Cov-2 Viral Kinetics And Infection Rebound: A Retrospective Cohort Study, James A. Hay, Stephen M. Kissler, Joseph R. Fauver, Christina Mack, Caroline G. Tai, Radhika M. Samant, Sarah Connolly, Deverick J. Anderson, Gaurav Khullar, Matthew Mackay, Miral Patel, Shannan Kelly, April Manhertz, Isaac Eiter, Daisy Salgado, Tim Baker, Ben Howard, Joel T. Dudley, Christopher E. Mason, Manoj Nair, Yaoxing Huang, John Difiori, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad

Journal Articles: Epidemiology

BACKGROUND: The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear.

METHODS: We characterized 1,280 infections from the National Basketball Association occupational health cohort identified between June 2020 and January 2022 using serial RT-qPCR testing. Logistic regression and semi-mechanistic viral RNA kinetics models were used to quantify the effect of age, variant, symptom status, infection history, vaccination status and antibody titer to the founder SARS-CoV-2 strain on the duration of potential infectiousness and overall viral kinetics. The frequency of viral rebounds was quantified under multiple cycle threshold (Ct) value-based definitions.

RESULTS: Among individuals detected …

Insect Cell Expression And Purification Of Recombinant Sars-Cov-2 Spike Proteins That Demonstrate Ace2 Binding, Lucas R. Struble, Audrey L. Smith, William E. Lutz, Gabrielle Grubbs, Satish Sagar, Kenneth W. Bayles, Prakash Radhakrishnan, Surender Khurana, Dalia El-Gamal, Gloria E. O. Borgstahl

Journal Articles: Pathology and Microbiology

The COVID-19 pandemic caused by SARS-CoV-2 infection has led to socio-economic shutdowns and the loss of over 5 million lives worldwide. There is a need for the identification of therapeutic targets to treat COVID-19. SARS-CoV-2 spike is a target of interest for the development of therapeutic targets. We developed a robust SARS-CoV-2 S spike expression and purification protocol from insect cells and studied four recombinant SARS-CoV-2 spike protein constructs based on the original SARS-CoV-2 sequence using a baculovirus expression system: a spike protein receptor-binding domain that includes the SD1 domain (RBD) coupled to a fluorescent tag (S-RBD-eGFP), spike ectodomain coupled …

Type I Ifn Signaling Protects Mice From Lethal Sars-Cov-2 Neuroinvasion., Md Bashir Uddin, Yuejin Liang, Shengjun Shao, Sunil Palani, Michael Mckelvey, Scott C. Weaver, Keer Sun

Journal Articles: Pathology and Microbiology

Multiple organ damage is common in patients with severe COVID-19, even though the underlying pathogenic mechanisms remain unclear. Acute viral infection typically activates type I IFN (IFN-I) signaling. The antiviral role of IFN-I is well characterized in vitro. However, our understanding of how IFN-I regulates host immune response to SARS-CoV-2 infection in vivo is incomplete. Using a human ACE2-transgenic mouse model, we show in the present study that IFN-I receptor signaling is essential for protection against the acute lethality of SARS-CoV-2 in mice. Interestingly, although IFN-I signaling limits viral replication in the lung, the primary infection site, it is dispensable …

Clinical Laboratory Testing Practices In Diffuse Gliomas Prior To Publication Of 2021 World Health Organization Classification Of Central Nervous System Tumors, Shakti H. Ramkissoon, Helen Fernandes, Dolores H. Lopez-Terrada, Meera R. Hameed, Dimitri G. Trembath, Julia A. Bridge, Neal I. Lindeman, Rhona J. Souers, Patricia Vasalos, Daniel J Brat, Joel T. Moncur

Journal Articles: Pathology and Microbiology

CONTEXT.—: Integration of molecular data into glioma classification supports diagnostic, prognostic, and therapeutic decision-making; however, testing practices for these informative biomarkers in clinical laboratories remain unclear.

OBJECTIVE.—: To examine the prevalence of molecular testing for clinically relevant biomarkers in adult and pediatric gliomas through review of a College of American Pathologists proficiency testing survey prior to the release of the 2021 World Health Organization Classification of Central Nervous System Tumors.

DESIGN.—: College of American Pathologists proficiency testing 2020 survey results from 96 laboratories performing molecular testing for diffuse gliomas were used to determine the use of testing for molecular biomarkers …

Editorial: Genetic Basis Of Tolerance Induction Defects Underlying The Development Of Autoimmune Pathologies., Jeremy Racine, Laurence Morel, Yi-Guang Chen, David V. Serreze

Faculty Research 2022

No abstract provided.

