Digital Commons Network^™

Application Of Artificial Intelligence And Machine Learning For Hiv Prevention Interventions, Yang Xiang, Jingcheng Du, Kayo Fujimoto, Fang Li, John Schneider, Cui Tao

Faculty, Staff and Student Publications

In 2019, the US Government announced its goal to end the HIV epidemic within 10 years, mirroring the initiatives set forth by UNAIDS. Public health prevention interventions are a crucial part of this ambitious goal. However, numerous challenges to this goal exist, including improving HIV awareness, increasing early HIV infection detection, ensuring rapid treatment, optimising resource distribution, and providing efficient prevention services for vulnerable populations. Artificial intelligence has had a pivotal role in revolutionising health care and has shown great potential in developing effective HIV prevention intervention strategies. Although artificial intelligence has been used in a few HIV prevention intervention …

The Neighborhood Environment And Hispanic/Latino Health, Natalia I Heredia, Tianlin Xu, Minjae Lee, Lorna H Mcneill, Belinda M Reininger

Faculty, Staff and Student Publications

PURPOSE: Hispanic/Latino adults on the Texas-Mexico border have high rates of chronic disease. Neighborhoods can influence health, though there is a limited research on neighborhood environment and health in Hispanics/Latinos. The purpose of this study was to assess the relation of neighborhood environment with health variables in Hispanic/Latino adults, including physical activity [PA], depression, anxiety, and lab-assessed conditions (type 2 diabetes, metabolic syndrome, and chronic inflammation).

METHODS: Participants were randomly-selected from a Hispanic/Latino cohort on the Texas-Mexico border. Neighborhood environment, self-reported PA, anxiety, and depression were assessed through questionnaires. Laboratory values determined Type 2 diabetes, metabolic syndrome, and C-reactive protein …

Maternal Occupational Exposures And Fetal Growth In A Spanish Birth Cohort, Jennifer Ish, David Gimeno Ruiz De Porras, Elaine Symanski, Ferran Ballester, Maribel Casas, George L Delclos, Mònica Guxens, Jesús Ibarluzea, Carmen Iñiguez, Loreto Santa-Marina, Michael D Swartz, Kristina W Whitworth

Faculty, Staff and Student Publications

While the epidemiologic literature suggests certain maternal occupational exposures may be associated with reduced measures of size at birth, the occupational literature employing fetal biometry data to assess fetal growth is sparse. The present study examines associations between maternal occupational exposures and ultrasound-measured fetal growth. We included 1,739 singleton pregnancies from the INfancia y Medio Ambiente (INMA) project (2003-2008). At 32 weeks of pregnancy, interviewers ascertained mothers' employment status and assessed job-related physical loads, work schedules, and job strain during pregnancy. Job titles were linked to a job-exposure matrix to estimate exposure to 10 endocrine disrupting chemical (EDC) groups. We …

Fiber Burden And Asbestos-Related Diseases: An Umbrella Review, José María Ramada Rodilla, Beatriz Calvo Cerrada, Consol Serra Pujadas, George L Delclos, Fernando G Benavides

Faculty, Staff and Student Publications

OBJECTIVE: What are the levels of asbestos exposure that cause each type of health effect? The objective of this study was to review the available scientific evidence on exposure levels for asbestos and their relationship to health effects.

METHOD: An umbrella review of English-language reviews and meta-analyses, from 1980 to March 2021 was conducted. We included reviews involving quantified asbestos exposures and health outcomes. The review has been adapted to the indications of the PRISMA declaration. Methodological quality of the selected studies was assessed using the AMSTAR instrument.

