Digital Commons Network^™

Assessing The Response Results Of An Mhealth-Based Patient Experience Survey Among People Receiving Hiv Care In Lusaka, Zambia: Cohort Study, Jacob Mutale, Kombatende Sikombe, Boroma Mwale, Mwansa Lumpa, Sandra Simbeza, Chama Bukankala, Njekwa Mukamba, Aaloke Mody, Laura K Beres, Charles B Holmes, Carolyn Bolton Moore, Elvin H Geng, Izukanji Sikazwe, Jake M Pry

2020-Current year OA Pubs

BACKGROUND: This pilot study evaluates the effectiveness of mobile talk-time incentives in maintaining participation in a longitudinal mobile health (mHealth) data collection program among people living with HIV in Lusaka, Zambia. While mHealth tools, such as mobile phone surveys, provide vital health feedback, optimal incentive strategies to ensure long-term engagement remain limited. This study explores how different incentive levels affect response rates in multiple survey rounds, providing insights into effective methods for encouraging ongoing participation, especially in the context of Zambia's prepaid mobile system and multi-SIM usage, a common practice in sub-Saharan Africa.

OBJECTIVE: This study aimed to assess the …

Enhancing Recovery: Surgical Techniques And Rehabilitation Strategies After Direct Anterior Hip Arthroplasty, Alberto Di Martino, Christopher Keating, Micahel J. Butsick, Daniela Platano, Lisa Berti, Louis N. Hunter, Cesare Faldini

Department of Physical Therapy Faculty Papers

Total hip arthroplasty (THA) is a common surgical procedure for hip joint pathologies, with the direct anterior approach (DAA) gaining popularity due to potential benefits in postoperative recovery. This review aims to provide a comprehensive analysis of rehabilitation strategies following DAA THA, focusing on surgical techniques, postoperative care, and outcomes. The evolution of the DAA to THA is discussed, highlighting historical advancements and comparisons with other surgical approaches. Surgical techniques and considerations specific to the DAA are detailed, including outcomes and complications compared to alternative approaches. The role of the surgical technique in influencing postoperative rehabilitation is explored, emphasizing the …

Exploring Racial Disparities In Awareness And Perceptions Of Oncology Clinical Trials: Cross-Sectional Analysis Of Baseline Data From The Mychoice Study, Ariel Hoadley, Linda Fleisher, Cassidy Kenny, Patrick Ja Kelly, Xinrui Ma, Jingwei Wu, Carmen Guerra, Amy E. Leader, Mohammed Alhajji, Paul D'Avanzo, Zoe Landau, Sarah Bauerle Bass

Kimmel Cancer Center Faculty Papers

BACKGROUND: Black/African American adults are underrepresented in oncology clinical trials in the United States, despite efforts at narrowing this disparity.

OBJECTIVE: This study aims to explore differences in how Black/African American oncology patients perceive clinical trials to improve support for the clinical trial participation decision-making process.

METHODS: As part of a larger randomized controlled trial, a total of 244 adult oncology patients receiving active treatment or follow-up care completed a cross-sectional baseline survey on sociodemographic characteristics, clinical trial knowledge, health literacy, perceptions of cancer clinical trials, patient activation, patient advocacy, health care self-efficacy, decisional conflict, and clinical trial intentions. Self-reported …

Single-Cell Transcriptomes And Chromatin Accessibility Of Endothelial Cells Unravel Transcription Factors Associated With Dysregulated Angiogenesis In Systemic Sclerosis, Mengqi Huang, Tracy Tabib, Dinesh Khanna, Shervin Assassi, Robyn Domsic, Robert Lafyatis

Faculty, Staff and Student Publications

Objectives: Vasculopathy emerges early in systemic sclerosis (SSc) and links to endothelial cell (EC) injury and angiogenesis. Understanding EC transcriptomes and epigenomes is crucial for unravelling the mechanisms involved.

