Digital Commons Network^™

Cytosignal Detects Locations And Dynamics Of Ligand-Receptor Signaling At Cellular Resolution From Spatial Transcriptomic Data, Jialin Liu, Hiroaki Manabe, Weizhou Qian, Shion Orikasa, Javid Ghaemmaghami, Yichen Wang, Yichen Gu, Angel Ka Yan Chu, Gaurav Gadhvi, Yuxuan Song, Patrick Mcclinden, Vibha N Lama, Noriaki Ono, Joshua D Welch

Faculty, Staff and Student Publications

Cells communicate through ligand-receptor (LR) signaling interactions, but identifying when and where these interactions are active remains challenging. We developed CytoSignal to infer the locations and dynamics of cell-cell communication at cellular resolution from spatial transcriptomic data. Here we show that our cellular resolution, spatially resolved signaling scores enable several important analyses-identifying spatial gradients in signaling strength, quantifying the locations of contact-dependent and diffusible interactions, detecting signaling-associated genes and identifying differential signaling across multisample data. Additionally, we can predict the temporal dynamics of a signaling interaction at each spatial location. We experimentally validate our results in situ by proximity ligation …

Nlrp3 Inflammasome: A Link Between Systemic Infection And Alzheimer’S Disease, Tatiana Barichello, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

No abstract provided.

Full-Body Ai Agent: A Perspective On Multi-Scale Collaborative Ai For Systemic Biology And Precision Medicine., Aoqi Wang, Jiajia Liu, Jianguo Wen, Yangyang Luo, Zhiwei Fan, Liren Yang, Xi Hu, Ruihan Luo, Yankai Yu, Sophia Li, Weiling Zhao, Xiaobo Zhou

Faculty, Staff and Student Publications

Artificial intelligence (AI) is increasingly applied to biomedical research, but most current systems remain limited to specific tasks, data types, or biological scales. This makes it difficult to connect molecular alterations, organelle dysfunction, cellular behavior, tissue remodeling, organ physiology, systemic regulation, and whole-body phenotypes into coherent biological reasoning. In this Perspective, we propose the Full-Body AI Agent as a hypothetical multi-agent framework and conceptual blueprint for future systemic biology and precision medicine, rather than a fully implemented software platform. This framework envisions a supervisory Full-Body AI Agent coordinating seven biological-level agents, namely Molecule, Organelle, Cell, Tissue, Organ, Organ System, and …

Ldm-Morph: Latent Diffusion Model Guided Deformable Image Registration, Jiong Wu, Tinsu Pan, Kuang Gong

Faculty, Staff and Student Publications

Deformable image registration plays an essential role in various medical image tasks. Existing deep learning-based deformable registration frameworks primarily utilize convolutional neural networks (CNNs) or Transformers to learn features to predict the deformations. However, the lack of semantic information in the learned features limits the registration performance. Furthermore, the similarity metric of the loss function is often evaluated only in the pixel space, which ignores the matching of high-level anatomical features and can lead to deformation folding. To address these issues, in this work, we proposed LDM-Morph, an unsupervised deformable registration algorithm for medical image registration. LDM-Morph integrated features extracted …

Triple Tracer Heterogeneity In Dual Neoplasia: The "Three Musketeers" In Discerning Squamous Cell Carcinoma And Paraganglioma In The Same Patient, Shyam Kumar Ravada, Gaurav Malhotra, Aaditya Daga, Anurag R Lila, Saba Memon, Tushar Bandgar

Faculty, Staff and Student Publications

Head and neck squamous cell carcinoma of unknown primary (HNSCCUP) comprises 2%-5% of head and neck squamous cell cancers (HNSCC). Its coexistence with abdominal paraganglioma is exceedingly rare. We report a unique case of a 48-year-old male with HNSCCUP presenting as cervical lymphadenopathy and a coexisting abdominal paraganglioma. 18 F-FDG showed uptake in both lesions, while 68 Ga-DOTATATE was avid only in paraganglioma, and 68 Ga-DOTA-FAPI-04 was avid only in cervical nodes. These differential uptake patterns reflect distinct tumor biology and underscore the potential for tailoring theranostic treatment strategies with 177 Lu/ 90 Y isotopes for FAPI-avid squamous cell cancers …

Oxytocin Dynamics And Synchrony In Mother-Child Dyads: Long-Term Neuroendocrine Effects Of Maternal Institutionalization, Olga V Burenkova, Ekaterina M Shurdova, Victoria Manasevich, Marina Norkina, Polina E Pashkina, Aleksei A Podturkin, Alena Vodneva, Marina A Zhukova, Elena L Grigorenko

