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Applied Sciences

MDPI AG

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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Empowering adults to manage their hearing loss: assessing the benefits of user-controlled, smartphone-connected hearing aids.

Maidment, D. W.; Habib, A.; Gomez, R.; Benton, C.; Ferguson, M. A.

2026-09-03 otolaryngology 10.64898/2026.08.30.26361775 medRxiv
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The availability of hearing aids that can connect wirelessly to smartphone technologies via Bluetooth has grown exponentially in recent years. However, there is limited evidence assessing the benefits of user-adjustability afforded by these devices. This study aimed to assess the benefits of smartphone-connected hearing aids and an accompanying application (or app) in new and existing hearing aid users. In this single-centre, prospective, observational study, 44 adult hearing aid users (14 new and 30 existing) were recruited. Participants were fitted bilaterally with smartphone-connected hearing aids that could be adjusted by the user via an app. Self-reported outcome measures were collected at fitting and after seven-weeks of using the device in everyday life. For both new and existing hearing aid users, significant improvements in social participation, hearing-related fatigue, and hearing aid benefit and satisfaction were found. For existing hearing aid users, all outcomes were significantly better for the smartphone-connected hearing aids plus app in comparison to their existing hearing aids that did not connect to a smartphone, all with moderate-to-large clinical effect sizes (d> .6). User-controllability via the app was identified as the key benefit, and most participants (68%) reported that the app met their needs 'extremely' or 'very well'. These results suggest that, when used in conjunction with an app, smartphone-connected hearing aids can improve hearing outcomes due to greater user-controllability to improve listening. Thus, smartphone-connected hearing aids have the potential to facilitate patient-centred care, empowering the individual to successfully manage their hearing loss.

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A Longitudinal Study of Real-World Physical Activity Assessed Using Cut-point Free Metrics, Mobility Capacity, and Mobility Perception Among Older Adults Recovering from Proximal Femoral Fracture

Younesian, H.; Singleton, D.; Vereijken, B.; Garcia-Aymerich, J.; Rochester, L.; Berge, M. A.; Engdal, M.; Buekers, J.; Koch, S.; Helbostad, J. L.; Alvarez, P.; Jansen, C.-P.; Klenk, J.; Aminian, K.; Paraschiv-Ionescu, A.; Becker, C.; Caulfield, B.

2026-08-10 public and global health 10.64898/2026.08.07.26359957 medRxiv
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Physical activity (PA) is measured objectively through daily wearable monitoring and mobility capacity tests, and subjectively via patient reported outcomes (mobility perception). This study investigated longitudinal changes in, and relationships between, different measures of PA among older adults recovering from proximal femoral fracture (PFF). Participants (N=201) were classified into four groups by time since surgery at baseline (T1) and followed over two assessments (T2, T3). They wore an accelerometer for 7 consecutive days. Daily PA was measured using cut-point free metrics including Average Acceleration, Intensity Gradient, and intensity of the most active accumulated X minutes (MX: M1-M90). Mobility capacity and perception of participants were evaluated using clinical tests (e.g., 6-minute Walking Test (6MinWT)) and questionnaires (Late-Life Function and Disability Instrument (LLFDI)). MX metrics, particularly M1-M15, increased significantly across the first three groups with higher sensitivity in group 1 (p<0.001). Distance covered during the 6MinWT increased significantly (p<0.01). Three of the seven LLFDI s domains showed the largest significant changes. Overall, sustained, moderate-strong positive correlations were observed between the clinical tests, LLFDI, and short-duration MX metrics in group 3 and 4 at T1, and across all participants at T2 and T3. Thus, MX metrics (M1-M15) can reveal change for daily PA intensities, especially among PFF groups in early recovery groups at T1 and reached the late stage at follow-ups. Clinicians may focus on specific LLFDI s domains to maximize assessment efficiency. The direct links between mobility capacity, perceived mobility, and short-duration MX metrics indicate the potential of these metrics to monitor patients remotely.