Methods: Transcriptomes and chromatin accessibility were assessed by single-cell RNA sequencing and single-nucleus transposase-accessible chromatin sequencing. Immunofluorescent staining of skin and proteomics assay were employed to confirm the altered SSc EC phenotypes. Gain-of-function assay was used to evaluate the effects of ETS transcription factors on human dermal ECs (hDECs).

Results: Both control and SSc ECs shared transcriptomic signatures of vascular linages (arterial, capillary and venous ECs) and lymphatic ECs. Arterial ECs …

Barriers And Facilitators To Dental Care Services Utilization Among Children With Disabilities: A Systematic Review And Thematic Synthesis, Shiamaa Al-Mashhadani, Mona Nasser, Anas Alsalami, Lorna Burns, Martha Paisi

Peninsula Dental School

BACKGROUND: This systematic review investigates barriers and enablers to dental care utilization by disabled children. Given the high global prevalence of disabilities in children, coupled with poor oral hygiene and a 45% rate of dental caries in this group, developing inclusive oral health strategies is critical. The review aims to synthesize literature on factors affecting oral healthcare improvement for disabled children, identifying barriers, facilitators and knowledge gaps.

METHODS: The review was conducted following the Joanna Briggs Institute's methods and reported according to PRISMA guidelines. A comprehensive search spanned multiple databases, considering perspectives from carers, parents, dentists and health professionals. The …

Impact Of Covid-19 Lockdown On Patient-Provider Electronic Communications, Michael A Hansen, Rebecca Chen, Jacqueline Hirth, James Langabeer, Roger Zoorob

Faculty, Staff and Students Publications

BACKGROUND: SARS CoV-2 virus (COVID-19) impacted the practice of healthcare in the United States, with technology being used to facilitate access to care and reduce iatrogenic spread. Since then, patient message volume to primary care providers has increased. However, the volume and trend of electronic communications after lockdown remain poorly described in the literature.

METHODS: All incoming inbox items (telephone calls, refill requests, and electronic messages) sent to providers from patients amongst four primary care clinics were collected. Inbox item rates were calculated as a ratio of items per patient encountered each week. Trends in inbox rates were assessed during …

Computational Immune Synapse Analysis Reveals T-Cell Interactions In Distinct Tumor Microenvironments., Victor G Wang, Zichao Liu, Jan Martinek, Ali Foroughi Pour, Jie Zhou, Hannah Boruchov, Kelly Ray, Karolina Palucka, Jeffrey Chuang

Faculty Research 2024

The tumor microenvironment (TME) and the cellular interactions within it can be critical to tumor progression and treatment response. Although technologies to generate multiplex images of the TME are advancing, the many ways in which TME imaging data can be mined to elucidate cellular interactions are only beginning to be realized. Here, we present a novel approach for multipronged computational immune synapse analysis (CISA) that reveals T-cell synaptic interactions from multiplex images. CISA enables automated discovery and quantification of immune synapse interactions based on the localization of proteins on cell membranes. We first demonstrate the ability of CISA to detect …

A Basally Active Cgas-Sting Pathway Limits Sars-Cov-2 Replication In A Subset Of Ace2 Positive Airway Cell Models, Maritza Puray-Chavez, Jenna E Eschbach, Ming Xia, Kyle M Lapak, Qianzi Zhou, Ria Jasuja, Jiehong Pan, Jian Xu, Zixiang Zhou, Shawn Mohammed, Qibo Wang, Dana Q Lawson, Sanja Djokic, Gaopeng Hou, Siyuan Ding, Steven L Brody, Michael B Major, Dennis Goldfarb, Sebla B Kutluay

2020-Current year OA Pubs

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism …

Crinophagic Granules In Pancreatic Β Cells Contribute To Mouse Autoimmune Diabetes By Diversifying Pathogenic Epitope Repertoire, Hao Hu, Anthony N Vomund, Orion J Peterson, Neetu Srivastava, Tiandao Li, Lisa Kain, Wandy L Beatty, Bo Zhang, Chyi-Song Hsieh, Luc Teyton, Cheryl F Lichti, Emil R Unanue, Xiaoxiao Wan

