Digital Commons Network^™

Development Of Competency-Based Online Genomic Medicine Training (Cogent), Susanne B Haga, Wendy K Chung, Luis A Cubano, Timothy B Curry, Philip E Empey, Geoffrey S Ginsburg, Kara Mangold, Christina Y Miyake, Siddharth K Prakash, Laura B Ramsey, Robb Rowley, Carolyn R Rohrer Vitek, Todd C Skaar, Julia Wynn, Teri A Manolio

Faculty, Staff and Student Publications

The fields of genetics and genomics have greatly expanded across medicine through the development of new technologies that have revealed genetic contributions to a wide array of traits and diseases. Thus, the development of widely available educational resources for all healthcare providers is essential to ensure the timely and appropriate utilization of genetics and genomics patient care. In 2020, the National Human Genome Research Institute released a call for new proposals to develop accessible, sustainable online education for health providers. This paper describes the efforts of the six teams awarded to reach the goal of providing genetic and genomic training …

Trends In Disease Severity Among Critically Ill Children With Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Multicenter Cohort Study In The United States, Catherine E Ross, Jeffrey P Burns, Anne V Grossestreuer, Pallav Bhattarai, Christine A Mckiernan, Jennifer D Franks, Sonja Lehmann, Jill L Sorcher, Matthew P Sharron, Kitman Wai, Haitham Al-Wahab, Konstantinos Boukas, Mark W Hall, George Ru, Anita I Sen, Hariprem R Rajasekhar, Lawrence C Kleinman, John K Mcguire, Amy S Arrington, Flor Munoz-Rivas, Christopher M Osborne, Lara S Shekerdemian

Faculty, Staff and Student Publications

OBJECTIVES: To describe trends in critical illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children over the course of the COVID-19 pandemic. We hypothesized that PICU admission rates were higher in the Omicron period compared with the original outbreak but that fewer patients needed endotracheal intubation.

DESIGN: Retrospective cohort study.

SETTING: This study took place in nine U.S. PICUs over 3 weeks in January 2022 (Omicron period) compared with 3 weeks in March 2020 (original period).

PATIENTS: Patients less than or equal to 21 years old who screened positive for SARS-CoV-2 infection by polymerase chain reaction or …

Optical Coherence Tomography For Dynamic Investigation Of Mammalian Reproductive Processes, Kohei Umezu, Irina V Larina

Faculty, Staff and Students Publications

The biological events associated with mammalian reproductive processes are highly dynamic and tightly regulated by molecular, genetic, and biomechanical factors. Implementation of live imaging in reproductive research is vital for the advancement of our understanding of normal reproductive physiology and for improving the management of reproductive disorders. Optical coherence tomography (OCT) is emerging as a promising tool for dynamic volumetric imaging of various reproductive processes in mice and other animal models. In this review, we summarize recent studies employing OCT-based approaches toward the investigation of reproductive processes in both, males and females. We describe how OCT can be applied to …

Indices Of Sarcopenic Obesity Are Important Predictors Of Finite Element Analysis-Derived Bone Strength In Older Adults With Obesity, Giulia Gregori, Arjun Paudyal, Yoann Barnouin, Alessandra Celli, Martha Belen Segoviano-Escobar, Reina Armamento-Villareal, Nicola Napoli, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

BACKGROUND: The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT).

METHODS: One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m

RESULTS: Both ALM/W and HGS were positively correlated explaining 28% …

Treatment And Life Goals Among Veterans With Gulf War Illness, Nicole Sullivan, Hannah Schorpp, Sarah Crosky, Scott Thien, Drew A Helmer, David R Litke, Wilfred R Pigeon, Karen S Quigley, Lisa M Mcandrew

Center for Medical Ethics and Health Policy Staff Publications

Medically unexplained syndromes (MUS), also termed persistent physical symptoms, are both prevalent and disabling. Yet treatments for MUS are marked by high rates of patient dissatisfaction, as well as disagreement between patients and providers on the management of persistent physical symptoms. A better understanding of patient-generated goals could increase collaborative goal setting and promote person-centered care, a critical component of MUS treatment; yet research in this area is lacking. This paper aimed to develop a typology of treatment and life goals among Gulf War veterans with a medically unexplained syndrome (Gulf War Illness). We examined participants’ responses to open-ended questions …