Causes Of Death And Conditional Survival Estimates Of Long-Term Lung Cancer Survivors., Qun Zhang, Yuan Dai, Hongda Liu, Wenkui Sun, Yuming Huang, Zheng Gong, Shanlin Dai, Hui Kong, Weiping Xie

Faculty Research 2022

INTRODUCTION: Lung cancer ranks the leading cause of cancer-related death worldwide. This retrospective cohort study was designed to determine time-dependent death hazards of diverse causes and conditional survival of lung cancer.

METHODS: We collected 816,436 lung cancer cases during 2000-2015 in the SEER database, after exclusion, 612,100 cases were enrolled for data analyses. Cancer-specific survival, overall survival and dynamic death hazard were assessed in this study. Additionally, based on the FDA approval time of Nivolumab in 2015, we evaluated the effect of immunotherapy on metastatic patients' survival by comparing cases in 2016-2018 (immunotherapy era, n=7135) and those in 2013-2016 (non-immunotherapy …

Access, Socioeconomic Environment, And Death From Covid-19 In Nebraska, He Bai, Michelle M. Schwedhelm, John-Martin Lowe, Rachel Lookadoo, Daniel R. Anderson, Abigail Lowe, James V. Lawler, M. Jana Broadhurst, David Brett-Major

Journal Articles: Epidemiology

Our study assesses whether factors related to healthcare access in the first year of the pandemic affect mortality and length of stay (LOS). Our cohort study examined hospitalized patients at Nebraska Medicine between April and October 2020 who were tested for SARS-CoV-2 and had a charted sepsis related diagnostic code. Multivariate logistic was used to analyze the odds of mortality and linear regression was used to calculate the parameter estimates of LOS associated with COVID-19 status, age, gender, race/ethnicity, median household income, admission month, and residential distance from definitive care. Among 475 admissions, the odds of mortality is greater among …

Ifn-Γ Transforms The Transcriptomic Landscape And Triggers Myeloid Cell Hyperresponsiveness To Cause Lethal Lung Injury, Atul K. Verma, Michael Mckelvey, Md Bashir Uddin, Sunil Palani, Meng Niu, Christopher Bauer, Shengjun Shao, Keer Sun

Journal Articles: Pathology and Microbiology

Acute Respiratory Distress Syndrome (ARDS) is an inflammatory disease that is associated with high mortality but no specific treatment. Our understanding of initial events that trigger ARDS pathogenesis is limited. We have developed a mouse model of inflammatory lung injury by influenza and methicillin-resistant Staphylococcus aureus (MRSA) coinfection plus daily antibiotic therapy. Using this pneumonic ARDS model, here we show that IFN-γ receptor signaling drives inflammatory cytokine storm and lung tissue damage. By single-cell RNA sequencing (scRNA-seq) analysis, we demonstrate that IFN-γ signaling induces a transcriptional shift in airway immune cells, particularly by upregulating macrophage and monocyte expression of genes …

Relationships Of Serum Cc16 Levels With Smoking Status And Lung Function In Copd, Kelli C. Gribben, Jill A. Poole, Amy J. Nelson, Paraskevi A. Farazi, Christopher S. Wichman, Art J. Heires, Debra J. Romberger, Tricia D. Levan

Journal Articles: Pulmonary & Critical Care Med

Background: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown.

Methods: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV₁/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation.

Results: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on …

Updated Perspectives On The Role Of Biomechanics In Copd: Considerations For The Clinician, Jennifer M. Yentes, Wai-Yan Liu, Kuan Zhang, Eric Markvicka, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Patients with chronic obstructive pulmonary disease (COPD) demonstrate extra-pulmonary functional decline such as an increased prevalence of falls. Biomechanics offers insight into functional decline by examining mechanics of abnormal movement patterns. This review discusses biomechanics of functional outcomes, muscle mechanics, and breathing mechanics in patients with COPD as well as future directions and clinical perspectives. Patients with COPD demonstrate changes in their postural sway during quiet standing compared to controls, and these deficits are exacerbated when sensory information (eg, eyes closed) is manipulated. If standing balance is disrupted with a perturbation, patients with COPD are slower to return to baseline …

An Artifact In Intracellular Cytokine Staining For Studying T Cell Responses And Its Alleviation., Zheng Gong, Qing Li, Jiayuan Shi, Guangwen Ren

