Medicine and Health Sciences Commons^™

Rapid Detection Of An Ebola Biomarker With Optical Microring Resonators, Abraham J Qavi, Krista Meserve, M Javad Aman, Hong Vu, Larry Zeitlin, John M Dye, Jeffrey W Froude, Daisy W Leung, Lan Yang, Frederick W Holtsberg, Ryan C Bailey, Gaya K Amarasinghe

2020-Current year OA Pubs

Ebola virus (EBOV) is a highly infectious pathogen, with a case mortality rate as high as 89%. Rapid therapeutic treatments and supportive measures can drastically improve patient outcome; however, the symptoms of EBOV disease (EVD) lack specificity from other endemic diseases. Given the high mortality and significant symptom overlap, there is a critical need for sensitive, rapid diagnostics for EVD. Facile diagnosis of EVD remains a challenge. Here, we describe a rapid and sensitive diagnostic for EVD through microring resonator sensors in conjunction with a unique biomarker of EBOV infection, soluble glycoprotein (sGP). Microring resonator sensors detected sGP in under …

Perceptions Of Covid-19 Self-Testing And Recommendations For Implementation And Scale-Up Among Black/African Americans: Implications For The Covid-19 Step Project, Ucheoma Nwaozuru, Thembekile Shato, Et Al.

2020-Current year OA Pubs

BACKGROUND: COVID-19 self-testing (ST) is an innovative strategy with the potential to increase the access and uptake of testing and ultimately to limit the spread of the virus. To maximize the uptake and reach of this promising strategy and inform intervention development and scale up, research is needed to understand the acceptability of and willingness to use this tool. This is vital to ensure that Black/African Americans are reached by the Biden-Harris Administration's free national COVID-19 ST program. This study aimed to explore the acceptability and recommendations to promote and scale-up the uptake of COVID-19 ST among Black/African Americans.

METHODS: …

Promoting Cancer Health Equity: A Qualitative Study Of Mentee And Mentor Perspectives Of A Training Program For Underrepresented Scholars In Cancer Health Disparities, Anastasia Rogova, Isabel Martinez Leal, Maggie Britton, Shine Chang, Kamisha H Escoto, Kayce D Solari Williams, Crystal Roberson, Lorna H Mcneill, Lorraine R Reitzel

Faculty, Staff and Student Publications

Racial and ethnic minorities, and women, experience stark disparities in cancer risk behaviors and mortality rates, yet often remain underrepresented in scientific research positions. We conducted an exploratory, qualitative study to examine the value of mentored research experience as part of an NCI-funded research training program designed to increase the representation of minority and women scientists in cancer disparities research. Using individual interviews, we explored 16 mentees' and 7 mentors' program experiences and perspectives to identify the most effective strategies to build strong mentoring relationships that could ultimately contribute to increased representation in health disparities research. Two expert analysts employed …

Hoxa9 Overexpression Contributes To Stem Cell Overpopulation That Drives Development And Growth Of Colorectal Cancer, Brian Osmond, Caroline O.B. Facey, Chi Zhang, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

HOX proteins are transcription factors that regulate stem cell (SC) function, but their role in the SC origin of cancer is under-studied. Aberrant expression of HOX genes occurs in many cancer types. Our goal is to ascertain how retinoic acid (RA) signaling and the regulation of HOXA9 expression might play a role in the SC origin of human colorectal cancer (CRC). Previously, we reported that aldehyde dehydrogenase (ALDH) and other RA pathway components are co-expressed in colonic cancer SCs (CSCs) and that overpopulation of ALDH-positive CSCs occurs during colon tumorigenesis. Our hypothesis is RA signaling regulates HOXA9 expression, and dysregulated …

Lilrb2-Mediated Trem2 Signaling Inhibition Suppresses Microglia Functions, Peng Zhao, Yuanzhong Xu, Lu-Lin Jiang, Xuejun Fan, Zhiqiang Ku, Leike Li, Xiaoye Liu, Mi Deng, Hisashi Arase, Jay-Jiguang Zhu, Timothy Y Huang, Yingjun Zhao, Chengcheng Zhang, Huaxi Xu, Qingchun Tong, Ningyan Zhang, Zhiqiang An

Faculty, Staff and Student Publications

Background: Microglia plays crucial roles in Alzheimer's disease (AD) development. Triggering receptor expressed on myeloid cells 2 (TREM2) in association with DAP12 mediates signaling affecting microglia function. Here we study the negative regulation of TREM2 functions by leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), an inhibitory receptor bearing ITIM motifs.

