Digital Commons Network^™

The Clinical Pharmacogenetics Implementation Consortium's Consensus-Based Framework For Assigning Allele Function., Bailey M. Tibben, Andrea Gaedigk, Li Gong, Katrin Sangkuhl, Michelle Whirl-Carrillo, Mary V. Relling, Roseann S. Donnelly, Teri E. Klein, Kelly E. Caudle

Manuscripts, Articles, Book Chapters and Other Papers

The Clinical Pharmacogenetics Implementation Consortium (CPIC) is dedicated to integrating pharmacogenetic testing into clinical practice by developing and disseminating peer-reviewed, evidence-based gene-drug clinical practice guidelines. A critical component of this effort is the assignment of clinical function to pharmacogene alleles, which informs the translation of genetic test results into actionable prescribing decisions. This technology review outlines the standardized procedures and framework used by CPIC to assign allele clinical functional status through the work of Pharmacogene Curation Expert Panels (PCEPs). These panels, comprising multidisciplinary experts, systematically review and evaluate evidence to assign functional status to pharmacogenetic haplotypes. The process includes rigorous …

Unconventional Binding Of Calmodulin To Chk2 Kinase Inhibits Catalytic Activity, Christopher R Horne, Tingting Wang, Samuel N Young, Toby A Dite, Hunter G Nyvall, Sushant Suresh, Katherine A Davies, Abner Gonzalez Castro, Vineet Vaibhav, Lucy J Mather, Laura F Dagley, Matthew J Belousoff, Gerard Manning, Anthony R Means, John E Burke, Janni Petersen, John W Scott, James M Murphy

Faculty, Staff and Students Publications

Calmodulin (CaM) serves an essential role in eukaryotic cells as a Ca2+ sensor. Ca2+ binding leads to conformation changes in CaM that enable engagement of a repertoire of enzymes and the regulation of their catalytic activities. Classically, Ca2+-CaM binds to an inhibitory pseudosubstrate sequence C-terminal to the kinase domain in members of the Ca2+-CaM-dependent protein kinase (CAMK) family and relieves inhibition to promote catalytic activity. Here, we report an unexpected mechanism by which CaM can bind CHK2 kinase to inhibit its kinase activity. Using biochemical, biophysical and structural mass spectrometry, we identify a direct interaction of Ca2+-CaM with the CHK2 …

Investigating Dysfunctional Cognition Change As A Putative Mechanism Of Cbt For Youth Anxiety, Ocd And Ptsd: Protocol For An Individual Participant Data Meta-Analysis, Ivana Buric, Anke Klein, Ronald M Rapee, Brooke Levis, Philip C Kendall, Eric A Storch, Lynn Mobach

Faculty, Staff and Students Publications

Introduction: Anxiety disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are common in children and adolescents and can lead to significant impairment. Cognitive behavioural therapy (CBT) with exposure is the first-line treatment, yet approximately half of treated youth do not achieve full remission. Dysfunctional cognitions-negative automatic thoughts, maladaptive beliefs and distorted interpretations-are considered key targets of CBT, but evidence in youth is mixed and underpowered. This study will examine whether change in dysfunctional cognitions mediates treatment outcome in anxiety, OCD and PTSD symptoms and whether this association varies across individual characteristics.

Methods and analysis: An individual participant data meta-analysis …

Resolving The Mysteries Of Brain Clearance And Immune Surveillance, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

Recent advances are transforming our understanding of brain fluid dynamics, highlighting cerebrospinal fluid (CSF) flow as a key process in brain waste clearance. While debates persist regarding its anatomical pathways and regulatory mechanisms, certain core principles have become widely accepted. CSF influx occurs primarily along periarterial spaces, solute clearance follows multiple routes, and glymphatic and meningeal lymphatic systems are functionally connected. Brain clearance is influenced by vascular pulsation, neural activity, and sleep. Immune cells at brain-border niches both monitor solute efflux and modulate flow, linking brain clearance to neuroimmune interactions. A deeper understanding of brain clearance could unlock new therapeutic …