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An Open Demonstrator for an Interoperable Clinical Decision Support System for the Detection of Systemic Inflammation and Sepsis in Pediatric Intensive Care

Schack, M.; Rathert, H.; Boehnke, J.; Ruebsamen, N.; Bode, L.; Karch, A.; Almekkawi, M. K.; Marschollek, M.; Beerbaum, P.; Wulff, A.; Jack, T.

2026-08-06 intensive care and critical care medicine 10.64898/2026.08.04.26359683 medRxiv
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Background: Sepsis is a life-threatening condition triggered by infection and associated with dysregulated immune response of the patient followed often by multiorgan dysfunction or failure. In the clinical evolution of sepsis towards organ dysfunction, early initiation of a suited therapy significantly increases patient outcomes and reduces mortality rates. Since electronic health records provide data in a machine-readable format, this process could be supported by computerized systems. Methods: We developed an interoperable, time-sensitive CDSS that able to detect systemic inflammation and the different classifications of sepsis (bacterial/viral, suspected/proven, on admission/PICU acquired) in pediatric patients based on the analysis of routine clinical data. This application is provided as part of this publication as an open demonstrator (web application), and the usability and accuracy of the CDSS is shown by a retrospective creation of sepsis outcome labels for a routine data set of 4,655 pediatric patients. As a reference standard, the patients were manually assessed by blinded clinical experts. Results: In comparison with the reference standard, the CDSS achieved sensitivity of 96.9% (95% CI: 80.9-99.6%) and specificity of 99.1% (95% CI: 95.1-99.8%). In the context of a sepsis outcome labeling for 4,655 patients, the CDSS detected 4,342 episodes of inflammation of which 1,723 were classified as sepsis. Conclusions: We demonstrated that our routine-data based CDSS is able to perform a complex sepsis detection process with high diagnostic accuracy. Such CDSS with the ability to differentiate between SIRS, sepsis on admission, suspected and proven sepsis can prospectively support clinical management, monitoring and quality management.

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Sleep Quality and Its Association with Life Satisfaction Among Employees in the United Arab Emirates: A Cross-Sectional Study

Ali, S. I.; Varatharajan, V.; Chacko, S. T.; Hazari, A.; Varghese, S. M.

2026-08-31 public and global health 10.64898/2026.08.28.26361603 medRxiv
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Objectives This study aimed to assess sleep patterns and life satisfaction among employees of a private company in Dubai, United Arab Emirates, and to examine the relationships among sleep quality, life satisfaction, and selected demographic variables. A quantitative descriptive cross-sectional survey design was adopted. Methods A convenience sample of 110 male employees participated in the study. Data were collected using the Sleep Disorder Assessment Scale (16 items; Cronbachs = 0.89) and the Life Satisfaction Scale (5 items). Statistical analysis was performed using SPSS version 29, including descriptive statistics, chi-square tests, and Pearson correlation analysis. Results Most participants (66.4%) were aged 20-30 years, and 82.7% experienced moderate sleep-related problems. Mobile phone use before bedtime was common, with 60.9% reporting occasional use and 35.5% reporting regular use. Overall, 41.8% reported neutral life satisfaction, while 25.5% and 24.6% were slightly and extremely satisfied, respectively. A significant negative correlation was found between poor sleep patterns and life satisfaction (r = -0.389, p < 0.001). Mobile phone use before bedtime and shift work were significantly associated with sleep patterns (p = 0.048). Conclusion Poor sleep quality, particularly among shift workers and frequent bedtime mobile phone users, is associated with lower life satisfaction. Workplace interventions promoting sleep hygiene may enhance employee well-being.

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Construction of a Standardized Time-Lapse Imaging Database and a Gradient Boosting Ensemble Framework for Integrating Zygote Morphokinetic Parameters with Conventional Embryo Assessment

ZHAO, M.; LIU, J.; HAN, D.; ZHANG, C.; ZHOU, Y.; CHEN, S.; LIU, C.