Biological Embedding Of Early Trauma: The Role Of Higher Prefrontal Synaptic Strength, Amanda J F Tamman, Lihong Jiang, Christopher L Averill, Graeme F Mason, Lynnette A Averill, Chadi G Abdallah

Staff and Researcher Publications

Background: Early trauma predicts poor psychological and physical health. Glutamatergic synaptic processes offer one avenue for understanding this relationship, given glutamate's abundance and involvement in reward and stress sensitivity, emotion, and learning. Trauma-induced glutamatergic excitotoxicity may alter neuroplasticity and approach/avoidance tendencies, increasing risk for psychiatric disorders. Studies examine upstream or downstream effects instead of glutamatergic synaptic processes in vivo, limiting understanding of how trauma affects the brain.Objective: In a pilot study using a previously published data set, we examine associations between early trauma and a proposed measure of synaptic strength in vivo in one of the largest human …

Figg At 5: An Update On Us Public Perspectives On Forensic Investigative Genetic Genealogy Five Years After Its Introduction To Criminal Investigations, Sophie L Schott, April Adams, Ryan J Dougherty, Taylor Montgomery, Folasade C Lapite, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

Nearly 50 years after Roe versus Wade, the United States Supreme Court's decision in Dobbs versus Jackson Women's Health Organization unraveled the constitutional right to abortion, allowing individual states to severely restrict or ban the procedure. In response, leading medical, public health, and community organizations have renewed calls for research to elucidate and address the burgeoning social and medical consequences of new abortion restrictions. Abortion research not only includes studies that establish the safety, quality, and efficacy of evidence-based abortion care protocols, but also encompasses studies on the availability of abortion care, the consequences of being denied an abortion, and …

Care4ad: A Technology-Driven Platform For Care Coordination And Management: Acceptability Study In Dementia, Ram Kinker Mishra, Catherine Park, Anmol Salim Momin, Nesreen El Rafaei, Mark Kunik, Michele K York, Bijan Najafi

Center on Aging Staff Publications

Introduction: The technology-driven solution can reduce the caregiving burden; however, the needs of dementia caregiving are unique, and attitudes towards adopting technology from the perspectives of all the stakeholders involved in dementia caregiving are unclear. This study aims to assess the acceptability and feasibility of a technology-driven platform to facilitate care coordination platform, Care4AD, from the end-user perspective.

Methods: Care4AD includes three components: (1) Care4AD app: the app is used by caregivers to coordinate care, monitor physical activity, and schedule reminders; (2) Care4AD tablet: a smart tablet is used by the care recipient to display scheduled reminders; and (3) Care4AD …

Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lise E Nigrovic, Nathan Kuppermann, Simona Ghetti, Jeff E Schunk, Michael J Stoner, Arleta Rewers, Julie K Mcmanemy, Kimberly S Quayle, Jennifer L Trainor, Leah Tzimenatos, Jonathan E Bennett, Maria Y Kwok, Sage R Myers, Kathleen M Brown, T Charles Casper, Cody S Olsen, Nicole S Glaser

Faculty, Staff and Students Publications

Background: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of childhood diabetes. However, the influence of demographic factors on presentation are not well-defined.

Methods: We included children from 12 centers who were < 18 years with DKA (glucose > 300 mg/dL, serum pH < 7.25, or serum bicarbonate < 15 mEq/L) enrolled in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Trial. Data were also collected for children who presented to the centers during the enrollment period but were not enrolled due to disease or treatment-related reasons. We compared demographic, clinical, and biochemical findings among children with newly and previously diagnosed diabetes and children in different age groups.