Faculty, Staff and Student Publications

Early institutional care (IC; orphanage) is a severe form of early psychosocial deprivation with documented long-term effects on social and caregiving functioning. Despite longstanding interest in oxytocin (OT) as a key neuroendocrine modulator of affiliative behavior and stress, OT dynamics and synchrony during mother-child interaction among mothers with IC history remain poorly understood. To our knowledge, this is the first study to characterize maternal and child OT responses and dyadic OT covariation in this population. We measured salivary OT in mothers with IC history and mothers raised in biological family care (BFC), and in their children, at baseline and after …

The Wake Of Addiction: Pharmacological Strategies For Sleep Disturbances In Stimulant Use Disorders, A Systematic Review, Isabella G Bourtin, Douglas J Calvillo, Jessica C Badawi, Joy M Schmitz, Scott D Lane, Jin Ho Yoon, Heather E Webber

Faculty, Staff and Student Publications

Background: A systematic review was conducted following PRISMA guidelines to identify human studies investigating pharmacological interventions and reported sleep outcomes among individuals with CUD or MUD.

Methods: PubMed and APA PsycInfo were searched from inception to January 2025 and risk of bias was assessed. Articles were included if they included human participants with either cocaine or methamphetamine dependence, administered a pharmacological treatment, and reported night-time sleep as an outcome using at least one rigorous measurement tool. Articles were excluded if they included animals, did not include pharmacological intervention (e.g., supplements or behavioral treatments), or only assessed baseline sleep or if …

Rural-Urban Differences In Hypertension Prevalence And Control In A Large Regional Health System Cohort, Yordanos M Tiruneh, Susan Mcbride, Huaxin Song, Matthew Decaro, Alaa Rihan, Theresa Byrd, Alex Baham, Jared W Magnani, Elmer V Bernstam, Jarett D Berry

Faculty, Staff and Student Publications

Background: Rural US populations bear a high burden of cardiovascular disease, with hypertension contributing to the rural-urban gap. We examined hypertension prevalence and control across the rural-urban continuum among patients in a large healthcare system in Northeast Texas.

Methods: We analyzed the electronic health record data from 363,539 patients with at least one outpatient encounter between September 2021 and April 2025. We defined hypertension using ICD-10-CM codes, antihypertensive prescriptions, or a blood pressure ≥ 130/80 mm Hg. We classified rurality using the Rural-Urban Commuting Area categories. Multivariable logistic regression models were adjusted for age, sex, race, ethnicity, insurance, and level …

Brain Age Prediction In Generalized Anxiety Disorder Using A Convolutional Neural Network, Corey Richier, André Zugman, Anita Harrewijn, Elise M Cardinale, Parmis Khosravi, Moji Aghajani, Willem B Bruin, Kevin Hilbert, Narcis Cardoner, Daniel Porta-Casteràs, Marta Cano, Savannah Gosnell, Ramiro Salas, Andrea P Jackowski, Pedro M Pan, Giovanni A Salum, Karina S Blair, James R Blair, Mohammed R Milad, Katie L Burkhouse, K Luan Phan, Heidi K Schroeder, Jeffrey R Strawn, Katja Beesdo-Baum, Neda Jahanshad, Sophia I Thomopoulos, Jared A Nielsen, Jordan W Smoller, Jair C Soares, Benson Mwangi, Mon-Ju Wu, Giovana B Zunta-Soares, Michal Assaf, Gretchen J Diefenbach, Paolo Brambilla, Eleonora Maggioni, David Hofmann, Thomas Straube, Carmen Andreescu, Rebecca B Price, Gisele G Manfro, Federica Agosta, Elisa Canu, Camilla Cividini, Massimo Filippi, Milutin Kostić, Ana Munjiza Jovanovic, Brenda Benson, Gabrielle F Freitag, Ellen Leibenluft, Grace V Ringlein, Kathryn Werwath, Hannah Zwiebel, Hans J Grabe, Sandra Van Der Auwera, Katharina Wittfeld, Henry Völzke, Robin Bülow, Nicholas L Balderston, Monique Ernst, Lilianne R Mujica-Parodi, Helena Van Nieuwenhuizen, Hugo D Critchley, Elena Makovac, Matteo Mancini, Frances Meeten, Cristina Ottaviani, Gregory A Fonzo, Martin P Paulus, Murray B Stein, Raquel E Gur, Ruben C Gur, Antonia N Kaczkurkin, Bart Larsen, Theodore D Satterthwaite, Jennifer Harper, Michael T Perino, Chad M Sylvester, Qiongru Yu, Patrick Mcclure, Francisco Pereira, Ulrike Lueken, Dick J Veltman, Paul M Thompson, Nynke A Groenewold, Janna Marie Bas-Hoogendam, Dan J Stein, Nic J A Van Der Wee, Anderson M Winkler, Daniel S Pine, Chelsea K Sawyers