2020-Current year OA Pubs

Autoimmune attack toward pancreatic β cells causes permanent loss of glucose homeostasis in type 1 diabetes (T1D). Insulin secretory granules store and secrete insulin but are also thought to be tissue messengers for T1D. Here, we show that the crinophagic granules (crinosome), a minor set of vesicles formed by fusing lysosomes with the conventional insulin dense-core granules (DCG), are pathogenic in T1D development in mouse models. Pharmacological inhibition of crinosome formation in β cells delays T1D progression without affecting the dominant DCGs. Mechanistically, crinophagy inhibition diminishes the epitope repertoire in pancreatic islets, including cryptic, modified and disease-relevant epitopes derived from …

Nur77 Protects The Bladder Urothelium From Intracellular Bacterial Infection, Christina A Collins, Chevaughn Waller, Ekaterina Batourina, Lokesh Kumar, Cathy L Mendelsohn, Nicole M Gilbert

2020-Current year OA Pubs

Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined. Here we show that Nur77 protects against intracellular infection in the bladder by uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections (UTI). Nur77 deficiency in mice promotes the formation of UPEC intracellular bacterial communities (IBCs) in the cells lining the bladder lumen, leading to persistent infection in bladder tissue. Conversely, treatment with …

Awareness Of, Willingness To Use, And Experiences With Pre-Exposure Prophylaxis Among Youth In Nigeria, Titilola Gbaja-Biamila, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Youth (ages 14-24) in Nigeria have disproportionately high rates of new HIV infection. Pre-exposure prophylaxis could substantially reduce new infections among youth but has not been scaled up. This cross-sectional study aimed to assess Pre-exposure prophylaxis awareness, willingness to use, and prior use of Pre-exposure prophylaxis among youth in Nigeria.

METHODS: This is a secondary analysis of cross-sectional data from a quasi-experimental pilot study (clinical trial NCT04070287). The analysis focused on Pre-exposure prophylaxis awareness, willingness to use, and prior use among 324 youth recruited between September 2019 to March 2020. Descriptive statistics were calculated as frequencies and percentages for …

The Association Of The Oral Microbiota With Cognitive Functioning In Adolescence, Oxana Y Naumova, Pavel V Dobrynin, Galina V Khafizova, Elena L Grigorenko

Faculty, Staff and Students Publications

Background: A growing body of research supports the role of the microbial communities residing in the digestive system in the host's cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged and older adults. There is an insufficiency of population-based research exploring the association of normative cognitive functioning with the microbiome particularly with the oral microbiota.

Methods: In this study, using metagenomics and metabolomics, we characterized the salivary microbiome diversity in a sample of 51 males of Hispanic and African American origin aged 12-18 years and explored …

Spatial Organization Of Adenylyl Cyclase And Its Impact On Dopamine Signaling In Neurons, Léa Ripoll, Yong Li, Carmen W Dessauer, Mark Von Zastrow

Faculty, Staff and Student Publications

The cAMP cascade is increasingly recognized to transduce physiological effects locally through spatially limited cAMP gradients. However, little is known about how adenylyl cyclase enzymes that initiate cAMP gradients are localized. Here we address this question in physiologically relevant striatal neurons and investigate how AC localization impacts downstream signaling function. We show that the major striatal AC isoforms are differentially sorted between ciliary and extraciliary domains of the plasma membrane, and that one isoform, AC9, is uniquely concentrated in endosomes. We identify key sorting determinants in the N-terminal cytoplasmic domain responsible for isoform-specific localization. We further show that AC9-containing endosomes …

Efficacy And Safety Of Glp-1 Analog Ecnoglutide In Adults With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial, Dalong Zhu, Weimin Wang, Guoyu Tong, Guoqing Ma, Jianhua Ma, Jie Han, Xin Zhang, Yang Liu, Shenglian Gan, Hong Qin, Qing Zheng, Jing Ning, Zhiyi Zhu, Mengying Guo, Yue Bu, Yao Li, Catherine L Jones, Martijn Fenaux, Mohammed K Junaidi, Susan Xu, Hai Pan

