Publications by Year: 2025

Background/Objectives: Speech and motor control share overlapping neural mechanisms, yet their quantitative relationships in Parkinson's disease (PD) remain underexplored. This study investigated bidirectional associations between acoustic voice features and objective motor metrics to better understand how vocal and motor systems relate in PD. Methods: Cross-sectional baseline data from participants in a randomized neuromodulation trial were analyzed (n = 13). Motor performance was captured using an Integrated Motion Analysis Suite (IMAS), which enabled quantitative, objective characterization of motor performance during balance, gait, and upper- and lower-limb tasks. Acoustic analyses included harmonic-to-noise ratio (HNR), smoothed cepstral peak prominence (CPPS), jitter, shimmer, median fundamental frequency (F0), F0 standard deviation (SD F0), and voice intensity. Univariate linear regressions were conducted in both directions (voice ↔ motor), as well as partial correlations controlling for PD motor symptom severity. Results: When modeling voice outcomes, faster motor performance and shorter movement durations were associated with acoustically clearer voice features (e.g., higher elbow flexion-extension peak speed with higher voice HNR, β = 8.5, R2 = 0.56, p = 0.01). Similarly, when modeling motor outcomes, clearer voice measures were linked with faster movement speed and shorter movement durations (e.g., higher voice HNR with higher peak movement speed in elbow flexion/extension, β = 0.07, R2 = 0.56, p = 0.01). Conclusions: Voice and motor measures in PD showed significant bidirectional associations, suggesting shared sensorimotor control. These exploratory findings, while limited by sample size, support the feasibility of integrated multimodal assessment for future longitudinal studies.

Background/Objectives: This study explores the perceptions, experiences, and expectations of pediatric healthcare professionals regarding the implementation of virtual visits (VVs) in routine pediatric practice. Methods: Using the Consolidated Framework for Implementation Research (CFIR) to analyze individual, organizational, and contextual factors influencing the adoption of pediatric virtual visits, we conducted a descriptive cross-sectional survey distributed nationwide among pediatricians, pediatric nurses, and residents. Results: A total of 308 Spanish healthcare professionals correctly completed the REDCap survey and were included in the analysis. The mean age was 44.3 years, and respondents represented both hospital-based (55.8%) and primary care professionals (44.2%). Overall, 74.8% had previous experience with telephone consultations, while only 11% had performed virtual visits. Most professionals believed VVs could be useful in primary care (81.3%) and hospital out-patient settings (73.9%), especially for follow-up appointments, communication of test results, and chronic-care monitoring. VVs were perceived as more appropriate for older children and adolescents than for infants. Major concerns included poor internet connection (52.6%), and data security (37.4%); however, a particularly relevant finding was the low confidence in using digital tools, particularly among older professionals. Comparative analyses by age and workplace setting identified differences in interest, perceived barriers, and access to technical resources. Hospital-based clinicians reported greater interest in adopting VVs and better access to technological resources compared with primary care professionals. The professionals' age was inversely associated with interest in VVs. Notably, 72.6% of respondents expressed interest in receiving specific VV training, and nearly 90% believed virtual visits should be offered in their workplace. Conclusions: These findings show a high overall acceptance of VVs but also underline persistent barriers related to infrastructure, digital literacy, and clinical applicability in younger children. Addressing these obstacles through training, improved equipment, and clear clinical protocols will be essential for the successful implementation of pediatric VV programs.

Large language models perform surprisingly well on many zero-shot classification tasks, but are difficult to fairly compare to supervised classifiers due to the lack of a modifiable decision boundary. In this work, we propose and evaluate a method that transforms binary classification tasks into pairwise comparisons between instances within a dataset, using LLMs to produce relative rankings of those instances. Repeated pairwise comparisons can be used to score instances using the Elo rating system (used in chess and other competitions), inducing a confidence ordering over instances in a dataset. We evaluate scheduling algorithms for their ability to minimize comparisons, and show that our proposed algorithm leads to improved classification performance, while also providing more information than traditional zero-shot classification.

