Digital Commons Network^™

Subjective Sleep Disruption, Coping, And Anxiety And Related Symptoms In The Perinatal Period: Findings From A Longitudinal Study, Jonathan S Abramowitz, Gerald Nestadt, Eric A Storch, Rashelle Musci, Paul Nestadt, Lauren M Osborne, Mary Kimmel

Faculty, Staff and Students Publications

Study objectives: Anxiety is common during the perinatal period and is associated with adverse maternal and infant outcomes, highlighting a need to identify predictors of perinatal anxiety. Accumulating research implicates sleep disruption in perinatal anxiety and related symptoms, including obsessive-compulsive symptoms. We examined the associations among insomnia symptoms and sleep duration with perinatal anxiety, obsessive beliefs, and obsessive-compulsive symptoms and the moderating role of coping from pregnancy through postpartum.

Methods: A sample of 231 women (agemean = 32.97 ± 4.36 years; 74% white) completed interview and self-report measures of sleep, coping, perinatal anxiety, obsessive beliefs, and obsessive-compulsive symptoms in early …

Slc Transporter-Mediated Functional Imaging In Cancer Diagnosis, Lumeng Zhang, Jun He

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Functional imaging has become an important approach for evaluating tumor physiology in vivo beyond morphologic assessment. Radiotracers used for cancer imaging are designed to mimic endogenous substrates or substrate analogues, and their accumulation can depend on membrane transport, intracellular metabolism, and clearance from normal tissues. Specifically, SLC transporters contribute to tracer uptake and signal formation, linking transporter activity with measurable imaging signals in cancer. While [18F]FDG PET/CT remains the most widely used example of transporter-associated metabolic imaging, SLC transporter-mediated imaging strategies have been developed to assess amino acid transport, sodium-dependent glucose uptake, redox metabolism, lactate exchange, nucleoside metabolism, choline metabolism, …

Leveraging Health Information Exchange (Hie) Data To Demonstrate The Impact On Health Outcomes Of Community Based Organization Interventions: Case Studies Of Housing Placement And Medically Tailored Meal Program, Kevin Kramer, Harm Scherpbier, William Marella

College of Population Health Faculty Papers

Objective

Methods

Birth-Size Reference Charts For Normal Nursery Newborns Between 35.0 And 41.6 Weeks., Fu-Sheng Chou, Hung-Wen Yeh, Crystal Hsueh, Irene E. Olsen, Veeral N. Tolia, Reese H. Clark

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Current birth-size reference charts for nursery use may inaccurately categorize newborn size, impacting care. We aimed to develop new charts using data from uncomplicated newborns admitted to US nurseries.

METHODS: We analyzed de-identified data from newborns admitted to US normal newborn nurseries between 2021 and 2024. Statistical outliers were excluded, and gestational age was recorded in days. Birth weight, length, head circumference, and BMI models were developed by a randomly selected subset and validated by the remaining data. Proportions of newborns below the 10th percentile and above the 90th percentile were compared with the 2010 Olsen and 2013 Fenton …

Feasibility And Acceptability Of Automated Texts To Offer, Screen, And Enroll Patients In A Cancer Clinical Trial Financial Reimbursement Program: Mixed Methods Study, Ashley E Santaniello, Hena Patel, Sarah Milinski, Mohan Balachandran, Vivian Nguyen, E. Paul Wileyto, Robert H. Vonderheide, Dana Dornsife, Robert G. Johnson, Carmen E. Guerra

Student Papers, Posters & Projects

BACKGROUND: Out-of-pocket (OOP) costs pose a significant barrier to participating in cancer clinical trials (CCTs). Financial reimbursement programs (FRPs) that reduce the burden of OOP costs can support participation in CCTs if the information is readily available to participants at the time of enrollment. Prior studies have shown the importance and impact of FRPs, but despite improvements, significant barriers still remain.

OBJECTIVE: This study was designed to explore the feasibility and acceptability of automated texts designed to offer, screen, and enroll CCT participants in an FRP for OOP travel and lodging-related clinical trial costs.