Results: Of the 1,679 DKA episodes in 1,553 children, 799 (47.5%) episodes occurred in children with newly diagnosed diabetes and 396 (23.6%) were severe (pH < 7.1). Newly diagnosed children < 6 years of age were not more likely to have severe DKA in terms of pH, but had more severe hypocarbia and higher blood urea nitrogen levels, factors previously associated with the risk of cerebral injury. Lower socioeconomic status (SES) (based on family income and maternal education level) were associated with more severe DKA in new onset children, and recurrent DKA in the previously diagnosed children.

Conclusions: Greater efforts are needed to identify the children with diabetes early and to prevent recurrent DKA, particularly among children in low-SES groups. Young children with DKA may need more intensive monitoring due to higher risk of cerebral injury.

Dual-Task Upper Extremity Motor Performance Measured By Video Processing As Cognitive-Motor Markers For Older Adults, Changhong Wang, Mohsen Zahiri, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Introduction: The use of dual-task model such as dual-task gait has been extensively studied to assess cognitive-motor performance among older adults. However, space restriction and safety factor limit its applications in remote assessment. To address the gap, we propose a video processing-based approach to remotely quantify cognitive-motor performance using a 20-s repetitive elbow flexion-extension test with dual-task condition, called video-based motoric-cognitive meter (MCM).

Methods: Eighteen older participants (age: 78.6 ± 6.5 years) who were clinically diagnosed as having either mild cognitive impairment or dementia were included in this study. Participants were asked to perform 20-s repetitive elbow flexion-extension exercise with …

Renewed Calls For Abortion-Related Research In The Post-Roe Era, Sophie L Schott, April Adams, Ryan J Dougherty, Taylor Montgomery, Folasade C Lapite, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

Nearly 50 years after Roe versus Wade, the United States Supreme Court's decision in Dobbs versus Jackson Women's Health Organization unraveled the constitutional right to abortion, allowing individual states to severely restrict or ban the procedure. In response, leading medical, public health, and community organizations have renewed calls for research to elucidate and address the burgeoning social and medical consequences of new abortion restrictions. Abortion research not only includes studies that establish the safety, quality, and efficacy of evidence-based abortion care protocols, but also encompasses studies on the availability of abortion care, the consequences of being denied an abortion, and …

Coronary Heart Disease And Ischemic Stroke Polygenic Risk Scores And Atherosclerotic Cardiovascular Disease In A Diverse, Population-Based Cohort Study, Allison Bebo, Jamie A Jarmul, Mark J Pletcher, Natalie R Hasbani, David Couper, Vijay Nambi, Christie M Ballantyne, Myriam Fornage, Alanna C Morrison, Christy L Avery, Paul S De Vries

Faculty, Staff and Student Publications

The predictive ability of coronary heart disease (CHD) and ischemic stroke (IS) polygenic risk scores (PRS) have been evaluated individually, but whether they predict the combined outcome of atherosclerotic cardiovascular disease (ASCVD) remains insufficiently researched. It is also unclear whether associations of the CHD and IS PRS with ASCVD are independent of subclinical atherosclerosis measures. 7,286 White and 2,016 Black participants from the population-based Atherosclerosis Risk in Communities study who were free of cardiovascular disease and type 2 diabetes at baseline were included. We computed previously validated CHD and IS PRS consisting of 1,745,179 and 3,225,583 genetic variants, respectively. Cox …

Alveolar Macrophages In Lung Cancer: Opportunities Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Alveolar macrophages (AMs) are critical components of the innate defense mechanism in the lung. Nestled tightly within the alveoli, AMs, derived from the yolk-sac or bone marrow, can phagocytose foreign particles, defend the host against pathogens, recycle surfactant, and promptly respond to inhaled noxious stimuli. The behavior of AMs is tightly dependent on the environmental cues whereby infection, chronic inflammation, and associated metabolic changes can repolarize their effector functions in the lungs. Several factors within the tumor microenvironment can re-educate AMs, resulting in tumor growth, and reducing immune checkpoint inhibitors (ICIs) efficacy in patients treated for non-small cell lung cancer …