Faculty, Staff and Student Publications

Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups …

Use Of Web-Based Decision Support To Improve Informed Choice For Chemoprevention: A Qualitative Analysis Of Pre-Implementation Interviews (Swog S1904), Alissa M Michel, Haeseung Yi, Jacquelyn Amenta, Nicole Collins, Anna Vaynrub, Subiksha Umakanth, Garnet Anderson, Katie Arnold, Cynthia Law, Sandhya Pruthi, Ana Sandoval-Leon, Rachel Shirley, Maria Grosse Perdekamp, Sarah Colonna, Stacy Krisher, Tari King, Lisa D Yee, Tarah J Ballinger, Christa Braun-Inglis, Debra A Mangino, Kari Wisinski, Claudia A Deyoung, Masey Ross, Justin Floyd, Andrea Kaster, Lindi Vanderwalde, Thomas J Saphner, Corrine Zarwan, Shelly Lo, Cathy Graham, Alison Conlin, Kathleen Yost, Doreen Agnese, Cheryl Jernigan, Dawn L Hershman, Marian L Neuhouser, Banu Arun, Katherine D Crew, Rita Kukafka

Faculty, Staff and Student Publications

Background: Women with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers.

Methods: The parent trial, MiCHOICE, is a cluster randomized controlled trial evaluating the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. For this pre-implementation analysis, 25 providers participated in semi-structured interviews prior to accessing decision support tools. …

Usf2 And Tfeb Compete In Regulating Lysosomal And Autophagy Genes, Jaebeom Kim, Young Suk Yu, Yehwa Choi, Do Hui Lee, Soobin Han, Junhee Kwon, Taichi Noda, Masahito Ikawa, Dongha Kim, Hyunkyung Kim, Andrea Ballabio, Keun Il Kim, Sung Hee Baek

Duncan NRI Faculty and Staff Publications

Autophagy, a highly conserved self-digestion process crucial for cellular homeostasis, is triggered by various environmental signals, including nutrient scarcity. The regulation of lysosomal and autophagy-related processes is pivotal to maintaining cellular homeostasis and basal metabolism. The consequences of disrupting or diminishing lysosomal and autophagy systems have been investigated; however, information on the implications of hyperactivating lysosomal and autophagy genes on homeostasis is limited. Here, we present a mechanism of transcriptional repression involving upstream stimulatory factor 2 (USF2), which inhibits lysosomal and autophagy genes under nutrient-rich conditions. We find that USF2, together with HDAC1, binds to the CLEAR motif within lysosomal …

Research Priorities For Childhood Apraxia Of Speech: A Long View, Patricia Mccabe, Molly Beiting, Elaine R Hitchcock, Edwin Maas, Amy Meredith, Angela T Morgan, Nancy L Potter, Jonathan L Preston, Laura Moorer, Pooja Aggarwal, Kirrie Ballard, Laura Baskall Smith, Nicole F Caballero, Kathryn Cabbage, Julie Case, Susan Caspari, Karen V Chenausky, Shina Cook, Ewa Grzelak, Maryane Gomez, Aubrie Hagopian, Chantelle Highman, Anne Hodits, Jenya Iuzzini-Seigel, Jillian Levos-Carlson, Barbara A Lewis, Patricia Mayro, Jyutika Mehta, Gabrielle Miller, Kimberly D Mory, Elizabeth Murray, Megan S Overby, Lucia Pasquel-Lefebvre, Derrick Peavy, Caitlin V Raaz, Brooke Rea, Denise Santos Ford, Lynn Smith, Michelle T. Swartz, Melissa Taberski, Hayo Terband, Donna C Thomas, Hannah Valentine, Mirjam Van Tellingen, Shelley Velleman, Emily Wang, Sarah White, Eddy C H Wong, Maria I Grigos

