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Applied Sciences

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Preprints posted in the last 30 days, ranked by how well they match Applied Sciences's content profile, based on 25 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Attention Is All You Need: A Universal Augmented Reality Surgical Navigation Framework

Zhao, D.; Qiu, Y.; Guo, Y.; Luo, X.; Liu, Y.; Li, X.; Chen, H.; Cai, X.; Tian, T.

2026-09-25 dentistry and oral medicine 10.64898/2026.09.20.26363284 medRxiv
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Hard-tissue surgery requires precise spatial control, while conventional computer-assisted navigation presents guidance separately from the operative field. Augmented reality can bring navigation information closer to the surgeon, but how best to translate this information into intuitive intraoperative guidance remains underexplored. We therefore developed an augmented reality navigation system (ANS) that translates real-time deviations from the planned trajectory into co-located holographic action cues. Evaluation comprised typodont and ex vivo porcine experiments, a randomized crossover study in 40 dental trainees, and eight clinical cases. In porcine mandibles, ANS showed lower angular deviation than static and dynamic navigation (1.78 vs 6.42 and 4.02 degrees). Among trainees, accuracy was comparable with dynamic navigation, while workload was lower (29.18 vs 33.15), usability higher (73.13 vs 68.88), and visual-focus ratings improved (3.55 vs 2.28). Clinical cases supported feasibility. These findings support co-located action guidance as an alternative interface paradigm for surgical navigation.

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Modelling assessment of the different paths of between-farm transmission of avian influenza HPAI in Northern Italy in 2021--2022

Sensi, M.; Sottile, S.; Fornasiero, D.; Monne, I.; Mulatti, P.; Pugliese, A.

2026-09-24 genetics 10.64898/2026.09.19.752832 medRxiv
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We propose a stochastic epidemic model to describe the spread of avian influenza in a network of poultry farms. We consider three main paths of infection transmission between poultry farms: from nearby farms, mainly through airborne diffusion; from farms belonging to the same company, through shared veterinarians, forage providers and similar; from undetected small farms or wildlife. From the parameter estimation, based on a modified Expectation-Maximization algorithm, we infer that approximately 63% of the farms were infected from nearby ones, with an infection force declining with distance; of these, more than one third belonged to the same company of the estimated infector. About 20% were infected from premises belonging to the same company but farther away than the distance threshold of 2 km; the remaining ones from wildlife or unidentified sources. These estimates have been validated by a comparison with genetic data, available for a subset of the farms: the genetic distance between two farms identified, with high probability, as an infector-infectee pair is much lower than between random pairs. These results may help in the implementation of tailored prevention and control measures for future outbreaks.

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HLA Genotype is Associated with Patient Reported Outcomes and Adverse Reactions to Metal Debris in Patients with Cobalt-Chrome Knee Arthroplasties

Langton, D.; Bhalekar, R.; Borikar, Y.; Wells, S.; Clement, N.; Deehan, D.; Guest, D.; Harrington, C.; Jameson, S.; Leitch, G.; McManus, R.; Pabbruwe, M.; Phillips, J.; Rushton, S.; Porteous, A.; Santini, A.; Tross, S.; Sidaginamale, R.

2026-10-13 orthopedics 10.64898/2026.10.12.26365276 medRxiv
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Purpose: To determine whether a cobalt-chrome genetic reactivity (CoGR) score - originally developed to identify patients at greater risk of developing adverse reaction to metal-on-metal hips - is associated with poorer patient-reported outcomes after knee arthroplasty (KA). Methods: In a prospective multicentre study, patients at a minimum two years post all cobalt-chrome KA were invited to research clinics. Participants provided samples for blood metal ion measurements and DNA sequencing and completed Forgotten Joint Scores (FJS). Component alignment was assessed on AP and lateral plain radiographs. The association between CoGR and FJS was assessed using regression adjusted for time since surgery, age, gender, BMI and tested for modification by blood cobalt. In a case-control analysis, CoGR scores of revised patients with histologically confirmed adverse reactions to metal debris (and specifically aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL)) were compared with controls (revised patients with no signs of ARMD and unrevised patients with FJS of 75 or more) using Firth logistic regression. Results: 376 patients were included: 312 unrevised patients and 64 patients who underwent revision. Each one-unit increase in CoGR score was associated with a 9.8 point lower FJS (95% confidence interval (CI) 4.2 to 15.4 points; p < 0.001). This increased to a 17.5 (9.4 to 25.5) point reduction per CoGR score unit in patients with blood cobalt above the median level. Comparing 28 ARMD cases (12 with ALVAL) with 177 controls, each one-unit CoGR increase was associated with odds ratios of 1.90 (CI 1.34 to 2.75) for ARMD and 3.05 (CI 1.89 to 5.34) for ALVAL. Conclusions: A higher CoGR score was associated with worse patient-reported outcome and higher odds of histologically confirmed adverse reaction to metal debris at revision. Adverse immune responses may be a more significant factor in unexplained pain after KA than is generally recognised.