Diversity And Evolution Of Computationally Predicted T Cell Epitopes Against Human Respiratory Syncytial Virus, Jiani Chen, Swan Tan, Vasanthi Avadhanula, Leonard Moise, Pedro A Piedra, Anne S De Groot, Justin Bahl

Faculty, Staff and Students Publications

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory infection. Despite more than 60 years of research, there is no licensed vaccine. While B cell response is a major focus for vaccine design, the T cell epitope profile of RSV is also important for vaccine development. Here, we computationally predicted putative T cell epitopes in the Fusion protein (F) and Glycoprotein (G) of RSV wild circulating strains by predicting Major Histocompatibility Complex (MHC) class I and class II binding affinity. We limited our inferences to conserved epitopes in both F and G proteins that have been experimentally …

Pregnancy-Induced Differential Expression Of Sars-Cov-2 And Influenza A Viral Entry Factors In The Lower Respiratory Tract, Tusar Giri, Santosh Panda, Arvind Palanisamy

2020-Current year OA Pubs

Despite differences in the clinical presentation of coronavirus disease-19 and pandemic influenza in pregnancy, fundamental mechanistic insights are currently lacking because of the difficulty in recruiting critically ill pregnant subjects for research studies. Therefore, to better understand host-pathogen interaction during pregnancy, we performed a series of foundational experiments in pregnant rats at term gestation to assess the expression of host entry factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) and genes associated with innate immune response in the lower respiratory tract. We report that pregnancy is characterized by a decrease in host factors mediating …

Genetics Of Vegetarianism: A Genome-Wide Association Study, Nabeel R. Yaseen, Catriona L. K. Barnes, Lingwei Sun, Akiko Takeda, John P. Rice

2020-Current year OA Pubs

A substantial body of evidence points to the heritability of dietary preferences. While vegetarianism has been practiced for millennia in various societies, its practitioners remain a small minority of people worldwide, and the role of genetics in choosing a vegetarian diet is not well understood. Dietary choices involve an interplay between the physiologic effects of dietary items, their metabolism, and taste perception, all of which are strongly influenced by genetics. In this study, we used a genome-wide association study (GWAS) to identify loci associated with strict vegetarianism in UK Biobank participants. Comparing 5,324 strict vegetarians to 329,455 controls, we identified …

Supplementary Feeding And Infection Control In Pregnant Adolescents-A Secondary Analysis Of A Randomized Trial Among Malnourished Women In Sierra Leone, Aminata S Koroma, Mariama Ellie, Kadiatu Bangura, Per O Iversen, David T Hendrixson, Kevin Stephenson, Mark J Manary

2020-Current year OA Pubs

Undernutrition during pregnancy in adolescence confers a high risk of maternal morbidity and adverse birth outcomes, particularly in low-resource settings. In a secondary analysis, we hypothesized that younger undernourished pregnant adolescents (<18 years) would benefit more than undernourished pregnant adults (>20 years) from the intervention of supplementary food and anti-infective treatments. The original trial in Sierra Leone enrolled 236 younger adolescents (<18 years), 454 older adolescents (aged 18-19 years), and 741 adults (≥20 years), all with a mid-upper arm circumference ≤23 cm. Younger adolescents had lower final fundal height as well as smaller newborns (-0.3 kg; 95% confidence interval [CI], -0.3, -0.2; p < 0.001) and shorter newborns (-1.1 cm; 95% CI, -1.5, -0.7; p < 0.001) than adults. The intervention's effect varied significantly between maternal age groups: adults benefited more than younger adolescents with respect to newborn birth weight (difference in difference, 166 g; 95% CI, 26, 306; interaction p = 0.02), birth length (difference in difference, 7.4 mm; 95% CI, 0.1, 14.8; interaction p = 0.047), and risk for low birth weight (<2.5 kg) (interaction p = 0.019). The differences in response persisted despite adjustments for maternal anthropometry, the number of prior pregnancies, and human immunodeficiency virus status. Older adolescents similarly benefited more than younger adolescents, though differences did not reach statistical significance. In conclusion, newborns born to younger adolescent mothers had worse outcomes than those born to adult mothers, and adults and their newborns benefited more from the intervention than younger adolescents.