2026-08-24 obstetrics and gynecology 10.64898/2026.08.20.26359523 medRxiv
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In vitro fertilization (IVF) laboratories equipped with timelapse incubators generate vast quantities of sequential embryo images, yet the absence of standardized, annotated databases impedes the development of reproducible computational tools for embryo assessment. Here we describe the construction of a standardized time-lapse imaging database comprising 631 normally fertilized zygotes from 218 treatment cycles, integrating timelapse image sequences, patient clinical records, and embryo developmental outcomes. We further present a gradient boosting decision tree (GBDT) ensemble framework that integrates zygote morphokinetic parameters-continuous time-series features extracted via a validated CNN-based segmentation algorithm (US Patent US11210494B2)-with conventional embryo assessment grades (categorical features per the Istanbul consensus). The fusion framework employs equal-weight initialization followed by iterative residual-decreasing training to optimally combine heterogeneous feature types. Ablation analysis demonstrated that the integrated model achieved an AUC of 0.78, significantly outperforming morphokinetics-only (AUC 0.71) and conventional-only (AUC 0.65) models, confirming the complementary value of the two data modalities. The database and fusion framework provide a reproducible foundation for embryo development assessment and are generalizable to other multimodal data integration tasks in reproductive medicine.

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Absolute measures of time-difference-of-arrival positioning error in underwater acoustic telemetry setups

Campbell, J. A.; Lundberg, P.; Hölker, F.

2026-08-25 ecology 10.64898/2026.08.24.746702 medRxiv
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This brief communication presents two solutions for calculating absolute measures of error from time-difference-of-arrival (TDOA) positioning in underwater acoustic telemetry arrays. First, a Monte Carlo estimation of TDOA positioning error is derived. Next, a computationally inexpensive, approximate solution to the Monte Carlo method is presented. This approximate solution is achieved by solving the Jacobian of a closed-form TDOA positioning model. The positioning error covariance matrix returned from either method can then be used to report the accuracy of TDOA positions or utilized in state-space positioning models. Finally, calculations of the expected radial error are shown which serves as a simple summary statistic for reporting positioning error in real units.

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The Role of Bone Marrow Microenvironment in Osteogenesis Imperfecta: Evidence from Single-Cell RNA Sequencing

Wu, Z.; den Haan, S. L.; Nijhuis, W. H.; Janda, C. Y.; Margaritis, T.; Weinans, H.; Sakkers, R. J. B.; Spaans, A. J.; Warmink, K.

2026-08-24 orthopedics 10.64898/2026.08.21.26361022 medRxiv
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INTRODUCTION: Osteogenesis imperfecta (OI) is a genetic disorder primarily due to mutations in collagen type I-encoding genes, resulting in fragile bones, frequent fractures, pain, and mobility issues. Disease severity and phenotype vary widely, even with the same mutation, suggesting the importance of other factors within the bone microenvironment that influence disease severity. To study the role of such factors, we analyzed bone samples from OI patients and healthy controls using single-cell RNA sequencing to reveal if RNA expression profiles may uncover mechanisms behind OI phenotype. METHODS: Bone samples from surgeries of OI patients and healthy individuals isolated and RNA single-cell sequencing was performed, followed by quality control and bioinformatics analysis. Two healthy and three OI patients were included: two with type-I OI, characterized by a mutation in COL1A1 (collagen type I), and another with type-VIII OI, associated with LEPRE1 mutations, which disrupt the 3-hydroxylation of type I collagen. RESULTS: Clustering and differential expression analysis showed distinct subpopulations in mesenchymal and immune cells. In all OI samples, mesenchymal stromal cell (MSC) proportions were reduced compared to healthy controls. OI type-I patients showed decreased osteoblast numbers alongside an increase in osteoclast precursor cells. Whereas in OI type-VIII, all bone turnover-related cells (osteoblast, osteoclast precursor, and osteoclast) were elevated. Notably, BMP5 and RUNX1 were downregulated in MSCs from both OI types. DISCUSSION: This study demonstrates that the bone marrow microenvironment in OI is significantly altered beyond the known collagen defects. Single-cell RNA sequencing revealed reduced MSC numbers and downregulated osteogenic gene expression. Furthermore, alterations are patient-specific: OI type-I is characterized by reduced osteoblast counts, whereas OI type-VIII exhibits increased osteoblasts and osteoclasts. These findings highlight the critical role of impaired osteogenic differentiation and an abnormal bone remodeling environment in the pathology of OI.

