Digital Commons Network^™

Stimulant Medications And Bone Health, Christine M Swanson, Julie H Wolfe, Chadi A Calarge

Faculty, Staff and Students Publications

Purpose of review: This review summarizes the potential impact of stimulant medications on bone health, to raise awareness and optimize their safe use.

Recent findings: Stimulant medications can impair bone health through inadequate nutrient/calorie intake and stimulation of the sympathetic nervous system, which regulates bone metabolism. However, their use decreases fracture risk in younger populations ([Formula: see text]25 years old) with attention deficit/hyperactivity disorder (ADHD), likely through reductions in impulsivity and injury. Special care may be needed when fractures occur while using these medications, as recent data suggest psychostimulants are associated with impaired fracture healing. Prescription and non-prescription use of …

Contemporary Management Of Acute Heart Failure: From Emergency Presentation To Long-Term Remission, Jolie Bruno, Mattia Arrigo, Guillaume Baudry, Jan Biegus, Biykem Bozkurt, Kamilė Čerlinskaitė-Bajorė, Laura P Cohen, Nick Hartshorne-Evans, Shiro Ishihara, Neusa Jessen, Pieter Martens, Peder Myhre, Matteo Pagnesi, Carolyn Rosner, Novi Yanti Sari, Gianluigi Savarese, Kristoffer Grundtvig Skaarup, Aferdita Spahillari, Jozine M Ter Maaten, Heli Tolppanen, Jim L Januzzi, Alexandre Mebazaa

Faculty, Staff and Students Publications

Acute heart failure (AHF) represents a major global health challenge, with a substantial impact on survival, morbidity, and health care resource utilization. The clinical and economic burden associated with this condition continues to grow, highlighting the need for a timely, structured, and patient-centered approach to care. In light of the expanding body of data and evidence accumulated over recent years, it is necessary to rethink how we approach the recognition and management of AHF. This need has motivated the development of the present review, which aims to provide an updated and practical synthesis of the management of AHF-from early diagnostic …

Assessment And Mitigation Of Covid-19 Occupational Hazards Among Small Businesses In A High-Risk Community, Sadie H Conway, Denise Vasquez, Soyoung Kwon, Kristina D Mena, Louis D Brown, Janelle Rios

Faculty, Staff and Student Publications

Purpose –: This project explored COVID-19 workplace hazards and factors influencing the implementation of risk mitigation approaches among small businesses in a high-risk community.

Design/methodology/approach –: Using a novel framework, data were collected from 90 workplaces through site visits and consultations with at least one owner, manager or supervisor ("employer") and at least one non-managerial staff member ("employee"). A risk assessment and mitigation plan were prepared based on site-specific hazards; later, a follow-up visit assessed whether recommendations had been implemented and factors influencing these decisions.

Findings –: A total of 84 businesses (93.3%) implemented at least one recommendation, citing ease …

Wnt-Dependent Ontogeny Of Acellular Cementum-Forming Cementoblasts On The Tooth Root Surface, Taishi Komori, Mizuki Nagata, Natnicha Praneetpong, Hanwen Fan, Yuxiao Zhou, Noriaki Ono, Wanida Ono

Faculty, Staff and Student Publications

Cementum is a specialized mineralized tissue that covers the tooth root surface and anchors the tooth to the surrounding periodontal ligament. The cervical acellular cementum (AC) is indispensable for periodontal attachment and represents a key target for periodontal regenerative therapies. However, the developmental origin and molecular identity of AC-forming cementoblasts remain poorly understood. Here, through an integrated spatial and single-cell transcriptomic analysis, we identify AC-forming cementoblasts as a distinct population of noncanonical mineralizing cells enriched for cell-matrix organization and Wnt signaling signatures, distinguishing them from cellular cementum-forming cementoblasts localized in the apical portion. Lineage tracing using a Wnt inhibitory factor …

Selective And Differential Roles Of Pvhcrh Neurotransmitters In Diet-Induced Obesity In Mice, Zhiying Jiang, Yuhan Cao, Michelle He, Cunjin Su, Runzhou Yang, Maojie Yang, Jing Cai, Hongli Li, Yuanzhong Xu, Shi-Bin Li, Hiroshi Yamaguchi, Luis De Lecea, Benjamin R Arenkiel, Qingchun Tong