Apolipoprotein E Genetic Variation, Atherogenic Index And Cardiovascular Disease Risk Assessment In An African Population: An Analysis Of Hiv And Malaria Patients In Ghana, Nicholas Ekow Thomford, Akwasi Anyanful, Richmond Owusu Ateko, Dee Blackhurst, Robert Peter Biney, Dennis Boadi, Samuel Badu Nyarko, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to …

Abundance Of Acvr1b Transcript Is Elevated During Septic Conditions: Perspectives Obtained From A Hands-On Reductionist Investigation, Anucha Preechanukul, Thatcha Yimthin, Sarunporn Tandhavanant, Tobias Brummaier, Chalita Chomkatekaew, Sukanta Das, Basirudeen Syed Ahamed Kabeer, Mohammed Toufiq, Darawan Rinchai, T Eoin West, Damien Chaussabel, Narisara Chantratita, Mathieu Garand

2020-Current year OA Pubs

Sepsis is a complex heterogeneous condition, and the current lack of effective risk and outcome predictors hinders the improvement of its management. Using a reductionist approach leveraging publicly available transcriptomic data, we describe a knowledge gap for the role of ACVR1B (activin A receptor type 1B) in sepsis. ACVR1B, a member of the transforming growth factor-beta (TGF-beta) superfamily, was selected based on the following: 1) induction upon

A Novel Interaction Between Extracellular Vimentin And Fibrinogen In Fibrin Formation, Marina Martinez-Vargas, Adrian Cebula, Lisa S Brubaker, Nitin Seshadri, Fong W Lam, Michele Loor, Todd K Rosengart, Andrew Yee, Rolando E Rumbaut, Miguel A Cruz

Faculty, Staff and Students Publications

INTRODUCTION: Thrombosis is frequently manifested in critically ill patients with systemic inflammation, including sepsis and COVID-19. The coagulopathy in systemic inflammation is often associated with increased levels of fibrinogen and D-dimer. Because elevated levels of vimentin have been detected in sepsis, we sought to investigate the relationship between vimentin and the increased fibrin formation potential observed in these patients.

MATERIALS AND METHODS: This hypothesis was examined by using recombinant human vimentin, anti-vimentin antibodies, plasma derived from healthy and critically ill patients, confocal microscopy, co-immunoprecipitation assays, and size exclusion chromatography.

RESULTS: The level of vimentin in plasma derived from critically ill …

A Novel Use Of Bar Code Medication Administration Data To Assess Nurse Staffing And Workload, Melissa K Knox, Paras D Mehta, Lynette E Dorsey, Christine Yang, Laura A Petersen

Faculty, Staff and Students Publications

OBJECTIVE: The aim of the study is to introduce an innovative use of bar code medication administration (BCMA) data, medication pass analysis, that allows for the examination of nurse staffing and workload using data generated during regular nursing workflow.

METHODS: Using 1 year (October 1, 2014-September 30, 2015) of BCMA data for 11 acute care units in one Veterans Affairs Medical Center, we determined the peak time for scheduled medications and included medications scheduled for and administered within 2 hours of that time in analyses. We established for each staff member their daily peak-time medication pass characteristics (number of patients, …

Allele-Specific Quantification Of Human Leukocyte Antigen Transcript Isoforms By Nanopore Sequencing, Andrew E O Hughes, Maureen C Montgomery, Chang Liu, Eric T Weimer

2020-Current year OA Pubs

INTRODUCTION: While tens of thousands of HLA alleles have been identified by DNA sequencing, the contribution of alternative splicing to HLA diversity is not well characterized. In this study, we sought to determine if long-read sequencing could be used to accurately quantify allele-specific HLA transcripts in primary human lymphocytes.

