Publications by Year: 2025

2025

Natterson-Horowitz, B., Wright, K., Van Steenkiste, G., Decloedt, A., Gagnon, A. L., Cai, X., & Mazmanian, A. (2025). Arrhythmias across the tree of life: comparative insights for human electrophysiology.. Frontiers in Cardiovascular Medicine, 12, 1652591. https://doi.org/10.3389/fcvm.2025.1652591 (Original work published 2025)

INTRODUCTION: Arrhythmias in non-human animals offer insights into human electrophysiology, yet physicians may be unaware of their occurrence and significance. This paper presents selected examples of arrhythmias in dogs, horses, and birds- as an invitation to human cardiologists to explore how animal models can illuminate mechanisms, genetics, and therapeutic approaches relevant to human electrophysiology.

METHODS: Leading veterinary cardiologists compiled overviews of common arrhythmias in dogs, cats, horses and birds. Genetic predisposition, natural history, therapeutic approaches, and epidemiology were compared across these species and humans, highlighting translational opportunities.

RESULTS: Common human arrhythmias including atrial fibrillation, bradycardia, ventricular tachycardia, and arrhythmogenic right ventricular cardiomyopathy occur naturally in dogs, cats, horses, and birds. Cross-species differences in disease expression provide unique insights into mechanisms of arrhythmia vulnerability and resistance. Dogs develop similar inherited arrhythmogenic diseases but with distinct phenotypes. Horses experience atrial fibrillation without thromboembolic complications, revealing potential protective pathways. They also demonstrate extreme exercise-induced arrhythmia susceptibility, isolating exercise as an arrhythmogenic trigger. Avian species exhibit remarkable adaptation to cardiac loading conditions that would be pathological in mammals. These comparative observations across species highlight novel mechanisms underlying both susceptibility and resistance to arrhythmias and conduction disorders, offering unexplored therapeutic targets for human patients.

DISCUSSION: Cross-species knowledge offers direct translational value for human electrophysiology-from genetic markers in Labrador Retrievers with supraventricular tachycardia to cardiac loading paradigms in broiler chickens. Breaking down disciplinary barriers through shared research initiatives and integrated training represents an essential, underutilized strategy for advancing arrhythmia diagnosis, treatment, and prevention in human patients.

Jurinić, A., Pranjić, M., Huang, A., Burkhart, T. A., Tan, D., & Namburi, P. (2025). The biomechanics of piano playing: a systematic review of kinematic, kinetic, and electromyographic literature.. Frontiers in Psychology, 16, 1690422. https://doi.org/10.3389/fpsyg.2025.1690422 (Original work published 2025)

Piano playing is one of the most complex human activities, involving an intricate interplay between the cognitive, neural, and musculoskeletal systems. Understanding the biomechanics of piano playing could have important implications for evidence-based pedagogy, optimizing skill acquisition, increasing practice efficiency, and minimizing the risk of performance-related injuries. This systematic review synthesizes existing literature in piano biomechanics. A comprehensive search across five databases (MEDLINE, PsycINFO, SCOPUS, Music Index, and ERIC) yielded 7,671 studies, of which 53 met inclusion criteria. These studies utilized kinematic, kinetic, and electromyographic measurements during piano performance under varying task conditions, including isolated keystrokes, novel excerpts, self-selected repertoire, and standard piano literature. The results were synthesized to address (1) how variations in pianistic technique (e.g., type of touch, finger independence) influence kinematics, kinetics, and muscle activation, and (2) how task demands (e.g., tempo, loudness), and performance demands (e.g., fatigue, ergonomics) affect pianists' biomechanical characteristics. Together, current biomechanical evidence indicates that touch type, finger independence, intersegmental kinematics, and muscular activation are modulated by pianists' skill level, anthropometry, task demands, and muscular fatigue. We further discuss and link the existing literature to pedagogy, practice, and performance, thereby demonstrating that biomechanical parameters are not merely abstract descriptors of motion but are integral to pedagogy, musical expression, and sustainable performance. While there is an accumulating wealth of biomechanical data involving piano playing, its integration into standardized pedagogy remains limited. Interdisciplinary collaboration in piano biomechanics is therefore essential to advance our understanding of musical expression, communication, and wellbeing, ultimately supporting the development of sustainable playing techniques that can be effectively translated into pedagogical frameworks. Systematic review registration: Unique Identifier: 10.17605/OSF.IO/TSNY8.