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PFAS and phthalates in follicular fluid of a Nebraska in vitro fertilization (IVF) cohort

Taiba, J.; Balu, N.; Castillo, A. C.; Barakat, R.; Lee, C.; Chen, A.; Gustin, S.; Constance, E.; Davis, J. S.; Bell, J. E.; Clark, K. L.

2026-09-29 obstetrics and gynecology 10.64898/2026.09.21.26363443 medRxiv
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Per- and polyfluoroalkyl substances (PFAS) and phthalate metabolites are understudied in follicular fluid of women undergoing assisted reproduction. We characterized these in previously collected follicular fluid from patients at a Nebraska fertility clinic (August 2022 to June 2025) and retrieved demographics and clinical characteristics from fertility records. Spearman correlations and nonparametric tests evaluated PFAS and phthalate correlations and exposure differences by age, race, BMI, and urbanicity. Seven PFAS and four phthalate metabolites were detected in at least half of participants. PFOS and PFHxS concentrations were higher in younger women, and mono-isobutyl phthalate (MiBP) was higher in younger and non-White women. PFAS and phthalate correlations were weak, and exposures did not differ by urbanicity, indicating multiple chemical exposures in follicular fluid with sociodemographic disparities.

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A Unified and Interpretable Geometric Optimization Framework for Intelligent Automated Implant Planning in CBCT from Single to Consecutive Multiple Missing Teeth

Zeng, Z.; Jiang, Y.; Li, J.; Cao, H.; Lu, Y.; Zhu, H.; Xiong, J.; Tang, Z.; Hu, N.; Ma, H.

2026-10-05 dentistry and oral medicine 10.64898/2026.10.03.26364640 medRxiv
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Automated dental implant planning using artificial intelligence (AI) faces challenges in interpretability, safety assurance, and applicability beyond single-tooth cases. This paper presents a unified explainable framework for cone-beam computed tomography (CBCT) that handles both single-tooth and consecutive multiple missing teeth. The method combines nnU-Net-based anatomical segmentation with a transparent geometric optimization pipeline. Implant placement is formulated as a lexicographic multi-objective constrained optimization problem that enforces clinical safety margins while balancing bone engagement, mesiodistal spacing, and buccolingual position. For multi-tooth cases, a global coordination strategy ensures inter-implant parallelism, minimum spacing, and a common insertion path. The framework was validated on 20 single-tooth and 9 consecutive multi-tooth cases. The AI plans achieved a centroid distance of 1.60+/-1.05 mm for single-tooth cases and 1.22+/-0.32 mm for multi-tooth cases, with approximately 7 degrees axial angle difference. All plans achieved 100% compliance with predefined safety thresholds. In a Turing-style test, experts were unable to distinguish AI from human intelligence (HI) plans under blinded conditions. By decoupling perception from reasoning and embedding clinical knowledge as explicit constraints, the framework offers an interpretable and clinically trustworthy solution for computer-aided implant dentistry.

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Robust Cooperative Learning for Multiview Regression via Soft-IPOD

Yoshimura, S.; Hiroyasu, T.; Tanioka, K.

2026-09-30 bioinformatics 10.64898/2026.09.24.754279 medRxiv
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Multiview data analysis has become increasingly important for integrating heterogeneous information from multiple data sources. Cooperative learning provides a flexible framework for multiview integration by bridging early and late fusion strategies. However, its use of squared loss makes it sensitive to outliers. In this study, we propose robust cooperative learning based on the soft-IPOD framework. The proposed method introduces an observation-specific outlier absorption vector into the cooperative learning objective, thereby reducing the influence of outlying observations while preserving information sharing across views. The resulting optimization problem can be formulated as a weighted Lasso-type problem using an augmented design matrix and can be naturally extended to more than two data views. Numerical simulations and a real-data application to labor onset prediction demonstrate the predictive performance of the proposed method in the presence of outliers.