METHODS: cDNA libraries were prepared from peripheral blood lymphocytes from 12 donors and sequenced by nanopore long-read sequencing. HLA reads were aligned to donor-specific reference sequences based on the known type of each donor. Allele-specific exon utilization was calculated as the proportion of reads aligning to each allele containing known exons, …

Treatment Of Severe Covid-19 Infection With Remdesivir In Peritoneal Dialysis, Ryan Geffin, Shazia Raheem, Lavannya M Pandit, Andrew S Hunter, Michael W Holliday, Aditya V Rao, Maulin K Shah

Faculty, Staff and Students Publications

End-stage kidney disease (ESKD) has been shown to be correlated with an increased risk of COVID-19 infection and mortality. Remdesivir is an effective non-EUA U.S. Food and Drug Administration (FDA)-approved antiviral agent for the treatment of COVID-19 in hospitalized adult and pediatric patients, though a lack of data has prevented its use in patients with severe kidney disease including dialysis patients. Some observational studies report the use of remdesivir in hemodialysis patients, but there are no reports of patients treated with remdesivir on peritoneal dialysis. Dialysis modalities may affect drug pharmacokinetics, and safety and efficiency of remdesivir in peritoneal dialysis …

Direct Proteomic Detection And Prioritization Of 19 Onchocerciasis Biomarker Candidates In Humans, Bruce A Rosa, Kurt Curtis, Petra Erdmann Gilmore, John Martin, Qiang Zhang, Robert Sprung, Gary J Weil, R Reid Townsend, Peter U Fischer, Makedonka Mitreva

2020-Current year OA Pubs

Onchocerca volvulus, the causative agent of onchocerciasis, infects over 20 million people and can cause severe dermatitis and ocular conditions including blindness. Current treatments employed in mass drug administration programs do not kill adult female worms, and common diagnostic tests cannot reliably assess viability of adult worms. There is an urgent need for better diagnostic tests to facilitate monitoring the efficacy of new treatments and disease elimination efforts. Here, eight plasma samples collected from individuals infected with O. volvulus and seven from uninfected individuals were analyzed by MS/MS spectrometry to directly identify O. volvulus proteins present in infected but absent …

Proteins In Tumor-Derived Plasma Extracellular Vesicles Indicate Tumor Origin, Meltem Barlin, Petra Erdmann-Gilmore, Jacqueline L Mudd, Qiang Zhang, Robert W Seymour, Zhanfang Guo, Julia R Miessner, S Peter Goedegebuure, Ye Bi, Omar A Osorio, Jennifer Alexander-Brett, Shunqiang Li, Cynthia X Ma, Ryan C Fields, R Reid Townsend, Jason M Held

2020-Current year OA Pubs

Cancer-derived extracellular vesicles (EVs) promote tumorigenesis, premetastatic niche formation, and metastasis via their protein cargo. However, the proteins packaged by patient tumors into EVs cannot be determined in vivo because of the presence of EVs derived from other tissues. We therefore developed a cross-species proteomic method to quantify the human tumor-derived proteome of plasma EVs produced by patient-derived xenografts of four cancer types. Proteomic profiling revealed individualized packaging of novel protein cargo, and machine learning accurately classified the type of the underlying tumor.

Engineered Cd4 T Cells Expressing A Membrane Anchored Viral Inhibitor Restrict Hiv-1 Through Cis And Trans Mechanisms, Weiming Wang, Khanghy Truong, Chaobaihui Ye, Suman Sharma, Huan He, Lihong Liu, Michael Wen, Anisha Misra, Paul Zhou, Jason T Kimata

Faculty, Staff and Students Publications

HIV-1 infection of target cells can occur through either cell-free virions or cell-cell transmission in a virological synapse, with the latter mechanism of infection reported to be 100- to 1,000-fold more efficient. Neutralizing antibodies and entry inhibitors effectively block cell-free HIV-1, but with few exceptions, they display much less inhibitory activity against cell-mediated HIV-1 transmission. Previously, we showed that engineering HIV-1 target cells by genetically linking single-chain variable fragments (scFvs) of antibodies to glycosyl phosphatidylinositol (GPI) potently blocks infection by cell-free virions and cell-mediated infection by immature dendritic cell (iDC)-captured HIV-1. Expression of scFvs on CD4