Department of Speech-Language Pathology Faculty Papers

This article introduces the Journal of Speech, Language, and Hearing Research Special Issue: Selected Papers From the 2022 Apraxia Kids Research Symposium. The field of childhood apraxia of speech (CAS) has developed significantly in the past 15 years, with key improvements in understanding of basic biology including genetics, neuroscience, and computational modelling; development of diagnostic tools and methods; diversity of evidence-based interventions with increasingly rigorous experimental designs; and understanding of impacts beyond impairment-level measures. Papers in this special issue not only review and synthesize the some of the substantial progress to date but also present novel findings addressing critical research …

Study Protocol For Writing To Heal: A Culturally Based Brief Expressive Writing Intervention For Chinese Immigrant Breast Cancer Survivors, Qian Lu, Di Lun, Lenna Dawkins-Moultin, Yisheng Li, Minxing Chen, Sharon Hermes Giordano, James W Pennebaker, Lucy Young, Carol Wang

Faculty, Staff and Student Publications

BACKGROUND: This study uses a randomized controlled trial (RCT) to test the health benefits of expressive writing that is culturally adapted for Chinese immigrant breast cancer survivors (BCSs) and to characterize how acculturation moderates the effects of expressive writing interventions.

METHODS: We will recruit Chinese immigrant BCSs (N = 240) diagnosed with stage 0-III breast cancer and within 5 years of completion of primary treatment. Recruitment will occur primarily through community-based organizations and cancer registries. Participants will be randomly assigned either to a control condition to write about neutral topics or to one of two intervention conditions, self-regulation or self-cultivation, …

Skin In The Game: A Review Of Single-Cell And Spatial Transcriptomics In Dermatological Research, Samuel Schepps, Jonathan Xu, Henry Yang, Jenna Mandel, Jaanvi Mehta, Julianna Tolotta, Nicole Baker, Volkan Tekmen, Neda Nikbakht, Paolo Fortina, Ignacia Fuentes, Bonnie Lafleur, Raymond J Cho, Andrew P South

Staff and Researcher Publications

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) are two emerging research technologies that uniquely characterize gene expression microenvironments on a cellular or subcellular level. The skin, a clinically accessible tissue composed of diverse, essential cell populations, serves as an ideal target for these high-resolution investigative approaches. Using these tools, researchers are assembling a compendium of data and discoveries in healthy skin as well as a range of dermatologic pathophysiologies, including atopic dermatitis, psoriasis, and cutaneous malignancies. The ongoing advancement of single-cell approaches, coupled with anticipated decreases in cost with increased adoption, will reshape dermatologic research, profoundly influencing disease characterization, …

In Vivo Crispr Screens Identify Mga As An Immunotherapy Target In Triple-Negative Breast Cancer, Xu Feng, Chang Yang, Yuanjian Huang, Dan Su, Chao Wang, Lori Lyn Wilson, Ling Yin, Mengfan Tang, Siting Li, Zhen Chen, Dandan Zhu, Shimin Wang, Shengzhe Zhang, Jie Zhang, Huimin Zhang, Litong Nie, Min Huang, Jae-Il Park, Traver Hart, Dadi Jiang, Kuirong Jiang, Junjie Chen

Faculty, Staff and Student Publications

Understanding the mechanisms underlying immune evasion is crucial for developing novel anticancer modalities. To systematically uncover tumor-intrinsic genetic modulators involved in immune escape in tumor microenvironment, we performed genome-scale in vivo CRISPR screens in two syngeneic models and later expanded up to seven syngeneic models with a focused validation library. These data help us better understand tumor immune evasion and pave the way for developing effective therapeutics. Importantly, we uncovered that Mga depletion elicited an antitumor immune response and inhibited tumor growth in triple-negative breast cancer. Our findings suggest that Mga may play a role in modulating the tumor immune …

Stimulation Of An Entorhinal-Hippocampal Extinction Circuit Facilitates Fear Extinction In A Post-Traumatic Stress Disorder Model, Ze-Jie Lin, Xue Gu, Wan-Kun Gong, Mo Wang, Yan-Jiao Wu, Qi Wang, Xin-Rong Wu, Xin-Yu Zhao, Michael X Zhu, Lu-Yang Wang, Quanying Liu, Ti-Fei Yuan, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging owing to the fragile nature of fear extinction, for which the ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low-gamma-band synchronization of the LEC-vCA1 activity during extinction learning. Bidirectional manipulations of either hippocampal PV-INs or LEC fan cells sufficed for fear extinction. Gamma entrainment of vCA1 …