Reducing Storage-Related Bias In Reproductive Vitamin D Research: Towards A Stable And Reliable Biomarker Of Ovarian Vitamin D Status, Evelin E Lara-Molina, Jason M. Franasiak, Almudena Devesa-Peiro, Marina López-Nogueroles, Alberto Vázquez, David Amorós, Agustín Ballesteros, Antonio Pellicer, Patricia Sebastian-Leon, Patricia Diaz-Gimeno

SKMC Student Presentations and Publications

Background/Objectives: One of the main reasons for discrepancies in the role of vitamin D in ART could be the measurement of the conventional biomarker 25(OH)D₃. It is known that this value is affected by multiple factors, such as tissue origin, assay variability, classification criteria, and potential storage-related degradation. In this study, we investigate 24,25(OH)₂D₃ as a new biomarker to improve vitamin D assessment in women’s reproductive health, particularly regarding oocyte development. Methods: A prospective cohort study including 35 oocyte donors undergoing controlled ovarian stimulation, who were recruited between October and November 2017, was conducted. Vitamin …

Per Se Driving Under The Influence Of Cannabis Statutes And Blood Delta-9-Tetrahydrocannabinol Concentrations Following Short-Term Cannabis Abstinence, Robert L. Fitzgerald, Anya Umlauf, Raymond T. Suhandynata, David J. Grelotti, Marilyn A. Huestis, Kyle F. Mastropietro, Igor Grant, Thomas D. Marcotte

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Several US states have per se laws using 2 or 5 ng/mL of delta-9-tetrahydrocannabinol (THC) as cutpoints for driving under the influence of cannabis, while some have zero-tolerance statutes. These cutpoints are considered prima facia evidence of driving impairment.

METHODS: In a cohort of people who regularly use cannabis (N = 190) we measured baseline concentrations of THC after instructing participants to abstain from cannabis for at least 48 hours. Baseline driving performance was evaluated using a driving simulator. We also measured blood THC concentrations serially following a smoking session (placebo or active cannabis).

RESULTS: Forty-three percent of the …

Epigenome-Wide Association Study Of Nuclear Dna Methylation In Relation To Mitochondrial Heteroplasmy, Meng Lai, Kyeezu Kim, Yinan Zheng, Christina A Castellani, Scott M Ratliff, Mengyao Wang, Xue Liu, Jeffrey Haessler, Tianxiao Huan, Kwadwo Bonsu, Charles Newcomb, Kyler Mckessy, Lawrence F Bielak, Wei Zhao, Roby Joehanes, Jiantao Ma, Xiuqing Guo, Joann E Manson, Megan L Grove, Jan Bressler, Kent D Taylor, Tuuli Lappalainen, Silva Kasela, Thomas W Blackwell, Nicole J Lake, Jessica D Faul, Kendra R Ferrier, Stephen C Ekker, Lifang Hou, Charles Kooperberg, Alexander P Reiner, Kai Zhang, Patricia A Peyser, Myriam Fornage, Eric Boerwinkle, Laura M Raffield, April P Carson, Stephen S Rich, Yongmei Liu, Daniel Levy, Jerome I Rotter, Jennifer A Smith, Dan E Arking, Chunyu Liu

Faculty, Staff and Student Publications

We analyze 10,986 participants (mean age 77; 63% women; 54% non-White) across seven U.S. cohorts to study the relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA methylation. We identify 597 CpGs associated with heteroplasmy burden, generally showing lower methylation. These CpGs are enriched in dynamically regulated island shores and depleted in CpG islands, indicating involvement in context-specific rather than constitutive gene regulation. In HEK293T cells, we introduce a truncating mtDNA mutation (MT-COX3, mt.9979) and observe a positive correlation between variant allele fraction and methylation at cg04569152, supporting a direct mtDNA-nDNA epigenetic link. Many heteroplasmy-associated CpGs overlap with known methylation-trait …

