Medicine and Health Sciences Commons^™

Computational Investigation Of A Series Of Small Molecules As Potential Compounds For Lysyl Hydroxylase-2 (Lh2) Inhibition, Yazdan Maghsoud, Erik Antonio Vázquez-Montelongo, Xudong Yang, Chengwen Liu, Zhifeng Jing, Juhoon Lee, Matthew Harger, Ally K Smith, Miguel Espinoza, Hou-Fu Guo, Jonathan M Kurie, Kevin N Dalby, Pengyu Ren, G Andrés Cisneros

Faculty, Staff and Student Publications

The catalytic function of lysyl hydroxylase-2 (LH2), a member of the Fe(II)/αKG-dependent oxygenase superfamily, is to catalyze the hydroxylation of lysine to hydroxylysine in collagen, resulting in stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs). Reports show that high amounts of LH2 lead to the accumulation of HLCCs, causing fibrosis and specific types of cancer metastasis. Some members of the Fe(II)/αKG-dependent family have also been reported to have intramolecular O

Rna Profiling Of Human Dorsal Root Ganglia Reveals Sex Differences In Mechanisms Promoting Neuropathic Pain, Pradipta R Ray, Stephanie Shiers, James P Caruso, Diana Tavares-Ferreira, Ishwarya Sankaranarayanan, Megan L Uhelski, Yan Li, Robert Y North, Claudio Tatsui, Gregory Dussor, Michael D Burton, Patrick M Dougherty, Theodore J Price

Faculty, Staff and Student Publications

Neuropathic pain is a leading cause of high-impact pain, is often disabling and is poorly managed by current therapeutics. Here we focused on a unique group of neuropathic pain patients undergoing thoracic vertebrectomy where the dorsal root ganglia is removed as part of the surgery allowing for molecular characterization and identification of mechanistic drivers of neuropathic pain independently of preclinical models. Our goal was to quantify whole transcriptome RNA abundances using RNA-seq in pain-associated human dorsal root ganglia from these patients, allowing comprehensive identification of molecular changes in these samples by contrasting them with non-pain-associated dorsal root ganglia. We sequenced …

Cd70 Is A Therapeutic Target Upregulated In Emt-Associated Egfr Tyrosine Kinase Inhibitor Resistance, Monique B Nilsson, Yan Yang, Simon Heeke, Sonia A Patel, Alissa Poteete, Hibiki Udagawa, Yasir Y Elamin, Cesar A Moran, Yukie Kashima, Thiruvengadam Arumugam, Xiaoxing Yu, Xiaoyang Ren, Lixia Diao, Li Shen, Qi Wang, Minying Zhang, Jacqulyne P Robichaux, Chunhua Shi, Allyson N Pfeil, Hai Tran, Don L Gibbons, Jason Bock, Jing Wang, John D Minna, Susumu S Kobayashi, Xiuning Le, John V Heymach

Faculty, Staff and Student Publications

Effective therapeutic strategies are needed for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations that acquire resistance to EGFR tyrosine kinase inhibitors (TKIs) mediated by epithelial-to-mesenchymal transition (EMT). We investigate cell surface proteins that could be targeted by antibody-based or adoptive cell therapy approaches and identify CD70 as being highly upregulated in EMT-associated resistance. Moreover, CD70 upregulation is an early event in the evolution of resistance and occurs in drug-tolerant persister cells (DTPCs). CD70 promotes cell survival and invasiveness, and stimulation of CD70 triggers signal transduction pathways known to be re-activated with acquired TKI resistance. …

Early Antibiotics And Risk For Necrotizing Enterocolitis In Premature Infants: A Narrative Review., Alain Cuna, Michael J. Morowitz, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

While prompt initiation of antibiotics at birth due to concerns for early onset sepsis is common, it often leads to many preterm infants being exposed to treatment despite negative blood cultures. Such exposure to early antibiotics can impact the developing gut microbiome putting infants at increased risk of several diseases. Necrotizing enterocolitis (NEC), a devastating inflammatory bowel disease that affects preterm infants, is among the most widely studied neonatal disease that has been linked to early antibiotics. While some studies have demonstrated an increased risk of NEC, other studies have demonstrated seemingly contrary findings of decreased NEC with early antibiotics. …

N-Of-1 Trials Vs Usual Care In Children With Hypertension: A Pilot Randomized Clinical Trial, Joyce P Samuel, Cynthia S Bell, Joshua A Samuels, Celin Rajan, Adrienne K Walton, Charles Green, Jon E Tyson

Faculty, Staff and Student Publications

BACKGROUND: Blood pressure (BP) is often inadequately controlled in children treated for hypertension, and personalized (n-of-1) trials show promise for tailoring treatment choices. We assessed whether patients whose treatment choices are informed by an n-of-1 trial have improved BP control compared to usual care.