Faculty Research 2022

Intracellular cytokine staining (ICS) is a widely employed ex vivo method for quantitative determination of the activation status of immune cells, most often applied to T cells. ICS test samples are commonly prepared from animal or human tissues as unpurified cell mixtures, and cell-specific cytokine signals are subsequently discriminated by gating strategies using flow cytometry. Here, we show that when ICS samples contain Ly6G⁺ neutrophils, neutrophils are ex vivo activated by an ICS reagent - phorbol myristate acetate (PMA) - which leads to hydrogen peroxide (H₂O₂) release and death of cytokine-expressing T cells. This artifact …

Genomic Heterogeneity Underlies Multidrug Resistance In Pseudomonas Aeruginosa: A Population-Level Analysis Beyond Susceptibility Testing., Laura J Rojas, Mohamad Yasmin, Jacquelynn Benjamino, Steven M Marshall, Kailynn J Deronde, Nikhil P Krishnan, Federico Perez, Andrew A Colin, Monica Cardenas, Octavio Martinez, Armando Pérez-Cardona, Daniel D Rhoads, Michael R Jacobs, John J Lipuma, Michael W Konstan, Alejandro J Vila, Andrea Smania, Andrew R Mack, Jacob G Scott, Mark D Adams, Lilian M Abbo, Robert A Bonomo

Faculty Research 2022

BACKGROUND: Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with Cystic Fibrosis (CF). Herein, we describe a longitudinal analysis of a series of multidrug resistant (MDR) P. aeruginosa isolates recovered in a 17-month period, from a young female CF patient who underwent double lung transplantation. Our goal was to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence evolution over time.

METHODS: Twenty-two sequential P. aeruginosa isolates were obtained within a 17-month period, before and after a double-lung transplant. At the end of the …

Genome-Wide Variant Calling In Reanalysis Of Exome Sequencing Data Uncovered A Pathogenic Tubb3 Variant., Elke De Boer, Burcu Yaldiz, Anne-Sophie Denommé-Pichon, Leslie Matalonga, Steve Laurie, Solve-Rd Snv-Indel Working Group, Daniel Danis, Peter N Robinson, Solve-Rd-Ditf Ithaca

Faculty Research 2022

Almost half of all individuals affected by intellectual disability (ID) remain undiagnosed. In the Solve-RD project, exome sequencing (ES) datasets from unresolved individuals with (syndromic) ID (n = 1,472 probands) are systematically reanalyzed, starting from raw sequencing files, followed by genome-wide variant calling and new data interpretation. This strategy led to the identification of a disease-causing de novo missense variant in TUBB3 in a girl with severe developmental delay, secondary microcephaly, brain imaging abnormalities, high hypermetropia, strabismus and short stature. Interestingly, the TUBB3 variant could only be identified through reanalysis of ES data using a genome-wide variant calling approach, despite …

Curation And Expansion Of Human Phenotype Ontology For Defined Groups Of Inborn Errors Of Immunity., Matthias Haimel, Julia Pazmandi, Raúl Jiménez Heredia, Jasmin Dmytrus, Sevgi Köstel Bal, Samaneh Zoghi, Paul Van Daele, Tracy A Briggs, Carine Wouters, Brigitte Bader-Meunier, Florence A Aeschlimann, Roberta Caorsi, Despina Eleftheriou, Esther Hoppenreijs, Elisabeth Salzer, Shahrzad Bakhtiar, Beata Derfalvi, Francesco Saettini, Maaike A A Kusters, Reem Elfeky, Johannes Trück, Jacques G Rivière, Mirjam Van Der Burg, Marco Gattorno, Markus G Seidel, Siobhan Burns, Klaus Warnatz, Fabian Hauck, Paul Brogan, Kimberly C Gilmour, Catharina Schuetz, Anna Simon, Christoph Bock, Sophie Hambleton, Esther De Vries, Peter N Robinson, Marielle Van Gijn, Kaan Boztug

Faculty Research 2022

BACKGROUND: Accurate, detailed, and standardized phenotypic descriptions are essential to support diagnostic interpretation of genetic variants and to discover new diseases. The Human Phenotype Ontology (HPO), extensively used in rare disease research, provides a rich collection of vocabulary with standardized phenotypic descriptions in a hierarchical structure. However, to date, the use of HPO has not yet been widely implemented in the field of inborn errors of immunity (IEIs), mainly due to a lack of comprehensive IEI-related terms.