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Effect of cyclic daytime versus continuous enteral nutrition on circadian rhythms in critical illness: a randomized controlled trial

Hiemstra, F. W.; van Gent, M. F.; Meijer, J. H.; Dashti, H. S.; de Jonge, E.; van Westerloo, D. J.; Kervezee, L.

2026-08-27 intensive care and critical care medicine 10.64898/2026.08.24.26361187 medRxiv
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Objective: Circadian rhythms are frequently disrupted in patients in the intensive care unit (ICU), potentially worsening clinical outcomes. Continuous enteral nutrition throughout the day and night is common in the ICU, but eliminates feeding-fasting cycles that serve as important timing cues for the circadian system. The objective of this study was to determine the effect of providing enteral nutrition in a cyclic daytime pattern, compared with continuous administration, on circadian rhythmicity in critically ill patients in the ICU. Design: Single-center randomized controlled trial Setting: Mixed medical-surgical tertiary intensive care unit in the Netherlands Patients: Adult ICU patients ([&ge;]18 yr) receiving enteral nutrition. Intervention: Patients were randomized to receive either continuous, or cyclic daytime enteral feeding (08:00-20:00), initiated from the start of nutritional support. Measurements and Main Results: Sixty-two ICU patients were enrolled, of whom 51 were included in the per-protocol analysis. While the amplitude of the 24-hour rhythm in core body temperature did not differ significantly between the cyclic daytime and continuous feeding groups (0.17 [interquartile range: 0.09-0.24] vs. 0.20 [0.13-0.30], p=0.182), the 24-hour rhythm in heart rate was enhanced in patients receiving cyclic daytime feeding, as reflected by significantly higher amplitudes and more synchronized peak times. No significant differences in 24-hour rhythmicity were observed between groups for the other vital signs or melatonin. Conclusions: Our findings suggest that cyclic daytime feeding may strengthen circadian rhythms in critically ill patients. Further studies are warranted to evaluate its impact on clinical outcomes.

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Time-Resolved Phenotypic and Transcriptomic Responses of Primary Canine Dermal Fibroblasts to Prolonged Hypothermic Stress

Wang, Y.; Shen, E.; Huang, A.; Lu, E.; Liu, Y.; Huang, J.; Yu, B.; Dai, Q.

2026-08-19 cell biology 10.64898/2026.08.14.744362 medRxiv
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Prolonged low-temperature exposure may extend the preservation window of mammalian cells but can also disrupt cellular homeostasis and ultimately compromise cell viability. This study investigated the time-dependent phenotypic and transcriptomic responses of primary canine dermal fibroblasts to sustained hypothermic stress. Passage-three fibroblasts were continuously maintained at 15 for up to 15 days, with samples collected on Days 0, 3, 6, 9, 12, and 15. Cellular morphology, metabolic activity and viability, and apoptosis were evaluated using bright-field microscopy, Cell Counting Kit-8 assays, and Annexin V-FITC/propidium iodide flow cytometry, respectively. RNA sequencing was performed to characterize dynamic transcriptional changes throughout the exposure period. Early low-temperature exposure was associated with relatively preserved cellular morphology and viability, suggesting a transient adaptive response. With increasing exposure duration, fibroblasts exhibited progressive morphological deterioration, reduced metabolic activity, loss of adhesion, and increased apoptosis. Time-series transcriptomic analysis further revealed temporally coordinated and stage-dependent gene-expression programs associated with metabolic regulation, cellular stress responses, structural homeostasis, and cell survival. Integration of phenotypic and transcriptomic data demonstrated that the response of primary canine dermal fibroblasts to 15 was dynamic rather than linear, progressing from early adaptation to cumulative dysfunction during prolonged exposure. These findings provide a framework for defining the low-temperature tolerance of primary canine dermal fibroblasts and may inform the optimization of protocols for their short- to medium-term preservation and transportation.