Methods: To specifically interrogate LILRB2-ligand (oAβ and PS) interactions and microglia functions, we generated potent antagonistic LILRB2 antibodies with sub-nanomolar level activities. The biological effects of LILRB2 antagonist antibody (Ab29) were studied in human induced pluripotent stem cell (iPSC)-derived microglia (hMGLs) for migration, oAβ phagocytosis, and upregulation of inflammatory …

Effects Of Paternal High-Fat Diet And Maternal Rearing Environment On The Gut Microbiota And Behavior., Austin C Korgan, Christine L Foxx, Heraa Hashmi, Saydie A Sago, Christopher E Stamper, Jared D Heinze, Elizabeth O'Leary, Jillian L King, Tara S Perrot, Christopher A Lowry, Ian C G Weaver

Faculty Research 2022

Exposing a male rat to an obesogenic high-fat diet (HFD) influences attractiveness to potential female mates, the subsequent interaction of female mates with infant offspring, and the development of stress-related behavioral and neural responses in offspring. To examine the stomach and fecal microbiome's potential roles, fecal samples from 44 offspring and stomach samples from offspring and their fathers were collected and bacterial community composition was studied by 16 small subunit ribosomal RNA (16S rRNA) gene sequencing. Paternal diet (control, high-fat), maternal housing conditions (standard or semi-naturalistic housing), and maternal care (quality of nursing and other maternal behaviors) affected the within-subjects …

Ros And Mirna Dysregulation In Ovarian Cancer Development, Angiogenesis And Therapeutic Resistance, David C Stieg, Yifang Wang, Ling-Zhi Liu, Bing-Hua Jiang

Kimmel Cancer Center Faculty Papers

The diverse repertoires of cellular mechanisms that progress certain cancer types are being uncovered by recent research and leading to more effective treatment options. Ovarian cancer (OC) is among the most difficult cancers to treat. OC has limited treatment options, especially for patients diagnosed with late-stage OC. The dysregulation of miRNAs in OC plays a significant role in tumorigenesis through the alteration of a multitude of molecular processes. The development of OC can also be due to the utilization of endogenously derived reactive oxygen species (ROS) by activating signaling pathways such as PI3K/AKT and MAPK. Both miRNAs and ROS are …

B- And T-Cell Subset Abnormalities In Monogenic Common Variable Immunodeficiency, Saba Fekrvand, Shaghayegh Khanmohammadi, Hassan Abolhassani, Reza Yazdani

Department of Neurology Faculty Papers

Common variable immunodeficiency (CVID) is a heterogeneous group of inborn errors of immunity characterized by reduced serum concentrations of different immunoglobulin isotypes. CVID is the most prevalent symptomatic antibody deficiency with a broad range of infectious and non-infectious clinical manifestations. Various genetic and immunological defects are known to be involved in the pathogenesis of CVID. Monogenic defects account for the pathogenesis of about 20-50% of CVID patients, while a variety of cases do not have a defined genetic background. Deficiencies in molecules of B cell receptor signaling or other pathways involving B-cell development, activation, and proliferation could be associated with …

Multisite Assessment Of Emergency Medicine Resident Knowledge Of Evidence-Based Medicine As Measured By The Fresno Test Of Evidence-Based Medicine., James Katsilometes, Michael Galuska, Chadd K Kraus, Howard W Levitin, Scott Leuchten, Jane Daugherty-Luck, Julie Lata, Grace Brannan, Anthony Santarelli, John Ashurst, Foem Research Network

Medical Education Articles

CONTEXT: Evidence-based medicine (EBM) is the application of scientific evidence while treating a patient. To date, however, there is very little evidence describing how residents in emergency medicine understand and incorporate EBM into practice.

OBJECTIVES: The aim of this study was to determine EBM theoretical and quantitative knowledge in emergency medicine residents in community hospital-based training programs.