OBJECTIVES: We sought to systematically review available terms in HPO for the depiction of IEIs, to expand HPO, yielding more comprehensive sets of …

Identification Of Quantitative Trait Loci For Survival In The Mutant Dynactin P150glued Mouse Model Of Motor Neuron Disease., Guillermo M Alexander, Terry D Heiman-Patterson, Frank Bearoff, Roger B Sher, Laura Hennessy, Shannon Terek, Nicole Caccavo, Gregory A Cox, Vivek M. Philip, Elizabeth A Blankenhorn

Faculty Research 2022

Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disorder. Although most cases of ALS are sporadic, 5-10% of cases are familial, with mutations associated with over 40 genes. There is variation of ALS symptoms within families carrying the same mutation; the disease may develop in one sibling and not in another despite the presence of the mutation in both. Although the cause of this phenotypic variation is unknown, it is likely related to genetic modifiers of disease expression. The identification of ALS causing genes has led to the development of transgenic mouse models of motor neuron disease. …

The Th1/Tfh-Like Biased Responses Elicited By The Rasp-1 Innate Adjuvant Are Dependent On Trif And Type I Ifn Receptor Pathways., Parakkal Jovvian George, Radu Marches, Djamel Nehar-Belaid, Jacques Banchereau, Sara Lustigman

Faculty Research 2022

No abstract provided.

Engineering A "Detect And Destroy" Skin Probiotic To Combat Methicillin-Resistant Staphylococcus Aureus., Changhui Guan, Peter J Larson, Elizabeth Fleming, Alexander P Tikhonov, Sara Mootien, Trudy H Grossman, Caroline Golino, Julia Oh

Faculty Research 2022

The prevalence and virulence of pathogens such as methicillin-resistant Staphylococcus (S.) aureus (MRSA), which can cause recurrent skin infections, are of significant clinical concern. Prolonged antibiotic exposure to treat or decolonize S. aureus contributes to development of antibiotic resistance, as well as depletion of the microbiome, and its numerous beneficial functions. We hypothesized an engineered skin probiotic with the ability to selectively deliver antimicrobials only in the presence of the target organism could provide local bioremediation of pathogen colonization. We constructed a biosensing S. epidermidis capable of detecting the presence of S. aureus quorum sensing autoinducer peptide and producing lysostaphin …

Gestational Age Impacts Birth To Placental Weight Ratio And Umbilical Cord Oxygen Values With Implications For The Fetal Oxygen Margin Of Safety, Bryan S Richardson, Barbra De Vrijer, Hilary K Brown, Larry Stitt, Sheryl Choo, Timothy R H Regnault

Obstetrics & Gynaecology Publications

Background: We determined the impact of gestational age (GA) from near term to term to post-term on birth/placental weight ratio and cord oxygen values with implications for placental transport efficiency for oxygen, fetal O2 consumption relative to delivery or fractional O2 extraction, and oxygen margin of safety.

Materials and methods: A hospital database was used to obtain birth/placental weight ratios, cord PO2 and other information on patients delivering between Jan 1, 1990 and Jun 15, 2011 with GA > 34 completed weeks (N=69,852). Oxygen saturation was calculated from the cord PO2 and pH data, while fractional O2 extraction was calculated from …

Radiation Exposure Determination In A Secure, Cloudbased Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Joan H.M. Knoll, Peter Rogan

Biochemistry Publications

Rapid sample processing and interpretation of estimated exposures will be critical for triaging exposed individuals after a major radiation incident. The dicentric chromosome (DC) assay assesses absorbed radiation using metaphase cells from blood. The Automated Dicentric Chromosome Identifier and Dose Estimator System (ADCI) identifies DCs and determines radiation doses. This study aimed to broaden accessibility and speed of this system, while protecting data and software integrity. ADCI Online is a secure web-streaming platform accessible worldwide from local servers. Cloud-based systems containing data and software are separated until they are linked for radiation exposure estimation. Dose estimates are identical to ADCI …

Longitudinal Physical Performance And Blood Pressure Changes In Older Women: Findings Form The Women's Health Initiative., Deepika R Laddu, Michael J Lamonte, Bernhard Haring, Hajwa Kim, Peggy Cawthon, Jennifer W Bea, Hailey Banack, Jane A Cauley, Matthew A Allison, Lisa Warsinger Martin, Meryl S Leboff, Marcia L Stefanick, Shane A Phillips, Jun Ma

Medicine Faculty Publications

No abstract provided.