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Adults experiences of comorbid insomnia and pain: Entangled vicious cycle, driven by four primary factors

Albertsdottir, A.; Islind, A. S.; Skuladottir, H.; Halldorsdottir, S.; Olafsdottir, K. A.; Bjornsdottir, E.; Vikingsson, A.; Pires, G. N.; Arnardottir, E. S.

2026-09-30 public and global health 10.64898/2026.09.29.26364320 medRxiv
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Chronic pain and insomnia are common, each has serious consequences and they often coexist [1-5]. This novel study employed a phenomenological method to explore adults lived experiences of the core and meaning of comorbid insomnia and pain, here conceptualized as COMIP. The empirical data is based on 22 semi-structured interviews with adults with COMIP. Each interview was analysed, developing themes and analytical frameworks for all participants, which were then compared to construct one main analytical framework. The consolidated criteria for reporting qualitative research were used [6]. The essence of COMIP was: A vicious cycle of insomnia and pain driven by four intertwined primary factors with cross effects, which reduced sleep quality and quality of life. Four main themes emerged: Firstly, insomnia with hyperarousal like racing thoughts, and difficulties with finding comfortable sleeping positions due to pain, disturbed sleep and decreased sleep quality. Secondly, daytime symptoms like reduced energy, with reduced daytime function and reduced quality of life. Thirdly, 24-hour hyperarousal, stress and distressing experiences such as suffering. Finally, contextual factors like treatment reduced and/or increased COMIP. The main contribution of this research is three-fold; mapping of the experiences of living with COMIP, the conceptualization of COMIP, and introduction of novel concepts. Our findings indicate that, when evaluating patients with COMIP, there is value in exploring the four COMIP factors. Although, it varies between individuals which factor/s is central to their COMIP experience, we emphasize that COMIP is distressing, and patients are likely to need emotional support and validation. Keywords: COMIP, sleep, phenomenology, disability, rehabilitation, ICF.

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Low-Cost Tissue Expansion Using a Saline-Based Device Shows Comparable Histological Outcomes in a Rat Model

Rosa, T. G.; da Silva, L. C. K.; de Abreu, T. Z.; Neto, J. S.; Ribas Filho, J. M.

2026-10-06 bioengineering 10.64898/2026.10.05.756788 medRxiv
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Tissue expansion is an established technique for the reconstruction of skin defects, but the cost of conventional silicone expanders may limit its application in contexts with lower resource availability. This study evaluated, in an experimental model, whether a container for storing saline solution could act as a low-cost alternative device for tissue expansion. An experimental, prospective, controlled and randomized study was carried out with 10 Wistar rats, distributed in two groups: conventional silicone expander and saline storage container. Both underwent the same surgical and expansion protocol. Abdominal circumference gain, final expanded skin length, histological and histomorphometric aspects of the skin, including collagen types I and III, as well as exploratory cost analysis, were analyzed. The conventional expander produced a greater gain in abdominal circumference, but the final length of the expanded skin was similar between the groups. Microscopic evaluation showed preservation of the cutaneous architecture, intact epidermis, cellularized dermis, and collagen deposition in both groups. There was no significant difference in the proportion of type I or type III collagen. The saline solution container had a substantially lower cost per centimeter of expanded skin than the conventional expander. These findings suggest that the saline container can produce experimental skin expansion with final length and collagen composition similar to the conventional method, at a lower cost, although additional studies are needed before clinical application.

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Spatial hearing in adults with sequential bilateral cochlear implants: a longitudinal prospective cohort study

Valzolgher, C.; Ghiselli, S.; Epifania, M. O.; Gullotta, J.; Zanetti, D.; Lilli, G.; Di Berardino, F.; Pozzi, M.; Ciorba, A.; Borin, M.; Brunelli, N.; Musumano, L. B.; Frau, G. N.; Tromballi, G.; Chini, A.; Rosi, T.; Malerba, P.; Cuda, D.; Pavani, F.