The Brown Foundation: Institute of Molecular Medicine

Stress and diet are known to synergistically promote risks of obesity but the underlying neural basis remains elusive. Corticotropin-releasing hormone neurons in the paraventricular hypothalamus (PVHCRH) are stress responsive and release both CRH and glutamate. Here we generated a mouse model with gain or loss of release in CRH or glutamate from PVHCRH neurons. While these models showed no changes in body weight when fed chow, they exhibited contrasting effects when fed high-fat high-caloric diets (HFD). Whereas disrupting glutamate release from PVHCRH neurons led to diet-induced obesity (DIO), that of CRH caused no impact. Conversely, augmented CRH release led to …

Implementation And Effectiveness Of An Enhanced Recovery Protocol For Children Undergoing Surgery: The Enrich-Us Stepped-Wedge Cluster-Randomized Trial, Mehul V Raval, Yao Tian, Willemijn Schäfer, Salva N Balbale, Mallory N Perez, Martha-Conley E Ingram, Alison Lehane, Charesa J Smith, Gwyneth A Sullivan, Audra J Reiter, Andrew Hu, Johanna M Borst, Sarah C Blake, Sharron Close, Teaniese L Davis, Bonnie S Essner, Kurt F Heiss, Lynn W Huang, Erin Wymore, Deysi Paniagua-Perez, Kirsty M Engelhardt, Peter M Graffy, Julie K Johnson, Craig W Lillehei, Brian W Gray, Seth D Goldstein, Scott S Short, Samir R Pandya, Janice A Taylor, Christopher Gayer, Adam B Goldin, Matthew M Boelig, Kristy L Rialon, Tim Jancelewicz, Aaron M Lipskar, Mubeen Jafri, Elisabeth T Tracy, Matthew T Harting, Jason P Sulkowski, P Benson Ham, Kaveh Vali, Robert A Cina, David T Schindel, Saleem Islam, Erin A Teeple, Sohail R Shah, Ankush Gosain, David H Rothstein, Megan A Brockel, Jillian Chown, Jane L Holl

Faculty, Staff and Student Publications

Importance: Despite evidence that enhanced recovery protocols (ERPs) improve outcomes in adults undergoing surgery, adoption for pediatric populations has lagged.

Objective: To assess the implementation and clinical effectiveness of a consensus-based ERP for pediatric patients undergoing elective gastrointestinal (GI) surgery.

Design, setting, and participants: A prospective type 2 hybrid implementation-effectiveness, stepped-wedge, cluster-randomized by entry date into implementation phase, trial of pediatrics patients, 10 to 18 years of age, undergoing elective GI surgery at 18 US sites from September 2019 to June 2024.

Interventions: Sites were randomized into 3 groups, each spending at least 9 months in a control phase, with …

A Lifecycle Governance And Learning Health System Framework For Trustworthy, Generalizable, And Sustainable Human-Ai Partnership In Clinical Practice: Lessons From The Asthma-Guidance And Prediction System (A-Gps), Chung-Il Wi, Shauna Overgaard, Momin Malik, Dave Watson, Deepak Sharma, Jennifer Le-Rademacher, Dan Kelleher, Lu Zheng, Joshua Ohde, Brian Lynch, Ashwani Khurana, Sunghwan Sohn, Mahmoud M Aljuhani, Chris Carpenter, Manuel Arteta, Jason Greenwood, Martha Hartz, Randy Foss, Elif Polat, Imad Absah, Carla Davis, Meera Gupta, Lynnea Myers, Björn Nordlund, Cui Tao, Mark L Wieland, Christi Patten, Amie Jones, Prathibha Varkey, Brenna T Loufek, David E Vidal, Nari Gopala, Eric Klee, Vijay H Shah, John D Halamka, Matthew R Callstrom, Nicholas L Rider, Hongfang Liu, Constantin Aliferis, Vesna D Garovic, Young J Juhn

