Digital Commons Network^™

A Remote Intervention To Improve Medication Nonadherence Guided By A Marker Of Risk Derived From The Electronic Health Records Of Adolescent Transplant Recipients, Eyal Shemesh, Ravinder Anand, Rachel A Annunziato, Emily M Fredericks, Jennifer Garcia, Nitika Arora Gupta, Lawrence C Kleinman, Alyssa Kriegermeier, Krupa R Mysore, Vicky L Ng, Steven J Lobritto, Shreena Patel, Emily Rothbaum Perito, Elizabeth B Rand, Rene Romero, Robert S Venick, Sarah Duncan-Park, Jeffrey Mitchell, Sarah G Anderson, Margaret L Stuber, Miguel Reyes-Múgica, George V Mazariegos, Benjamin L Shneider

Faculty, Staff and Students Publications

Improving medication adherence in adolescents who had a liver transplant (iMALT), a prospective, block-randomized, single-blind, controlled multisite study in 13 pediatric transplant centers, used the medication level variability index (MLVI) to identify nonadherent adolescents. It compared a 2-year remote behavioral telemetric intervention (TI) that focused on adherence and addressed barriers to standard of care (SOC). The primary endpoint was the composite incidence of centrally determined (3 masked pathologists) rejection, death, retransplantation, or consent withdrawal. In 148 participants (TI group, n = 72 and the SOC group, n = 76), with a mean age 15.5 years, there were twice as many …

Cardiac Resynchronization Therapy: A Review, Caique M Ternes, Jitae A Kim, Anirban Basu, Kenneth A Ellenbogen, Mihail G Chelu

Faculty, Staff and Students Publications

Importance: Heart failure (HF) affects more than 64 million individuals worldwide, and acute HF is associated with 1-year mortality rates of 23.6% in North America and Europe. Cardiac dyssynchrony from conduction system disease may cause HF progression, particularly in patients with left ventricular (LV) systolic dysfunction.

Observations: Electrical dyssynchrony in HF most commonly presents as left bundle-branch block and affects 20% to 30% of patients with reduced LV ejection fraction (LVEF). Cardiac resynchronization therapy, which includes biventricular pacing and conduction system pacing, restores synchronous ventricular contraction and is recommended for patients with symptomatic HF despite optimal medical therapy, LVEF of …

O-Glcnacylation As A Metabolic Integrator In Cardiovascular Physiology And Disease, Saima Shakil Malik, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

No abstract provided.

Targeted Suppression Of Spp1 Inhibits Tumor Invasion And Metastasis In Nrf2 Hyperactivated Cisplatin Resistant Hnscc, Mutsuki Kawabe, Sujuan Yang, Lorena I Gomez-Bolanos, Shiro Takamatsu, Sylvia Flores, Patricia D Castro, Tsung-You Tsai, Arisa Nishikawa Kaga, Kento Okamoto, Mitchell J Frederick, Vlad C Sandulache, Humam Kadara, Jeffrey N Myers, Abdullah A Osman

Faculty, Staff and Students Publications

Background: Cisplatin remains the standard systemic therapy for the definitive treatment of head and neck squamous cell carcinoma (HNSCC), however, resistance to cisplatin continues to be a major barrier to effective treatment, particularly in tumors with NRF2 hyperactivation. Recent studies identify secreted phosphoprotein 1 (SPP1/osteopontin) as a key NRF2 target frequently overexpressed in cancers, where it drives aggressive tumor behavior, metastasis, chemoresistance, and, in some cases, immune suppression. Our recent data highlight SPP1 as one of the top 10 NRF2-upregulated genes in cisplatin-resistant HNSCC. However, its specific role in therapy resistance and metastasis in HNSCC remains unclear. Here, we investigate …

The Perijunctional Zone Is A Molecularly Distinct Muscle Subdomain Altered In Duchenne Muscular Dystrophy, Seth G Haddix, Chuansheng Zhang, Yanhong Liu, Juan Oses-Prieto, Alma L Burlingame, Matthew N Rasband

Faculty, Staff and Students Publications

The neuromuscular junction (NMJ) is a well-established model for synapse development, structure, and function. Surrounding the NMJ is a narrow perijunctional zone (PJZ), enriched in muscle-specific voltage-gated sodium channels that prevent synaptic fatigue. Despite this role, the PJZ remains poorly characterized. To determine its molecular composition, we engineered mice to express the biotin ligase TurboID fused to the cell adhesion molecule neurofascin (Nfasc), and that localizes to the PJZ through ankyrin scaffolding proteins. Using proximity proteomics, we identify numerous PJZ-associated proteins, including Perilipin 4 (Plin4), that are highly enriched and clustered at the PJZ. We also perform proximity proteomics on …

