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Faculty Recruitment, Retention, And Representation In Leadership: An Evidence-Based Guide To Best Practices For Diversity, Equity, And Inclusion From The Council Of Residency Directors In Emergency Medicine, Dayle Davenport, Al'ai Alvarez, Sreeja Natesan, Martina T. Caldwell, Moises Gallegos, Adaira Landry, Melissa Parsons, Michael Gottlieb Jan 2022

Faculty Recruitment, Retention, And Representation In Leadership: An Evidence-Based Guide To Best Practices For Diversity, Equity, And Inclusion From The Council Of Residency Directors In Emergency Medicine, Dayle Davenport, Al'ai Alvarez, Sreeja Natesan, Martina T. Caldwell, Moises Gallegos, Adaira Landry, Melissa Parsons, Michael Gottlieb

Emergency Medicine Articles

Improving the recruitment, retention, and leadership advancement of faculty who are under-represented in medicine is a priority at many academic institutions to ensure excellence in patient care, research, and health equity. Here we provide a critical review of the literature and offer evidence-based guidelines for faculty recruitment, retention, and representation in leadership. Recommendations for recruitment include targeted recruitment to expand the candidate pool with diverse candidates, holistic review of applications, and incentivizing stakeholders for success with diversity efforts. Retention efforts should establish a culture of inclusivity, promote faculty development, and evaluate for biases in the promotion and tenure process. We …


Comparison Of Etdrs 7-Field To 4-Widefield Digital Imaging In The Evaluation Of Diabetic Retinopathy Severity, Barbara A Blodi, Amitha Domalpally, Ashley H Tjaden, Nancy Barrett, Emily Y Chew, William C Knowler, Christine G Lee, Xavier Pi-Sunyer, Amisha Wallia, Neil H White, Marinella Temprosa Jan 2022

Comparison Of Etdrs 7-Field To 4-Widefield Digital Imaging In The Evaluation Of Diabetic Retinopathy Severity, Barbara A Blodi, Amitha Domalpally, Ashley H Tjaden, Nancy Barrett, Emily Y Chew, William C Knowler, Christine G Lee, Xavier Pi-Sunyer, Amisha Wallia, Neil H White, Marinella Temprosa

Open Access Publications

Purpose: To compare Early Treatment Diabetic Retinopathy Study (ETDRS) severity levels between two digital fundus imaging protocols for research studies of diabetic retinopathy: the gold standard 7-field (7F) imaging and the more recent 4-widefield (4W) imaging.

Methods: Two hundred twenty-two participants enrolled in the Diabetes Prevention Program Outcomes Study underwent concurrent 7F and 4W imaging. The ETDRS levels from 220 paired gradable images were determined by masked graders. Each image was graded by two independent graders with adjudication by a senior grader, if necessary. Percent agreement between graders and between imaging protocols was evaluated with kappa statistics and weighted kappa …


Venetoclax Plus Azacitidine In Japanese Patients With Untreated Acute Myeloid Leukemia Ineligible For Intensive Chemotherapy, Kazuhito Yamamoto, Atsushi Shinagawa, Courtney D Dinardo, Keith W Pratz, Kenichi Ishizawa, Toshihiro Miyamoto, Norio Komatsu, Yasuhiro Nakashima, Chikashi Yoshida, Noriko Fukuhara, Kensuke Usuki, Takahiro Yamauchi, Noboru Asada, Norio Asou, Ilseung Choi, Yasushi Miyazaki, Hideyuki Honda, Sumiko Okubo, Misaki Kurokawa, Ying Zhou, Jiuhong Zha, Jalaja Potluri, Itaru Matsumura Jan 2022

Venetoclax Plus Azacitidine In Japanese Patients With Untreated Acute Myeloid Leukemia Ineligible For Intensive Chemotherapy, Kazuhito Yamamoto, Atsushi Shinagawa, Courtney D Dinardo, Keith W Pratz, Kenichi Ishizawa, Toshihiro Miyamoto, Norio Komatsu, Yasuhiro Nakashima, Chikashi Yoshida, Noriko Fukuhara, Kensuke Usuki, Takahiro Yamauchi, Noboru Asada, Norio Asou, Ilseung Choi, Yasushi Miyazaki, Hideyuki Honda, Sumiko Okubo, Misaki Kurokawa, Ying Zhou, Jiuhong Zha, Jalaja Potluri, Itaru Matsumura

Faculty, Staff and Student Publications

Background: The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients.

Methods: Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on …


Psychosis-Induced Exertional Rhabdomyolysis Without Acute Kidney Injury Or Myoglobinuria., Joann M Butkus, Mackenzie Kramer, Vincent Chan, Eunha Kim Jan 2022

Psychosis-Induced Exertional Rhabdomyolysis Without Acute Kidney Injury Or Myoglobinuria., Joann M Butkus, Mackenzie Kramer, Vincent Chan, Eunha Kim

Abington Jefferson Health Papers

BACKGROUND Rhabdomyolysis is a clinical syndrome that results from skeletal muscle breakdown and the release of intracellular enzymes into systemic circulation [1,2]. We present a case of non-traumatic rhabdomyolysis with transaminitis, without myoglobinuria or acute kidney injury. Cases reports of rhabdomyolysis with elevation of serum creatine kinase (hyperCKemia) in the absence of myoglobinuria or renal failure are limited in the literature.