METHODS: This study used a mixed …

Recent Advances In Alzheimer's Disease: From Molecular Mechanisms To Therapeutic Strategies, Michelle D Rudman, Jason D Ulrich, David M Holtzman

2020-Current year OA Pubs

Alzheimer's disease (AD) remains the leading cause of dementia worldwide and an escalating global health crisis. The hallmark amyloid plaques and neurofibrillary tangles (NFT) are now known to be accompanied by a complex array of pathologies that culminate in neurodegeneration and cognitive decline. New disease-modifying therapies for AD can now slow cognitive decline through the removal of amyloid plaques from the brain, but treatments to stop or prevent cognitive impairment remain elusive. In this review, we summarize the most recent updates in AD research on pathologic disease mechanisms and therapeutic strategies, highlighting advancements in apolipoprotein E (APOE) biology, neuroimmunology, biomarker …

Gene Dosage Differences And Non-Linear Impacts On Complex Traits., Craig Smail

Manuscripts, Articles, Book Chapters and Other Papers

Large differences in gene dosage are usually associated with opposite phenotypic effects but show a bias toward one direction in aggregate genome wide. Milind et al. suggest that this is explained by differences in regulatory mechanisms by which genes influence phenotypes and by the increased selective pressures acting on a subset of genes.

Perceived Sensitivity Of Sensor-Based Digital Health Data: Qualitative Interview Study, Christine Deeney, Anika Sonig, Meghan E Hurley, Birkan Tunç, Eric A Storch, John D Herrington, Jennifer Blumenthal-Barby, Kristin Kostick-Quenet

Center for Medical Ethics and Health Policy Staff Publications

Background: Digital health tools are increasingly used in mental health care to passively collect patient data and analyze health status outside of clinical settings. While technologies such as digital phenotyping, affective computing, and computational behavioral analysis offer new insights into symptom manifestation in daily life, they generate large volumes of potentially sensitive data that raise significant data privacy concerns, requiring high levels of patient awareness and consent. Empirical research is lacking on stakeholder understandings toward the sensitivity of these data and expectations for data stewardship, perspectives that are critical for developing robust informed consent and data protection policies for digital …

Unbiased Avidity-Based Isolation Of Antigen-Specific T Cells, Amanda Montoya, Meredith L Frank, Peixin Jiang, Hui Nie, Minying Zhang, Emily Bontekoe, Jared K Slone, Ludovica L Posta, Sofia Rosy Caterina Sorice, Tina Cascone, Maura Gillison, Don L Gibbons, Jianjun Zhang, Eleonora Dondossola, Lydia Kavraki, Pamela L Wenzel, John V Heymach, Alexandre Reuben

The Brown Foundation: Institute of Molecular Medicine

Background: Cancer immunotherapies have significantly improved treatment efficacy and patient survival by exploiting antigen-specific T cells to eliminate cancer cells. However, current approaches for identifying and isolating antigen-specific T cells typically require prior knowledge of target antigens, limiting discovery, and reducing the ability to consistently detect rare tumor-reactive T cells. We therefore sought to develop an unbiased platform for the identification and enrichment of antigen-specific T cells using naturally processed and presented tumor antigens.

Methods: We developed ATTACH (Assessment of T cells Tethered to Antigen Class I Histocompatibility), a microfluidic platform that applies controlled shear stress and leverages tumor cells …

Food As Medicine: Effects Of A Culinary Medicine Food-Demonstration On Medical Students' Nutrition Knowledge, Confidence, And Satisfaction: An Exploratory Pilot Non-Randomized Pre-Post Intervention Study., Niayesh Mardmomen, Cyrus Fatemi, Olivia K Smith, Michael B. Roberts, Farzaneh Daghigh

PCOM Scholarly Works

Background: Diet plays a central role in the development of chronic diseases, making nutrition-focused interventions a powerful tool for improving population health. However, substantial gaps in nutrition education persist in the U.S. medical education, and medical students frequently report receiving limited nutrition training despite its importance in patient care. Methods: A non-randomized pre-post intervention study with a one-month follow-up was conducted among osteopathic medical students. Participants attended a culinary medicine food-demonstration featuring five case-based topics and three chef-prepared recipes. Nutrition knowledge, satisfaction with nutrition education, confidence in nutrition counseling, and personal nutrition-related behaviors were assessed at baseline, immediately …

Trends In Lung Cancer Survival: Superior Outcomes In Us Veterans Compared With The General Population, Nikki E Rossetti, Brendan T Heiden, Steven Tohmasi, Nahom Seyoum, Theodore Thomas, Whitney S Brandt, Sara Malone, Yan Yan, Ana Baumann, Su-Hsin Chang, Daniel Kreisel, Ruben Nava, Bryan Meyers, Benjamin Kozower, Varun Puri, Et Al.