Circulating Metabolites Associated With Protection Against Mycobacterium Tuberculosis Infection And Inhibition Of Mycobacterial Growth, Todia P Setiabudiawan, Lika Apriani, Julian Avila-Pacheco, Edwin Ardiansyah, Vinod Kumar, Bachti Alisjahbana, Ayesha J Verrall, Andrew R Dinardo, Agnes R Indrati, Vera P Mourits, L Charlotte J De Bree, Simone J C F M Moorlag, Clary B Clish, Leo A B Joosten, Arjan Van Laarhoven, Krista E Van Meijgaarden, Mihai G Netea, Simone A Joosten, Valerie A C M Koeken, Philip C Hill, Reinout Van Crevel

Faculty, Staff and Students Publications

A significant proportion of individuals who are heavily exposed to infectious tuberculosis patients do not acquire Mycobacterium tuberculosis (Mtb) infection, as detected by an interferon gamma release assay (IGRA). We examined circulating metabolite profiles and metabolic genotypes in 199 heavily exposed IGRA-negative tuberculosis household contacts in Indonesia. Based on differentially abundant metabolites, activity of several pathways including arachidonic acid, arginine and proline, glutathione, and tryptophan metabolism, correlated with a negative IGRA at three months. SNPs near PRODH (involved in arginine and proline metabolism) were associated with circulating proline concentrations and persistently negative IGRA results, while SNPstudys near AFMID (involved in …

Childcare Challenges Among Surgical Trainees And Faculty: A Single-Institution Study, Emma G Burke, Sarah Peiffer, Melissa Koci, Lindsay Dean, Kristy L Rialon, Michele Loor, Alice King

Faculty, Staff and Students Publications

Background: Previous studies have demonstrated the challenges of parenthood in surgical training and careers. However, certain aspects of childrearing for surgeons remain understudied. We aim to leftacterize the complexity and costs of childcare amongst surgical trainees and faculty.

Methods: An anonymous, self-administered survey was conducted within the Department of Surgery at a large academic medical center. Both male and female trainees and faculty were included in the analysis. Chi-square or Fisher's Exact test was performed.

Results: Forty-six respondents provided information about childcare costs, with 37% of respondents being residents or fellows. Trainees worked longer workhours (p = 0.003) than their …

Phkg2 Confers Resistance Of Escc To Cisplatin And Enhances Cxcl8-Dependent Immunosuppression To Exacerbate Tumorigenesis, Jiayan Wu, Chengrui Zhong, Haosheng Zheng, Fei Qin, Xianyu Qin, Yuzhen Zheng, Junguo Chen, Gengfeng Wang, Bozhu Jian, Zui Liu, Xingping Yang, Chao Cheng, Guolin Li, Hongying Liao

Faculty, Staff and Students Publications

Cisplatin (DDP)-based chemotherapy serves as a foundational cornerstone in the clinical management of esophageal squamous cell carcinoma (ESCC). However, intrinsic or acquired resistance to DDP persists as a significant clinical challenge, severely undermining therapeutic efficacy and contributing to unfavorable patient prognoses. Through functional screening with a CRISPR/Cas9 knockout library, transcriptomic profiling of cisplatin-resistant cell lines and clinical specimens, and in vitro/in vivo validation assays, we identified PHKG2 as a key mediator of cisplatin resistance in ESCC. Mechanistically, PHKG2-mediated cisplatin resistance is driven by the phosphorylation of IGF2BP3 at residues T225 and T306. This post-translational modification enhances IGF2BP3 phase separation, thereby …

Movement-Stabilized Three-Dimensional Optical Recordings Of Membrane Potential Changes And Calcium Dynamics In Hippocampal Ca1 Dendrites, Kevin C Gonzalez, Satoshi Terada, Asako Noguchi, George N Zakka, Cliodhna O'Toole, Giuliana Bilbao, Luke Reynolds, Anna Jász, Borbála Kertész, Zoltán Szadai, Alissa Shen, François St-Pierre, Franck Polleux, Attila Losonczy, Balázs Rózsa

Faculty, Staff and Students Publications

Local dendritic computations are thought to critically influence neuronal signaling and plasticity yet remain largely unexplored in vivo due to challenges in stably imaging small structures at ultrafast timescales. We developed a 3D real-time motion correction platform for movement-stabilized, ultrafast two-photon voltage imaging. By co-labeling CA1 pyramidal neurons with voltage and calcium indicators, we simultaneously measured somato-dendritic and electro-calcium coupling at multiple dendritic sites. We characterized isolated dendritic spikes and distance-dependent backpropagation of naturally occurring and photostimulation-evoked bursts and single spikes. We found that bursts backpropagated more reliably than single spikes, validated that somato-dendritic coupling decreases with distance from soma, …