RESULTS: We retrieved 196 references. After applying the search strategy and quality …

Evaluation Of The Kitchen Microbiome And Food Safety Behaviors Of Predominantly Low-Income Families, Christina K Carstens, Joelle K Salazar, Shreela V Sharma, Wenyaw Chan, Charles Darkoh

Faculty, Staff and Student Publications

Bacterial pathogens in the domestic environment present a risk to residents, particularly among susceptible populations. However, the impact of consumer demographic characteristics and food handling methods on kitchen microbiomes is not fully understood. The domestic kitchen bacterial communities of ten predominantly low-income families in Houston, TX, were assessed in conjunction with a cross-sectional food safety survey to evaluate differences in household and surface-specific microbiomes and bacterial foodborne pathogen presence. Three kitchen surfaces within each household, including the sink drain, the refrigerator handle, and the counter, were environmentally sampled and metataxonomically evaluated via targeted 16S rRNA sequencing. Disposable dish sponges were …

Feasibility And Acceptability Of Technology-Supported Sexual Health Education Among Adolescents Receiving Inpatient Psychiatric Care, Allison E Olmsted, Christine M Markham, Ross Shegog, Ana M Ugueto, Erica L Johnson, Melissa F Peskin, Susan T Emery, Kimberley A Baker, Elizabeth W Newlin

Faculty, Staff and Student Publications

Mental illness in adolescence is associated with high-risk sexual behaviors including multiple sex partners, infrequent or inconsistent condom use, and nonuse of contraception. Inpatient psychiatric care represents a promising setting to provide sexual health education. This pilot study investigates the feasibility and acceptability of online sexual health education in this group by assessing usability and impact on short-term psychosocial outcomes. We administered online modules on healthy relationships, pregnancy prevention, condom use, and sexually transmitted infection (STI) prevention to youth. We evaluated outcomes using a single group, pre/post-intervention design. One quality improvement session assessed staff acceptability of the programming. Participants included …

Determinants Of Social Distancing Adherence, Philip Gerretsen, Julia Kim, Eric E Brown, Lena C Quilty, Samantha Wells, Fernando Caravaggio, Jianmeng Song, Marcos Sanches, Branka Agic, Bruce G Pollock, Ariel Graff-Guerrero

Faculty, Staff and Student Publications

Introduction: Governments and public health authorities across many jurisdictions implemented social (physical) distancing measures to contain the spread of the 2019 novel coronavirus disease (COVID-19). Adherence to these measures is variable and likely influenced by various factors. This study aimed to 1) identify the individual sociodemographic, COVID-19 and social distancing related, and psychological determinants of social distancing adherence, and 2) explore regional differences in social distancing adherence in the United States (U.S.) and English-speaking Canada based on each region's discrepant response to social distancing restrictions.

Methods: A web-based repeated cross-sectional survey was conducted in 4,942 English-speaking participants from the four …

Anti-Grp-R Monoclonal Antibody Antitumor Therapy Against Neuroblastoma, Jingbo Qiao, Junquan Liu, Jillian C Jacobson, Rachael A Clark, Sora Lee, Li Liu, Zhiqiang An, Ningyan Zhang, Dai H Chung

Faculty, Staff and Student Publications

Standard treatment for patients with high-risk neuroblastoma remains multimodal therapy including chemoradiation, surgical resection, and autologous stem cell rescue. Immunotherapy has demonstrated success in treating many types of cancers; however, its use in pediatric solid tumors has been limited by low tumor mutation burdens. Gastrin-releasing peptide receptor (GRP-R) is overexpressed in numerous malignancies, including poorly-differentiated neuroblastoma. Monoclonal antibodies (mAbs) to GRP-R have yet to be developed but could serve as a potential novel immunotherapy. This preclinical study aims to evaluate the efficacy of a novel GRP-R mAb immunotherapy against neuroblastoma. We established four candidate anti-GRP-R mAbs by screening a single-chain …

Risk Of Developing Alzheimer's Disease And Related Dementias In Allhat Trial Participants Receiving Diuretic, Ace-Inhibitor, Or Calcium-Channel Blocker With 18 Years Of Follow-Up, Xianglin L Du, Lara M Simpson, Mikala C Osani, Jose-Miguel Yama, Barry R Davis

Faculty, Staff and Student Publications

BACKGROUND: There is no any large randomized clinical trial of antihypertensive drug treatment with 18-year passive follow-up to examine the risk of Alzheimer's Disease (AD) or Related Dementias (ADRD).