Faculty, Staff and Students Publications

The integration of artificial intelligence (AI) into clinical decision support (CDS) holds promise for proactive, personalized, and precision care. However, current understanding of how to establish trustworthy human-AI partnerships is in its infancy, despite its critical importance for implementing AI in healthcare. We present the Asthma-Guidance and Prediction System (A-GPS) as a case study of a practice-integrated AI platform that demonstrates how trustworthy, generalizable and sustainable AI can be developed, evaluated, and implemented in real-world asthma care. We describe major challenges and solutions based on our real-world experience during the process and offer the practical framework, approaches, tools and workflow …

Robust Magnetoelectric Backscatter Communication System For Bioelectronic Implants, Fatima Alrashdan, Joshua E Woods, Ellie C Chen, Wendy Tan, Zhanghao Yu, Wei Wang, Mathews John, Lukas Jaworski, Drew Bernard, Allison Post, Angel Moctezuma-Ramirez, Abdelmotagaly Elgalad, Kaiyuan Yang, Mehdi Razavi, Jacob T Robinson

Faculty, Staff and Students Publications

Wireless communication technologies for bioelectronic implants enable remote monitoring for diagnosis and adaptive therapeutic intervention without the constraints of wired connections. However, wireless data uplink from millimeter-scale devices deep in the body struggles to achieve low power consumption while maintaining large misalignment tolerances. Here, we report a passive wireless backscatter communication system based on magnetoelectric transducers that consumes less than 0.3 pJ/bit and achieves less than 1E-6 bit error rate at a distance of 55 mm while tolerating a misalignment of 10 mm. Using this robust data uplink, we designed a wireless cardiac sensing node that can transmit electrocardiogram signals …

Fall Prevention In A Medical Intermediate Care Unit (Mimu) Through Use Of A Collaborative Fall Bundle, Sara M. Jose

Doctor of Nursing Practice Final Project Abstract

PURPOSE

This DNP project focused on reducing the fall rate in a medical intermediate care unit by half, from 1.81 falls per 1000 patient days to 0.91 falls per 1000 patient days.

BACKGROUND

The number of patient falls poses a significant concern in a medical intermediate care unit. The fall rate goal is zero.

METHODOLOGY

The Collaborative Fall Bundle includes implementing the Fall TIPS Toolkit, an 11 x 17 bedside poster informing patients and staff of their fall risk factors and interventions to counteract; an alarm buddy system pairing two nurses to answer each other's call lights and assist with …

Implementing A Mindfulness Mobile Application, Smiling Mind To Reduce Stress Experienced By Inpatient Psychiatric Nurses, Justin Ruiz, Emma Mowery

Doctor of Nursing Practice Final Project Abstract

Purpose

To investigate the impact of implementing the use of the Smiling Mind app (a free and easily accessible mobile application that teaches mindfulness skills) among inpatient psychiatric nurses. The aims were to see a 20% reduction in Perceived Stress and improved Workplace Satisfaction after 10 weeks.

Background

Stressors experienced at work by inpatient psychiatric nurses include patient acuity, emotional demands, environmental factors, and policy implementation. Unmanaged stress can disrupt a nurse's work-life and harm the quality of care provided to patients.

Methodology

Using a pre-post implementation design, 7-day shift and 10-night shift nurses used the Smiling Mind app for …

Evaluating Lingualai: A Prospective Validation Of Ai-Based Real-Time Translation Against Certified Human Interpreters, Uday P Singh, Carlos A Jaimes Garcia, Gabriel M Aisenberg, Javier Barreda Garcia, Jessica A Hernandez-Chilatra, Cecilia Wang, Dalilah Reyes De Jesus, Eileen Whalen, Veronica Santos Canellas, Amanda R Falk Vargas, Brian O Rodriguez Echevarria, Martin J Citardi, Babatope O Fatuyi, Xiaoqian Jiang

Faculty, Staff and Student Publications

Limited English proficiency affects over 25 million people in the United States and is associated with disparities in healthcare access, safety, and outcomes. We conducted a prospective, within-subject, simulation-based comparison to evaluate whether an in-house AI application (LingualAI) achieves non-inferior translation quality versus certified medical interpreters in English-Spanish otorhinolaryngology encounters. Standardized clinician-patient scripts were translated by LingualAI and by certified interpreters, and bilingual clinicians rated anonymized audio across multidomain quality measures. Using a prespecified non-inferiority margin of 0.30 points (Human - AI) on 5-point scales, LingualAI met non-inferiority for 2 of 3 primary factors (terminology accuracy Δ = 0.07; adequacy …

Implementing A Mindfulness Mobile Application, Smiling Mind To Reduce Stress Experienced By Inpatient Psychiatric Nurses, Emma Jade Mowery, Justin D. Ruiz

Doctor of Nursing Practice Final Project Abstract

Purpose: To investigate the impact of implementing use of the Smiling Mind app (a free and easily accessed mobile application that teaches mindfulness skills) in inpatient psychiatric nurses. The aims: A 20% reduction in Perceived Stress and improved Workplace Satisfaction after 10 weeks.