METHODS: A sample of emergency medicine residents from nine hospitals was enrolled to complete a cross-sectional assessment of EBM skills from April 2021 through June 2021. Performance on the Fresno Test of Evidence-Based Medicine (FTEBM) was assessed utilizing descriptive statistics,

RESULTS: A total …

Genomic Features Underlie The Co-Option Of Sva Transposons As Cis-Regulatory Elements In Human Pluripotent Stem Cells, Samantha M Barnada, Andrew Isopi, Daniela Tejada-Martinez, Clément Goubert, Sruti Patoori, Luca Pagliaroli, Mason Tracewell, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, the mechanisms behind why some TEs are co-opted as functional enhancers while others are not are underappreciated. SINE-VNTR-Alus (SVAs) are the youngest group of transposons in the human genome, where ~3,700 copies are annotated, nearly half of which are human-specific. Many studies indicate that SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such processes have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA domestication …

Chemotherapy Coupled To Macrophage Inhibition Induces T-Cell And B-Cell Infiltration And Durable Regression In Triple-Negative Breast Cancer, Swarnima Singh, Nigel Lee, Diego A Pedroza, Igor L Bado, Clark Hamor, Licheng Zhang, Sergio Aguirre, Jingyuan Hu, Yichao Shen, Yitian Xu, Yang Gao, Na Zhao, Shu-Hsia Chen, Ying-Wooi Wan, Zhandong Liu, Jeffrey T Chang, Daniel Hollern, Charles M Perou, Xiang H F Zhang, Jeffrey M Rosen

Duncan NRI Faculty and Staff Publications

Immunosuppressive elements within the tumor microenvironment, such as tumor-associated macrophages (TAM), can present a barrier to successful anti-tumor responses by cytolytic T cells. Here we employed preclinical syngeneic p53 null mouse models of triple-negative breast cancer (TNBC) to develop a treatment regimen that harnessed the immunostimulatory effects of low-dose cyclophosphamide coupled with the pharmacologic inhibition of TAMs using either a small molecule CSF1R inhibitor or an anti-CSF1R antibody. This therapeutic combination was effective in treating several highly aggressive TNBC murine mammary tumor and lung metastasis models. Single cell RNA sequencing characterized tumor-infiltrating lymphocytes (TIL) including helper T cells and antigen-presenting …

Stat3 Activates The Pentraxin 3 Gene In Chronic Lymphocytic Leukemia Cells, Uri Rozovski, Ivo Veletic, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Taghi Manshouri, Alessandra Ferrajoli, Jan A Burger, Prithviraj Bose, Phillip A Thompson, Nitin Jain, William G Wierda, Srdan Verstovsek, Michael J Keating, Zeev Estrov

Faculty, Staff and Student Publications

Pentraxin-related protein 3 (PTX3), commonly produced by myeloid and endothelial cells, is a humoral pattern recognition protein of the innate immune system. Because PTX3 plasma levels of patients with chronic lymphocytic leukemia (CLL) are high and most circulating cells in patients with CLL are CLL cells, we reasoned that CLL cells produce PTX3. Western immunoblotting revealed that low-density cells from seven of seven patients with CLL produce high levels of PTX3, flow cytometry analysis revealed that the PTX3-producing cells are B lymphocytes coexpressing CD19 and CD5, and confocal microscopy showed that PTX3 is present in the cytoplasm of CLL cells. …

Neoadjuvant Immunotherapy Across Cancers: Meeting Report From The Immunotherapy Bridge-December 1st–2nd, 2021, Elizabeth M Burton, Rodabe N Amaria, Tina Cascone, Myriam Chalabi, Neil D Gross, Elizabeth A Mittendorf, Richard A Scolyer, Padmanee Sharma, Paolo A Ascierto

Faculty, Staff and Student Publications

After the success of immunotherapy in the treatment of advanced metastatic cancer, further evaluation in earlier settings, including high-risk, surgically-resectable disease is underway. Potential benefits of a neoadjuvant immunotherapeutic approach include presurgical tumor shrinkage, reduced surgical morbidity, early eradication of micrometastases and prevention of distant disease, and greater antigen-specific T cell response. For some cancers, pathologic response has been established as a surrogate measure for long-term outcomes, therefore offering the ability for early and objective assessment of treatment efficacy and the potential to inform and personalize adjuvant treatment clinical decision-making. Leveraging the neoadjuvant treatment setting offers the ability to deeply …

Real-World Use Of Palbociclib Monotherapy In Retroperitoneal Liposarcomas At A Large Volume Sarcoma Center, Elise F Nassif, Brandon Cope, Raymond Traweek, Russell G Witt, Derek J Erstad, Christopher P Scally, Prapassorn Thirasastr, Maria Alejandra Zarzour, Joseph Ludwig, Robert Benjamin, Andrew J Bishop, B Ashleigh Guadagnolo, Davis Ingram, Khalida Wani, Wei-Lien Wang, Alexander J Lazar, Keila E Torres, Kelly K Hunt, Barry W Feig, Christina L Roland, Neeta Somaiah, Emily Z Keung