METHODS: Post-trial passive follow-up study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants in 1994-1998 by linking with their Medicare claims data through 2017 among 17,158 subjects in 567 U.S. centers who were free of ADRD at baseline on January 1, 1999. Main outcome was the occurrence of ADRD over 18 years of follow-up.

RESULTS: The 18-year cumulative incidence rates were 30.9% for AD, 59.2% for non-AD …

Blood Metabolites Predicting Mild Cognitive Impairment In The Study Of Latinos-Investigation Of Neurocognitive Aging (Hchs/So), Shan He, Einat Granot-Hershkovitz, Ying Zhang, Jan Bressler, Wassim Tarraf, Bing Yu, Tianyi Huang, Donglin Zeng, Sylvia Wassertheil-Smoller, Melissa Lamar, Martha Daviglus, Maria J Marquine, Jianwen Cai, Thomas Mosley, Robert Kaplan, Eric Boerwinkle, Myriam Fornage, Charles Decarli, Bruce Kristal, Hector M Gonzalez, Tamar Sofer

Faculty, Staff and Student Publications

INTRODUCTION: Blood metabolomics-based biomarkers may be useful to predict measures of neurocognitive aging.

METHODS: We tested the association between 707 blood metabolites measured in 1451 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), with mild cognitive impairment (MCI) and global cognitive change assessed 7 years later. We further used Lasso penalized regression to construct a metabolomics risk score (MRS) that predicts MCI, potentially identifying a different set of metabolites than those discovered in individual-metabolite analysis.

RESULTS: We identified 20 metabolites predicting prevalent MCI and/or global cognitive change. Six of them were novel and 14 were previously reported as …

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …

A Phase I, Open-Label, Dose-Escalation Study Of The Ox40 Agonist Ivuxolimab In Patients With Locally Advanced Or Metastatic Cancers, Adi Diab, Omid Hamid, John A Thompson, Willeke Ros, Ferry A L M Eskens, Toshihiko Doi, Siwen Hu-Lieskovan, Samuel J Klempner, Bishu Ganguly, Catherine Fleener, Xiao Wang, Tenshang Joh, Ken Liao, Shahram Salek-Ardakani, Carrie Turich Taylor, Jeffrey Chou, Anthony B El-Khoueiry

Faculty, Staff and Student Publications

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab …

Inhibition Of The Cd47-Sirpα Axis For Cancer Therapy: A Systematic Review And Meta-Analysis Of Emerging Clinical Data, Ji Son, Rodney Cheng-En Hsieh, Heather Y Lin, Kate J Krause, Ying Yuan, Amadeo B Biter, James Welsh, Michael A Curran, David S Hong

Faculty, Staff and Student Publications

CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). …

Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger

Faculty, Staff and Student Publications

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and

Checkpoint Inhibitors As Immunotherapy For Fungal Infections: Promises, Challenges, And Unanswered Questions, Sebastian Wurster, Stephanie S Watowich, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic …

Enhancing Mesenchymal Stromal Cell Potency: Inflammatory Licensing Via Mechanotransduction, Max A Skibber, Scott D Olson, Karthik S Prabhakara, Brijesh S Gill, Charles S Cox

Faculty, Staff and Student Publications

Mesenchymal stromal cells (MSC) undergo functional maturation upon their migration from bone marrow and introduction to a site of injury. This inflammatory licensing leads to heightened immune regulation via cell-to-cell interaction and the secretion of immunomodulatory molecules, such as anti-inflammatory mediators and antioxidants. Pro-inflammatory cytokines are a recognized catalyst of inflammatory licensing; however, biomechanical forces, such as fluid shear stress, are a second, distinct class of stimuli that incite functional maturation. Here we show mechanotransduction, achieved by exposing MSC to various grades of wall shear stress (WSS) within a scalable conditioning platform, enhances the immunomodulatory potential of MSC independent of …

Factors Associated With Ventilator Weaning Success And Failure In People With Spinal Cord Injury In An Acute Inpatient Rehabilitation Setting: A Retrospective Study, Radha Korupolu, Hannah Uhlig-Reche, Emmanuel Chigozie Achilike, Colton Reeh, Claudia Pedroza, Argyrios Stampas

Faculty, Staff and Student Publications

OBJECTIVES: To evaluate baseline characteristics, describe pulmonary outcomes, and identify weaning predictors for people with acute traumatic spinal cord injury (SCI) who are dependent on mechanical ventilation at admission to acute inpatient rehabilitation (AIR).