Individualized Perioperative Blood Pressure Management In Patients Undergoing Major Abdominal Surgery: The Improve-Multi Randomized Clinical Trial, Bernd Saugel, Agnes S Meidert, Frank M Brunkhorst, Robert Bischoff, Joseph Esser, Minca Mattis, Pauline Naue, Katharina Vogel, Alina Bergholz, Moritz Flick, Alina Kröker, Dominik X Müller, Kristen K Thomsen, Christina Vokuhl, Mirja Wegge, Sebastian Bratke, Martin Graeßner, Bettina Jungwirth, Sebastian Schmid, Carla D Grundmann, Jan M Wischermann, Patrick Kellner, Moritz Steinhaus, Linda Grüßer, Sina M Coldewey, Kai Zacharowski, Patrick Meybohm, Marit Habicher, Alexander Zarbock, Amelie Zitzmann, Svenja Letz, Claudia Neumann, Jan Larmann, Thomas Renné, Linda Krause, Eik Vettorazzi, Antonia Zapf, Annemarie Carlstedt, Daniel I Sessler, Karim Kouz

Faculty, Staff and Student Publications

Importance: Intraoperative hypotension is associated with organ injury. However, it remains unknown if targeted blood pressure management during surgery can improve clinical outcomes.

Objective: To evaluate whether individualized vs routine perioperative blood pressure management during major abdominal surgery improves clinical outcomes in patients considered at high risk of postoperative complications.

Design, setting, and participants: This randomized single-blind clinical trial enrolled patients 45 years or older undergoing elective major abdominal surgery with general anesthesia expected to last 90 minutes or longer who had at least 1 additional high-risk criterion between February 26, 2023, and April 25, 2024, at 15 German university …

Patient-Reported Experience Measures For Person-Centred Care: A Survey For The Development And Psychometric Testing Of A Targeted Measure, The Epcc-14, Ryan Statton, Lena Rosenlund, James Close, Anna Dencker, Helen Lloyd

School of Psychology

Objectives This study aims to develop a robust, targeted measure of patient experiences of person-centred care (PCC), informed by the lived experiences of patients with chronic illness using the psychometric theory of Rasch measurement. Design The Rasch measurement model was used to analyse the psychometric functioning of 57 candidate items and select appropriate items for a targeted measure. Setting Participants were recruited from Prolific.com, having experience of both chronic or long-term illness and first-hand experience of primary or secondary care in the UK healthcare setting and completed a survey containing PCC items and descriptors of healthcare experience. Participants Data from …

Using Gnotobiotic Mice To Decipher Effects Of Gut Microbiome Repair In Undernourished Children On Tuft And Goblet Cell Function, Yi Wang, Hao-Wei Chang, Jiye Cheng, Daniel M Webber, Hannah M Lynn, Matthew C Hibberd, Clara Kao, Ishita Mostafa, Tahmeed Ahmed, Michael J Barratt, Jeffrey I Gordon

2020-Current year OA Pubs

Studies have implicated perturbations in the postnatal development of the gut microbiome as a contributing factor to childhood undernutrition. Compared to a standard ready-to-use supplementary food, a microbiome-directed complementary food (MDCF-2) designed to repair these perturbations produced superior improvements in ponderal and linear growth in clinical trials of Bangladeshi children with moderate acute malnutrition. Here, "reverse translation" experiments are performed where intact fecal microbiomes collected from trial participants before and at the end of treatment are introduced into female gnotobiotic mice just after delivery of their pups. Pups received diets designed to resemble those consumed by children in the trials …

Statistically Significant Association Does Not Imply Improvement In Prediction Of Clinical Outcomes, Shu Jiang, Bernard A Rosner, Graham A Colditz

2020-Current year OA Pubs

UNLABELLED: In the current landscape of clinical studies, the concept of statistically significant association is often mixed up with the expectation of improved prediction performance. We discuss the two concepts, association and prediction, and present the epidemiologic principles and statistical constructs that underlie the discrepancy between statistically significant associations and the rationale for their lack of impact on improving prediction in terms of discrimination. This issue is illustrated using an existing breast cancer dataset. The concept of statistically significant association should not be mixed up with the expectation of improved discrimination performance. Although some markers may not markedly improve discrimination, …