Agarwal, A., Marek, K., Andrews, N. C., Vazquez, D. R., Incalcaterra, J., Lei, M., Fox, H., Gordon-Larsen, P., Lodge, J. K., Wigginton, N., Droegemeier, K., & Group, on behalf of the S. M. E. T. of the J. A. (2025). Funding FAIRly: A New Model for Biomedical Research.. Journal of the American Society of Nephrology : JASN. https://doi.org/10.1681/ASN.0000001003 (Original work published 2025)
Gutierrez-Contreras, R., Gallego-Muñoz, P., De La Hoz, A., Fernández-Gutierrez, M., Kochevar, I. E., Martínez-García, C., & Marcos, S. (2025). Photobonding of silk fibroin-based hydrogels to rabbit corneas.. Frontiers in Bioengineering and Biotechnology, 13, 1739461. https://doi.org/10.3389/fbioe.2025.1739461 (Original work published 2025)

INTRODUCTION: Corneal abrasions are common ocular injuries characterized by the loss of epithelial cells. Severe cases are often treated with amniotic membrane transplantation. However, as an allogenic tissue, it can trigger immune responses, it is scarce and costly, and may require suturing to the cornea. In this study, we propose and evaluate two silk fibroin-based hydrogels implanted in rabbit corneas with a sutureless photobonding technique as a surrogate for the amniotic membrane in corneal wound healing.

METHODS: Silk fibroin-based hydrogels were developed with polyethylene glycol (PEG) 300 or 3350. The hydrogels were stained with 0.01% Rose Bengal and photobonded to ex vivo de-epithelialized rabbit corneal strips using a custom-developed irradiation system (532 nm; 0.13 or 0.15 W/cm2 irradiance for 6.6 min). Bonding strength after 24 and 72 h under hydrated conditions was measured using a uniaxial stretcher, with five samples per experiment. An in vivo proof of concept study was also performed: hydrogels were implanted in four anesthetized rabbits that were euthanized immediately after photobonding for bonding assessment after 24 and 72 h in hydration. Two additional rabbits received in vivo implants, were clinically monitored for 15 and 30 days, and euthanized for histological evaluation.

RESULTS: Bonding strengths measured 24- or 72-h after irradiation at 0.13 or 0.15 W/cm2 of 532 nm light reached 2-3 N/cm2 for both types of Rose Bengal-stained hydrogels. In vivo bonding strength was consistent with the ex vivo results. At 15 and 30 days after the procedure, the corneas exhibited complete re-epithelialization beneath the hydrogel.

CONCLUSION: Silk fibroin-based hydrogels can be successfully bonded to ex vivo rabbit corneas using a sutureless photobonding technique, achieving high bonding strength. The in vivo proof-of-concept study demonstrated the feasibility of the surgical procedure and confirmed corneal re-epithelialization.

Richardson, L. A., Porcerelli, J. H., Stein, M., DeLorenzo, B., Massey, C., Lindquist, E., McNamee, S., & Blais, M. (2025). The relationship between overall defensive functioning and the Personality Assessment Inventory borderline and treatment outcome scales.. Research in Psychotherapy (Milano), 28(3). https://doi.org/10.4081/ripppo.2025.883 (Original work published 2025)