Milder Loss Of Insulin-Containing Islets In Individuals With Type 1 Diabetes And Type 2 Diabetes-Associated Tcf7l2 Genetic Variants, Maria J Redondo, Sarah J Richardson, Daniel Perry, Charles G Minard, Alice L J Carr, Todd Brusko, Irina Kusmartseva, Alberto Pugliese, Mark A Atkinson

Faculty, Staff and Students Publications

AIMS/HYPOTHESIS: TCF7L2 variants are the strongest genetic risk factor for type 2 diabetes. In individuals with type 1 diabetes, these variants are associated with a higher C-peptide AUC, a lower glucose AUC during an OGTT, single autoantibody positivity near diagnosis, particularly in individuals older than 12 years of age, and a lower frequency of type 1 diabetes-associated HLA genotypes. Based on initial observations from clinical cohorts, we tested the hypothesis that type 2 diabetes-predisposing TCF7L2 genetic variants are associated with a higher percentage of residual insulin-containing cells (ICI%) in pancreases of donors with type 1 diabetes, by examining genomic data …

Second Virtual International Symposium On Cellular And Organismal Stress Responses, September 8-9, 2022, Patricija Van Oosten-Hawle, Sarah J Backe, Anat Ben-Zvi, Dimitra Bourboulia, Mara Brancaccio, Jeff Brodsky, Melody Clark, Giorgio Colombo, Marc B Cox, Paolo De Los Rios, Frank Echtenkamp, Adrienne Edkins, Brian Freeman, Pierre Goloubinoff, Walid Houry, Jill Johnson, Paul Lapointe, Wei Li, Valerie Mezger, Len Neckers, Nadinath B Nillegoda, Veena Prahlad, Adam Reitzel, Ruth Scherz-Shouval, Lea Sistonen, Francis T F Tsai, Mark R Woodford, Mehdi Mollapour, Andrew W Truman

Faculty, Staff and Students Publications

The Second International Symposium on Cellular and Organismal Stress Responses took place virtually on September 8-9, 2022. This meeting was supported by the Cell Stress Society International (CSSI) and organized by Patricija Van Oosten-Hawle and Andrew Truman (University of North Carolina at Charlotte, USA) and Mehdi Mollapour (SUNY Upstate Medical University, USA). The goal of this symposium was to continue the theme from the initial meeting in 2020 by providing a platform for established researchers, new investigators, postdoctoral fellows, and students to present and exchange ideas on various topics on cellular stress and chaperones. We will summarize the highlights of …

Multi-Omic Analysis Of The Tumor Microenvironment Shows Clinical Correlations In Ph1 Study Of Atezolizumab +/- Soc In Mm, Sandy Wong, Habib Hamidi, Luciano J Costa, Selma Bekri, Natalia Neparidze, Ravi Vij, Tina G Nielsen, Aparna Raval, Rajan Sareen, Elisabeth Wassner-Fritsch, Hearn J Cho

2020-Current year OA Pubs

Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel …

The Pace Of Biological Aging Helps Explain The Association Between Insomnia And Chronic Low Back Pain, Edwin N Aroke, Asia M Wiggins, Joanna M Hobson, Vinodh Srinivasasainagendra, Tammie L Quinn, Pooja Kottae, Hemant K Tiwari, Robert E Sorge, Burel R Goodin

2020-Current year OA Pubs

Chronic low back pain (cLBP) is associated with insomnia and advanced age. Emerging evidence suggests that the severity of both sleep disorders (like insomnia) and chronic pain are associated with a faster pace of biological aging. We aimed to determine whether the pace of biological age mediates the relationship between insomnia and the impact of cLBP in a sample of community-dwelling adults ages 19 to 85 years. Participants (49 with no pain, 32 with low-impact pain, and 37 with high-impact pain) completed sociodemographic, pain, insomnia, and short physical performance battery assessments. We calculated the pace of biological aging using DunedinPACE …