Disparities In Awareness Of And Willingness To Participate In Cancer Clinical Trials Between African American And White Cancer Survivors, Gaurav Kumar, Jungyoon Kim, Paraskevi A. Farazi, Hongmei Wang, Dejun Su

Journal Articles: Epidemiology

BACKGROUND: Cancer clinical trials (CCTs) are essential for cancer care, yet the evidence is scarce when it comes to racial disparities in CCT participation among cancer survivors in the Midwest. This study aimed to 1) assess disparities in the awareness of and willingness to participate in CCTs between African American and White cancer survivors; and 2) compare perceptions about CCTs between the two racial groups.

METHODS: The study was based on cross-sectional data from the survey "Minority Patient Participation in Cancer Clinical Trials" that collected information from 147 Black and White cancer survivors from Nebraska between 2015 and 2016. Chi-square …

Ecdysoneless Overexpression Drives Mammary Tumorigenesis Through Upregulation Of C-Myc And Glucose Metabolism, Bhopal C. Mohapatra, Sameer Mirza, Aditya Bele, Channabasavaiah B. Gurumurthy, Mohsin Raza, Irfana Saleem, Matthew D. Storck, Aniruddha Sarkar, Sai Sundeep Kollala, Surendra K. Shukla, Siddesh Southekal, Kay-Uwe Wagner, Fang Qiu, Subodh M. Lele, Mansour A. Alsaleem, Emad A. Rakha, Chittibabu Guda, Pankaj K. Singh, Robert D. Cardiff, Hamid Band, Vimla Band

Journal Articles: Pharmacology & Experimental Neuroscience

Ecdysoneless (ECD) protein is essential for embryogenesis, cell-cycle progression, and cellular stress mitigation with an emerging role in mRNA biogenesis. We have previously shown that ECD protein as well as its mRNA are overexpressed in breast cancer and ECD overexpression predicts shorter survival in patients with breast cancer. However, the genetic evidence for an oncogenic role of ECD has not been established. Here, we generated transgenic mice with mammary epithelium-targeted overexpression of an inducible human ECD transgene (ECDTg). Significantly, ECDTg mice develop mammary hyperplasia, preneoplastic lesions, and heterogeneous tumors with occasional lung metastasis. ECDTg tumors exhibit epithelial to mesenchymal transition …

Distinct Synaptic Vesicle Proteomic Signatures Associated With Pre- And Post-Natal Oxycodone-Exposure, Katherine E. Odegaard, Gabriel Gallegos, Sneh Koul, Victoria L. Schaal, Neetha N. Vellichirammal, Chittibabu Guda, Andrea P. Dutoit, Steven J. Lisco, Sowmya V. Yelamanchili, Gurudutt Pendyala

Journal Articles: Anesthesiology

The current opioid crisis, which has ravaged all segments of society, continues to pose a rising public health concern. Importantly, dependency on prescription opioids such as oxycodone (oxy) during and after pregnancy can significantly impact the overall brain development of the exposed offspring, especially at the synapse. A significant knowledge gap that remains is identifying distinct synaptic signatures associated with these exposed offspring. Accordingly, the overall goal of this current study was to identify distinct synaptic vesicle (SV) proteins as signatures for offspring exposed to oxy in utero (IUO) and postnatally (PNO). Using a preclinical animal model that imitates oxycodone …

Clinically Adjudicated Deceased Donor Acute Kidney Injury And Graft Outcomes, Sherry G. Mansour, Nadeen J. Khoury, Ravi Kodali, Sarthak Virmani, Peter P. Reese, Isaac E. Hall, Yaqi Jia, Yu Yamamoto, Heather R. Thiessen-Philbrook, Wassim Obeid, Mona D. Doshi, Enver Akalin, Jonathan S. Bromberg, Meera N. Harhay, Sumit Mohan, Thangamani Muthukumar, Pooja Singh, Francis L. Weng, Dennis G. Moledina, Jason H. Greenberg, Francis P. Wilson, Chirag R. Parikh

Nephrology Articles

BACKGROUND: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association.