2026-10-06 otolaryngology 10.64898/2026.10.01.26364332 medRxiv
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Bilateral cochlear implantation (BCI) can improve spatial hearing in adults with bilateral hearing loss, but the early development of spatial hearing following sequential BCI remains poorly understood. This prospective longitudinal study investigated changes in spatial hearing experience in 23 adults undergoing sequential BCI, assessed before and at ~1, 3, and 8 months after bilateral implantation under two conditions: spontaneous and restrained head movements. Using a motion-tracking system combined with virtual reality, sound localization was assessed through absolute and signed errors, along with self-reported localization confidence and listening effort. Subjective spatial hearing was also assessed using the Speech, Spatial and Qualities of Hearing Scale (SSQ). Localization performance improved by 1 month after bilateral implantation, as evidenced by a reduction of absolute error and in the bias toward the first-implanted ear. Participants reported greater localization confidence and lower listening effort at 1 month, although these changes were not consistently maintained at later follow-ups. SSQ scores showed improved spatial hearing at 1 month, speech perception at 3 months, and sound clarity and discriminability at 8 months. Compared with head-restrained condition, accuracy and confidence improved when spontaneous head rotations were allowed. The temporal trajectories of localization bias, confidence, and effort were modulated by the duration of experience with the first CI. These findings indicate that changes in spatial hearing can emerge soon after second CI activation. They further highlight the contribution of spontaneous head movements and previous CI experience, and support the use of complementary measures to monitor the early development of bilateral listening.

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The effect of an ultrasound-activated electrospun piezoelectric hydrogel scaffold on post-traumatic brain injury motor function in Drosophila melanogaster

Nimkar, M.; Gopal, R.

2026-09-25 neuroscience 10.64898/2026.09.20.752928 medRxiv
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Traumatic brain injury (TBI) is a leading cause of long-term neurological disability, affecting 50-60 million people annually. Cascading secondary injury mechanisms, including oxidative stress and neuroinflammation, impair motor and cognitive function, while current therapies often manage symptoms rather than restore lost neurological function. This study investigated an ultrasound-activated piezoelectric hydrogel scaffold composed of barium titanate nanoparticles (BTNPs), sodium alginate (SA), and polyethylene oxide (PEO). The hypothesis was that TBI flies receiving the scaffold and ultrasound would display a higher climbing assay pass rate than TBI flies receiving no treatment or BTNPs alone. TBI was induced in Drosophila melanogaster with a high-impact trauma (HIT) apparatus. Treatments were applied by opening and resealing the fly head cuticle, followed by ultrasound stimulation. Motor recovery was quantified with a climbing assay across four groups (N=10 flies per group), which measured the percentage of flies that could cross a 5 cm mark within 30 seconds. Assay validity was supported by a statistically significant difference between flies without TBI and those with TBI using Mann-Whitney U testing (p=0.0035). Although TBI treatment groups did not differ significantly (p>0.05), median pass rates increased from injury control (35%) to BTNPs (45%) to scaffold (50%). However, high inter-trial variation, a 45.2% procedural mortality rate, and small sample size limited statistical power. These results suggest that piezoelectric electrospun hydrogel scaffolds may be a pathway for safer and more biocompatible restoration after TBI, but provide insufficient evidence to conclude that the scaffold significantly improved motor recovery.

11
Mapping the response of primary human chondrocytes to an osteoarthritis-relevant stimulus by single-cell RNA sequencing

Stuppy, S. R.; Shine, J.; D'Costa, S.; Fernandez Davila, J. G.; Yanke, A. B.; Loeser, R. F.; Burgess, J. D.; Phanstiel, D. H.; Diekman, B. O.

2026-09-29 genetics 10.64898/2026.09.24.754148 medRxiv
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Objective: To determine how fibronectin fragment (Fn-f), a matrikine that induces an osteoarthritis (OA)-like phenotype, reshapes chondrocyte states and transcriptional programs at single-cell resolution. Design: Primary human ankle chondrocytes from two cadaveric donors without OA were treated with PBS or purified recombinant Fn-f for 18 hours and profiled by single-cell RNA sequencing. Transcriptional states were characterized by marker genes and functional enrichment, compared with classifications used for OA chondrocytes, and evaluated for Fn-f-dependent changes in abundance and transcriptional programs. Results: Five transcriptionally distinct populations were identified with features that matched previous classifications of effector, inflammatory, pre-hypertrophic/fibrochondrocyte, reparative, and homeostatic chondrocytes. Fn-f markedly redistributed cells among these states, enriching inflammatory chondrocytes while reducing effector and reparative populations. Within transcriptional states, Fn-f differentially altered matrix/cartilage, inflammatory, and stress/immediate-early programs. These responses did not uniformly correspond to assigned subtype identities, demonstrating that transcriptional programs can be dynamically deployed across chondrocyte states. Conclusions: Controlled perturbations of healthy chondrocytes complement observational OA atlases by resolving stimulus-dependent changes in chondrocyte state abundance and transcriptional programs. Discordance between subtype annotations and dynamic functional programs further highlights the need for harmonized definitions of chondrocytes across phenotypic states.