METHODS: A randomized clinical trial was conducted in a pediatric hypertension clinic in Houston from April 2018 to September 2020. Hypertensive adolescents and young adults 10-22 years old were randomized 1:1 to a strategy of n-of-1 trial using ambulatory BP monitoring to inform treatment choice or usual care, with treatment selected by physician preference. The primary …

Cell-Membrane-Coated Nanoparticles For Targeted Drug Delivery To The Brain For The Treatment Of Neurological Diseases, Jianzhuang Li, Yanhao Wei, Chunlin Zhang, Rentang Bi, Yanmei Qiu, Yanan Li, Bo Hu

Faculty, Staff and Student Publications

Neurological diseases (NDs) are a significant cause of disability and death in the global population. However, effective treatments still need to be improved for most NDs. In recent years, cell-membrane-coated nanoparticles (CMCNPs) as drug-targeting delivery systems have become a research hotspot. Such a membrane-derived, nano drug-delivery system not only contributes to avoiding immune clearance but also endows nanoparticles (NPs) with various cellular and functional mimicries. This review article first provides an overview of the function and mechanism of single/hybrid cell-membrane-derived NPs. Then, we highlight the application and safety of CMCNPs in NDs. Finally, we discuss the challenges and opportunities in …

The Clinical Suitability Of An Artificial Intelligence-Enabled Pain Assessment Tool For Use In Infants: Feasibility And Usability Evaluation Study, Jeffery David Hughes, Paola Chivers, Kreshnik Hoti

Research outputs 2022 to 2026

Background: Infants are unable to self-report their pain, which, therefore, often goes underrecognized and undertreated. Adequate assessment of pain, including procedural pain, which has short- and long-term consequences, is critical for its management. The introduction of mobile health–based (mHealth) pain assessment tools could address current challenges and is an area requiring further research. Objective: The purpose of this study is to evaluate the accuracy and feasibility aspects of PainChek Infant and, therefore, assess its applicability in the intended setting. Methods: By observing infants just before, during, and after immunization, we evaluated the accuracy and precision at different cutoff scores of …

Emerging Therapeutic Strategies For Diffuse Intrinsic Pontine Glioma: A Systematic Review, Shahrukh Farrukh, Shagufta Habib, Amna Rafaqat, Zouina Sarfraz, Azza Sarfraz, Muzna Sarfraz, Karla Robles-Velasco, Miguel Felix, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Background: Of all central nervous systems tumors, 10-20% are located in the brainstem; diffuse intrinsic pontine glioma (DIPG) is diagnosed in 80% of them. With over five decades of clinical trial testing, there are no established therapeutic options for DIPG. This research article aims to collate recent clinical trial data and provide a landscape for the most promising therapies that have emerged in the past five years.
Methods: PubMed/MEDLINE, Web of Science, Scopus, and Cochrane were systematically searched using the following keywords: Diffuse intrinsic pontine glioma, Pontine, Glioma, Treatment, Therapy, Therapeutics, curative, and/or Management. Both adult and pediatric patients with …

Cross-Cultural Collaborations For Addressing Opioid Use Disorder In Utah, Michelle Q. Chapoose, Cassandra Manning, Erin Fanning Madden, Katie Zaman, Claire Warnick, Suzanne M. Prevedel, Sandra H. Sulzer

All Current Publications

Cross-cultural collaboration allows for more effective interventions for opioid use disorder among tribal communities. Practicing cultural humility, incorporating Indigenous knowledge, and amplifying Indigenous voices are crucial to the cross-cultural collaboration process. This process can ensure that interventions that address opioid use disorder meet the needs of tribal communities.

Community Research Fellows Training Program: Evaluation Of A Covid-19-Precipitated Virtual Adaptation, Nicole Ackermann, Sarah Humble, Jacquelyn V Coats, Carlette Lewis Rhone, Craig Schmid, Vetta Sanders Thompson, Kia L Davis

2020-Current year OA Pubs

Community engagement is important for promoting health equity. However, effective community engagement requires trust, collaboration, and the opportunity for all stakeholders to share in decision-making. Community-based training in public health research can build trust and increase community comfort with shared decision-making in academic and community partnerships. The Community Research Fellows Training (CRFT) Program is a community-based training program that promotes the role of underserved populations in research by enhancing participant knowledge and understanding of public health research and other relevant topics in health. This paper describes the process of modifying the original 15-week in-person training program to a 12-week online, …