2020-Current year OA Pubs

BACKGROUND: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality in the United States, but survival outcomes are shifting with evolving therapies and screening. Recent findings suggest that survival improvements vary across health-care systems, with favorable trends observed in the Veterans Health Administration (VHA). We sought to compare NSCLC survival trends across US health systems.

METHODS: We conducted a retrospective cohort study of patients with NSCLC (2007-2019) using data from the VHA and the National Cancer Database (NCDB), representing the non-VHA US general population. The primary exposure was health system (VHA vs non-VHA), and the primary outcome …

Pneumococcal Colonization In Pediatric Patients Undergoing Hematopoietic Cell Transplantation., Liset Olarte, Jennifer E. Schuster, Ibrahim Ahmed, Kristina G. Hulten

Manuscripts, Articles, Book Chapters and Other Papers

Despite the increased risk of invasive pneumococcal disease among pediatric hematopoietic cell transplant (HCT) recipients, pneumococcal colonization has not been evaluated in this population. We prospectively assessed longitudinal pneumococcal colonization in 22 pediatric HCT recipients from conditioning therapy to 100 days post-HCT. A higher likelihood of pneumococcal colonization was observed in the late post-HCT period (weeks 9-14) compared with the early post-HCT period (weeks 1-8), with odds increasing with each additional week after conditioning.IMPORTANCEThis is the first study to longitudinally evaluate pneumococcal colonization in pediatric hematopoietic cell transplant (HCT) recipients from the onset of conditioning therapy to 100 days post-HCT. …

Biophysical Insights Into A Cryptic Ligand Site In The Hydrophobic Core Of Human Pcna, Alexis N. Dispensa, Sharon N, Greenwood, Jason Yang, Daniel E. Logatto, James Fusco, E. Railey White, Roderic G. Eckenhoff, Zhiwei Liu, Brian P. Weiser

Department of Anesthesiology Faculty Papers

Proteins contain small pockets that form due to imperfections in residue packing or the rotational and conformational movement of amino acids. In this work, we used the fluorescent probe 1-aminoanthracene (AMA) to detect a small ligand pocket in the hydrophobic core of human proliferating cell nuclear antigen (PCNA), which is a critical protein for DNA replication and repair. Fluorescence measurements of AMA reported that the core of PCNA had a dielectric constant (ε) of 4, which was very apolar and similar to cyclohexane (ε = 2). Protein mutagenesis, photoaffinity labeling, and molecular dynamics simulations localized the binding site for AMA …

Longitudinal Genomic Surveillance Of Sars-Cov-2 In A University Microcosm Reflects Global Evolutionary Trends, Rebecca S B Fischer, Jo Ann Culpepper, Eric Boerwinkle, Kurt A Zuelke

Faculty, Staff and Student Publications

SARS-CoV-2 transmission has declined, yet ongoing viral evolution continues to pose public health challenges. This study conducted long-term (2020-2024) genomic surveillance within a large and globally diverse university community. Viral genomes obtained from clinical (n = 1,786) and surveillance (n = 888) testing samples were classified under clade, lineage, and variant systems, and compared with global genomic data sets. Local patterns broadly paralleled global evolutionary trends, including the phased emergence of major variants, episodic introductions of new lineages, and shifts in dominant clades. Lineage diversity peaked during fall semesters and was highest among undergraduate-aged individuals, with similar distributions …

The Human Lrrk2-R1441g Mutation Drives Age-Dependent Oxidative Stress And Mitochondrial Dysfunction In Dopaminergic Neurons, Yuanxin Chen, Lianteng Zhi, Shiquan Cui, Huaixin Wang, Chenbo Zeng, Hui Zhang

Department of Neuroscience Faculty Papers

BACKGROUND: Mitochondrial dysfunction and oxidative stress are central to the pathogenesis of Parkinson's disease (PD), particularly affecting substantia nigra pars compacta (SNc) dopamine (DA) neurons. Here, we investigate how the R1441G mutation in leucine-rich repeat kinase 2 (LRRK2), a key genetic contributor to familial and sporadic PD, impacts mitochondrial function in midbrain DA neurons.