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Validity and reliability of the Japanese version of the Movement Behaviour Questionnaire-Child (MBQ-C) for assessing active play, screen time, and sleep in preschool children

Komura, K.; Yamakita, M.; Kyan, A.; Inoue, S.; Nagano, M.; Takenaga, R.; Breugelmans, R.; Jego, E. H.; Trost, S. G.

2026-09-29 public and global health 10.64898/2026.09.28.26364096 medRxiv
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Background: Valid and feasible measures of preschoolers' 24-hour movement behaviours are needed for population-level research. We developed a Japanese version of the Movement Behaviour Questionnaire-Child (MBQ-C) and evaluated its measurement properties and practicality. Methods: After translation and cross-cultural adaptation following the COSMIN procedure, including cognitive interviews, we evaluated the questionnaire in a cross-sectional validation study of Japanese children aged 3-6 years. Concurrent validity was assessed against hip-worn accelerometry and a 7-day diary; we also examined test-retest reliability, measurement error, agreement between response formats and modes, and practicality (completion time, burden, and clarity). Analyses used Spearman correlations, intraclass correlation coefficients, the SEM, smallest detectable change (SDC), and Wilcoxon signed-rank tests. Results: Of 208 children, 170 provided valid accelerometer and diary data for the concurrent-validity analysis, and 187 completed the MBQ-C for the questionnaire-based analyses. Concurrent validity was weak for active and energetic play (Spearman {rho} = 0.12-0.26), strong for total screen time (0.78-0.85), and moderate for total sleep (0.48-0.58). Test-retest reliability was moderate to good (ICC, 0.66-0.81), and within-child variability was lowest for sleep (CV 3%) and highest for the physical activity items (21-33%). The open- and closed-ended versions showed no significant differences; paper-electronic agreement was good for screen time and sleep but poor for active play. Completion took approximately 6-9 minutes, with low reported burden. Findings were robust in sensitivity analyses. At the group level, SDC for a mean was SDCind/{surd}N: 119.8/{surd}N, 74.0/{surd}N, 112.6/{surd}N, and 92.5/{surd}N min/day for active play, energetic play, total screen time, and total sleep, respectively (N = number of children surveyed). The systematic differences between the two test-retest occasions were +15.7, +6.5, +4.0, and -5.4 min/day, respectively. Conclusions: The Japanese MBQ-C is a practical option for assessing preschoolers' active play, screen time, and sleep at the group level. By quantifying its group-level measurement error, this study provides benchmarks for interpreting group-level differences and change, supporting the use of the MBQ-C in surveillance and evaluation of programmes delivered at scale.

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'I love my AI girlfriend': a content analysis of youth social AI risk in online communities

Bischops, A. C.; Berkane, T.; Martoma, D.; Majumder, M.

2026-10-01 pediatrics 10.64898/2026.09.25.26363809 medRxiv
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Youth are increasingly engaging with generative AI beyond its use as a productivity tool, with a growing share turning to AI for social interaction and emotional support. This leads to unknown risks for their well-being and development. Online community discussions reveal that youth already perceive risks that caregivers have not recognized.

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A mathematical model of the HPA axis demonstrates bifurcations under varying stress and systemic conditions

Violaris, I. G.; Pinotsis, D.; Tsipouras, M.; Kalafatakis, K.

2026-10-11 bioinformatics 10.64898/2026.10.07.757338 medRxiv
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In this study, we develop a mathematical model of the hypothalamic pituitary adrenal (HPA) axis and systematically investigate the model complexity required to reproduce observed hormone dynamics. The model is fitted to ACTH and cortisol measurements from five healthy volunteers reported in the literature. We show that simultaneous reproduction of both hormone profiles requires a delay differential equation model with at least five state variables among the model architectures considered. Following fitting the volunteer data, we investigate the response of the model to sustained stress using bifurcation analysis. The coupled system exhibits bifurcations over a range of stress intensities. This analysis reveals bifurcations whose critical stress thresholds depend strongly on the modulatory state of the system. These results provide a mathematical framework for investigating transitions between physiological and dysregulated HPA axis dynamics, which may be related to states of health and disease.