Visualization Of Preimplantation Uterine Fluid Absorption In Mice Using Alexa Fluor™ 488 Hydrazide†, Yuehuan Li, Taylor Elijah Martin, Jonathan Matthew Hancock, Rong Li, Suvitha Viswanathan, John P Lydon, Yi Zheng, Xiaoqin Ye

Faculty, Staff and Students Publications

Uterine fluid plays important roles in supporting early pregnancy events and its timely absorption is critical for embryo implantation. In mice, its volume is maximum on day 0.5 post-coitum (D0.5) and approaches minimum upon embryo attachment ~D4.0. Its secretion and absorption in ovariectomized rodents were shown to be promoted by estrogen and progesterone (P4), respectively. The temporal mechanisms in preimplantation uterine fluid absorption remain to be elucidated. We have established an approach using intraluminally injected Alexa Fluor™ 488 Hydrazide (AH) in preimplantation control (RhoAf/f) and P4-deficient RhoAf/fPgrCre/+ mice. In control mice, bulk entry (seen as smeared cellular staining) via uterine …

Epigenetic And Integrative Cross-Omics Analyses Of Cerebral White Matter Hyperintensities On Mri, Yunju Yang, Maria J Knol, Ruiqi Wang, Aniket Mishra, Dan Liu, Michelle Luciano, Alexander Teumer, Nicola Armstrong, Joshua C Bis, Min A Jhun, Shuo Li, Hieab H H Adams, Nasir Ahmad Aziz, Mark E Bastin, Mathieu Bourgey, Jennifer A Brody, Stefan Frenzel, Rebecca F Gottesman, Norbert Hosten, Lifang Hou, Sharon L R Kardia, Valerie Lohner, Pascale Marquis, Susana Muñoz Maniega, Claudia L Satizabal, Farzaneh A Sorond, Maria C Valdés Hernández, Cornelia M Van Duijn, Meike W Vernooij, Katharina Wittfeld, Qiong Yang, Wei Zhao, Eric Boerwinkle, Daniel Levy, Ian J Deary, Jiyang Jiang, Karen A Mather, Thomas H Mosley, Bruce M Psaty, Perminder S Sachdev, Jennifer A Smith, Nona Sotoodehnia, Charles S Decarli, Monique M B Breteler, M Arfan Ikram, Hans J Grabe, Joanna Wardlaw, W T Longstreth, Lenore J Launer, Sudha Seshadri, Stephanie Debette, Myriam Fornage

Faculty, Staff and Student Publications

Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA methylation has received little attention. We investigated the association between white matter hyperintensity burden and DNA methylation in blood at ∼450 000 cytosine-phosphate-guanine (CpG) sites in 9732 middle-aged to older adults from 14 community-based studies. Single CpG and region-based association analyses were carried out. Functional annotation and integrative cross-omics analyses were performed to …

Amniotes Co-Opt Intrinsic Genetic Instability To Protect Germ-Line Genome Integrity, Yu H Sun, Xiaoyu Zhuo, Et Al.

2020-Current year OA Pubs

Unlike PIWI-interacting RNA (piRNA) in other species that mostly target transposable elements (TEs), >80% of piRNAs in adult mammalian testes lack obvious targets. However, mammalian piRNA sequences and piRNA-producing loci evolve more rapidly than the rest of the genome for unknown reasons. Here, through comparative studies of chickens, ducks, mice, and humans, as well as long-read nanopore sequencing on diverse chicken breeds, we find that piRNA loci across amniotes experience: (1) a high local mutation rate of structural variations (SVs, mutations ≥ 50 bp in size); (2) positive selection to suppress young and actively mobilizing TEs commencing at the pachytene …

Rate Of Tarsal And Metatarsal Bone Mineral Density Change In Adults With Diabetes Mellitus And Peripheral Neuropathy: A Longitudinal Study, Nicholas J Youmans, Rachana S Vaidya, Ling Chen, Hyo-Jung Jeong, Alexa York, Paul K Commean, Mary K Hastings, Jennifer A Zellers

2020-Current year OA Pubs

BACKGROUND: In people with diabetes (DM) and peripheral neuropathy (PN), loss of bone mineral density (BMD) in the tarsals and metatarsals contribute to foot complications; however, changes in BMD of the calcaneal bone is most commonly reported. This study reports rate of change in BMD of all the individual bones in the foot, in participants with DM and PN. Our aim was to investigate whether the rate of BMD change is similar across all the bones of the foot.