Fucosylated N-Glycan Landscape Of Triple-Negative Breast Cancer, Danielle A Scott, Souvik Seal, Laura Spruill, Jaclyn Dunne, Graham Colditz, Anand S Mehta, Richard R Drake, Marvella E Ford, Peggi M Angel

2020-Current year OA Pubs

UNLABELLED: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking targeted therapies. Although aberrant N-glycosylation is a hallmark of malignancy, the specific roles of core-fucosylated (CF) and outer arm-fucosylated (OAF) N-glycans in TNBC progression and patient survival remain underexplored. This study utilized multiplexed glycomics by matrix-assisted laser desorption/ionization imaging mass spectrometry to spatially profile 348 N-glycans in 59 TNBC tumors with clinical characteristics including survival data. Spatial analysis revealed distinct localization patterns of CF and OAF isomers within tumor microenvironments. Strikingly, OAF glycans, but not CF, were strongly associated with tumor stage, with expression increasing from stage …

Hif-2-Dependent Regulation Of Pthrp And Paraneoplastic Hypercalcemia In Aggressive Clear-Cell Renal Cell Carcinoma, Arijit Mal, Bingqing Xie, Zane Gray, Charlotte Small, Susmita G Ramanand, Yunpeng Gao, Vanina Toffessi Tcheuyap, Sashi Debnath, Alana Christie, Jeffrey Miyata, Brooklyn Jackson, Hua Zhong, Boning Gao, Jay Lohrey, Naim M Maalouf, Sangeetha M Reddy, John D Minna, Ivan Pedrosa, Xiankai Sun, Ram S Mani, Payal Kapur, James Brugarolas

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) patients with hypercalcemia (HC) have worse outcomes. HC often involves PTHrP, and the role of HIF-2 is incompletely understood. Leveraging RCC tumorgraft (TG) models of HC, which were characterized by tumor cell autonomous inflamatory/immune signatures, we show that HIF-2 inhibition with PT2399 frequently normalized calcium, downregulated circulating PTHrP and reduced HIF-2 binding to the PTHLH (PTHrP) promoter. Likely contributing to the selective induction of PTHrP in a subset of HIF-2-dependent tumors, the PTHLH locus was generally more accessible in TG(HC). However, PTHLH chromatin accessibility was grossly unaffected by PT2399, unlike elsewhere (including EPO locus in a …

Engaging Ukrainian Tf-Cbt Therapists In A Practice Skills Course To Support Their Wellbeing, Elisabeth Pollio, Esther Deblinger, Beth Cooper, Maike Garbade, Julie P Harrison, Elisa Pfeiffer

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background: Burnout and secondary traumatic stress (STS) are common among therapists working with trauma-exposed clients, which can negatively impact them professionally and personally. The shared trauma of war exposure may put therapists at greater risk. To help support their wellbeing, an eight-session course was offered to Ukrainian therapists following training in Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). This course involves therapists personally utilizing the PRACTICE skills taught to clients in TF-CBT for professional and personal benefit.

Objective: The objective was to gather preliminary evidence on the potential impact of implementing the course with Ukrainian therapists providing TF-CBT during a period of …

High-Risk Medications In Pediatric Dentistry: Patterns, Outcomes, And Clinical Implications, Yilei Liu, Kawtar Zouaidi, Colin C Hubbard, Muhammad F Walji, Matthew R Cooke, Donald B Rindal, Kristin N Ray, Elsbeth Kalenderian, Katie J Suda

Faculty, Staff and Student Publications

Background: High-risk medications such as opioids and benzodiazepines are frequently prescribed in pediatric dental care, yet their prescribing patterns and associated adverse outcomes remain poorly understood. The aim of this study was to determine the extent of such prescribing to pediatric patients and factors associated with adverse outcomes.