METHODS: The retrospective study was conducted at an AIR facility in the United States. It included 91 adults with acute traumatic SCI from 2015 to 2019 who were dependent on mechanical ventilation.

RESULTS: People who successfully weaned (85%) had fewer days from time of SCI to AIR admission (22 vs. 30,

CONCLUSION: In this retrospective study, there was an increased risk of pneumonia in people with …

Neurovascular Disease: 2022 Update, Louise D Mccullough

Faculty, Staff and Student Publications

In this update we present a series of papers focused on topics that have emerged in vascular disease over the prior year. The first two papers focus on the pathogenesis of vascular malformations, the first on brain arteriovenous malformations, and the second on cerebral cavernous malformations. These disorders can lead to significant brain injuries from intracerebral hemorrhage (if they rupture) or other neurological complications, including seizures. The next set of papers reflects work that has advanced our understanding of how the brain and the immune system "communicate" after brain injury, including stroke (papers 3-6). The first of these shows that …

Cytokines And Chemokines Profile In Encephalitis Patients: A Meta-Analysis, Alireza Soltani Khaboushan, Mohammad-Taha Pahlevan-Fallahy, Parnian Shobeiri, Antônio L Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

Background: Encephalitis is caused by autoimmune or infectious agents marked by brain inflammation. Investigations have reported altered concentrations of the cytokines in encephalitis. This study was conducted to determine the relationship between encephalitis and alterations of cytokine levels in cerebrospinal fluid (CSF) and serum.

Methods: We found possibly suitable studies by searching PubMed, Embase, Scopus, and Web of Science, systematically from inception to August 2021. 23 articles were included in the meta-analysis. To investigate sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. The protocol of the study has been registered in PROSPERO with a registration ID of CRD42021289298. …

Dysregulated Hypothalamic-Pituitary-Adrenal Axis Is Associated With Increased Inflammation And Worse Outcomes After Ischemic Stroke In Diabetic Mice, Sehee Kim, Eun S Park, Peng R Chen, Eunhee Kim

Faculty, Staff and Student Publications

Diabetic patients have larger infarcts, worse neurological deficits, and higher mortality rate after an ischemic stroke. Evidence shows that in diabetes, the hypothalamic-pituitary-adrenal (HPA) axis was dysregulated and levels of cortisol increased. Based on the role of the HPA axis in immunity, we hypothesized that diabetes-dysregulated stress response exacerbates stroke outcomes via regulation of inflammation. To test this hypothesis, we assessed the regulation of the HPA axis in diabetic mice before and after stroke and determined its relevance in the regulation of post-stroke injury and inflammation. Diabetes was induced in C57BL/6 mice by feeding a high-fat diet and intraperitoneal injection …

Targeting Etosis By Mir-155 Inhibition Mitigates Mixed Granulocytic Asthmatic Lung Inflammation, Ji Young Kim, Patrick Stevens, Manjula Karpurapu, Hyunwook Lee, Joshua A Englert, Pearlly Yan, Tae Jin Lee, Navjot Pabla, Maciej Pietrzak, Gye Young Park, John W Christman, Sangwoon Chung

Faculty, Staff and Student Publications

Asthma is phenotypically heterogeneous with several distinctive pathological mechanistic pathways. Previous studies indicate that neutrophilic asthma has a poor response to standard asthma treatments comprising inhaled corticosteroids. Therefore, it is important to identify critical factors that contribute to increased numbers of neutrophils in asthma patients whose symptoms are poorly controlled by conventional therapy. Leukocytes release chromatin fibers, referred to as extracellular traps (ETs) consisting of double-stranded (ds) DNA, histones, and granule contents. Excessive components of ETs contribute to the pathophysiology of asthma; however, it is unclear how ETs drive asthma phenotypes and whether they could be a potential therapeutic target. …