A Review Of Robotic Vnotes Surgery: Current Applications, Advantages, And Future Directions, Daniel Y Lovell, Qiannan Yang, Xiaoming Guan

Faculty, Staff and Students Publications

Over the past 500 years, the convergence of three distinct paths - vaginal surgery, laparoscopy, and robotic technologies - has enabled the development of robot-assisted vaginal natural orifice transluminal endoscopic surgery (RA-vNOTES). The ongoing evolution of vaginal surgery has led to contemporary procedures such as hysterectomy, myomectomy, sacrocolpopexy, adnexal interventions, and oncologic operations, applicable to a wide range of diagnoses and pathologies. This approach offers patients significant benefits, including superior cosmetic outcomes, less pain, lower infection rates, and faster recovery of baseline quality of life. Surgeons benefit from improved ergonomics, better visualization, the ability to use multiple instruments, and enhanced …

Deep-Learning Endomicroscope With Large Field-Of-View And Depth-Of-Field For Real-Time In Vivo Imaging Of Epithelial Cancer Hallmarks, Huayu Hou, Jimin Wu, Jinyun Liu, Vivek Boominathan, Argaja Shende, Karthik Goli, Jennifer Carns, Richard A Schwarz, Ann M Gillenwater, Preetha Ramalingam, Mila P Salcedo, Kathleen M Schmeler, Tomasz S Tkaczyk, Jacob T Robinson, Ashok Veeraraghavan, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep learning-enabled endomicroscope that breaks these constraints and achieves 20 mm2 FOV and 500 µm DOF with 4 µm resolution, representing approximately 5× increase in FOV and 8× larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep learning-optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface …

Human Papillomavirus Vaccine Discourse And Sentiment On Reddit Before And After Covid-19: Mixed Methods Retrospective Cross-Sectional Study, Marcin Marciniak, Sean A Setzen, Deeya Bhattacharya, Jamie Masliah, Robin Powszok, Erich M Sturgis, Vanessa C Stubbs, Mihir K Bhayani

Faculty, Staff and Students Publications

Background: Human papillomavirus (HPV) is a sexually transmitted virus that causes various oropharyngeal and anogenital cancers. The HPV vaccine provides protection against several strains of HPV and is a key preventative tool against HPV-related cancers; however, vaccination rates remain suboptimal in the United States due to variable state mandates and misperceptions of vaccine efficacy and risks. As social media becomes an increasingly popular avenue for health discussions, platforms such as Reddit offer opportunities to understand public vaccine discourse, particularly among underrepresented groups. Furthermore, vaccine hesitancy and mistrust generally increased during the COVID-19 pandemic, potentially impacting HPV vaccination rates.

Objective: This …

Association Of Polygenic Risk Scores With Aortic Valve Calcium: The Multi-Ethnic Study Of Atherosclerosis, Seamus P Whelton, Jie Yao, Clary Clish, Alexis C Wood, Kent D Taylor, Michael J Blaha, Matthew Budoff, Natalie Marrero, George Thanassoulis, Wendy S Post, Xiuqing Guo, Jerome I Rotter

Faculty, Staff and Students Publications

Background: Aortic valve calcification (AVC) is the primary process leading to aortic stenosis. We examined whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors.

Methods: We included 6812 participants in MESA (Multi-Ethnic Study of Atherosclerosis) with computed tomography-measured AVC at Visit 1. Using previously published PRS we calculated weighted PRS, standardized within each ancestry group. The cross-sectional association per 1 SD higher PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction. The mean age was 62 years old, 53% were female, and 913 (13.4%) had AVC >0 at …

Latest In Resuscitation Research: Highlights From The 2025 American Heart Association's Resuscitation Science Symposium, Caleb T Suh, Clark G Owyang, Lindsay Shepard, Betty Yang, Ryan W Morgan, Daniel M Rolston, Catherine R Counts, Tommaso Scquizzato, James Horowitz, Tatyana Shvilkina, Katherine Berg, Sam Parnia, Sanam Alilou, Catherine Swarts, Ryan A Coute, Lama A Ammar, William C Herring, Thomas Lederer, Joaquin Araos, Benjamin S Abella, Cameron Dezfulian, Sarah M Perman, Felipe Teran

Faculty, Staff and Students Publications

No abstract provided.

Cohort Study Of Opioid Utilization In Post-Tonsillectomy Pediatric Patients, Sainiteesh Maddineni, Varun Vendra, Hareem Khan, Noor Ali, Tulio Valdez, Anna Messner, Iram Ahmad

Faculty, Staff and Students Publications

Objectives: Prospective observational cohort study at a tertiary care academic center to evaluate the post-operative use of oxycodone in pediatric tonsillectomy patients and caregiver knowledge of opioid disposal.