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Epithelial-endothelial barrier dysfunction and oxidative stress in ARDS subphenotypes: comparative efficacy of extracellular vesicles derived from bone marrow (MSC-EVs) and adipose tissue (ASC-EVs) mesenchymal stem cells

Burello, A.; Tiberi, G.; Villegas, P. A. D.; Scagliotti, A.; Gai, C.; Kopecka, J.; Scrivanti, S.; Cappello, P.; Riganti, C.; Brazzi, L.; Camussi, G.; Del Sorbo, L.; Reddy, K.; O'Kane, C. M.; Cantaluppi, V.; McAuley, D. F.; Fanelli, V.

2026-09-23 intensive care and critical care medicine 10.64898/2026.09.22.26363677 medRxiv
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BackgroundReactive oxygen species (ROS) overproduction, inflammatory cytokines, and plasma mediators disrupt alveolar tight junction integrity and perpetuate oxidative injury in acute respiratory distress syndrome (ARDS). Biological heterogeneity of ARDS, reflected by hyper- and hypoinflammatory subphenotypes with distinct plasma mediator profiles, may contribute to heterogeneity of treatment effect. Stem cell-derived EVs have been shown to exert regenerative and immunomodulatory effects by horizontal transfer of proteins, lipids and genetic material to injured target cells. This study investigated whether extracellular vesicles derived from bone marrow (MSC-EVs) and adipose tissue (ASC-EVs) mesenchymal stem cells restore barrier integrity and redox homeostasis, and whether efficacy differs across subphenotypes. MethodsBronchial epithelial cells (BEAS-2B), microvascular endothelial cells (HMEC-1), and small airway epithelial cells (SAEC) were challenged with plasma from patients with hyperinflammatory or hypoinflammatory ARDS subphenotypes, including those treated with venovenous ECMO. MSC-EVs or ASC-EVs were added concomitantly with plasma exposure or six hours later, at a dose of 5,000 particles/cell. After 24 h, the expression of actin and tight junction proteins, zonula occludens (ZO)-1, occludin, and vascular endothelial (VE)-cadherin, was evaluated by immunofluorescence. Oxidative stress parameters, antioxidant defenses, and antioxidant enzyme activities, were measured. ResultsPlasma from patients with the hyperinflammatory ARDS subphenotype induced marked disruption of ZO-1, occludin, and VE-cadherin expression, together with actin cytoskeletal rearrangement, across BEAS-2B, HMEC-1, and SAEC cells. Barrier disruption was accompanied by increased oxidative stress markers and altered antioxidant enzyme activity. Both MSC-EVs and ASC-EVs restored tight junction protein expression and cytoskeletal organization when administered either concurrently with ARDS plasma or 6 hours after exposure, and both effectively modulated redox parameters. Delayed administration 6 hours after injury produced greater effects for several oxidative stress endpoints, particularly in cells challenged with hypoinflammatory plasma. ConclusionARDS-associated plasma mediators induce subphenotype-dependent impairment of epithelial-endothelial barrier integrity through oxidative mechanisms. Both MSC-EVs and ASC-EVs mitigate this injury, with efficacy that varies according to ARDS subphenotype and timing of administration.

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Validation of an EEG-based Delirium Monitor in the ICU

Onyemekwu, C. A.; Karunakaran, S.; Armenta Salas, M.; Prendergast, N. T.; Toth, K. M.; Miller, M. D.; Lee, S.; Kamousi, B.; Mulkey, M. A.; Sadaka, F. G.; Striegel, T.; Girard, T. D.

2026-09-29 intensive care and critical care medicine 10.64898/2026.09.23.26361767 medRxiv
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Purpose Delirium affects around 40% of intensive care unit (ICU) patients and adversely affects survival, length of stay, and cognitive recovery. Despite this, implementation of systematic clinical delirium assessments is variable. We sought to validate a point-of-care electroencephalography (EEG)-based system (Ceribell, Inc.) for the detection of delirium in the ICU. Methods In this multicenter, prospective cohort study, we monitored adult ICU patients with the Ceribell EEG system for 6-8 hours for a minimum of three days. Up to three times per day, expert clinicians assessed participants for delirium and research coordinators completed Confusion Assessment Method for the ICU (CAM-ICU) assessments, which we used to calculate CAM-ICU-7 severity scores. We compared expert clinician diagnoses with Ceribell EEG algorithm output using data from 30-minute periods surrounding each clinician assessment. Results Among 225 participants analyzed (median age: 64 years, 60% male, 21% mechanically ventilated), expert clinicians performed 857 assessments and found 24% of participants were delirious during at least one assessment. The Ceribell EEG system detected delirium with a sensitivity of 81% (95% CI: 76% to 87%) and specificity of 81% (95% CI: 78% to 84%). The continuous Ceribell EEG system score correlated with CAM-ICU-7 delirium severity scores (bootstrapped median rho 0.58, IQR: 0.54-0.62, p <0.001). Conclusion In a mixed adult ICU population, the Ceribell EEG system identified delirium with good sensitivity and specificity. Its continuous output was associated with delirium severity, highlighting its potential ability to characterize underlying physiological patterns across the clinical delirium spectrum.