METHODS: Participants with DM and PN (n = 60) were included in this longitudinal cohort study. Rate of BMD change of …

Severe Ocular Alkali Injury Managed With An Externally Sutured Amniotic Membrane And Customized Symblepharon Ring, Sophia S. Lam, Bonnie Sklar, Marisa Schoen, Christopher J. Rapuano

Student Papers, Posters & Projects

Alkali injuries are ocular emergencies that require immediate evaluation and therapy to preserve vision. Severe alkali injuries can result in long‑term vision‑threatening sequelae including symblepharon, corneal ulceration, corneal scarring, limbal stem cell deficiency, xerophthalmia, cicatricial changes of the eyelid and adnexa, glaucoma, uveitis, and permanent vision loss. Treatment is aimed at neutralizing the pH, controlling inflammation, and restoring the ocular surface. Here, we present the case of a 35‑year‑old male who sustained direct ocular exposure to sodium hydroxide, resulting in significant corneal and conjunctival epithelial defects despite aggressive initial medical therapy. The patient subsequently received a large, externally sutured amniotic …

Experiences Of Covid-19-Related Racism And Impact On Depression Trajectories Among Racially/Ethnically Minoritized Adolescents, Sabrina R. Liu, Elysia Poggi Davis, Anton M. Palma, Hal S. Stern, Curt A. Sandman, Laura M. Glynn

Psychology Faculty Articles and Research

Purpose

In 2020, racially/ethnically minoritized (REMD) youth faced the “dual pandemics” of COVID-19 and racism, both significant stressors with potential for adverse mental health effects. The current study tested whether short- and long-term trajectories of depressive symptoms from before to during the COVID-19 pandemic differed between REMD adolescents who did and did not endorse exposure to COVID-19-era-related racism (i.e., racism stemming from conditions created or exacerbated by the COVID-19 pandemic).

Methods

A community sample of 100 REMD adolescents enrolled in an ongoing longitudinal study of mental health was assessed before and during the COVID-19 pandemic. Participants were 51% girls, mean …

My Life During Covid, Anonymous

Community Reflections

I remember being in chemistry and all of my friends were so excited to have this vacation, not knowing the severity of our indefinite situation. I went home with a group of my friends and I vividly remember my best friend's father telling us that this will be the craziest thing to happen in our lifetime. Obviously we did not care and proceeded to have fun and do everything we wanted. Looking back on that day it was very childish of us all to think that everything would be fine.

Small Molecule Inhibitors Of 15-Pgdh Exploit A Physiologic Induced-Fit Closing System, Wei Huang, Hongyun Li, Janna G. Kiselar, Stephen P. Fink, Sagar Regmi, Alexander Day, Yiyuan Yuan, Mark R. Chance, Sanford D. Markowitz, Derek J. Taylor

Faculty Scholarship

15-prostaglandin dehydrogenase (15-PGDH) is a negative regulator of tissue stem cells that acts via enzymatic activity of oxidizing and degrading PGE2, and related eicosanoids, that support stem cells during tissue repair. Indeed, inhibiting 15-PGDH markedly accelerates tissue repair in multiple organs. Here we have used cryo-electron microscopy to solve the solution structure of native 15-PGDH and of 15-PGDH individually complexed with two distinct chemical inhibitors. These structures identify key 15-PGDH residues that mediate binding to both classes of inhibitors. Moreover, we identify a dynamic 15-PGDH lid domain that closes around the inhibitors, and that is likely fundamental to the physiologic …

Glucose 6-P Dehydrogenase Overexpression Improves Aging-Induced Endothelial Dysfunction In Aorta From Mice: Role Of Arginase Ii, Eva Serna, Maria D Mauricio, Teresa San-Miguel, Sol Guerra-Ojeda, David Verdú, Alicia Valls, Coralie Arc-Chagnaud, Adrián De La Rosa, José Viña

Faculty, Staff and Student Publications

The increase of vascular arginase activity during aging causes endothelial dysfunction. This enzyme competes with the endothelial nitric oxide synthase (eNOS) for L-arginine substrate. Our hypothesis is that glucose 6-P dehydrogenase (G6PD) overexpression could improve the endothelial function modulating the arginase pathway in aorta from mice. For this study, three groups of male mice were used: young wild type (WT) (6-9 months), old WT (21-22 months) and old G6PD-Tg (21-22 months) mice. Vascular reactivity results showed a reduced acetylcholine-dependent relaxation in the old WT but not old G6PD-Tg group. Endothelial dysfunction was reverted by nor-NOHA, an arginase inhibitor. Mice overexpressing …

Adapting International Clinical Trials During Covid-19 And Beyond, Kamala Thriemer, Kamala Thriemer, Mohammad Shafiul Alam, Bipin Adhikari, Rupam Tripura, Mohammad Sharif Hossain, Michael Christian, Najia Bano Ghanchi, Hellen Mnjala, Muhammad Asim