Emerging Evidence For Intrathecal Management Of Neuropathic Pain Following Spinal Cord Injury, Jay Karri, James Doan, Christian Vangeison, Marissa Catalanotto, Ameet S Nagpal, Sheng Li

Faculty, Staff and Student Publications

A high prevalence of patients with spinal cord injury (SCI) suffer from chronic neuropathic pain. Unfortunately, the precise pathophysiological mechanisms underlying this phenomenon have yet to be clearly elucidated and targeted treatments are largely lacking. As an unfortunate consequence, neuropathic pain in the population with SCI is refractory to standard of care treatments and represents a significant contributor to morbidity and suffering. In recent years, advances from SCI-specific animal studies and translational models have furthered our understanding of the neuronal excitability, glial dysregulation, and chronic inflammation processes that facilitate neuropathic pain. These developments have served advantageously to facilitate exploration into …

Cushioned On The Way Up, Controlled On The Way Down During Resuscitative Endovascular Balloon Occlusion Of The Aorta (Reboa): Investigating A Novel Compliant Balloon Design For Optimizing Safe Overinflation Combined With Partial Reboa Ability, Adam Power, Asha Parekh, Neil Parry, Laura J Moore

Faculty, Staff and Student Publications

Background: There are a variety of devices capable of performing resuscitative endovascular balloon occlusion of the aorta (REBOA), with most containing compliant balloon material. While compliant material is ideal for balloon inflation due to its "cushioning" effect, it can be problematic to "control" during deflation. The COBRA-OS (Control Of Bleeding, Resuscitation, Arterial Occlusion System) was designed to optimize inflation and deflation of its compliant balloon and was tested in vitro and in vivo with respect to its overinflation and partial REBOA abilities.

Methods: For overinflation, the COBRA-OS was inflated in three differently sized inner diameter (ID) vinyl tubes until balloon …

Traumatized Triad Of Complementopathy, Endotheliopathy, And Coagulopathy – Impact On Clinical Outcomes In Severe Polytrauma Patients, Zhangsheng Yang, Tuan D Le, Milomir O Simovic, Bin Liu, Tamara L Fraker, Tomas S Cancio, Andrew P Cap, Charles E Wade, Jurandir J Dallelucca, Yansong Li

Faculty, Staff and Student Publications

Complementopathy, endotheliopathy, and coagulopathy following a traumatic injury are key pathophysiological mechanisms potentially associated with multiple-organ failure (MOF) and mortality. However, the heterogeneity in the responses of complementopathy, endotheliopathy, and coagulopathy to trauma, the nature and extent of their interplay, and their relationship to clinical outcomes remain unclear. Fifty-four poly-trauma patients were enrolled and divided into three subgroups based on their ISS. Biomarkers in blood plasma reflecting complement activation, endothelial damage, and coagulopathy were measured starting from admission to the emergency department and at 3, 6, 12, 24, and 120 hours after admission. Comparative analyses showed that severely injured patients …

Mri Free Water As A Biomarker For Cognitive Performance: Validation In The Markvcid Consortium, Pauline Maillard, Laura J Hillmer, Hanzhang Lu, Konstantinos Arfanakis, Brian T Gold, Christopher E Bauer, Joel H Kramer, Adam M Staffaroni, Lara Stables, Danny J J Wang, Sudha Seshadri, Claudia L Satizabal, Alexa Beiser, Mohamad Habes, Myriam Fornage, Thomas H Mosley, Gary A Rosenberg, Baljeet Singh, Herpreet Singh, Kristin Schwab, Karl G Helmer, Steven M Greenberg, Charles Decarli, Arvind Caprihan

Faculty, Staff and Student Publications

Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging-based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function.

Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years).

Results: Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores (p …