Lymphovenous anastomosis (LVA) has emerged as an important physiologic microsurgical procedure for patients with breast cancer-related lymphedema (BCRL) with the goal of restoring lymphatic drainage rather than providing just palliative care for symptoms of swelling. A multicenter randomized controlled trial (RCT) in 2024 (N-LVA) found improvements in the Lymph-ICF physical and mental function domains, and decreased use of compression garments, despite modest changes in total quality of life (QoL) and limb volume at 6 months. Meta-analyses have found average reductions of 30%-35% in excess limb size and nearly two fewer cellulitis episodes per year after LVA and vascularized lymph node transfer (VLNT). As the surgical technology continues to improve (e.g., prophylactic LYMPHA procedures, high-resolution lymphatic imaging, robotic supermicrosurgery) and as LVA becomes more widely adopted within experienced surgical centers, precision surgery will be increasingly considered in lymphedema care. Collectively, these advancements represent a movement toward physiologic reconstruction in lymphedema care and the next initiatives will focus on patient selection and eligibility optimization, state-of-the-art surgical technology optimization, and standardizing outcome measures to achieve sustained improvements in QoL.

Event-related spectral perturbations (ERSPs) capture dynamic changes in electroencephalography (EEG) power across frequency and trial time. Even though they are obtained at the trial level, they are commonly averaged across trials and analyzed at the subject level for enhancing the signal-to-noise ratio. While evoked activity is stimulus-locked, representing the brain's predictable response to stimuli, induced signals that are not strictly locked to stimulus presentation are thought to be generated by higher-order processes, such as attention and integration. Motivated by joint modeling of multilevel (trials nested in subjects) and multivariate (evoked and induced) ERSP data from a visual-evoked potentials (VEP) task, we propose a multilevel multivariate functional principal components analysis (FPCA) for high-dimensional functional outcomes as a function of time and frequency. The proposed estimation procedure utilizes multilevel univariate FPCA decompositions along each variate of the multivariate outcome using fast covariance estimation and incorporates the dependency across outcome variates at each level of the data. Hence, the proposed approach for multilevel multivariate FPCA can efficiently scale up to higher dimensional functional outcomes and increasing number of variates in the multivariate functional outcome vector. Extensive simulations show the efficacy of the proposed approach, while applications to VEP data lead to new insights on autism-specific neural activity patterns. The autistic group shows significantly lower evoked and higher induced gamma power compared to the neurotypical group. In addition, while subject level variation is dominated by variation in the stimulus-locked evoked signal in neurotypical development, it is dominated by induced power in autism.

Calcium (Ca2+) is a signal messenger for ion flow in and out of microbial, parasitic, and host defense cells. Manipulation of calcium ion signaling with ion blockers and calcineurin inhibitors may improve host defense while decreasing microbial/parasitic resistance to therapy. Ca2+ release from intracellular storage sites controls many host defense functions (cell integrity, movement, and growth). The transformation of phospholipids in the erythrocyte membrane is associated with changes in deformability. This type of lipid bilayer defense mechanism helps to prevent attack by Plasmodium. Patients with sickle cell disease (SS hemoglobin) do not have this protection and are extremely vulnerable to massive hemolysis from parasitic infestation. Patients with thalassemia major also lack parasite protection. Alteration of Ca2+ ion channels responsive to environmental stimuli (transient receptor potential) results in erythrocyte protection from Plasmodium. Similarly, calcineurin inhibitors (cyclosporine) reduce heart and brain inflammation injury with Trypanosoma and Taenia. Ca2+ channel blockers interfere with malarial life cycles. Several species of parasites are known to invade hepatocytes: Plasmodium, Echinococcus, Schistosoma, Taenia, and Toxoplasma. Ligand-specific membrane channel constituents (inositol triphosphate and sphingosine phospholipid) constitute membrane surface signal messengers. Plasmodium requires Ca2+ for energy to grow and to occupy red blood cells. A cascade of signals proceeds from Ca2+ to two proteins: calmodulin and calcineurin. Inhibitors of calmodulin were found to blunt the population growth of Plasmodium. An inhibitor of calcineurin (cyclosporine) was found to retard population growth of both Plasmodium and Schistosoma. Calcineurin also controls sensitivity and resistance to antibiotics. After exposure to cyclosporine, the liver directs Ca2+ ions into storage sites in the endoplasmic reticulum and mitochondria. Storage of large amounts of Ca2+ would be useful if pathogens began to occupy both red blood cells and liver cells. We present scientific evidence supporting the benefits of calcium channel blockers and calcineurin inhibitors to potentiate current antiparasitic therapies.

State-of-the-art minimally invasive in utero interventions involving stem cell, protein, and nucleic acid-based therapies represent a new frontier in medicine, which offers hope for devastating fetal diagnoses and promises the restoration of lifetimes. Yet they also introduce serious concerns regarding health risks posed to mother, fetus, and future generations. Recent international consensus statements provide general guidance for structuring trials to maximize health and minimize the risk of experimental treatments for both a pregnant mother and fetus. This article offers additional ethical guidance for translating interventions from first-in-human studies by focusing on a more holistic and nondirective consent process and encouraging pretrial publication of proposed studies to increase dialogue, fine-tune protocols, and potentially improve access.