METHODS: We employed a BAC transgenic mouse model overexpressing human LRRK2-R1441G (BAC-hR1441G) and crossed it with TH-mito-roGFP mice to enable mitochondria-targeted redox imaging specifically in DA neurons. Acute midbrain slices from 3-, 6-, and 12-month-old mice were imaged using two-photon microscopy to assess mitochondrial oxidative stress. …

Pneumococcal Colonization In Pediatric Patients Undergoing Hematopoietic Cell Transplantation, Kristina G Hulten

Faculty, Staff and Students Publications

Despite the increased risk of invasive pneumococcal disease among pediatric hematopoietic cell transplant (HCT) recipients, pneumococcal colonization has not been evaluated in this population. We prospectively assessed longitudinal pneumococcal colonization in 22 pediatric HCT recipients from conditioning therapy to 100 days post-HCT. A higher likelihood of pneumococcal colonization was observed in the late post-HCT period (weeks 9-14) compared with the early post-HCT period (weeks 1-8), with odds increasing with each additional week after conditioning.IMPORTANCEThis is the first study to longitudinally evaluate pneumococcal colonization in pediatric hematopoietic cell transplant (HCT) recipients from the onset of conditioning therapy to 100 days post-HCT. …

Association Between Author Specialty And Reported Outcomes In Non-Randomized Comparisons Of Prostatectomy Versus Radiation, Ramez Kouzy, Jie Jane Chen, Shalin Shah, Tarek Al Bitar, Sherif M Gadoue, Comron Hassanzadeh, Steven Frank, Phuoc Tho Tran, Chad Tang, Seungtaek Choi, Ryan Jin-Hyung Park, Karen Hoffman, Sean Eric Mcguire, Henry Mok, Quynh-Nhu Nguyen, Adam B Samman, Zain Rahman, Mohamed Shelan, Toufic Eid, Osama Mohamad

Faculty, Staff and Students Publications

Background: While the ProtecT randomized trial demonstrated comparable oncologic outcomes between radical prostatectomy (RP) and radiation therapy (RT) for localized prostate cancer, several retrospective studies have reported mixed findings. In this study, we investigated whether non-randomized studies tend to favor RP or RT and assessed whether the specialty of leading authors-urologists or radiation oncologists-correlates with study conclusions.

Methods: We identified non-randomized clinical studies published between 1993 and 2024 that compared RP and RT for localized prostate cancer and reported oncologic outcomes including biochemical, metastasis, and/or survival outcomes. Author specialty was determined based on whether the first and senior authors were …

Tau Pathology In Epilepsy: Emerging Mechanisms And Translational Opportunities, Maria Thom, Eleonora Aronica, Lucy Vivash, Martin Hardmeier, Action Amos, Stephan Rueegg, Matthias Koepp, Yaroslav Winter, Christoph Helmstaedter, Jeffrey L Noebels, Hilal A Lashuel, Terence J O'Brien

Faculty, Staff and Students Publications

The onset of epilepsy in adulthood occurs most commonly after 55 years of age. Given the ageing global population, this disorder represents an increasing burden on healthcare and society. The bidirectional link between epilepsy and dementia is a focus of intense research with underlying tau pathology highlighted as a potential mechanistic link. In this review, we examine the evidence for tau-related neurodegenerative processes in epilepsy beginning with how changes in biochemical and structural properties of the tau protein can lead to abnormal phosphorylation and pathological aggregation. We consider the role of tau in seizure occurrence and cognitive difficulties in experimental …

Multiple Event Segmentation Mechanisms In The Human Brain, Tan T Nguyen, Joset A Etzel, Matthew A Bezdek, Jeffrey M Zacks

2020-Current year OA Pubs

The human brain segments continuous experience into discrete events, with theoretical accounts proposing two distinct mechanisms: creating boundaries at points of high

Long-Term Outcomes Of A Drug-Eluting Resorbable Scaffold Vs Angioplasty In Infrapopliteal Chronic Limb-Threatening Ischemia: 3-Year Results From The Life-Btk Trial., Sahil A Parikh, Brian G Derubertis, Marc P Bonaca, Prakash Krishnan, Richard H Pin, Jen-Kuang Lee, David C Metzger, Raghu Kolluri, Mehdi H Shishehbor, Andrew H Holden, Osamu Iida, Ehrin Armstrong, Steven W C Kum, David J O'Connor, Danielle R Bajakian, Lawrence A Garcia, Shih-Wa Ying, Jin Wang, Karine Ruster, Brad J Martinsen, Zsuzsanna Igyarto, Ramon L Varcoe