Methods: MarketScan data for patients younger than 18 years with a dental visit from 2014 through 2019 were analyzed. High-risk medications included benzodiazepines, barbiturates, and opioids. Composite outcomes included hospitalization, emergency department visit, or urgent care visit within 7 days after the dental visit. Opioid-attributable outcomes included opioid-related overdose within 7 days …

Comparison Of In-Hospital Complication Rates After Transcatheter Aortic Valve Replacement In Patients With Bicuspid Versus Tricuspid Aortic Valves: A Retrospective Cohort Study, Tingxi Zhu, Jiawei Luo, Xuan Huang, Lulu Liu, Kehan Li, Wei He, Xiaobo Zhou, Yingqiang Guo, Xiaoyan Yang

Faculty, Staff and Student Publications

Background: Transcatheter aortic valve replacement (TAVR) has become a popular alternative to surgical aortic valve replacement (SAVR) for patients with valvular heart disease (VHD), particularly for those with aortic anomalies.

Aims: The study aimed to compare the risks of post-TAVR complications between patients with bicuspid and tricuspid aortic valves and to identify associated risk factors.

Methods: The association between complications and valve type (bicuspid or tricuspid) was assessed. The study also explored various combinations of factors to understand their impact on complications. Separate analyses were conducted to identify specific risk factors for each complication.

Results: Out of the 1154 eligible …

The Him Profession And Roles: Understanding Our Path, To Plan For The Future, Kerryn Butler-Henderson, Susan H Fenton, Karima Lalani, Trixie Kemp, Salma Arabi

Faculty, Staff and Student Publications

The health information management (HIM) profession has a history spanning more than a century, with the first peak body established in Australia more than 75 years ago (Health Information Management Association of Australia [HIMAA], 2024a). While the role title of the health information manager has changed over time, its primary function has remained the same—tooversee the governance of health data and information. This chapter presents the history of the HIM profession and professional bodies, including their involvement in informing policy and systems in Australia and other countries, and international organisations. Next, the chapter draws on literature examining the roles of …

Artificial Intelligence Biomarker Detects High-Risk Childhood Asthma Subgroup For Respiratory Infections And Exacerbations, Young J Juhn, Chung-Il Wi, Euijung Ryu, Katherine S King, Sunghwan Sohn, Elham Sagheb, Greg Jenkins, David Watson, Miguel A Park, Sergio E Chiarella, Hirohito Kita, Mir Ali, W Charles Huskins, Elizabeth H Ristagno, Imad Absah, Charles Grose, Kathy Ihrke, Elizabeth A Krusemark, Thanai Pongdee, Björn Nordlund, Carla M Davis, Robert J Pignolo, Hongfang Liu

Faculty, Staff and Student Publications

Background: Asthma is associated with an increased risk of acute respiratory infections (ARI). Little is known about whether natural language processing (NLP)-powered digital biomarkers can identify a high-risk asthma subgroup for ARI during early childhood.

Objective: We assessed whether a digital biomarker could identify a high-risk subgroup of childhood asthma for ARI.

Methods: We applied validated NLP algorithms for Predetermined Asthma Criteria (NLP-PAC) and Asthma Predictive Index (NLP-API) to electronic health records of the 1997-2016 Mayo Clinic Birth Cohort. We categorized the cohort into 4 subgroups: both criteria positive (NLP-PAC+/NLP-API+), PAC positive only (NLP-PAC+), API positive only (NLP-API+), and both …

Single-Cell Landscape Of Sex-Specific Drivers Of Alzheimer's Disease., Yiyang Wu, Kyle J Travaglini, Mariano Gabitto, C Dirk Keene, Amy R Dunn, Catherine C Kaczorowski, Philip L De Jager, Vilas Menon, Julie A Schneider, David A Bennett, Logan Dumitrescu, Timothy J Hohman

Faculty Research 2025

INTRODUCTION: We investigated sex-specific gene expression associations with the neuropathology and cognitive manifestation of Alzheimer's disease (AD) leveraging single-nucleus transcriptomic datasets including 2.84 million nuclei from the dorsolateral prefrontal cortex (DLPFC).