Faculty, Staff and Student Publications

Palbociclib has been evaluated in early phase trials for well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) patients, with reported median progression-free survival (PFS) of 18 weeks. Here, we report on real-world use and surgical outcomes associated with palbociclib treatment. We retrospectively reviewed 61 consecutive patients with retroperitoneal WDLPS (n = 14) or DDLPS (n = 47) treated with palbociclib monotherapy between 1 March 2016 and 28 February 2021 at The University of Texas MD Anderson Cancer Center. At palbociclib initiation, median age was 64 (interquartile range [IQR] 56-72). In WDLPS and DDLPS cohorts, the median number of prior systemic treatments …

Csf Tau Phosphorylation At Thr205 Is Associated With Loss Of White Matter Integrity In Autosomal Dominant Alzheimer Disease, Jeremy F. Strain, Nicolas Barthelemy, Kanta Horie, Brian A. Gordon, Collin Kilgore, Andrew Aschenbrenner, Carlos Cruchaga, Chengjie Xiong, Nelly Joseph-Mathurin, Jason Hassenstab, Anne M. Fagan, Yan Li, Celeste M. Karch, Richard J. Perrin, Sarah B. Berman, Jasmeer P. Chhatwal, Neill R. Graff-Radford, Hiroshi Mori, Johannes Levin, James M. Noble, Ricardo Allegri, Peter R. Schofield, Daniel S. Marcus, David M. Holtzman, John C. Morris, Tammie L. S. Benzinger, Eric M. Mcdade, Randall J. Bateman, Beau M. Ances

2020-Current year OA Pubs

BACKGROUND: Hyperphosphorylation of tau leads to conformational changes that destabilize microtubules and hinder axonal transport in Alzheimer's disease (AD). However, it remains unknown whether white matter (WM) decline due to AD is associated with specific Tau phosphorylation site(s).

METHODS: In autosomal dominant AD (ADAD) mutation carriers (MC) and non-carriers (NC) we compared cerebrospinal fluid (CSF) phosphorylation at tau sites (pT217, pT181, pS202, and pT205) and total tau with WM measures, as derived from diffusion tensor imaging (DTI), and cognition. A WM composite metric, derived from a principal component analysis, was used to identify spatial decline seen in ADAD.

RESULTS: The …

Anxiety Symptoms And Suicidal Thoughts And Behaviors Among Patients With Mood Disorders, Marsal Sanches, Linh K Nguyen, Tong Han Chung, Paul Nestadt, Holly C Wilcox, William H Coryell, Jair C Soares, Sudhakar Selvaraj

Faculty, Staff and Student Publications

Background: Though the association between anxiety disorders and suicidal behavior is well-described, the impact of anxiety symptoms on suicidal thoughts and behaviors (STB) across different mood disorders is still unclear.

Methods: We performed a registry-based retrospective study utilizing outcome measure data collected by the National Network of Depression Centers (NNDC), a nationwide nonprofit consortium of 26 leading clinical and academic member centers in the United States. The sample consisted of 2607 outpatients with mood disorders (major depressive disorder or bipolar disorders). Demographic and clinical variables were compared based on the presence or absence of STB and severity of anxiety symptoms …

The Csf In Neurosarcoidosis Contains Consistent Clonal Expansion Of Cd8 T Cells, But Not Cd4 T Cells, Michael A Paley, Brandi J Baker, S Richard Dunham, Nicole Linskey, Claudia Cantoni, Kenneth Lee, Lynn M Hassman, Jennifer Laurent, Elisha D O Roberson, David B Clifford, Wayne M Yokoyama

2020-Current year OA Pubs

The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing of CSF and blood cells from neurosarcoid participants coupled to T and B cell receptor sequencing. In contrast to pulmonary sarcoidosis, which is driven by CD4 T cells, we found CD8 T cell clonal expansion enriched in the neurosarcoid CSF. These CSF-enriched CD8 T cells were composed of two subsets with differential expression of EBI2, CXCR3, and CXCR4. Lastly, our data suggest that IFNγ signaling may distinguish neurosarcoidosis from other neurological disorders.