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Enhancing the hyaline cartilage regenerative potential of induced pluripotent stem cell-derived chondrocyte cell sheets

Takahashi, T.; Uchiyama, R.; Toyoda, E.; Maehara, M.; Takahashi, Y.; Wasai, S.; Oomura, H.; Ogawa, M.; Yamashita, A.; Watanabe, M.; Tsumaki, N.; Sato, M.

2026-09-28 bioengineering 10.64898/2026.09.25.754531 medRxiv
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Introduction Autologous and allogeneic chondrocyte cell sheet transplantation has shown safety and potential efficacy for cartilage defects associated with knee osteoarthritis. Although polydactyly-derived chondrocyte (PDC) cell sheets have been used clinically for allogeneic transplantation, a scalable and reliable alternative cell source is needed. This study aimed to establish a proof-of-concept protocol for generating chondrocyte cell sheets from clinical-grade human induced pluripotent stem cells (iPS cells). Methods Cartilaginous tissue was generated from human iPS cells, and isolated chondrocytes were used to fabricate iPS cell-derived chondrocyte sheets. In Phase 1, sheets were produced in high-serum medium under normoxic, hypoxic, or hypoxic/high-seeding-density conditions and compared with PDC sheets using a three-dimensional in vitro model and xenogeneic orthotopic transplantation in an immunodeficient rat model. In Phase 2, sheets were produced in low-serum medium under hypoxic/high-seeding-density conditions and evaluated for cartilage-related gene expression, secreted factors, cell surface marker expression, and in vivo cartilage repair. Results In Phase 1, hypoxic/high-seeding-density culture enhanced in vitro chondrogenic properties. However, after transplantation, iPS cell-derived chondrocyte sheets formed fibrotic repair tissue, whereas PDC sheets generated hyaline-like cartilage. In Phase 2, low-serum culture increased expression of cartilage-related genes, including collagen type II alpha 1 (COL2A1) and SRY-box transcription factor 9 (SOX9), enhanced secretion of transforming growth factor beta 1 and melanoma inhibitory activity, and upregulated CD9, CD26, CD56, CD201, CD227, and GD2. Low-serum iPS cell-derived chondrocyte sheets regenerated hyaline cartilage at 4 weeks, and the repair tissue was maintained at 12 weeks without bone formation. Conclusions A robust fabrication protocol enabled human iPS cell-derived chondrocyte sheets to regenerate hyaline-like cartilage in vivo. These findings support their potential as a scalable cell source for clinical cartilage repair.

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Stage-Aware and Explainable Machine Learning for Predicting IVF Implantation

Sharma, H.; Yemelong, K.; Carmona, A.; Naghibi Harat, Z.; Rahmani, B.

2026-10-14 obstetrics and gynecology 10.64898/2026.10.13.26365427 medRxiv
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Predicting implantation outcomes in vitro fertilization (IVF) is challenging because clinically relevant information becomes available at different points during treatment. In this study, we developed a stage-aware, leakage-conscious, and explainable machine-learning framework to predict implantation using a public IVF dataset. {beta}-HCG was excluded to avoid potential downstream target leakage. The data were divided into training, validation, and independent test sets. Several machine-learning models, including Logistic Regression, Random Forest (RF), Extra Trees, XGBoost, and Hist Gradient Boosting, were optimized using stratified cross-validation. A fixed RF model was then evaluated at three stages of the IVF process, using baseline couple characteristics, gamete and fertilization variables, and embryological variables, respectively. Model performance improved as additional treatment-related information became available, with the largest improvement observed after the inclusion of embryological variables. The final RF model showed good predictive performance on the independent test set. The number of embryos was consistently identified as the most important predictor across RF, permutation, and SHAP analyses. Overall, the findings suggest that IVF implantation prediction becomes more accurate as later-stage treatment information is incorporated, particularly information related to embryological characteristics. The proposed approach also provides interpretable predictions while reducing the risk of information leakage. Further evaluation using independent clinical datasets is needed before the framework can be considered for clinical use.