The Centrosomal Protein Fgfr1op Controls Myosin Function In Murine Intestinal Epithelial Cells, Tihana Trsan, Vincent Peng, Takahiro E Ohara, Wandy L Beatty, Raki Sudan, Praveen Krishnamoorthy, Patrick Fernandes Rodrigues, Jose L Fachi, Gary Grajales-Reyes, Natalia Jaeger, James A J Fitzpatrick, Marina Cella, Susan Gilfillan, Marco Colonna, Et Al.

2020-Current year OA Pubs

Recent advances in human genetics have shed light on the genetic factors contributing to inflammatory diseases, particularly Crohn's disease (CD), a prominent form of inflammatory bowel disease. Certain risk genes associated with CD directly influence cytokine biology and cell-specific communication networks. Current CD therapies primarily rely on anti-inflammatory drugs, which are inconsistently effective and lack strategies for promoting epithelial restoration and mucosal balance. To understand CD's underlying mechanisms, we investigated the link between CD and the FGFR1OP gene, which encodes a centrosome protein. FGFR1OP deletion in mouse intestinal epithelial cells disrupted crypt architecture, resulting in crypt loss, inflammation, and fatality. …

Metadegron: Multimodal Feature-Integrated Protein Language Model For Predicting E3 Ligase Targeted Degrons, Mengqiu Zheng, Shaofeng Lin, Kunqi Chen, Ruifeng Hu, Liming Wang, Zhongming Zhao, Haodong Xu

Faculty, Staff and Student Publications

Protein degradation through the ubiquitin proteasome system at the spatial and temporal regulation is essential for many cellular processes. E3 ligases and degradation signals (degrons), the sequences they recognize in the target proteins, are key parts of the ubiquitin-mediated proteolysis, and their interactions determine the degradation specificity and maintain cellular homeostasis. To date, only a limited number of targeted degron instances have been identified, and their properties are not yet fully characterized. To tackle on this challenge, here we develop a novel deep-learning framework, namely MetaDegron, for predicting E3 ligase targeted degron by integrating the protein language model and comprehensive …

Examining Management And Employees' Perceptions Of Occupational Heat Exposure And The Effectiveness Of A Heat Stress Prevention Intervention On Safety And Well-Being Among Natural Gas Construction Workers: A Qualitative Field-Based Study, Muinat Abolore Idris, Christine Markham, Kristina D Mena, William B Perkison

Faculty, Staff and Student Publications

BACKGROUND: Numerous risk factors have been identified as significantly influencing outdoor workers' risk for heat stress and heat-related conditions, impacting their health, well-being, and productivity. However, the specific effects of these factors on construction workers' safety, health, and well-being remain under-researched. With climate change increasing temperatures, assessing heat stress among construction workers is imperative.

OBJECTIVE: To identify the barriers and facilitators influencing the safety of natural gas construction workers and evaluate an implemented heat stress intervention.

METHODS: In the summer of 2023, two semi-structured interviews and six focus groups were conducted with twenty-one stakeholders at a Texas natural gas construction …

Cyp1b1-Rmdn2 Alzheimer's Disease Endophenotype Locus Identified For Cerebral Tau Pet, Kwangsik Nho, Muhammad Ali, Tammie Benzinger, Carlos Cruchaga, Diana Hobbs, Et Al.

2020-Current year OA Pubs

Determining the genetic architecture of Alzheimer's disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated with tau deposition. The most significant signal is at rs2113389, explaining 4.3% of the variation in cortical tau, while APOE4 rs429358 accounts for 3.6%. rs2113389 is associated with higher tau and faster cognitive decline. Additive effects, but no interactions, are observed between rs2113389 and diagnosis, APOE4, and amyloid beta positivity. CYP1B1 expression is upregulated in AD. …

Oxa-Iboga Alkaloids Lack Cardiac Risk And Disrupt Opioid Use In Animal Models, Václav Havel, Amanda Hunkele, Rohini S Ople, Susruta Majumdar, Et Al.