A Dual-Center Cohort Study On The Association Between Early Deep Sedation And Clinical Outcomes In Mechanically Ventilated Patients During The Covid-19 Pandemic: The Covid-Sed Study, Robert J Stephens, Erin M Evans, Michael J Pajor, Ryan D Pappal, Haley M Egan, Max Wei, Hunter Hayes, Jason A Morris, Nicholas Becker, Brian W Roberts, Marin H Kollef, Nicholas M Mohr, Brian M Fuller

2020-Current year OA Pubs

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes.

STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over …

The Microbiome Restrains Melanoma Bone Growth By Promoting Intestinal Nk And Th1 Cell Homing To Bone, Subhashis Pal, Daniel S. Perrien, Tetsuya Yumoto, Roberta Faccio, Andreea Stoica, Jonathan Adams, Craig M. Coopersmith, Rheinallt M. Jones, M. Neale Weitzmann, Roberto Pacifici

2020-Current year OA Pubs

Bone metastases are frequent complications of malignant melanoma leading to reduced quality of life and significant morbidity. Regulation of immune cells by the gut microbiome influences cancer progression, but the role of the microbiome in tumor growth in bone is unknown. Using intracardiac or intratibial injections of B16-F10 melanoma cells into mice, we showed that gut microbiome depletion by broad-spectrum antibiotics accelerated intraosseous tumor growth and osteolysis. Microbiome depletion blunted melanoma-induced expansion of intestinal NK cells and Th1 cells and their migration from the gut to tumor-bearing bones. Demonstrating the functional relevance of immune cell trafficking from the gut to …

Pluripotent Cell States And Unexpected Fates., Martin Pera

Faculty Research 2022

Pluripotent stem cells provide a powerful model for the study of human development and its disorders. Recent studies, including two in this issue of Stem Cell Reports, raise important questions concerning the developmental potential of human pluripotent stem cells, and how the behavior of these cells in vitro mirrors normal embryogenesis.

Navigation Programs Relevant For African American Men With Prostate Cancer: A Scoping Review Protocol, Nynikka R. Palmer, Ashley Nicole Smith, Brittany A. Campbell, Ghilamichael Andemeskel, Peggy Tahir, Tisha M. Felder Phd, Msw, Barbara Cicerelli

Publications

BACKGROUND:

The excess incidence and mortality due to prostate cancer that impacts African American men constitutes the largest of all cancer disparities. Patient navigation is a patient-centered healthcare system intervention to eliminate barriers to timely, high-quality care across the cancer continuum and improves health outcomes among vulnerable patients. However, little is known regarding the extent to which navigation programs include cultural humility to address prostate cancer disparities among African American men. We present a scoping review protocol of an in-depth examination of navigation programs in prostate cancer care-including navigation activities/procedures, training, and management-with a special focus on cultural context and …

Challenges And Opportunities For Advancing Patient-Centered Clinical Decision Support: Findings From A Horizon Scan, Prashila Dullabh, Shana F Sandberg, Krysta Heaney-Huls, Lauren S Hovey, David F Lobach, Aziz Boxwala, Priyanka J Desai, Elise Berliner, Chris Dymek, Michael I Harrison, James Swiger, Dean F Sittig

Faculty, Staff and Student Publications

OBJECTIVE: We conducted a horizon scan to (1) identify challenges in patient-centered clinical decision support (PC CDS) and (2) identify future directions for PC CDS.

MATERIALS AND METHODS: We engaged a technical expert panel, conducted a scoping literature review, and interviewed key informants. We qualitatively analyzed literature and interview transcripts, mapping findings to the 4 phases for translating evidence into PC CDS interventions (Prioritizing, Authoring, Implementing, and Measuring) and to external factors.

RESULTS: We identified 12 challenges for PC CDS development. Lack of patient input was identified as a critical challenge. The key informants noted that patient input is critical …

Sirpα+ Macrophages Are Increased In Patients With Fl Who Progress Or Relapse After Frontline Lenalidomide And Rituximab, Mario L Marques-Piubelli, Edwin R Parra, Lei Feng, Luisa Solis Soto, Mariana Gallardo, Sushanth Gouni, Felipe Samaniego, Mansoor Noorani, Fredrick B Hagemeister, Jason R Westin, Hun Ju Lee, Maria A Rodriguez, Sattva S Neelapu, Jillian R Gunther, Nathan H Fowler, Christopher R Flowers, Ignacio I Wistuba, Loretta J Nastoupil, Francisco Vega, Paolo Strati