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Effectiveness of Osteopathic Manipulative Treatment for Structural Musculoskeletal Pain: A Meta-Analysis of Randomized Controlled Trials.

Hsiao, A. L.; Schimmel, G. C.; Kale, R. U.; Dimanlig, M. G.; Ortegosa da Cunha, M.; Myers, N. E.

2026-08-19 orthopedics 10.64898/2026.08.12.26359899 medRxiv
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Structural musculoskeletal pain, defined as pain associated with musculoskeletal conditions of the spine and peripheral joints, afflicts persons widely, independent of demographic, and continues to contribute substantially to disability on a global scale. Osteopathic manipulative treatment (OMT) is a non-invasive therapy performed by osteopathic physicians, encompassing a wide variety of techniques meant to heal the dysfunctions manifesting structural musculoskeletal pain. However, the efficacy of OMT in relieving pain symptomatology remains subject to debate. This meta-analysis examines the effect OMT serves to manage structural musculoskeletal pain, measured on a Visual Analog Scale. Three randomized control studies (RCTs) were included, with a total of 231 participants, 117 of which received OMT as part of pain management treatment, the other 114 receiving other treatment modalities. Using the random effects model, the mean difference between OMT and non-OMT treated groups was -1.80 (-7.31; 3.78). Although this mean difference favors OMT with regard to greater reduction in pain, the finding is not statistically significant. Heterogeneity was found to be extraordinarily high (I2 = 96%) and statistically significant (p = <0.0001), albeit attributed to one of the papers, deemed an outlier. With its removal, heterogeneity was still moderate (I2 = 54.4%). Given these findings, the efficacy of OMT in reducing structural musculoskeletal pain cannot be proven. A significant limitation of this study was a low sample size, consisting of 3 RCTs, reducing statistical power. In addition, there was high heterogeneity between studies. More high-quality RCTs with larger sample sizes, standardized methods, and an examination of a broader set of structural musculoskeletal conditions are necessitated to better evaluate the contribution of OMT in pain reduction. Key Words: Pain Management, Osteopathic Manipulative Medicine, Osteopathic Manipulative Treatment, Structural Pain, Orthopaedics, Knee Arthritis, Shoulder Pain, Cervical Spondylosis

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Morphological and phenotypic characterization of adipose-derived mesenchymal stem cells isolated from locally adapted Indonesian goat breed

Budipitojo, T.; Padeta, I.; Purwaningrum, M.; Budiariati, V.; Pirarat, N.

2026-08-24 cell biology 10.64898/2026.08.23.746531 medRxiv
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Adipose-derived mesenchymal stem cells (gAD-MSCs) are promising candidates for veterinary regenerative medicine, yet the characterization of gAD-MSCs from locally adapted Indonesian goat breeds remains limited. This study aimed to isolate and characterize gAD-MSCs from Peranakan Ettawa (PE) goats using tissue explant culture. Subcutaneous adipose tissue was collected from the base of the tail of healthy PE goats (n=3). Primary cell outgrowth from explants was observed by Day 5, displaying characteristic fibroblast-like, spindle-shaped morphology and strong plastic adherence. Serial passaging to Passage 3 (P3) yielded a morphologically stable, homogeneous cell population. Assessment of cellular metabolic activity via the resazurin assay demonstrated sustained cell viability and a statistically significant increase in metabolic activity between Day 3 and Day 5 (p < 0.05). Furthermore, functional clonogenic capacity, evaluated using the colony-forming unit (CFU) assay, showed continuous temporal expansion of colonies over 14 days, yielding an average of 52.0 + - 4.1 colonies per dish. These findings confirm that expanded gAD-MSCs P3from PE goats maintain characteristic mesenchymal morphology, sustained metabolic activity, and clonogenic capacity. This work provides a baseline cellular profile of PE goat gAD-MSCs, supporting their potential use in veterinary regenerative medicine and tissue engineering.