METHODS: We delineated the full scope of sex-specific transcript associations, differential gene expression, signaling pathway, and cell-cell communication network changes in eight major DLPFC cell types.

RESULTS: Nine female-specific associations were identified and replicated, involving ADGRV1, OR3A3, IFI27L1, LYRM1, STAP2, TSTD2, PDYN, and TMEM50B. We observed the preponderance of protective female-specific associations in neurons. Sex-specific genes were enriched in the immune-, inflammation-, and damage-related stress-response pathways. Six ITGB1-mediated microglia-specific …

Integrated Phenotypic And Proteomic Screening Identifies Top-Tier Alzheimer's Disease Therapeutic Targets., Gregory Cary, Qianjin Li, Jesse C Wiley, Carolyn Paisie, Yuhong Du, Elizabeth L Zoeller, Duc Duong, Haian Fu, Nicholas T Seyfried, Allan I Levey, Ranjita Betarbet, Gregory W. Carter, The Emory-Sage-Sgc-Jax Treat-Ad Center

Faculty Research 2025

INTRODUCTION: Alzheimer's disease (AD) is a complex neurodegenerative disorder. Hundreds of therapeutic targets have been nominated through genetic and multi-omic studies, but effective prioritization remains a major bottleneck.

METHODS: We applied an integrative screening framework to assess 29 candidate targets from risk-enriched biological domains. Using disease-relevant murine BV2 microglial cell lines with stable Psen2 knockdown, we performed small interfering RNA-mediated perturbations followed by cellular phenotypic assays and quantitative proteomics.

RESULTS: Twenty-five candidate targets significantly altered at least one phenotype, with stronger effects in Psen2 knockdown cells. Integrated proteomic analyses identified several perturbations that reversed AD-associated molecular patterns. Five targets-Ap2a2, Pdhb, …

Plasma Metabolomic And Proteomic Signatures Of Blood Pressure Management After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Juan Pablo Lewinger, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Carmen Chen, Todd M Jenkins, Stephanie Sisley, Stephen R Daniels, Douglas I Walker, Max T Aung, Erika Garcia, Rob Mcconnell, Sandrah P Eckel, Michele A La Merrill, Tanya L Alderete, Zhuanghua Chen, Frank D Gilliland, Thomas H Inge, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Background: Emerging omics approaches, including metabolomics and proteomics, can be integrated into obesity treatment for better blood pressure management. We tested whether preoperative metabolomic and proteomic profiles predict long-term elevated blood pressure (EBP) changes better than known risk factors in adolescents undergoing bariatric surgery.

Methods: We included 108 participants from the Teen-LABS (Teen-Longitudinal Assessment of Bariatric Surgery). Plasma untargeted metabolomics (via liquid chromatography with high-resolution mass spectrometry) and Olink proteomics were assessed pre surgery. An elastic net model with stability selection was used to identify features predictive of EBP reductions 5 years post surgery. Models including identified metabolites, proteins, and …

Abca4-Mutant Human Retinal Organoids Sequencing Reveals Organoids Application In Inherited Retinal Diseases, Yourong Bao, Sujung Soh, Jean Li, Zhen Zuo, Salma Ferdous, Xinye Qian, Jin Li, Jiaxiong Lu, Xuesen Cheng, Anna Matynia, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

In the studies of Inherited Retinal Diseases (IRDs), the knockout of traditional animal models like mice often fails to accurately replicate human phenotypes due to genetic and anatomical differences. Human retinal organoids (ROs) derived from stem cells have emerged as promising developmental models in retinal studies to delineate cell growth, but their ability to represent the characteristics of late-onset IRDs remains unclear. This study aims to validate ROs as a disease model for Stargardt's Disease (STGD) caused by ABCA4 mutations. Using single-cell RNA sequencing, ROs from 2 STGD patients were compared with healthy control-derived ROs at two developmental stages on …

Implications Of Cooccurring Adhd For The Cognitive Behavioural Treatment Of Anxiety In Autistic Children, Elise Ng-Cordell, Eric A Storch, Philip C Kendall, Jeffrey J Wood, Amori Yee Mikami, Connor M Kerns

Faculty, Staff and Students Publications

Background: Childhood mental health conditions commonly cooccur, with potential treatment implications. Autistic children frequently experience anxiety and attention deficit/hyperactivity disorder (ADHD). We investigated the implications of this cooccurrence for Cognitive Behavioural Therapy (CBT), a front-line treatment for anxiety in autistic children. We tested whether (1) ADHD predicts anxiety treatment response, (2) ADHD improves in response to anxiety treatment and (3) ADHD improvement is related to reductions in anxiety.