Faculty, Staff and Student Publications

Limited data exist regarding the outcome of patients with follicular lymphoma (FL) who relapse or progress after frontline lenalidomide and rituximab (R2). Moreover, mechanisms of resistance to R2 in FL remain unclear, with increased protumoral macrophages suspected as a major contributory culprit to this phenomenon. This retrospective study analyzed the outcome of patients with advanced-stage FL grade 1 to 3A who relapsed or progressed after frontline R2. A multiplex immunofluorescence macrophage panel, including CD47, CD14, CD68, CD115 (also known as colony-stimulating factor 1 receptor [CSF1R]), CD163, CD172a (also known as signal regulatory protein α [SIRPα]), and CD274 (also known as …

Up To 8-Year Follow-Up From Resonate-2: First-Line Ibrutinib Treatment For Patients With Chronic Lymphocytic Leukemia, Paul M Barr, Carolyn Owen, Tadeusz Robak, Alessandra Tedeschi, Osnat Bairey, Jan A Burger, Peter Hillmen, Steve E Coutre, Claire Dearden, Sebastian Grosicki, Helen Mccarthy, Jian-Yong Li, Fritz Offner, Carol Moreno, Cathy Zhou, Emily Hsu, Anita Szoke, Thomas J Kipps, Paolo Ghia

Faculty, Staff and Student Publications

We report long-term follow-up from the RESONATE-2 phase 3 study of the once-daily Bruton's tyrosine kinase inhibitor ibrutinib, which is the only targeted therapy with significant progression-free survival (PFS) and overall survival (OS) benefit in multiple randomized chronic lymphocytic leukemia (CLL) studies. Patients (≥65 years) with previously untreated CLL, without del(17p), were randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease progression/unacceptable toxicity (n = 136) or chlorambucil 0.5-0.8 mg/kg ≤12 cycles (n = 133). With up to 8 years of follow-up (range, 0.1-96.6 months; median, 82.7 months), significant PFS benefit was sustained for ibrutinib vs chlorambucil (hazard ratio …

Indoleamine 2,3-Dioxygenase 1 Activation In Mature Cdc1 Promotes Tolerogenic Education Of Inflammatory Cdc2 Via Metabolic Communication, Marco Gargaro, Carlos G. Briseño, Prachi Bagadia, Vivek Durai, Derek J. Theisen, Sunkyung Kim, Marco Colonna, Theresa L. Murphy, Kenneth M. Murphy, Et Al.

2020-Current year OA Pubs

Conventional dendritic cells (cDCs), cDC1 and cDC2, act both to initiate immunity and maintain self-tolerance. The tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is used by cDCs in maintaining tolerance, but its role in different subsets remains unclear. At homeostasis, only mature CCR7

Associations Of Maternal Lipoprotein Particle Distribution In Mid-Pregnancy With Birth Outcomes: A Pilot Study., Todd C. Rideout, Xiaozhong Wen, Divya Choudhary, Marissa Catanzaro, Richard W. Browne, Vanessa M. Barnabei, Kai Ling Kong

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: An excessive rise in maternal lipids during pregnancy may have detrimental impacts on maternal and fetal health leading to adverse pregnancy outcomes. However, knowledge gaps exist with respect to the association between lipid biomarkers and birth outcomes.

METHODS: We conducted a secondary data analysis of healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22-28 weeks of gestation and birth outcome data. Serum was analyzed for conventional lipid profile (total-C, HDL-C, LDL-C, and triglycerides) and lipoprotein subclass distribution, including particle number (nM) and size (nm), for very low-density lipoprotein (VLDL)/chylomicron (CM), low density lipoprotein (LDL), …

Estimating Circadian Phase In Elementary School Children: Leveraging Advances In Physiologically Informed Models Of Circadian Entrainment And Wearable Devices, Jennette P Moreno, Kevin M Hannay, Olivia Walch, Hafza Dadabhoy, Jessica Christian, Maurice Puyau, Abeer El-Mubasher, Fida Bacha, Sarah R Grant, Rebekah Julie Park, Philip Cheng

Faculty, Staff and Students Publications

STUDY OBJECTIVES: Examine the ability of a physiologically based mathematical model of human circadian rhythms to predict circadian phase, as measured by salivary dim light melatonin onset (DLMO), in children compared to other proxy measurements of circadian phase (bedtime, sleep midpoint, and wake time).