Background: Workplace stressors experienced by psychiatric nurses include high patient acuity, emotional strain, environmental factors, and new policies. Unmanaged stress can harm nurse's well being and affect quality of care.

Methodology: Using a pre-post implementation design, 7 dayshift and 10 night-shift nurses used the Smiling Mind app for 10 weeks. Perceived stress (PSS-10) and workplace satisfaction (WPS) …

Smart Pediatric Oncology Tracker Of Symptoms (Spots), A Web-Based Interface For The Pediatric Pro-Ctcae: Development And Usability Study, Stacey Crane, Deevakar Rogith, Melody Hellsten, Andrew D Miller, Jacqueline Castillo, Brandy Boeger, Susan Vidaurre, Stefanie Pieper, Cecile Nguyen, Duc Anh Thanh Huynh, Jessica Wooden, Amy Franklin, Karen Moody, Wenyaw Chan, Pamela S Hinds, Constance Johnson

Faculty, Staff and Student Publications

Background: Children undergoing cancer treatment experience a range of treatment-related toxicities that significantly affect quality of life and adherence to therapy. Current methods for symptom reporting rely heavily on clinician interpretation of caregiver or child verbal reports, which can result in incomplete or inaccurate records. The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Pediatric PRO-CTCAE; National Cancer Institute) provides a validated mechanism for direct symptom reporting by children and caregivers, yet its traditional administration and preselection of questions limit the breadth of symptom capture.

Objective: This research aimed to co-design and conduct formative usability testing …

Postapproval Study For Brain-Responsive Neurostimulation For Drug-Resistant Focal Epilepsy: Three-Year Efficacy And Interim Safety Results, Dawn Eliashiv, Vikram R Rao, Barbara C Jobst, Jerzy P Szaflarski, John D Rolston, Lesley C Kaye, Taneeta Mindy Ganguly, Katie Bullinger, Patricia C Dugan, David E Burdette, Angela Y Peters, Atif Sheikh, Kevin F Haas, Dileep R Nair, Lilit Mnatsakanyan, Imran H Quraishi, Meriem K Bensalem-Owen, Rns System Pas Study, Michael J Doherty, Babak Razavi, Tiffany L Fisher, Christopher Skidmore, Pradeep N Modur, Tawnya M Constantino, Vicenta Salanova, Andrew J Cole, Olga Taraschenko, Angelica Rivera-Cruz, James W Wheless, Nitin Tandon, Antoaneta Balabanov, Sami Aboumatar, Itzhak Fried, Cornelia Drees, Hae Won Shin, Zeenat Jaisani, Stephanie E Maciver, Sanjay E Patra, Edward F Chang, Jon T Willie, Ryder Gwinn, Travis Stoub, John M Stern, Tami Crabtree, Cairn G Seale, Sharon C Mcfadden, Jacob F Norman, Lise Johnson, Martha J Morrell

Faculty, Staff and Student Publications

Background and objectives: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT.

Methods: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will …

Water-Soluble Fullerene Derivatives Mitigate Cranial Radiation-Induced Neuroinflammation And Cognitive Dysfunction, Naren Gundapaneni, Iona Hill, Lydia W T Cheung, Khadijeh Koushki, Alyssa Fausnaught, Phuoc Minh Quan Mai, Arjun Vasan, Prapannajeet Biswal, Ashutosh Tripathi, Anilkumar Pillai, Vijayasree V Giridharan, Tatiana Barichello, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