Faculty, Staff and Student Publications

Higher predicted brain age difference has been associated with several psychiatric disorders. Generalized anxiety disorder (GAD) is associated with markers of accelerated aging. In this study, we determined brain predicted age difference (PAD) in individuals with GAD and healthy controls (HC) as well as group differences in PAD variability using voxel-wise structural MRI. The training dataset included 3511 controls, and the testing dataset included 1595 individuals with GAD and 4552 HC from the ENIGMA-Anxiety GAD Working Group. A convolutional neural network model using four input modalities per subject and a model ensemble approach was used to predict brain age. The …

Using The Socio-Ecological Model To Explore Parents' Resilience And Perceptions Of Adverse Childhood Experiences: A Qualitative Study In The Southeastern United States, Maribel G Dominguez, Christine Markham, Andrew E Springer, Louis D Brown

Faculty, Staff and Student Publications

Background: The negative impact of adverse childhood experiences (ACEs) on child development is documented. The parent-child relationship protects against ACEs and improves healthy child development, playing a crucial role in preventing and mitigating ACEs by strengthening parental resilience. However, there is a gap in the literature on our understanding of parental resilience's impact on the parent-child relationship within the social-ecological model (SEM) (i.e., intra- and interpersonal, community, and societal levels). Objective: This study explores parents' perspectives on parental resilience as a protective factor for preventing and mitigating ACEs at every level of the SEM. Method: This study uses a thematic …

Brain-Wide Structural Markers Of Familial And Clinical Risk For Bipolar Disorder In Youth, Danella M Hafeman, Jamie Feldman, John Merranko, Mary L Phillips, Boris Birmaher, Si Gao, Yizhou Ma, Peter Kochunov

Faculty, Staff and Student Publications

Background: Bipolar Disorder (BD) is a severe mental illness, often emerging during adolescence, that is associated with significant psychosocial impairment. BD risk is elevated in offspring of affected parents, particularly those with antecedent symptoms (e.g., mood lability, subthreshold manic symptoms). However, robust, replicable brain-based markers of risk in this population are lacking. We assessed the degree to which the Regional Vulnerability Index for BD (RVI-BD), quantified as an individual's brain-wide similarity to BD patterns derived from meta-analytic studies, is elevated in youth at familial risk and correlates with symptom predictors of BD.

Methods: We recruited n=82 adolescents (10-15 years old), …

Tumor Implantation Site Of Syngeneic Oral Cancer Models Differentially Induces Site-Dependent Local And Systemic Immunosuppression, Andrea H Molina, Gemalene M Sunga, Shawn Nguyen, Neeraja Dharmaraj, Ratna Veeramachaneni, Roberto Rangel, Jeffrey N Myers, Jeffrey D Hartgerink, Andrew G Sikora, Simon Young

Faculty, Staff and Student Publications

Background/objectives: Preclinical studies of head and neck squamous cell carcinoma (HNSCC) commonly use subcutaneous heterotopic (flank) tumor models for simplicity; however, orthotopic models may better reflect the native tumor environment. Direct comparisons of the tumor immune microenvironments (TIME) and tumor-draining lymph nodes (tdLNs) between these models remain limited. Better understanding of site-specific immune differences could improve model selection and interpretation of translational HNSCC studies.

Methods: ROC1 tumors were established in murine heterotopic and orthotopic sites, followed by assessment of tumor growth kinetics, survival, and the tumor microenvironment. Immune composition of tumors, blood, tdLNs, and spleen was evaluated at three tumor …

Exploring Spike-Dependent And Ace2-Independent Sars-Cov-2 Interactions With Salivary Epithelial Cells In The Absence Of Ace2, Caitlynn M L Barrows, Thaise C Geremias, Simon Young, Mary C Farach-Carson

Faculty, Staff and Student Publications

Salivary gland infection by SARS-CoV-2 requires viral entry via routes and mechanisms that remain unresolved. This study examined the expression of the angiotensin-converting enzyme 2 (ACE2) receptor in salivary tissues and basal cell-derived human salivary progenitor cells (hS/PCs), an unstudied potential entry point for SARS-CoV-2. Multiple detection modalities, including immunocytochemistry, Western blotting, flow cytometry and RT-PCR, demonstrated a consistent lack of ACE2 protein and transcript in both tissue specimens and primary salivary epithelial cells. Antigen retrieval at pH 9 was determined to be optimal for immunodetection protocols, yet ACE2 remained undetectable. Small intestine tissue served as a positive control, confirming …

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 …

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 …

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.