2020-Current year OA Pubs

Ibogaine and its main metabolite noribogaine provide important molecular prototypes for markedly different treatment of substance use disorders and co-morbid mental health illnesses. However, these compounds present a cardiac safety risk and a highly complex molecular mechanism. We introduce a class of iboga alkaloids - termed oxa-iboga - defined as benzofuran-containing iboga analogs and created via structural editing of the iboga skeleton. The oxa-iboga compounds lack the proarrhythmic adverse effects of ibogaine and noribogaine in primary human cardiomyocytes and show superior efficacy in animal models of opioid use disorder in male rats. They act as potent kappa opioid receptor agonists …

Paediatric Mass Casualty Response Through The Lens Of Functional Resonance Analytical Methodology- Lessons Learned., R J Mackinnon, D Slater, R Jenner, T Stenfors, Christopher S. Kennedy, K P Härenstam

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Mass Casualty Incidents are rare but can significantly stress healthcare systems. Functional Resonance Analytical Methodology (FRAM) is a systematic approach to model and explore how complex systems adapt to variations and to understand resilient properties in the face of perturbations. The aim of this study was to use FRAM to create a model of a paediatric trauma system during the initial response to the Manchester Arena Attack to provide resilience-based insights for the management of future Mass Casualty Incidents (MCI).

METHODS: Qualitative interviews in the immediate aftermath of a terrorist bombing, were followed up with further in-depth probing of …

Variant Surface Protein Gp60 Contributes To Host Infectivity Of Cryptosporidium Parvum, Muxiao Li, Fuxian Yang, Tianyi Hou, Xiaoqing Gong, Na Li, L David Sibley, Yaoyu Feng, Lihua Xiao, Yaqiong Guo

2020-Current year OA Pubs

Biological studies of the determinants of Cryptosporidium infectivity are lacking despite the fact that cryptosporidiosis is a major public health problem. Recently, the 60-kDa glycoprotein (GP60) has received attention because of its high sequence polymorphism and association with host infectivity of isolates and protection against reinfection. However, studies of GP60 function have been hampered by its heavy O-linked glycosylation. Here, we used advanced genetic tools to investigate the processing, fate, and function of GP60. Endogenous gene tagging showed that the GP60 cleavage products, GP40 and GP15, are both highly expressed on the surface of sporozoites, merozoites and male gametes. During …

Diagnostic Error In Mental Health: A Review, Andrea Bradford, Ashley N D Meyer, Sundas Khan, Traber D Giardina, Hardeep Singh

Faculty, Staff and Students Publications

Diagnostic errors are associated with patient harm and suboptimal outcomes. Despite national scientific efforts to advance definition, measurement and interventions for diagnostic error, diagnosis in mental health is not well represented in this ongoing work. We aimed to summarise the current state of research on diagnostic errors in mental health and identify opportunities to align future research with the emerging science of diagnostic safety. We review conceptual considerations for defining and measuring diagnostic error, the application of these concepts to mental health settings, and the methods and subject matter focus of recent studies of diagnostic error in mental health. We …

Generalized Encoding Of The Relative Subjective Value Of Cognitive Effort In The Dorsal Acc, Jennifer L Crawford, Rachel E Brough, Sarah A Eisenstein, Jonathan E Peelle, Todd S Braver

2020-Current year OA Pubs

Making choices about whether and when to engage cognitive effort are a common feature of everyday experience, with important consequences for academic, career, and health outcomes. Yet, despite their hypothesized importance, very little is understood about the underlying mechanisms that support this form of human cost-benefit decision-making. To investigate these mechanisms, we used the Cognitive Effort Discounting Paradigm (Cog-ED) during fMRI scanning to precisely quantify the neural encoding of varying cognitive effort demands relative to reward outcomes, within two distinct cognitive domains (working memory, speech comprehension). The findings provide strong evidence that the dorsal anterior cingulate cortex (dACC) plays a …