Department of Pathology and Laboratory Medicine

Background: The COVID-19 pandemic and resulting restrictions, particularly travel restrictions, have had significant impact on the conduct of global clinical trials. Our clinical trials programme, which relied on in-person visits for training, monitoring and capacity building across nine low- and middle-income countries, had to adapt to those unprecedented operational challenges. We report the adaptation of our working model with a focus on the operational areas of training, monitoring and cross-site collaboration.
The new working model: Adaptations include changing training strategies from in-person site visits with three or four team members to a multi-pronged virtual approach, with generic online training for …

Outcomes In Participants With Ventilated Nosocomial Pneumonia And Organ Failure Treated With Ceftolozane/Tazobactam Versus Meropenem: A Subset Analysis Of The Phase 3, Randomized, Controlled Aspect-Np Trial, Ignacio Martin-Loeches, Andrew F Shorr, Richard G Wunderink, Marin H Kollef, Jean-François Timsit, Brian Yu, Jennifer A Huntington, Erin Jensen, Christopher J Bruno

2020-Current year OA Pubs

BACKGROUND: The pivotal ASPECT-NP trial showed ceftolozane/tazobactam was non-inferior to meropenem for the treatment of ventilated hospital-acquired/ventilator-associated bacterial pneumonia (vHABP/VABP). Here, we evaluated treatment outcomes by degree of respiratory or cardiovascular dysfunction.

METHODS: This was a subset analysis of data from ASPECT-NP, a randomized, double-blind, non-inferiority trial (ClinicalTrials.gov NCT02070757). Adults with vHABP/VABP were randomized 1:1 to 3 g ceftolozane/tazobactam or 1 g meropenem every 8 h for 8-14 days. Outcomes in participants with a baseline respiratory component of the Sequential Organ Failure Assessment (SOFA) score (R-SOFA) ≥ 2 (indicative of severe respiratory failure), cardiovascular component of the SOFA score (CV-SOFA) …

Advanced Practice Providers Recognized As Valuable Healthcare Resources: Increasing The Illinois Pa’S Scope Of Practice To Match Their Np Cohort, Cheri Kelly Dmsc, Pa-C, Molly Johnson Ms, Apn, Cnp

SIU Journal of Medical Science Scholarly Works

Abstract:

Nurse practitioners (NPs) and physician assistants (PAs) represent a group of non-physician, advanced-practice providers (APPs) within our healthcare system. Non-physician providers are part of an inter-disciplinary team, working alongside physicians and a variety of allied healthcare providers. The purpose of this paper is to take a closer look at these two professions (NP and PA), with a focus on Illinois providers and the legislative strategies that guide their roles and abilities to practice. Illinois is a region where APP practices are inequitably regulated. Their Nurse Practice Act outlines a broad scope of practice for Advanced Practice Registered Nurses (APRNs). …

My Covid Travel Experience, Anonymous

Community Reflections

When I first heard that we were all getting two weeks off from school because of some weird virus, I was really excited. I didn’t know the severity of it until two weeks turned into three weeks, and three turned into six, and then we were out for the rest of the school year. I didn’t get Covid until the very end of it. I was in Europe on Vacation with my family and I was on a cruise.

Mental Toll, Madison Abood

Community Reflections

This is a short reflection on my experience with Covid-19, virtual school, and anxiety throughout the pandemic. This is a reflection of the years 2020 and early 2021.

Senior Night, Anonymous

Community Reflections

This content refelcts on my experience because as the world seemed to be going back to normal, COVID-19 ruined my special night of senior year in 2021 that I looked forward to since being a freshman.

Covid Stress, Anonymous

Community Reflections

My COVID-19 experience was definitely something that I will never forget. At the time with me working in the healthcare field, being a CNA. It brought much stress and especially chaos. After coming home from long shifts helping with elderly patients who were sickened by covid, it definitely was hard to see and it took a toll on me.

Byproduct Of Covid, Anonymous

Community Reflections

No abstract provided.

Covid- 19 Reflection, Anonymous

Community Reflections

I wrote about what was going through my head and what I want people to know about how it affected me.

Covid Pandemic Reflection, Anonymous

Community Reflections

At first feelings of shock, confusion and disappointment started flooding my mind, but over'me as more and more media coverage on the virus surfaced this original two week shut down became a much more serious and scary reality. At first so called “zoom school” didn’t seem so bad, but then the crushing realiza'on of not being able to go out, see friends or even show our faces without a mask quickly came over me.

Hidden Benefit, Anonymous

Community Reflections

During the COVID-19 pandemic, everything that was normal for me was no longer normal.