Method: Autistic children with elevated anxiety (N = 167) enrolled in a multisite, randomised controlled trial comparing standard CBT, autism-adapted CBT and treatment as usual. ADHD symptoms and severity were assessed via …

How Well Can Commonly Used Anxiety Scales Detect Treatment Outcomes In The Context Of Autism?, Huilin Chen, Jeffrey J Wood, Connor M Kerns, Eric A Storch, Philip C Kendall, Gaia Scerif, Cathy Creswell

Faculty, Staff and Students Publications

Anxiety is one of the most prevalent mental health challenges in autistic children, yet there is limited evidence on effective tools to measure treatment outcomes. Previous research with non-autistic children has found that the Child Anxiety Impact Scale, Parent Version achieved good diagnostic accuracy when measuring treatment outcomes and performed better than a commonly used symptom measure. However, this has not been evaluated for autistic children. The present study examined the psychometric properties of the Child Anxiety Impact Scale, Parent Version in autistic children and compared its utility against other anxiety symptom measures, to detect treatment outcomes as assessed by …

Nortriptyline Inhibits Lysosomal Exocytosis-Mediated Sasp During Gastric Cancer Progression Via Targeting Hoxa1-Pitx2 Phase Separation, Yi Zhou, Chunhui Yang, Xinyue Li, Xiaojing Wang, Wanju Jiao, Xiaolin Wang, Jiaying Qu, Bosen Zhao, Shunchen Zhou, Qiangsong Tong, Liduan Zheng

Faculty, Staff and Students Publications

Lysosomal exocytosis, a calcium-dependent secretory process, facilitates extracellular release of cargos that promote cancer progression, though its regulatory pathways and therapeutic strategies are poorly understood. Herein, using combined transcriptomic and proteomic approaches, we identify homeobox A1 (HOXA1) as a functional partner of paired like homeodomain 2 (PITX2) within biomolecular condensates forming via liquid-liquid phase separation. Mechanistically, HOXA1-PITX2 complex facilitates the expression of mucolipin 1 (MCOLN1) and RAS-related protein Rab-3A (RAB3A), which drive lysosomal exocytosis of galectin-1 (LGALS1) and insulin like growth factor binding protein 7 (IGFBP7) from senescent gastric cancer cells. This process potentiates AKT activation and epithelial-mesenchymal transition, accelerating …

Emerging Tick-Borne Disease Risk In An Urban Center Of Harris County, Texas, Alisa Nelson, Michelle Downey, Maya Murry, Brianna Weber, Erik Aguirre, Richard Scott Mccrea, Jerrod Mims, Max Vigilant, Courtney Standlee, Kristy O Murray, Alex Kneubehl, Eric L Brown, Heather T Essigmann, Sarah M Gunter

Faculty, Staff and Students Publications

Background: Tick-borne diseases are an endemic and emerging public health concern in the United States. Ongoing tick range expansion, invasive species, and newly identified pathogens are rapidly altering disease epidemiology. Surveillance is critical to understanding vector ecology and disease risk. Harris County, Texas, with nearly five million residents and diverse ecological zones, offers a unique setting to study local tick dynamics.