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Sub-Analysis of a Randomized Controlled Trial of Neuromuscular Electrostimulation of the Common Peroneal Nerve after Forefoot Surgery

Piftor, A.-M.; Bain, D. S.; Day, K.

2026-08-24 orthopedics 10.64898/2026.08.21.26361007 medRxiv
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Gaps remain in the evidence base for postoperative management following forefoot surgery. A recent randomized controlled trial (ClinicalTrials.gov NCT04927234) demonstrated improved outcomes with intermittent one Hertz (Hz) neuromuscular electrical stimulation (NMES) of the common peroneal nerve. This sub-analysis evaluates its effect in patients undergoing forefoot surgery. Forty-two patients undergoing forefoot procedures were included; 26 received NMES plus standard of care (SOC) and 16 received SOC alone. Wound healing was assessed at 14 days. Edema was measured using the figure-of-eight (FO8) method. Patient-reported outcomes were assessed using the Manchester-Oxford Foot Questionnaire (MOXFQ). At 14 days, complete wound healing occurred in 77% of patients receiving NMES plus SOC compared with 40% in the SOC group (p<0.05). Edema reduction was significantly greater in the NMES group, with a 74% relative reduction compared with SOC (p=0.02). Intermittent one Hz NMES of the common peroneal nerve was associated with improved wound healing and reduced postoperative edema following forefoot surgery.

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Association between thyroid function and thyroid homeostasis parameters and female urinary incontinence: A population-based study

deng, k.; zhang, j.; yang, q.; huang, j.; yang, h.; li, r.; Tevorn, K.

2026-08-06 obstetrics and gynecology 10.64898/2026.08.04.26359698 medRxiv
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Background: Female urinary incontinence (UI) is a prevalent disorder associated with pelvic floor dysfunction. The abnormalities in neuromuscular function that cause the clinical symptoms of UI are rarely thought to be related to metabolic function, and may be especially related to thyroid hormone levels. Objective: To examine the connection among thyroid function, thyroid homeostasis parameters, and UI, along with its various subtypes in females. Methods: A total of 3,443 adult females who participated in the National Health and Nutrition Examination Survey from 2007 to 2012 were included. Further classification of the UI group was made into urge urinary incontinence (UUI), stress urinary incontinence (SUI), and mixed urinary incontinence (MUI). Thyroid homeostasis parameters, such as thyroid feedback quantile index (TFQI), were calculated from thyroid hormones to reflect thyroid hormone sensitivity. To examine the associations among thyroid function, thyroid homeostasis parameters and UI, we utilized weighted multivariate logistic regression and restricted cubic splines in the analysis. Results: Thyroid stimulating hormone was significantly negatively correlated with UI (OR = 0.97, 95% CI: 0.96-0.99, p = 0.006), while TFQIFT3 showed a U-shaped association with UI (p for nonlinear = 0.014). In the analysis of subtypes, the FT3/FT4 ratio showed a negative correlation with UUI and MUI, evidenced by a J-shaped relationship, with change points identified at 0.301(p for all = 0.033, p for nonlinear =0.031; p for all = 0.010, p for nonlinear =0.005). Subgroup analysis showed consistent associations, and there was an interaction between BMI and FT3/FT4 ratio and UUI (p for interaction < 0.05). Conclusions: The FT3/FT4 ratio may serve as a promising biomarker for assessing the risk of UUI and MUI. The associations among thyroid dysfunction, thyroid homeostasis, and UI in women suggest varying patterns across different UI subtypes.