Methods: Pediatric patients 6-18 years old undergoing tonsillectomy were enrolled. Patients were excluded if they required prolonged inpatient care, had a history of organ transplantation, chronic pain or narcotic use, congenital or chromosomal disorders, inability to take acetaminophen or ibuprofen, and other significant medical diagnoses that could potentially alter postoperative pain management. All patients were prescribed a standard amount of oxycodone to be used for breakthrough pain in addition to ibuprofen and …

Developing A Durable, Memory-Driven, Cspz-Targeting Lyme Disease Vaccine By Rationale Adjuvant Selection\, Miranda Mccarty, Sergio A Hernández, Jill Malfetano, Ana Carolina Leão, Maria Jose Villar, Xiuli Yang, Yi-Lin Chen, Jungsoon Lee, Zhuyun Liu, Ulrich Strych, Maria Elena Bottazzi, Utpal Pal, Klemen Strle, Wen-Hsiang Chen, Yi-Pin Lin

Faculty, Staff and Students Publications

Rational adjuvant selection is a systematic approach based on adjuvant-mediated immunomodulation to identify safe vaccine regimens that enhance protective immunity. Transmitted through ticks and caused by the bacterium Borrelia burgdorferi (Bb), Lyme disease (LD) is the most common vector-borne disease in the Northern hemisphere. There are no approved human vaccines, making it suitable for testing the concept of rational adjuvant selection. Here, we formulated our previously developed and effective LD vaccine antigen, CspZ-YAC187S, with different adjuvants suitable for human use; we analyzed the immune response by transcriptomics and tested the vaccine efficacy after Bb infection. We identified Alum-CpG and Alum-αGal …

Pediatric Home-Based Hospice And Palliative Care: A Scoping Review, Ellen Davis, Daniel H Grossoehme, Toluwalase Ajayi, Justin N Baker, Pamela S Hinds, Lisa Humphrey, Jill Ann Jarrell, Rachel Thienprayoon, Sarah Friebert

Faculty, Staff and Students Publications

Pediatric palliative and/or hospice care is provided across a broad spectrum of settings, ranging from inpatient to outpatient to a child's home. Pediatric home-based hospice and/or palliative care teams offer a specialized, interdisciplinary approach to care, allowing children to stay in the home while offering comprehensive support. This scoping review seeks to summarize what is known about pediatric home-based hospice and/or palliative care and to identify gaps in the current research. Following Arskey and O'Malley's scoping review framework, we searched four databases for studies focused on pediatric home-based hospice and/or palliative care programs. Studies were included if they were published …

Cardiac Hdac3 Disruption Contributes To Hdac Inhibitor-Induced Qt Prolongation, Jiao Lu, Christopher Ward, Sichong Qian, Lilei Zhang, Jiang Chang, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylase (HDAC) inhibitors are approved for cancer treatment and are being investigated for a wide range of other diseases. Despite their therapeutic promise, clinical studies have reported cardiac side effects, particularly electrocardiogram (EKG) abnormalities, with QT interval prolongation being one of the most consistently reported findings. The mechanisms underlying these cardiac effects remain unclear. In this study, we investigated the role of HDAC3 in cardiac electrophysiology. We found that postnatal depletion of cardiac HDAC3 in mice caused QT interval prolongation, recapitulating the EKG abnormalities reported with HDAC inhibitor use. Adult-onset inducible depletion of cardiac HDAC3 induced additional EKG abnormalities, …

Correction: Watts Et Al. Multi-Antigen Elephant Endotheliotropic Herpesvirus (Eehv) Mrna Vaccine Induces Humoral And Cell-Mediated Responses In Mice, Jessica R Watts, Jennifer L Spencer Clinton, Jeroen Pollet, Rongsheng Peng, Jie Tan, Paul D Ling

Faculty, Staff and Students Publications

The authors would like to make the following corrections to this published paper [...].

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 …

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 …

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 …

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 …

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 …

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 …

Small Partial Deletion Of A Highly Gc-Rich Foxf1 Exon 1 In Two Deceased Siblings With Alveolar Capillary Dysplasia, Hiuling Chan Joiner, Shruti A Pande, Przemyslaw Szafranski, Partha Sen, Gail Deutsch, Pawel Stankiewicz

Faculty, Staff and Students Publications

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder caused by haploinsufficiency of FOXF1. While larger-sized coding and noncoding copy-number variant (CNV) deletions involving the FOXF1 locus are detected in approximately half of histopathologically-diagnosed ACDMPV patients, small CNVs remain diagnostically challenging. Here, we revisited an unsolved case of familial ACDMPV with two affected siblings. Whole genome sequencing (WGS) of 30-year-old archival lung autopsy tissue analyzed using AI powered platform revealed a 151 bp CNV deletion involving a highly GC-rich portion of exon 1 of FOXF1 that was not detected using Sanger sequencing and …