Radiotherapy is widely used to treat malignant and benign brain tumors. A major constraint, however, is the low tolerance of normal brain tissue to radiation. Cranial irradiation-induced injury manifests as inflammatory responses and neurodegeneration, which jointly contribute to progressive cognitive decline. These complications can restrict the delivery of optimal therapeutic doses, cause persistent neurological symptoms, and ultimately compromise quality of life. Thus, neuroprotective agents have emerged as a strategy to safeguard normal tissues from radiation-induced neurotoxicity. This study investigated the efficacy of a highly soluble [60]fullerene (C60) derivative, C60-ser, a carbon-based nanomaterial, to mitigate radiation-induced brain injury. Oral administration of …

Correction: Berezowski Et Al. Biomarkers In Renal Cell Carcinoma: A Systematic Review And Immunohistochemical Validation Study, Brett Berezowski, Robert Boothe, Billy Chaplin, Sharon J Del Vecchio, Zakariya Fares, Tyrone L R Humphries, Keng Lim Ng, Taylor Noonan, Hemamali Samaratunga, Aaron Urquhart, David A Vesey, Simon T Wood, Glenda C Gobe, Robert J Ellis

Faculty, Staff and Student Publications

This corrects the article "Biomarkers in Renal Cell Carcinoma: A Systematic Review and Immunohistochemical Validation Study" in volume 17, 2588.

Animal Models Of Delirium: A Narrative Review, Tatiana Barichello, Carla Sasso Simon, Diogo Dominguini, Cristiane Ritter, Tsuyoshi Nishiguchi, Gen Shinozaki, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

Delirium is an acute cognitive failure characterized by an acute onset and psychomotor disturbances. It is associated with poor outcomes in hospitalized patients, resulting in prolonged hospital stays, elevated rates of mortality, and cognitive dysfunctions after hospital discharge. The pathophysiology of delirium remains poorly understood, making the development of animal models a promising avenue for researchers to elucidate the mechanisms underlying human delirium. These models not only aid in understanding the pathophysiology and etiology of the disease but also enhance the efficacy of nonpharmacological interventions and identify pharmacological therapies. This review aims to present the most relevant and translational animal …

Is2c2: A Cointelligent Platform For Mechanistic Discovery Of Disease Cellular Crosstalk, Jianting Sheng, Ju Young Ahn, Li Yang, Zhihao Wan, Shaohua Qi, Xiaohui Yu, Zhan Xu, Yuliang Cao, Matthew Vasquez, Amna Irfan, Yuanyuan Zhu, Hong Zhao, Zheng Yin, Ying Zhu, Yunfeng Ding, Alireza Faridar, Lin Wang, Fengshuo Liu, Hongxia Wang, Zhigang Ji, Dongxue Mao, Michael Chan, Daniel Kermany, Wenjuan Dong, Doo Yeon Kim, Xiang H-F Zhang, Stephen T C Wong

Faculty, Staff and Students Publications

Large language models (LLMs) have demonstrated impressive capabilities in summarization, reasoning, and content generation, yet their inability to directly interpret large-scale omics data has limited their utility in data-driven hypothesis generation-particularly in mechanism discovery that demands the integration and interpretation of multimodal datasets, heterogeneous models, and deep domain expertise. Conversely, traditional computational algorithms excel at quantitative analysis of omics data but often rely heavily on labor-intensive, expert-driven interpretation to extract biologically meaningful insights. Here, we introduce (cointelligent single-cell spatial cell‒cell communication: iS2C2), a novel cointelligent platform that synergizes mathematically rigorous computational algorithms with the contextual reasoning capabilities of LLMs to …

Natural History Of Ngly1 Deficiency: Motor Function & Clinical Features, Grace Morrison, Selina Dwight, Hal Landy, William F Mueller, Pam Ventola, Regina Deck, Becky Schweighardt, Matt Wilsey, Kevin J Lee, Bernhard Suter

Faculty, Staff and Students Publications

N-glycanase 1 (NGLY1) Deficiency is an ultra-rare neurodevelopmental disorder caused by biallelic loss-of-function mutations in the NGLY1 gene, leading to severe impairments in neurocognitive and motor function abilities in the affected patient population. Its core clinical features include global developmental delay, hyperkinetic movement disorders, elevation of liver transaminases, (hypo)alacrima, and progressive sensorimotor neuropathy. Due to the range of phenotypes and severity within the confirmed patient population, ongoing characterization of the disease is critical. A prospective natural history study (NHS) was conducted to further elucidate disease phenotypes and examine any changes in neurocognitive or motor function over a one-year period. Fifteen …

Implementation Of A Planned Extubation Nurse-Led Safety Bundle In A Pediatric Cardiac Intensive Care Unit, Broderick Sutton

Doctor of Nursing Practice Final Project Abstract

Purpose: To implement and evaluate a nurse-led planned extubation safety bundle designed to improve nurse preparedness, interdisciplinary communication, workflow consistency, and confidence during planned extubation events in a pediatric Cardiac Intensive Care Unit (CICU).