Mature defense mechanisms support patients' engagement in psychotherapy. The Overall Defensive Functioning (ODF) scale of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Defensive Functioning Scale (DFS) is a measure of the maturity of patients' defenses. Immature defenses (e.g., splitting) and poor emotion regulation are hallmarks of borderline personality organization, and both can interfere with positive treatment engagement. We predicted that ODF would significantly and negatively correlate with the Personality Assessment Inventory Borderline (PAI-BOR) scales, PAI Treatment Rejection (PAI-RXR) scale, and the PAI Treatment Process Index (PAI-TPI). To our knowledge, no studies have examined the relationship between ODF scores, as measured by the DFS rating of Thematic Apperception Test (TAT) narratives, and defense levels, PAI-BOR Full Scale (PAI-BOR-FS), PAI-RXR, and PAI-TPI scales. The sample included 73 outpatients from an academic hospital. Patients were administered the PAI and a TAT protocol. Two psychologists independently rated 40 TAT protocols with the observer-rated DFS for reliability. Healthy defenses showed significant negative correlations with PAI-BOR-FS (r=-.27), PAI-BOR Negative Relationships (PAI-BOR-N) (r=-.38), and PAI-RXR (r=.30). The pathological defenses had positive correlations with four of the five PAI-BOR scales and the PAI-TPI. There were significant correlations between ODF and the treatment related scales, PAIRXR (r=.37, p<.01) and PAI-TPI (r=-.32, p<.01). ODF significantly and negatively correlated with the PAI BOR-FS (r=-.36, p<.01) and its subscales, Affective Instability (r=-.35, p<.01) and Negative Relationships (r=-.39, p<.01). High and low ODF groups had significant and meaningful differences on all seven PAI scales. Overall, these findings provide support for the construct validity and clinical utility of the DFS defense levels (healthy, neurotic, and pathological) and the global ODF.

Al-Asad, R. K., Luu, N.-N. C., Edge, A. S., & Kempfle, J. S. (2025). A novel minimally invasive stereotaxic technique to target inner ear neurons in the mouse.. Frontiers in Neurology, 16, 1696492. https://doi.org/10.3389/fneur.2025.1696492 (Original work published 2025)

Sensorineural hearing loss (SNHL), a leading cause of disability worldwide, arises from damage to hair cells (HCs) or spiral ganglion neurons (SGNs) within the cochlea. Among its etiologies, auditory neuropathy (AN) is characterized by disrupted signal transmission due to SGN damage. Traditional interventions, such as hearing aids and cochlear implants, provide limited benefit in cases of AN, where neuronal damage impairs signal transduction to the brain. Emerging regenerative therapies, including cell replacement and gene delivery, hold potential to restore SGN function, but their application is limited by challenges in delivering therapeutic agents to cochlear targets. In this study, we developed a novel stereotaxic approach for minimally invasive, precise delivery of therapeutic agents to murine SGNs. Utilizing pre-determined coordinates, we successfully accessed the cochlea and SGNs. Immunohistochemistry confirmed accurate delivery and integration of therapeutic agents. Functional hearing assessments showed that the approach preserved HC function and demonstrated minimal adverse effects. This technique offers a scalable platform for advancing cell and gene therapies aimed at restoring auditory function in AN and other forms of SNHL.

Ashkani-Esfahani, S., Borjali, A., Hollander, J., Waryasz, G., Guss, D., Maas, M. M., DiGiovanni, C. W., Muratoglu, O. K., & Kerkhoffs, G. M. (2025). Deep Learning Enhances Weightbearing CT Detection of Lisfranc Instability: A FIXUS-AI Ankle Insight 3D Algorithm.. Cureus, 17(12), e99658. https://doi.org/10.7759/cureus.99658 (Original work published 2025)

Background Recent deep learning (DL) techniques have demonstrated multiple breakthroughs in improving the detection of musculoskeletal pathologies through clinical imaging. Weightbearing CT (WBCT) has been shown to improve diagnostic accuracy in Lisfranc instability, particularly when it is subtle. The aim of the present study was to investigate the impact of applying DL algorithms on WBCT images for the diagnosis of isolated Lisfranc instability. Methods The WBCT scans of 280 patients were evaluated (140 cases who had isolated Lisfranc instability, 140 controls without any foot injuries). The entire data set in each group was divided into the training set, validation set, and test set with an 80:10:10 split ratio, in a random manner. Three DL models were developed: (1) a 3D convolutional neural network (3D-CNN); (2) a CNN with long short-term memory (LSTM); and (3) a differential CNN-LSTM. After training, the models' performance was assessed by means of sensitivity, specificity, accuracy, F1-score, and the area under the receiver operating characteristic (ROC) curve. Results The case group included 41% males, and the control group 43%. Mean age and BMI were 35.7 and 26.6, respectively, in the case group, and 32.6 and 27.1 in controls. No significant baseline differences were found. Model 1 had an F1-score of 0.72, while Models 2 and 3 demonstrated substantially higher F1-scores of 0.92 and 0.99, respectively. Conclusion This study developed a DL model for 3D WBCT-based Lisfranc injury detection with excellent accuracy. The findings suggest that DL integration has the potential to improve diagnostic accuracy. Further research should focus on larger datasets and external validation.