Methods: From January 2021 to December 2022, we conducted weekly tick surveillance across 63 sites in Harris County (City of Houston), Texas. Ticks were morphologically identified and tested for Rickettsia, Borrelia, Ehrlichia, and Anaplasma via real-time PCR. Samples positive …

Where, How, And How Much? A Multicenter Cohort Study Of The Relationship Across Lupus Decision-Aid Modality, Place Of Administration, Interruption And Viewing Completeness, And Patient-Reported Outcomes, Jasvinder A Singh, Mark Beasley, Larry R Hearld

Faculty, Staff and Students Publications

Objective: We assessed whether shared decision-making (SDM) and patient acceptability, feasibility, and overall satisfaction with a computerized patient decision aid (PtDA) for patients with systemic lupus erythematosus (SLE) differs by PtDA setting, modality, and the viewing experience.

Methods: Patients with SLE were invited to view a self-administered computerized SLE PtDA during regular clinic visits at 15 rheumatology clinics in an implementation trial. Patients completed a survey that included SDM measures including the decision conflict scale (DCS), Preparation for Decision Making (PDM) scale, and CollaboRATE scale, and we measured perceived patient acceptability, feasibility, and satisfaction. Patients viewed the SLE PtDA in …

Bypassing Cisplatin Resistance In Nrf2 Hyperactivated Head And Neck Cancer Through Effective Pi3kinase Targeting, Pedram Yadollahi, Kelli A Mccord, Yang Li, Hussam Dayoub, Kalil Saab, Fonma Essien, Sean Hyslop, Emerald Kan, Kazi M Ahmed, Parker R Kirby, Vasanta Putluri, Chandra Shekar R Ambati, Karthik Reddy Kami Reddy, Patricia Castro, Heath D Skinner, Cristian Coarfa, William K Decker, Abdullah A Osman, Rutulkumar Patel, Jeffrey N Myers, Stephen Y Lai, Nagireddy Putluri, Faye M Johnson, Mitchell J Frederick, William H Hudson, Vlad C Sandulache

Faculty, Staff and Students Publications

Background: For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined with cisplatin nearly universally results in death. Although hyperactivation of the Nrf2 pathway can drive radiation and cisplatin resistance along with suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary to synergistic lethality with other oncogenic drivers (e.g., NOTCH1 mutations).

Methods: Using state of the science mechanistic, metabolomic and spatial transcriptomic approaches combined with preclinical models of HNSCC, we tested whether a novel PI3K inhibitor, gedatolisib, can bypass hyperactivation of the Nrf2 pathway.

Results: The PI3K pathway is activated in …

Detection Of Phase-Binning And Interpolation Artifacts In 4-Dimensional Computed Tomography Imaging Using Deep Learning And Rule-Based Approaches, Jorge Cisneros, Nathan H. Feldt, Yevgeniy Vinogradskiy, Richard Castillo, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Four-dimensional computed tomography (4DCT) imaging is a crucial component to lung cancer radiotherapy planning and enables CT-ventilation-based functional avoidance planning to mitigate radiation toxicity. However, 4DCT scans are frequently impaired by acquisition artifacts that corrupt downstream analyses that depend on lung segmentation and deformable image registration, such as CT-ventilation and dose accumulation.

PURPOSE: This study develops 3D deep learning models to identify phase-binning artifacts at the voxel level and a heuristic, rule-based method to identify interpolation slices within 4DCT images.

METHODS: We introduce a generator that systematically inserts synthetic phase-binning and interpolation artifacts into any artifact-free breathing phase obtained …

Telehealth And Virtual Supervision Practices For Health Professions Education In The Department Of Veterans Affairs, Nancy D. Harada, Kimberly Falco, Marjorie Bowman, John M. Byrne

Population and Public Health Sciences Faculty Publications

Background Telehealth and virtual supervision practices in health professions clinical education has grown rapidly, including in the Department of Veterans Affairs (VA) which oversees the largest interprofessional training effort in the United States. Telehealth is the provision of healthcare that is provided remotely through telecommunication technology, and virtual supervision is clinical supervision of health professions trainees (HPTs) that occurs through telecommunication technology. In this study we evaluate participation in telehealth and virtual supervision for physician, nursing, and associated health HPTs, and describe prevalent themes concerning HPT perceptions of telehealth and virtual supervision. Methods The survey study cohort included 10,865 HPTs …