Large-Scale Genetic Characterization Of Parkinson’S Disease In The African And African Admixed Populations, Fulya Akçimen, Kimberly Paquette, Peter Wild Crea, Kathryn Step, Emily Waldo, Mathew J Koretsky, Paula Saffie-Awad, Charles Achoru, Funmilola Taiwo, Simon Ozomma, Gerald Onwuegbuzie, Marzieh Khani, Spencer Grant, Lukman Owolabi, Chiamaka Okereke, Olajumoke Oshinaike, Emmanuel Iwuozo, Suleyman Can Akerman, Paul Suhwan Lee, Shyngle Oyakhire, Nosakhare Osemwegie, Kensuke Daida, Sani Abubakar, Adedunni Olusanya, Mariam Isayan, Christiane Alvarez, Rami Traurig, Adebimpe Ogunmodede, Sarah Samuel, Mary B Makarious, Fadimatu Sa'ad, Rashidat Olanigan, Kristin Levine, Ewere Marie Ogbimi, Dan Vitale, Francis Odiase, Francis Ojini, Olanike Odeniyi, Zih-Hua Fang, Nkechi Obianozie, Deborah A Hall, Ernest Nwazor, Tao Xie, Francesca Nwaokorie, Mahesh Padmanaban, Paul Nwani, Ejaz A Shamim, Alero Nnama, David Standaert, Morenikeji Komolafe, Marissa Dean, Godwin Osaigbovo, Elizabeth Disbrow, Ismaila Ishola, Ashley Rawls, Frank Imarhiagbe, Shivika Chandra, Cyril Erameh, Vanessa Hinson, Naomi Louie, Ahmed Idowu, J Solle, Scott A Norris, Abdullahi Ibrahim, Camilla Kilbane, Gauthaman Sukumar, Lisa M Shulman, Daniel Ezuduemoih, Julia Staisch, Sarah Breaux, Clifton Dalgard, Erin R Foster, Abiodun Bello, Andrew Ameri, Raquel Real, Erica Ikwenu, Huw R Morris, Roosevelt Anyanwu, Erin Furr Stimming, Kimberley Billingsley, Wemimo Alaofin, Pilar Alvarez Jerez, Osigwe Agabi, Dena G Hernandez, Rufus Akinyemi, Sampath Arepalli, Laksh Malik, Raymond Owolabi, Yakub Nyandaiti, Hampton L Leonard, Kolawole Wahab, Oladunni Abiodun, Carlos F Hernandez, Fatima Abdulai, Hirotaka Iwaki, Soraya Bardien, Christine Klein, John Hardy, Henry Houlden, Kamalini Ghosh Galvelis, Mike A Nalls, Nabila Dahodwala, Whitley Aamodt, Emily Hill, Alberto Espay, Stewart Factor, Chantale Branson, Cornelis Blauwendraat, Andrew B Singleton, Oluwadamilola Ojo, Lana M Chahine, Njideka Okubadejo, Sara Bandres-Ciga

Faculty, Staff and Student Publications

Elucidating the genetic contributions to Parkinson's disease aetiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11 827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity in prioritized early onset and familial cases. Our study identified rare GBA1 coding variants to be the most frequent mutations among patients with Parkinson's disease, with a frequency of 4% in our case cohort. Of the 18 …

Donor Sex And Platelet Storage Change The Therapeutic Effects Of Platelet-Derived Extracellular Vesicles On Endothelium, Mandeep Kaur, Malvika Gupta, Sowmya Shree Gopal, Charles E Wade, Jessica C Cardenas, Amit K Srivastava

Faculty, Staff and Student Publications

Platelet-derived extracellular vesicles (PEVs) play an active role in vascular protection and repair and are being explored as a viable alternative to platelet therapy. Because platelet function and stability are shaped by donor sex and storage conditions, these same factors are likely to influence the PEVs they release. Understanding these influences is key to developing PEVs into a safe and dependable therapeutic option. In this study, we investigated how donor sex and platelet storage affect the therapeutic properties of PEVs. To address this, PEVs were isolated from platelets of healthy male and female donors. Platelets were either processed immediately after …