CASE REPORT A 21-year-old man presented to the Emergency Department following an acute psychotic episode. One week earlier, his bloodwork had been within normal limits. Biochemical investigations on admission revealed hyperCKemia (590 000 U/L), transaminitis (AST, 628; ALT, 160), …


Interlaboratory Performance In Measurement Of Dabigatran And Rivaroxaban, Oksana Volod, Marian Rollins-Raval, Andrew J. Goodwin, Russell A. Higgins, Thomas Long, Wayne L. Chandler, Neil Sa Harris, Huy P. Pham, James Alexander Isom, Karen Moser, John D. Olson, Kristi J. Smock, Amanda Vansandt, Geoffrey Wool, Dong Chen Jan 2022

Interlaboratory Performance In Measurement Of Dabigatran And Rivaroxaban, Oksana Volod, Marian Rollins-Raval, Andrew J. Goodwin, Russell A. Higgins, Thomas Long, Wayne L. Chandler, Neil Sa Harris, Huy P. Pham, James Alexander Isom, Karen Moser, John D. Olson, Kristi J. Smock, Amanda Vansandt, Geoffrey Wool, Dong Chen

Pathology Research and Scholarship

CONTEXT.—: Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios.

OBJECTIVE.—: To evaluate the performance of DOAC-specific assays for various concentrations of dabigatran and rivaroxaban, assess the interlaboratory variability in measurement of these DOACs, and investigate the responsiveness of the routine clotting assays to various concentrations of these oral anticoagulants.

DESIGN.—: College of American Pathologists proficiency testing survey data from 2013 to 2016 were summarized and analyzed.

RESULTS.—: For dabigatran, the interlaboratory coefficient of variation (CV) of ecarin chromogenic assay was broad (ranging from 7.5% to 29.1%, 6.3% to 15.5%, …


The Efficacy And Safety Of Thrombopoietin Receptor Agonists In Patients With Chronic Liver Disease Undergoing Elective Procedures: A Systematic Review And Meta-Analysis, Ingrid Lindquist, Sven R Olson, Ang Li, Hanny Al-Samkari, Janice H Jou, Owen J T Mccarty, Joseph J Shatzel Jan 2022

The Efficacy And Safety Of Thrombopoietin Receptor Agonists In Patients With Chronic Liver Disease Undergoing Elective Procedures: A Systematic Review And Meta-Analysis, Ingrid Lindquist, Sven R Olson, Ang Li, Hanny Al-Samkari, Janice H Jou, Owen J T Mccarty, Joseph J Shatzel

Faculty, Staff and Students Publications

Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. …


Co-Designing Implementation Strategies For The Walk-Cph Intervention In Denmark Aimed At Increasing Mobility In Acutely Hospitalized Older Patients: A Qualitative Analysis Of Selected Strategies And Their Justifications, Jeanette Wassar Kirk, Per Nilsen, Ove Andersen, Byron J Powell, Tine Tjørnhøj-Thomsen, Thomas Bandholm, Mette Merete Pedersen Jan 2022

Co-Designing Implementation Strategies For The Walk-Cph Intervention In Denmark Aimed At Increasing Mobility In Acutely Hospitalized Older Patients: A Qualitative Analysis Of Selected Strategies And Their Justifications, Jeanette Wassar Kirk, Per Nilsen, Ove Andersen, Byron J Powell, Tine Tjørnhøj-Thomsen, Thomas Bandholm, Mette Merete Pedersen

2020-Current year OA Pubs

BACKGROUND: Selecting appropriate strategies to target barriers to implementing interventions represents a considerable challenge in implementation research and practice. The aim was to investigate what categories of implementation strategies were selected by health care practitioners and their managers in a co-design process and how they justified these strategies aimed at facilitating the implementation of the WALK-Cph intervention.

METHODS: The study used a qualitative research design to explore what implementation strategies were selected and the justifications for selecting these strategies. Workshops were used because this qualitative method is particularly well suited for studying co-design processes that involve substantial attention to social …


Organizational Impact On Healthcare Workers' Moral Injury During Covid-19: A Mixed-Methods Analysis., Katie E Nelson, Ginger C Hanson, Danielle Boyce, Cathaleen D Ley, Deborah Swavely, Michelle Reina, Cynda Hylton Rushton Jan 2022

Organizational Impact On Healthcare Workers' Moral Injury During Covid-19: A Mixed-Methods Analysis., Katie E Nelson, Ginger C Hanson, Danielle Boyce, Cathaleen D Ley, Deborah Swavely, Michelle Reina, Cynda Hylton Rushton

Reading Hospital Nursing Scholarly Activity

OBJECTIVE: The aim of this study was to explore relationships between organizational factors and moral injury among healthcare workers and the impact of perceptions of their leaders and organizations during COVID-19.

BACKGROUND: COVID-19 placed healthcare workers at risk for moral injury, which often involves feeling betrayed by people with authority and can impact workplace culture.

METHODS: Secondary data from a Web-based survey of mid-Atlantic healthcare workers were analyzed using mixed methods. Data were synthesized using the Reina Trust & Betrayal Model.

RESULTS: Fifty-five percent (n = 328/595) of respondents wrote comments. Forty-one percent (n = 134/328) of commenters had moral …


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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 Jan 2022

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 …