Surgery Articles

Background: Chronic limb-threatening ischemia (CLTI) caused by infrapopliteal disease is a major therapeutic challenge, with percutaneous transluminal angioplasty (PTA) associated with high rates of restenosis and reintervention. The LIFE-BTK trial previously demonstrated superior efficacy of the Esprit (Abbott Vascular) BTK drug-eluting resorbable scaffold (DRS) over PTA at 1 year, with sustained benefits at 2 years, with comparable safety at both time points. This report presents the 3-year outcomes.

Objectives: We aimed to compare the 3-year safety and efficacy of DRS vs PTA in patients with CLTI and infrapopliteal artery disease.

Methods: In this randomized trial, 261 patients with CLTI were …

Association Between Trainee Involvement During Pediatric And Congenital Cardiac Catheterization And Procedural Outcomes., Natalie Jayaram, John A. Spertus, Kevin F. Kennedy, Andrew C. Glatz

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Participation in the cardiac catheterization laboratory is a requirement of cardiology fellowship training. We sought to determine whether trainee presence is associated with outcomes during pediatric and congenital cardiac catheterization.

METHODS: We identified catheterizations between January 2011 and September 2020 within the IMPACT (Improving Pediatric and Adult Congenital Treatment) Registry. Multivariable multilevel regression was used to determine the association between trainee presence and procedural outcomes.

RESULTS: Of 122 760 catheterizations at 107 academic hospitals, a trainee was present in 71 651 (58.4%) cases. Rates of major adverse events were similar between trainee and nontrainee cases (9.0% versus 8.0%). Contrast …

Prenatal Predictors Of Fetal And Neonatal Death In Truncus Arteriosus: A Fetal Heart Society Research Collaborative Study., Kelly Cox, Nazia Husain, Deidra Ansah, Tiffany Knight, Alexandra Channing, Bettina Cuneo, Preeta Dhanantwari, Mary Donofrio, Miwa Geiger, Lisa Howley, Lisa K. Hornberger, Simone Javeri, Edward G. Jones, Michelle Kaplinski, Ann Kavanaugh-Mchugh, Maria Kiaffas, Katherine Kosiv, Christina Laternser, Olivia Low, Anita J. Moon-Grady, Shabnam Peyvandi, Nelangi Pinto, Avaliese Porlier, Aaron Prosnitz, Rashmi Rao, David Schidlow, Elena Sinkovskaya, Ranjini Srinivasan, Corey Stiver, Emilio Quezada, Bhawna Arya, Sheetal Patel

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Fetal and neonatal outcomes and factors increasing mortality risk in fetal truncus arteriosus are not well characterized. We aimed to examine the prenatally encountered cardiac spectrum, define extracardiac and genetic associations, explore clinical outcomes and identify prenatal factors associated with worse outcomes in a contemporary large cohort.

METHODS: A multicenter retrospective cohort study was conducted via the Fetal Heart Society Research Collaborative including fetal truncus arteriosus cases encountered between January 1, 2010, and September 1, 2021, within 22 North American cardiac centers. Demographic, clinical, anatomic, and functional fetal echocardiographic variables were analyzed for associations with presurgical death (fetal death/neonatal …

Feasibility Evaluation Of Tumor Treating Fields For Brainstem Gliomas, Anthony Chen, Ryan Shah, William Shi, Noa Urman, Nadav Shapira, Nicholas Avgeropoulos, Patrick Conlon, Neil Mookerjee, Wenyin Shi

Department of Radiation Oncology Faculty Papers

PURPOSE: Tumor treating fields (TTFields) are FDA-approved for supratentorial glioblastoma, but feasibility in infratentorial tumors remains poorly defined. This simulation study evaluated TTFields dose in brainstem gliomas using patient-specific modeling with scalp-only transducer arrays.