Ultrasonic Cavity Preparation With Cvd Diamond Tips: A Scanning Electron Microscopy Study Of Dentin Surface Morphology And Smear Layer Formation, Mauricio Schneider, Jefferson David Melo De Matos, Mário Alexandre Coelho Sinhoreti, Diego Telomaro Peiter, José Eduardo Bastian, Daher Antonio Queiroz

Faculty, Staff and Student Publications

Background: Minimally invasive dentistry has driven the development of alternative cavity preparation techniques aimed at preserving tooth structure and improving biological outcomes. Ultrasonic systems associated with chemical vapor deposition (CVD) diamond tips have emerged as a potential alternative to conventional rotary instruments; however, evidence regarding their effects on dentin surface morphology and smear layer characteristics under SEM remains limited. This study aimed to evaluate the morphological characteristics of dentin surfaces after cavity preparation using ultrasonic and conventional rotary techniques.

Materials and methods: Twenty extracted human teeth were sectioned longitudinally to obtain standardized specimens. Samples were assigned to ultrasonic preparation using …

An Integrated Framework For Early Detection And Transmissibility Assessment Of Emerging Variants In Wastewater, Xingwen Chen, Tin Phan, Wei Lin Lee, Katie Clark, Steven F Rhode, Samantha Brozak, Bruce Pell, Tsultrim Palden, Mats Leifels, Anna Gitter, Yang Kuang, Stefan Wuertz, Janelle Thompson, Kristina D Mena, Eric J Alm, Fuqing Wu

Faculty, Staff and Student Publications

Tracking the emergence of new viral variants is critical for epidemic preparedness, but remains challenging because variants typically circulate at low prevalence during the early phase of outbreaks. Here, we present an integrated framework that combines sensitive variant detection in wastewater with quantitative assessment of transmissibility through dynamic epidemic modeling. Using the SARS-CoV-2 Omicron variant as a proof of concept, we developed a novel nested allele-specific RT-qPCR assay (NAS-PCR) that achieved a thousand-fold increase in sensitivity compared with allele-specific RT-qPCR (limit of detection: 0.5 copies/μl). NAS-PCR detected Omicron in wastewater samples from the Greater Boston area starting in September 2021, …

Addressing Nonignorable Missing Data And Heterogeneity In Prognostic Biomarker Assessment, Xinran Huang, Ruosha Li, Jing Ning, For The Alzheimer's Disease Neuroimaging Initiative

Faculty, Staff and Student Publications

Covariate-specific and time-dependent area-under-curve (AUC) is often used to evaluate the discriminative performance of biomarkers with time-to-event outcomes, particularly when certain covariates influence biomarkers' accuracy. In biomarker research, despite extensive efforts, missing data remain unavoidable, with nonignorable missingness posing significant challenges. This article focuses on estimating the impact of covariates on time-dependent AUC in the presence of nonignorable missing biomarkers. Assuming a parametric model on the missing probability, we leverage instrumental variables to address the identifiable issue and estimate the unknown parameters. We integrate the inverse probability weighting approach into the score equation of a pseudo partial likelihood for estimation …

Race To Mitigate Aortic Dissection: Exercise, Pde5a, And The Dissecting Aorta, Siddharth K Prakash

Faculty, Staff and Student Publications

No abstract provided.

Quantitative Muscle Magnetic Resonance Imaging Demonstrates Resolution Of Muscle Edema In Refractory Dermatomyositis: A Post Hoc Analysis Of A Proof-Of-Concept Clinical Trial Of Tofacitinib, Mona Dabiri, Anshula Nallapati, Marwin Groener, Patrick Debs, Jemima Albayda, Eleni Tiniakou, Lisa Christopher-Stine, Laura Fayad, Julie J Paik

Faculty, Staff and Student Publications

Objective: To evaluate changes in muscle edema using short-tau inversion recovery (STIR) imaging and quantitative diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping in patients with refractory dermatomyositis (DM) treated with tofacitinib.