Perin, J. P., Pastora-Sesín, C., Kang, S., Navarro-Flores, A., Fregni, F., & Pacheco-Barrios, K. (2025). Potential of Vagus Nerve Stimulation to Modulate Fibromyalgia’s Network Physiology: A Systematic Review.. Journal of Functional Morphology and Kinesiology, 11(1). https://doi.org/10.3390/jfmk11010015 (Original work published 2025)

Background: Chronic pain conditions such as fibromyalgia syndrome (FMS) reflect maladaptive network physiology across perceptual-autonomic-immune axes, yet most treatments remain symptomatic and incompletely effective. Methods: We conducted a comprehensive systematic review to evaluate vagus nerve stimulation (VNS) and FMS within a network physiology framework. PubMed, Embase, and Cochrane CENTRAL were searched on October 24, 2025. Risk of bias was assessed using the ROB-2 tool. An iterative thematic synthesis was performed to develop an integrative conceptual framework and to identify knowledge gaps and future research directions. Results: We first summarize physiological evidence showing autonomic imbalance (e.g., decreased heart rate variability), neuroinflammatory activation, and aberrant cortical network connectivity in FMS, supporting a network-dysregulation model. We then included 6 studies (4 clinical studies and 2 protocols) on VNS effects, highlighting improvements in pain, fatigue, sleep disturbance and autonomic regulation, along with emerging mechanistic insights. Key methodological heterogeneity-such as stimulation parameters, outcome metrics, type of control arm, sham definition, and small samples-limits current interpretability. Finally, we outline a research agenda centered on network-based biomarkers, immunophenotyping, adaptive trial designs and stratification of responders, with the aim of validating taVNS as a scalable neuromodulatory intervention for FMS. Conclusions: By reframing FMS from a symptom-centric pharmacologic model to a network-centric neuromodulation approach, taVNS is a promising tool for mechanism-based therapeutics in central sensitization syndromes and chronic pain.

Lee, S., Heydarian, N., Pulimamidi, V. K., Zidan, A. A., Sandhu, S., Xi, L., Chen, Y., Yin, J., Dohlman, T. H., Chauhan, S. K., & Dana, R. (2025). Myeloid-Derived Suppressor Cells Enhance Wound Healing in a Murine Model of Corneal Injury.. Cornea. https://doi.org/10.1097/ICO.0000000000004056 (Original work published 2025)

PURPOSE: Corneal injury is a leading cause of vision loss and demands rapid, coordinated regeneration. Myeloid-derived suppressor cells (MDSC), innate immunoregulatory cells that aid repair in peripheral tissues, have not been evaluated in corneal healing. We tested whether MDSC promote epithelial closure and temper postinjury inflammation.

METHODS: For scratch assays, 1.0 × 105 human corneal epithelial cells were cocultured with 1.5 × 106 MDSC or CD11b+Gr-1- control cells, and wound areas at 18 and 24 hours were quantified in ImageJ. In vivo, corneal epithelial debridement was induced in BALB/c mice using an Algerbrush-II, followed by subconjunctival injection of MDSC or control cells (5 × 104 cells in 50 μL saline). Epithelial healing was assessed by fluorescein staining and slitlamp imaging at 6, 22, and 28 hours, with ImageJ analysis. At 28 hours, corneas were collected for real-time polymerase chain reaction and flow cytometry to assess inflammatory markers. On day 3, corneas were harvested for hematoxylin and eosin staining and histological analysis.

RESULTS: MDSC significantly enhanced human corneal epithelial cells migration in vitro versus controls. In vivo, MDSC delivery accelerated epithelial wound closure, reduced CD11b+Ly6G+ neutrophil infiltration, and lowered corneal tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) expression compared with saline or CD11b+Gr-1- control cells. Histology confirmed restoration of epithelial integrity in MDSC-treated eyes.

CONCLUSIONS: MDSC expedite corneal epithelial repair and attenuate acute inflammation after injury. These findings identify a previously unrecognized reparative function for MDSC in the cornea and support their development as a cell-based therapy for ocular surface injury.