METHODS: MRI and CT imaging from seven patients with brainstem gliomas were used for TTFields planning with MAXPOINT® (Novocure, Switzerland). Clinical target volume (CTV) was defined as enhancing tumor on T1 post-contrast MRI (Gross tumor volume, GTV) plus a 3 mm peritumoral expansion. The platform optimized scalp-only array layouts, and finite element calculations generated maps of local minimum field intensity (LMiFI, V/cm) and local minimum power …

Lats1/2-Cd38 Metabolic Rewiring Links Senescence To Intraplaque Thrombosis, Sivareddy Kotla, Jonghae Lee, Kyung Ae Ko, Weiqing Chen, Venkata Subrahmanya Kumar Samanthapudi, Oanh Hoang, Gilbert F Mejia, Shengyu Li, Hani Lee, Aijun Zhang, Min Soon Cho, Keri L Schadler, Luis Antonio Rivera, Masaki Imanishi, Kay Carlene Tavares Samperio, Jung Hyun Kim, Kelia C Ostos-Mendoza, Karla N Mariscal-Reyes, Anita Deswal, John P Cooke, Keigi Fujiwara, Nicolas L Palaskas, Efstratios Koutroumpakis, Young Jin Gi, Rajneesh Pathania, Craig Morrell, Philip L Lorenzi, Lin Tan, Iqbal Mahmud, Nordin M J Hanssen, Vahid Afshar-Kharghan, Dale J Hamilton, Laurent Yvan-Charvet, Eduardo N Chini, Joerg Herrmann, Hernan G Vasquez, Ying H Shen, James F Martin, Haodong Xu, Erin H Seeley, Jared K Burks, Paul S Brookes, Guangyu Wang, Nhat-Tu Le, Jun-Ichi Abe

Faculty, Staff and Students Publications

Background: Atherothrombosis, which underlies most acute coronary syndromes and is driven by intraplaque thrombosis, preferentially occurs in regions of disturbed blood flow (d-flow). Although LATS1/2 (large tumor suppressor kinases 1 and 2) are known regulators of endothelial mechanotransduction, the mechanisms by which d-flow connects endothelial senescence, proliferation, and intraplaque thrombosis remain poorly understood.

Methods: We investigated endothelial cell (EC)-specific roles of Lats1/2 using inducible EC-specific knockout mice in a partial carotid ligation model. Spatial multiomics of human and mouse plaques was performed using imaging mass cytometry, COMET sequential immunofluorescence, and spatial metabolomics.

Results: Tamoxifen-induced deletion of both Lats1 and Lats2 …

Long-Term Inactivation Mediated By Different Fgf-A Homologues On Heterologously Expressed Nav1.2 Currents, Yenisleidy Lorenzo-Ceballos, Pedro L Martinez-Espinosa, Xiao-Ming Xia, Christopher J Lingle

2020-Current year OA Pubs

A-isoforms of cytosolic growth factor homologous factors (FGF11-14) mediate long-term inactivation (LTI) of voltage-dependent sodium (NaV) channels. LTI is a rapid onset process that is competitive with the fast inactivation (IF) intrinsic to NaV channels, with little or no interconversion between inactivated states. Since recovery from LTI is orders of magnitude slower than recovery from IF, repetitive depolarizations lead to use-dependent accumulation of NaV channels in slow recovery states, thereby limiting NaV availability during trains of action potentials. Of the two or more N-terminal splice variants of the various FGF homologues, LTI specifically arises only from the A-isoform of each …

High-Order Brain Interactions During Ketamine-Induced State Changes: A Functional Marker Of Response In Late-Life Treatment-Resistant Depression?, Brittany O'Brien, Rahul Balakrishnan, Sanjay J Mathew, Nicholas Murphy

Faculty, Staff and Students Publications

Ketamine is a fast-acting intervention for treatment-resistant depression (TRD), yet only a subset of patients show robust clinical response, and the underlying neural mechanisms remain unclear. High-order interactions (HOI) derived from multivariate information theory provide a framework for examining nonlinear dependencies among brain regions beyond pairwise connectivity. One such metric, the O-information, captures the balance between synergistic and redundant interactions across three or more variables. In this secondary analysis of a randomized, double-blind, midazolam-controlled trial (NCT02556606), we examined EEG-derived HOI in 30 late-life veterans with TRD following a single 40-minute intravenous infusion of ketamine (0.1, 0.25, 0.5 mg/kg; n = …

Tranexamic Acid In High-Risk Shoulder Arthroplasty Patients: Safety Across Thromboembolic, Cardiac, Renal, And Neurologic Risk Profiles, Tarishi Parmar, Akin Adio, Asim Handy, Mohammad Daher, Alec Kellish, Adam Khan, Joseph A. Abboud

Rothman Institute Papers

INTRODUCTION: Tranexamic acid (TXA) effectively reduces blood loss and transfusion requirements in shoulder arthroplasty. However, concerns regarding thromboembolic, neurologic, cardiac, and renal complications have limited its use in medically high-risk patients. This study evaluated temporal trends and the safety of TXA in high-risk patients undergoing total shoulder arthroplasty (TSA).