Background: Planned extubation in critically ill pediatric cardiac patients requires effective interdisciplinary coordination. Variability in nurse preparation, communication, and knowledge of sedation pharmacokinetics contributed to workflow inefficiencies and patient safety concerns. Evidence supports standardized nurse-led protocols to improve extubation readiness and reduce practice variability.

Methodology: A prospective pre-post quality improvement project was conducted over eight weeks in a pediatric CICU. The intervention included a nurse-led planned …

Improving Postoperative Handoff For Placenta Accreta: Implementing A Structured Handoff Communication Tool, Isabelle L. Gerrard

Doctor of Nursing Practice Final Project Abstract

Purpose Implement a standardized postoperative handoff tool to improve interdisciplinary communication during transfer of placenta accreta spectrum (PAS) patients from the operating room to an obstetric intensive care unit at an academic women's hospital.

Background Placenta accreta spectrum (PAS) is a high-risk obstetric condition requiring coordinated multidisciplinary care. At the project site, operating room (OR)-to-obstetric intensive care unit (OB ICU) handoffs lacked a standardized process. This resulted in inconsistent communication and omission of critical information. Nurses reported reduced confidence. Standardized handoff tools can improve communication and promote safer transitions of care.

Methodology This 10-week quality improvement project used Plan-Do-Study-Act methodology …

Dna Methylation Signatures Associated With Bipolar Disorder In Peripheral Blood Improve Prediction Models, Markos Tesfaye, Anne-Kristin Stavrum, Kira D Höffler, Kevin S O'Connell, Friederike S David, Melanie E Garrett, Sonia Hesam-Shariati, Bronwyn J Overs, Claudia Pisanu, Luana Spano, Oliver J Watkeys, Antoine Weihs, Rafaella Ardau, Allison E Ashley-Koch, Lavinia Athanasiu, Jean C Beckham, Kyle J Bourassa, Caterina Chillotti, Srdjan Djurovic, Ole K Drange, Josef Frank, Anouar Khayachi, Nathan A Kimbrel, Lourdes Martorell, Susanne Meinert, Ingrid Melle, Gunnar Morken, Pasquale Paribello, Marco Pinna, Gloria Roberts, Guy Rouleau, Peter R Schofield, Esteban Sepúlveda, Giovanni Severino, Vidar M Steen, Frederike Stein, Fabian Streit, Va Mid-Atlantic Mirecc Workgroup, Trine Vik Lagerberg, Martin Alda, Udo Dannlowski, Andreas J Forstner, Janice M Fullerton, Hans J Grabe, Melissa J Green, Tilo Kircher, Javier Labad, Mirko Manchia, Philip B Mitchell, Jair C Soares, Alessio Squassina, Alexander Teumer, Leonardo Tondo, Elisabet Vilella, Ole A Andreassen, Boris Chaumette, Gabriel R Fries, Stephanie Le Hellard

Faculty, Staff and Student Publications

Background: Bipolar disorder (BD) is a major mood disorder influenced by both genetic and environmental factors. While DNA methylation from peripheral tissues can reflect both genetic and environmental influences and reveal insights into disease biology, it remains understudied in BD. DNA methylation signatures may complement polygenic scores (PGS) and hold potential as biomarkers. Here, we conducted the largest epigenome-wide association study (EWAS) of BD to date and evaluated the predictive value of polymethylation scores (PMS) in classifying case-control status.