Cite this article as: Ashkani-Esfahani S, Aslan L. AOTT special issue Editorial. Acta Orthop Traumatol Turc., 2025;59(6):337-339.

OBJECTIVE: This study aimed to computationally evaluate the effects of lesions of varying sizes and locations on stress distribution and ankle stiffness across the nine-zone grid of the talar dome in three different ankle positions.

METHODS: An adult ankle geometry was modeled with 1 mm of cartilage on both sides of the tibiotalar contact. Lesions with diameters of 4.5, 6.4, and 9 mm were created on the talar dome at each grid partition, ranging from section 1 (anteromedial) to 9 (posterolateral). The key innovation of the study was the use of tilted talar planes to account for the dome's curvature, enabling more accurate lesion model ing and biomechanical analysis. Percent changes in osteochondral von Mises stress distribution and ankle stiffness parameters were investigated using finite element analysis. Based on the designated design parameters, 81 different cases were modeled and simulated.

RESULTS: Zones 7 (posteromedial, -33.2% change in stiffness for a 9 mm defect), 3 (anterolateral, -24.2% change in stiffness for a 9 mm defect), and 8 (mid-posterior, -48.8% change in stiffness for a 9 mm defect) were found to be the most critical zones, showing evidence of decreased ankle stiffness in neutral, dorsiflexion, and plantarflexion positions, respectively. Zone 9 (posterolateral; neutral -4.7%, dorsi flexion 5.4%, plantarflexion 0.17% stiffness change for a 9 mm defect) was found to be the least critical zone in terms of biomechanical stiffness.

CONCLUSION: From a clinical standpoint, since lesions in zones 8, 7, and 3 significantly impact joint biomechanics compared to other zones, more aggressive cartilage restoration or augmentation could be required while lesions in less problematic zones like zone 9 can be treated withmicrofracture surgery.   Cite this article as: Aslan L, Subasi O, Karaismailoglu B, et al. In silico assessment of talus osteochondral lesion size and location on biomechanical load distribution using tilted talar dome planes. Acta Orthop Traumatol Turc., 2025;59(6):361-367.

OBJECTIVE: To evaluate the accuracy and fluoroscopy shot count of a novel skin-matched, patient specific Instrument (PSI) for subtalar arthrodesis compared with the conventional freehand technique in a cadaveric setting.

METHODS: Twelve cadaveric specimens were randomized into PSI-guided (n = 6) and freehand (n = 6) groups, with preoperative computed tomography scans used to design 3D-printed guides. Each PSI incorporated 2 pre-angled cannulated sleeves to allow optimal guidewire placement from the calcaneus into the talus. Outcomes included fluoroscopy usage, number of wire placement attempts, angular devia tion between planned and actual wire trajectories (assessed in sagittal, coronal, and axial planes), and linear deviations at entry (calcaneal) and distal (talar) points. Statistical analysis used the Mann-Whitney U and Wilcoxon signed-rank tests with significance set at P < .05.

RESULTS: Fluoroscopy usage was significantly lower in the PSI group (median 3.0 [interquartile range, IQR 3.0-6.0]) compared with the free hand group (17.0 [15.3-18.8]; P = .009). Similarly, the number of attempts was reduced in the PSI group (2.0 [2.0-2.8]) versus the freehand group (6.0 [5.3-6.8]; P = .009). Angular deviation from the preoperative plan was low (median 3.0° [IQR 1.8°-4.7°]), indicating high trajec tory fidelity. Linear deviation at the calcaneal entry point was minimal (median 0.9 mm [IQR 0.4-1.2 mm]), whereas greater variability occurred distally at the talar point (median 3.6 mm [IQR 2.0-5.1 mm]), remaining within clinically acceptable limits.

CONCLUSION: The use of a skin-matched PSI for subtalar arthrodesis significantly reduced the number of fluoroscopy shots and wire place ment attempts while ensuring high accuracy of guidewire trajectory. These findings support the potential of 3D-printed PSIs to improve surgical precision, suggesting clinical applicability for subtalar arthrodesis and related hindfoot interventions.   Cite this article as: Karaismailoglu B, Subasi O, Tung W, et al. Improving subtalar arthrodesis with a skin-matched patient-specific surgical guide: a comparative cadaveric study. Acta Orthop Traumatol Turc., 2025;59(6):368-373.