Methods: This post hoc imaging analysis included patients from a 12-week, open-label trial of tofacitinib 11 mg daily in refractory DM. Bilateral thigh magnetic resonance imaging was obtained at baseline and week 12 using standardized STIR, T1-weighted, and DWI sequences. Muscle edema (ME) and fascial edema were assessed qualitatively on STIR imaging. ADC values were measured in muscles demonstrating baseline STIR hyperintensity using three nonoverlapping regions of …

Severe, Non-Apneic Respiratory Dysfunction And Hypoxia Following Generalized Convulsive Seizures, Haley E Pysick, Rup K Sainju, Roshni Nair, Deidre N Dragon, Eduardo Bravo, Laura Vilella, Xiaojin Li, Samden D Lhatoo, George B Richerson, Brian K Gehlbach

Faculty, Staff and Student Publications

Objective: Sudden unexpected death in epilepsy (SUDEP) is a devastating consequence of some generalized convulsive seizures (GCS). Recent work has focused on seizure related apnea as a biomarker of SUDEP risk, frequently without characterizing the adequacy of non-apneic ventilation or identifying other dysfunctional breathing patterns. We hypothesized that GCS frequently induce immediate, severe, non-apneic respiratory dysfunction that can induce critical hypoxia and bradycardia and sought to characterize breathing patterns after GCS.

Methods: Adult patients admitted to an epilepsy monitoring unit were studied. The effects of GCS on breathing and heart rate were analyzed using nasal pressure transducers, chest and abdominal …

Neurointerventional Advances In 2025, Amol Mehta, Sunil A Sheth, Ashutosh P Jadhav

Faculty, Staff and Student Publications

No abstract provided.

Optimized Ultrasound Imaging Of Phase-Change Nanodroplets, Charles R Dyall, Dmitry Nevozhay, Andy Liu, Trevor M Mitcham, George J Lu, Konstantin V Sokolov, Richard R Bouchard

Faculty, Staff and Student Publications

Phase-change nanodroplets (PCNDs) continue to generate significant research interest due to their potential to extravasate into tissue, to be targeted for molecular imaging and drug delivery, and to undergo an induced phase-change to "activated" microbubbles (MBs) for ultrasound (US) imaging. To accurately quantify molecular markers, however, one assumes a consistent proportion of PCNDs in a region of interest (ROI) are stably activated and imaged. Herein we present a framework for developing a diagnostic sequence that is optimized for PCND activation uniformity, contrast, and acquisition time. To develop this framework, activation was examined at three scales of increasing complexity: single, adjacent, …

Multidisciplinary Approach To Complex Lower Extremity Limb Salvage In Pyogenic Arthritis, Pyoderma Gangrenosum, And Acne (Papa) Syndrome: A Case Report, Michael M Talanker, Anthony V Basta, Tien Do, Robert Tung, Addison Allen, Morgan Martin, Bryan L Ruygrok, Patrick J Kellam, Jeffrey G Trost, Mohin A Bhadkamkar

Faculty, Staff and Student Publications

Limb salvage using free tissue transfer in patients with rare autoinflammatory syndromes is poorly described, and the safety of microvascular reconstruction in this population remains uncertain. Hereditary pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is characterized by dysregulated inflammation, pathergy, and impaired wound healing, raising concern for flap compromise and postoperative complications. We report a rare case of lower extremity free tissue transfer in a patient with PAPA syndrome. A 66-year-old woman with rheumatoid arthritis and PAPA syndrome presented with rapid wound breakdown, violaceous ulceration, exposed hardware, and periprosthetic joint infection following left total knee arthroplasty (TKA). Examination revealed …

Potential Impact Of Parasites In The Transmission Of Chronic Wasting Disease, Paulina Soto, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

Long Covid Persistence And Surveillance Gaps Across 58 Us Hospitals, Jiazi Tian, Alaleh Azhir, Matthew Decaro, Ngan Chau, Jonas Hügel, Michele Morris, Jingya Cheng, Pedram Fard, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Shyam Visweswaran, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri

Faculty, Staff and Student Publications

Importance: Surveillance of postacute sequelae of SARS-CoV-2 infection (PASC) depends on diagnostic coding systems that capture fewer than one-half of affected individuals, rendering millions invisible to health systems and policymakers.

Objective: To quantify the gap between true PASC burden and diagnostic code-based estimates, determine the proportion representing chronic disease, and characterize organ system heterogeneity and temporal trends across diverse populations.

Design, setting, and participants: This retrospective cohort study used electronic health record data from 58 hospitals and affiliated clinics in 4 US regions, from 2017 to 2025. Adults (aged ≥18 years) with laboratory-confirmed SARS-CoV-2 infection or a COVID-19 diagnosis code …