Methods: DNA methylation from peripheral blood of 1729 cases and 1747 controls, comprising twelve cohorts, was obtained. We performed meta-analyses for …

Identifying Novel Gene Dysregulation Associated With Opioid Overdose Death: A Meta-Analysis Of Differential Gene Expression In Human Prefrontal Cortex, Javan K Carter, Bryan C Quach, Caryn Willis, Melyssa S Minto, Dana B Hancock, Janitza Montalvo-Ortiz, Olivia Corradin, Ryan W Logan, Consuelo Walss-Bass, Brion S Maher, Eric Otto Johnson

Faculty, Staff and Student Publications

Only recently have human postmortem brain studies of differential gene expression (DGE) associated with opioid overdose death (OOD) been published; sample sizes from these studies have been modest (N = 40-153). To increase statistical power to identify OOD-associated genes, we leveraged human prefrontal cortex RNA-seq data from four independent OOD studies and conducted a transcriptome-wide DGE meta-analysis (N = 272). Using a unified gene expression data processing and analysis framework across studies, we meta-analyzed 20, 098 genes and found 335 significant differentially expressed genes (DEGs) by OOD status (false discovery rate <  0.05). Of these, 66 DEGs were among the list of 303 genes reported as OOD-associated in prior prefrontal cortex molecular studies (e.g., genes/gene families OPRK1, NPAS4, DUSP, EGR). The remaining 269 DEGs were not previously reported (e.g., NR4A2, SYT1, HCRTR2, BDNF). There was little evidence of genetic drivers for the observed differences in gene expression between opioid addiction cases and controls. Enrichment analyses for the DEGs across molecular pathway and biological process databases highlight an interconnected set of genes and pathways linked to orexin and tyrosine kinase receptors through MEK/ERK/MAPK signaling to affect neuronal plasticity.

Development Of Novel Plasma Proteomic Biomarkers For Cancer-Associated Thrombosis In An Advanced Cancer Cohort, Preeti, Mrinal Ranjan, Dang Pham, Juan L Bueno, Micheline M Resende, Michael E Scheurer, Christopher I Amos, Chao Cheng, Ang Li

Faculty, Staff and Students Publications

Background: Existing risk models for cancer-associated thrombosis (CAT) show suboptimal performance in selective high-risk populations with cancer. Affinity-based plasma proteomics offers a novel approach for detecting CAT risk.

Objectives: To identify plasma biomarkers for CAT using proximity extension assays in an advanced cancer cohort.

Methods: We performed a nested case-control study using the Olink Explore HT panel. The final cohort included 57 patients with CAT and 113 matched control patients from 5 selected cancer types who had samples collected between cancer diagnosis and chemotherapy initiation. Random survival forest model was used to assess nonlinear associations with CAT in 5416 normalized …

Progressive Cardiac Phenotypes And Reduced Reversibility From Long-Term Cugexp Rna Expression In A Dm1 Mouse Model, Rong-Chi Hu, Mohammadreza Tabary, Xander Ht Wehrens, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is caused by an expanded CTG repeat in the DMPK gene, resulting in mutant transcripts that form expanded CUG (CUGexp) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins. DM1 is multisystemic, with progressive worsening of disease manifestations in affected tissues. Disease progression is attributed to somatic expansion of the CTG repeats with age, resulting in production of CUGexp RNA with enhanced intrinsic toxicity due to increased MBNL sequestration. To determine the degree to which cardiac disease progression can occur independently of repeat expansion, we used a transgenic DM1 mouse model with inducible heart-specific expression of …

Genetic Analysis Of The X-Linked Adrenoleukodystrophy Gene Abcd1 In Drosophila Uncovers A Conserved Phenotype, Joshua Manor, Sharayu V Jangam, Hyung-Lok Chung, Pranjali Bhagwat, Jonathan C Andrews, Hillary Chester, Shu Kondo, Saurabh Srivastav, Juan Botas, Ann B Moser, Suzette M Huguenin, Michael F Wangler

Duncan NRI Faculty and Staff Publications

X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder caused by a loss-of-function (LOF) mutation in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, leading to the accumulation of very long-chain fatty acids (VLCFAs). This disorder exhibits striking heterogeneity; some male patients develop an early childhood neuroinflammatory demyelination disorder, while other patients, including adult males and most affected female carriers, experience a chronic progressive myelopathy. Adrenocortical failure is observed in almost all male patients, with the age of onset varying, sometimes being the first diagnostic finding. The gene underlying this spectrum of disease encodes an ATP-binding cassette (ABC) transporter that …