METHODS: As part of an ongoing clinical trial, a sample of 29 elementary school children (mean age: 7.4 ± .97 years) completed 7 days of wrist actigraphy before a lab visit to assess DLMO. Hourly salivary melatonin samples were collected under dim light conditions (<5 >lx). Data from actigraphy were used to generate predictions of circadian …

Variants In Asph Cause Exertional Heat Illness And Are Associated With Malignant Hyperthermia Susceptibility, Yukari Endo, Linda Groom, Alper Celik, Natalia Kraeva, Chang Seok Lee, Sung Yun Jung, Lois Gardner, Marie-Anne Shaw, Susan L Hamilton, Philip M Hopkins, Robert T Dirksen, Sheila Riazi, James J Dowling

Faculty, Staff and Students Publications

Exertional heat illness (EHI) and malignant hyperthermia (MH) are life threatening conditions associated with muscle breakdown in the setting of triggering factors including volatile anesthetics, exercise, and high environmental temperature. To identify new genetic variants that predispose to EHI and/or MH, we performed genomic sequencing on a cohort with EHI/MH and/or abnormal caffeine-halothane contracture test. In five individuals, we identified rare, pathogenic heterozygous variants in ASPH, a gene encoding junctin, a regulator of excitation-contraction coupling. We validated the pathogenicity of these variants using orthogonal pre-clinical models, CRISPR-edited C2C12 myotubes and transgenic zebrafish. In total, we demonstrate that ASPH variants represent …

Assessing Covid-19 Testing Strategies In K-12 Schools In Underserved Populations: Study Protocol For A Cluster-Randomized Trial, Samantha Hayes, Sara Malone, Brittany Bonty, Nancy Mueller, Summer M Reyes, Sydney A Reyes, Christina Evans, Myisha Wilcher-Roberts, Tremayne Watterson, Sewuese Akuse, Jamee Shelley, Grace Yuan, Ian Lackey, Jasmine Prater, Brock Montgomery, Cynthia Williams, Sheretta T Butler-Barnes, Kelly Harris, Charlene Caburnay, Nikole Lobb Dougherty, Jingxia Liu, Albert Lai, Julie Neidich, Stephanie Fritz, Jason G Newland

2020-Current year OA Pubs

BACKGROUND: Since March 2020, COVID-19 has disproportionately impacted communities of color within the United States. As schools have shifted from virtual to in-person learning, continual guidance is necessary to understand appropriate interventions to prevent SARS-CoV-2 transmission. Weekly testing of students and staff for SARS-CoV-2 within K-12 school setting could provide an additional barrier to school-based transmission, especially within schools unable to implement additional mitigation strategies and/or are in areas of high transmission. This study seeks to understand the role that weekly SARS-CoV-2 testing could play in K-12 schools. In addition, through qualitative interviews and listening sessions, this research hopes to …

Atr-Mediated Cd47 And Pd-L1 Up-Regulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Rodney Cheng-En Hsieh, Sunil Krishnan, Ren-Chin Wu, Akash R Boda, Arthur Liu, Michelle Winkler, Wen-Hao Hsu, Steven Hsesheng Lin, Mien-Chie Hung, Li-Chuan Chan, Krithikaa Rajkumar Bhanu, Anupallavi Srinivasamani, Ricardo Alexandre De Azevedo, Yung-Chih Chou, Ronald A Depinho, Matthew Gubin, Eduardo Vilar, Chao Hsien Chen, Ravaen Slay, Priyamvada Jayaprakash, Shweta Mahendra Hegde, Genevieve Hartley, Spencer T Lea, Rishika Prasad, Brittany Morrow, Coline Agnes Couillault, Madeline Steiner, Chun-Chieh Wang, Bhanu Prasad Venkatesulu, Cullen Taniguchi, Yon Son Betty Kim, Junjie Chen, Nils-Petter Rudqvist, Michael A Curran

Faculty, Staff and Student Publications

Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, abscopal tumor remissions are extremely rare, and the postirradiation immune escape mechanisms in CRC remain elusive. Here, we found that irradiated CRC cells used ATR-mediated DNA repair signaling pathway to up-regulate both CD47 and PD-L1, which through engagement of SIRPα and PD-1, respectively, prevented phagocytosis by antigen-presenting cells and thereby limited TAA cross-presentation and innate immune activation. This postirradiation CD47 and PD-L1 up-regulation was observed across various human solid tumor cells. Concordantly, rectal cancer patients with poor responses to neoadjuvant RT exhibited …