METHODS: A retrospective cohort study was conducted using TriNetX, identifying patients who underwent shoulder arthroplasty (2012-2025). Patients were stratified by preexisting high-risk conditions, including prior thromboembolism, renal failure, atrial fibrillation, seizure disorders, and visual disturbances. Within each subgroup, patients receiving TXA were propensity score-matched to those who did not. Perioperative TXA …

Advancing Bioinformatics With Language Models: Components, Applications, And Perspectives, Tiangang Wang, Kang Li, Xiaobo Zhou

Faculty, Staff and Student Publications

Large language models (LLMs) are deep learning-based artificial intelligence models that have achieved remarkable success in natural language processing. Typically composed of neural networks with billions of parameters, they are trained on massive unlabeled datasets using self-supervised or semi-supervised learning. Beyond language, LLMs hold immense potential for addressing complex bioinformatics challenges. This review provides a comprehensive overview of transformer-based model applications in genomics, transcriptomics, proteomics, drug discovery, and single-cell analysis. We discuss critical components, including tokenization strategies for diverse biological data, transformer architectures, attention mechanisms, and pretraining approaches. We also survey currently available foundation models and their downstream applications across …

Bi-Allelic Loss-Of-Function Variants In Tmem63b Cause Syndromic Surfactant Dysfunction Disorder, Mir Reza Bekheirnia, Lindsay C Burrage, Matthew Hoi Kin Chau, Chaerish Eint Myet Chae Htoo, Eric C Kao, Shamika Ketkar, Wan Wan Lim, Xi Luo, Rifhan Mazlan, Elizabeth Mizerik, Kein Seong Mun, Kalyani R Patel, Lorraine Potocki, Christina K Rapp, Xavier Roca, Ana Saianda, Ignacio Iglesias-Serrano, Everlyn C Siew, Donald Yuhui Sim, David R Spielberg, Sok-Kun Tae, Jing Xian Teo, Julian Warfsmann, Fan Xia, Child-Eu Registry, Saumya S Jamuar, Ee Shien Tan, Matthias Griese, Weng Khong Lim, Meow-Keong Thong, Keren Machol

Faculty, Staff and Students Publications

Transmembrane protein 63B gene (TMEM63B) encodes a mechanosensitive ion channel expressed in alveolar type II epithelial cells, where it mediates stretch-induced surfactant secretion. While heterozygous gain-of-function variants in TMEM63B have been associated with developmental and epileptic encephalopathy, no human disorder has previously been linked to bi-allelic loss-of-function variants. Here, we report five individuals from four unrelated families with childhood interstitial lung disease and bi-allelic predicted loss-of-function variants in TMEM63B. Affected individuals presented with early-onset respiratory distress, chronic hypoxemia, and diffuse parenchymal lung abnormalities on chest imaging. One individual died in infancy, two underwent bilateral lung transplantation, and two require oxygen …

Towards Clinical Translation Of Nanomedicines: Formulation Scale-Up And Model Systems., Owen M Kelly, Andrew R Hanna, Addison K Byrne, Jonathan A Green, Iuri Viotti Perisse, Kevin D Wells, Stephen A. Murray, Jie Xu, Y Eugene Chen, Irina A Polejaeva, Alice F Tarantal, David Issadore, Alexandra S Piotrowski-Daspit

Faculty Research 2026

Non-viral nanomedicines, including nanoparticles (NPs) composed of lipids and polymers, represent a transformative approach to drug and gene therapy. However, clinical translation of these technologies is limited by two key barriers: the scale-up of NP formulations and the challenge of conducting predictive preclinical studies in relevant animal models. Efficient upscaling of nanomedicines, from cost and material requirement perspectives, requires manufacturing processes that can reliably provide products across the many orders of magnitude of scale from discovery (kg of product). Additionally, initial preclinical studies are often performed in mouse models for discovery; however, mid- to large-size animal models such as rabbits, …