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Extracellular matrix stiffness in oral squamous cell carcinoma: a systematic review and meta-analysis of associations with tumor progression and prognosis

Lima, I. F. P.; Toebe Silva, A. C.; Engler, A. J.; Bittencourt, L. d. S.; Lamers, M. L.

2026-10-05 dentistry and oral medicine 10.64898/2026.09.28.26363990 medRxiv
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Objective: To critically evaluate the influence of extracellular matrix stiffness on tumor progression, prognosis, and clinical implications in patients with oral squamous cell carcinoma. Design: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and the protocol was registered in PROSPERO (CRD420251156429). Five databases (PubMed, Scopus, Embase, Web of Science, and OATD) were searched without restrictions on publication year or language. Human studies that evaluated extracellular matrix stiffness in oral squamous cell carcinoma, either as an assessment method or as a prognostic factor, were included; in vitro and animal studies were excluded. Results: Eight human studies involving 436 patients were included. Elastography was the most frequent measurement method, employed in four studies. Mean tumor thickness was reported in three studies and ranged from 3.0 to 4.4 mm. Extracellular matrix stiffness was expressed in various units (e.g., 37.7 gf, 23.5 kPa) and was consistently higher in tumor tissue than in normal mucosa in all studies. Three studies demonstrated a significant positive correlation between stiffness and tumor thickness. One study identified predictive cut-off values for lymph node metastasis and reported that high matrix stiffness was an independent predictor of worse overall survival (HR = 4.022; 95% CI: 1.294-12.495; p = 0.016) and recurrence-free survival (HR = 5.680; 95% CI: 1.146-28.143; p = 0.033). A meta-analysis of five studies (307 patients) showed a significantly higher standardized stiffness in oral squamous cell carcinoma compared with normal oral mucosa (standardized mean difference = 5.28; 95% CI: 2.61-7.94; p < 0.001), with substantial heterogeneity (I2= 98.6%). Conclusions: Extracellular matrix stiffness is elevated in oral squamous cell carcinoma and is associated with greater tumor thickness, lymph node metastasis and, in one study, worse survival. These findings support extracellular matrix stiffness as a potential biomechanical marker, pending further validation in standardized prospective studies.

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Prevalence and Patterns of Lumbar Spine Modic Changes Among Adult Patients with a History of Low Back Pain in the Northern Zone, Tanzania.

Lutatina, J.; Temu, R.; Magembe, P. M.; Mandari, F. N.; Majuka, L.; Mtui, D.; Mollel, J.; Olottu, F.; Uisso, F.; Kawiche, G.; Ncheye, M. S.; Massawe, H. H.

2026-09-29 orthopedics 10.64898/2026.09.24.26363960 medRxiv
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Introduction Low back pain (LBP) is a common leading cause of functional disability in adults worldwide, presenting with Modic changes that are visible within the endplates of the vertebral body under magnetic resonance imaging (MRI). Modic changes (MC) are not just a coincidental imaging finding; they reflect underlying pathology that needs treatment focus. This study aimed to ascertain the prevalence and patterns of Modic changes in the lumbar spine among adult patients with a history of low back pain attending the Kilimanjaro Christian Medical Centre (KCMC) Orthopedic clinic. Methods A descriptive cross-sectional study was conducted at the KCMC orthopedic clinic from 2nd October 2024 to 30th May 2025. Data from adult patients with a history of low back pain who had undergone lumbar spine MRI were collected, cleaned, and analyzed in SPSS (version 25). Categorical variables were summarized by frequency and proportion, while continuous variables were summarized using the mean and standard deviation. Frequency tables, histograms, and pie charts were used for results presentation. Results Of the 283 patients enrolled in the study, the mean age was (57.2 {+/-}15.7) years, with the majority (145; 51.2%) being aged > 59 years. Most patients, 203 (71.7%), were females, while 176 (62.2%) were married, and 142 (50.2%) were overweight. The prevalence of MC on the lumbar spine among patients with a history of low back pain was 66.4% (n=188). Among patients with lumbar spine MC, the majority, 112 (59.6%), were aged over 59 years, and 125 (66.5%) had lumbar spine MC type II, which was the most predominant compared to other types of MC. Conclusion Modic changes on the lumbar spine are prevalent in adult patients with low back pain, particularly those over 59 years, with type II being the most common. Healthcare professionals and policymakers should recognize Modic changes as clinically relevant findings that require consideration in the management of patients with a history of low back pain rather than dismissing them as mere incidental or coincidental observations.