Pharmacogenomic-Guided Prescribing And Polypharmacy Across Age Groups In Obsessive-Compulsive Disorder: A Retrospective Study, Sheldon R Garrison, Matthew W Boyer, Anthony W Zoghbi, Rachel A Schwartz, Nicolette Weisensel, Martin E Franklin, Madeline M Hartig, Maharaj Singh, Sreya Vadapalli

Faculty, Staff and Students Publications

Background: This study evaluated medication utilization in children, adolescents, and adults with obsessive-compulsive disorder (OCD), a chronic psychiatric condition characterized by intrusive thoughts and repetitive behaviors. Although first-line treatments include selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT), the heterogeneous biological underpinnings contribute to suboptimal outcomes, with 40-60% of individuals not responding to SSRIs. This complex phenotype often leads to psychotropic polypharmacy, which may be mitigated by incorporating combinatorial pharmacogenomic (PGx) testing into protocol-based care to identify potential gene-drug interactions.

Methods: A retrospective review was conducted of individuals with OCD aged 8 to 65 years who received either …

Cd8+ T Cell Differentiation Into Nk-Like Effector Cells Drives Transplant Rejection, Dawei Zou, Stephanie G Yi, Yulin Dai, Luan Truong, Lillian W Gaber, Richard J Knight, Xiang Xiao, Rafik M Ghobrial, Xian C Li, Zhongming Zhao, Wenhao Chen, A Osama Gaber

Faculty, Staff and Student Publications

T cells are central drivers of transplant rejection, yet the differentiation fates underlying this process remain unclear. Using single-cell transcriptomic profiling of human kidney allograft biopsies, we identified a predominant infiltrating CD8+ T cell subset exhibiting killer cell lectin-like receptor (KLR)+ NK-like features. Mechanistic studies in mice showed that the KLR+ subset emerged de novo post-transplantation and dominated the CD8+ T cell infiltrate in rejecting allografts. These NK-like CD8+ T cells expressed high levels of interferon regulatory factor 4 (IRF4), and Irf4 deletion disrupted their differentiation and induced transplant acceptance. Therapeutically, either costimulation blockade or mTOR inhibition substantially reduced the …

Immediate Nerve And Tendon Transfers After Wide Resection Of A Radial Nerve Malignant Peripheral Nerve Sheath Tumor: A Case Report And Surgical Technique, Joanne Zhou, Sai Shreya Kambham, Andrew Fang, Christopher Frey, Michael Macavoy

Faculty, Staff and Student Publications

The authors have reported on immediate nerve and tendon transfers postresection of a radial nerve-based malignant peripheral nerve sheath tumor in a 15-year-old female with neurofibromatosis. The median nerve branch to flexor carpi radialis was transferred to the posterior interosseous nerve, the median nerve branch to flexor digitorum superficialis was transferred to the nerve to extensor carpi radialis brevis, and the pronator teres tendon was transferred to the extensor carpi radialis brevis tendon, with 3-year outcomes reported. Tumor excision, tendon, and nerve transfer yielded negative margins and remission. Functional wrist/finger extension appeared at 6 months and increased until 3 years …

Applying User-Centered Design To Develop A Culturally Sensitive, Low-Calorie Meal Plan For Enhancing Dietary Behavioral Control In Masld, Maya Balakrishnan, Paola Martinez, Brett Deng, Ivonne Arguelles, Crystal Arguelles, Terri L Fletcher, Natalia I Heredia, Myriam Ibarra, Anna Christine Rome

Faculty, Staff and Students Publications

Background: Dietary changes are essential for managing metabolic dysfunction-associated steatotic liver disease (MASLD), yet patients often face barriers related to knowledge, skills, cost, time, and cultural fit.

Aims: The purpose of this paper is to report a process for culturally tailoring a dietary intervention and its application to create a calorie-restricted meal plan for Mexican and Central American patients with MASLD. Guided by the Theory of Planned Behavior and user-centered design, we produced a culturally tailored seven-day structured meal plan aligned with dietary guidelines for MASLD and weight loss.

Methods: We conducted a three-phase, mixed-methods process among Mexican/Central American patients …