METHODS: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among …

Pulmonary Function And Blood Dna Methylation: A Multiancestry Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Tianxiao Huan, Daniel L. Mccartney, Geetha Chittoor, Maaike De Vries, Lies Lahousse, Jennifer N. Nguyen, Jennifer A. Brody, Juan Castillo-Fernandez, Natalie Terzikhan, Cancan Qi, Roby Joehanes, Josine L. Min, Gordon J. Smilnak, Jessica R. Shaw, Chen Xi Yang, Elena Colicino, Thanh T. Hoang, Mairead L. Bermingham, Hanfei Xu, Anne E. Justice, Cheng-Jian Xu, Stephen S. Rich, Simon R. Cox, Judith M. Vonk, Ivana Prokić, Nona Sotoodehnia, Pei-Chien Tsai, Joel D. Schwartz, Janice M. Leung, Sinjini Sikdar, Rosie M. Walker, Sarah E. Harris, Diana A. Van Der Plaat, David J. Van Den Berg, Traci M. Bartz, Tim D. Spector, Pantel S. Vokonas, Riccardo E. Marioni, Adele M. Taylor, Yongmei Liu, R. Graham Barr, Leslie A. Lange, Andrea A. Baccarelli, Ma'en Obeidat, Myriam Fornage, Tianyuan Wang, James M. Ward, Alison A. Motsinger-Reif, Gibran Hemani, Gerard H. Koppelman, Jordana T. Bell, Sina A. Gharib, Guy Brusselle, H. Marike Boezen, Kari E. North, Daniel Levy, Kathryn L. Evans, Josée Dupris, Charles E. Breeze, Ani Manichaikul, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication.

Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.

Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV₁, FVC, and FEV₁/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics.

Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery …

Editorial: Stromal And Immune Microenvironment In Breast Cancer Metastasis., Xin Lu, Xia Liu, Toni Celià-Terrassa, Guangwen Ren

Faculty Research 2022

No abstract provided.

Epidermal Growth Factor Receptor Inhibition Is Protective In Hyperoxia-Induced Lung Injury., Zachary M Harris, Ying Sun, John Joerns, Brian Clark, Buqu Hu, Asawari Korde, Lokesh Sharma, Hyeon Jun Shin, Edward P Manning, Lindsey Placek, Derya Unutmaz, Gail Stanley, Hyung Chun, Maor Sauler, Govindarajan Rajagopalan, Xuchen Zhang, Min-Jong Kang, Jonathan L Koff

Faculty Research 2022

AIMS: Studies have linked severe hyperoxia, or prolonged exposure to very high oxygen levels, with worse clinical outcomes. This study investigated the role of epidermal growth factor receptor (EGFR) in hyperoxia-induced lung injury at very high oxygen levels (>95%).

RESULTS: Effects of severe hyperoxia (100% oxygen) were studied in mice with genetically inhibited EGFR and wild-type littermates. Despite the established role of EGFR in lung repair, EGFR inhibition led to improved survival and reduced acute lung injury, which prompted an investigation into this protective mechanism. Endothelial EGFR genetic knockout did not confer protection. EGFR inhibition led to decreased levels …

Integrins As Therapeutic Targets For Sars-Cov-2, Timothy E. Gressett, Danielle Nader, Juan Pablo Robles, Tione Buranda, Steven W. Kerrigan, Gregory Bix

Pathology Research and Scholarship

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA virus of the genus Betacoronavirus. Its genome is composed of four structural proteins known as spike (S), envelope (E), membrane (M), and nucleocapsid (N), of which E, M, and N are integrated into the viral envelope. The S glycoprotein, which protrudes from the surface of mature virions as a spike, is essential for virus attachment, fusion, and entry into the host cell. While the relationship between the spike protein of SARS-CoV-2 and the angiotensin- converting enzyme 2 (ACE2) receptor has been readily established, the S1 subunit also …

Whistling Scrotum: An Unusual Presentation Of Pneumomediastinum In The Setting Of An Open Scrotal Wound, Brant Bickford, Andrew J. Berglund, Ronald J. Markert, Hari Polenakovik

Internal Medicine Faculty Publications

BACKGROUND Pneumoscrotum is a rare clinical occurrence in which air accumulates in the scrotum. The origin of air is primarily from trauma, but spontaneous pneumoscrotum can develop from gastrointestinal or pulmonary sources. Physical examination of pneumoscrotum typically includes crepitus of the perineal region and scrotal swelling and associated findings depending on the origin of the free air. However, pneumoscrotum in the setting of a scrotal wound, which allows air to pass freely outside the body, has not been previously documented in the literature. CASE REPORT A 72-year-old man who recently underwent a scrotal incision and drainage for recurrent epididymitis presented …