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Extracellular matrix particle treatment induces digit regeneration in soft-tissue preserved amputation (SPA) model of adult mice

Liu, Y.; Li, B.; Bao, C.; Zeng, L.; Wang, Z.; Sun, X.; Sun, G.

2026-08-06 cell biology 10.64898/2026.08.05.742898 medRxiv
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BackgroundIn mouse classic amputation model, second phalanx (P2) is incapable of regeneration. Extracellular matrix (ECM) solution has shown limited ability to induce digit regeneration in classical amputation model of the murine digit. However, the effect of solid ECM particles on bone regeneration is not well understood due to difficulties in treating solid particles in classical amputation model. MethodsWe examined the regenerative effects of ECM particles in mice digit by establishing a soft tissue preserved amputation (SPA) model on P2, through removing the amputated bone whilst preserving soft tissue. ECM particles implanted into the amputation site and wrapped in the preserved soft tissues. Bone regeneration was assessed by morphological examination and micro-CT scans. ResultsWe observed bone regeneration in the SPA model; specifically, new bone formed at the P2 distal end. Implantation of ECM particles exerted a pro-regenerative effect, characterized by increased bone volume and decreased bone density. Moreover, the ECM induced the formation of free-floating bone, further supporting its role in bone regeneration. Combined treatment with ECM particles and bone morphogenetic protein 2 (BMP2) resulted in a significant increase in bone volume. ConclusionsWe demonstrate that soft tissue preservation at the amputation site can overcome the intrinsic regenerative limitationsl. Using SPA model, we found that ECM particles have a proven ability to promote bone regeneration, and that the combination of ECM particles with BMP2 further enhances bone regeneration. These findings underscore the therapeutic promise of ECM-based strategies, for clinical translation in non-regenerative finger injuries. Summary statementSolid-state Extracellular matrix can induce mice digit regeneration and has the potential for clinical application. HighlightsThe SPA model we developed enables ECM particles to adhere to wounds, and our research has found that: O_LIDigit bone regeneration was shown in SPA model . C_LIO_LIECM particles treatment promoted bone regeneration and can generate free-floating bone in SPA model. C_LIO_LICombination of ECM + BMP2 treatment induced strong digit regeneration in SPA model. C_LI

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Inflammation Beyond the Disc: Circulating Inflammatory Biomarkers in Lumbar Disc Herniation and Degeneration--A Case-Control Study

Withanage, N. D.; Perera, S.; Athiththan, L.

2026-08-31 orthopedics 10.64898/2026.08.28.26361607 medRxiv
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Background: Lumbar disc herniation, with or without concomitant disc degeneration, is a major cause of lumbar radiculopathy and low back pain, which also a key public musculoskeletal disorder without an exact pathophysiology. Studies have suggested that inflammatory cells and biochemical markers of inflammation also play an important role in lumbar radiculopathy in addition to nerve compression. The aim of the present study was to assess the association of selected circulatory inflammatory markers (CRP, hs-CRP and E-selectin) in patients with lumbar disc herniation without radiological degeneration (LDH) and lumbar disc herniation with radiological degeneration (LDHD). Materials & methods: This case-control study included 208 participants, comprising 104 patients with lumbar disc pathology and 104 controls. Patients were further stratified into LDH (n=67) and LDHD (n=37). Serum CRP, hs-CRP and E-selectin concentrations were measured. Results: Among the patients, 35.6 % presented with LDHD while 64.4 % had only LDH. Significantly increased median hs-CRP (p<0.001) and CRP (p<0.001) were observed in patients groups compared to controls, while CRP showing a consistent independent association across the combined disease (OR=1.68, 95% CI=1.33-2.14, p<0.001), LDHD (OR=1.62, 95% CI=1.16-2.20, p=0.005) and LDH (OR=1.69, 95% CI=1.30-2.20, p<0.001) multivariable models. No significant difference was observed in serum E-selectin between the study groups. Multivariable models incorporating inflammatory and clinical variables demonstrated substantially greater discriminatory performance than individual biomarkers alone. Conclusion: Elevated circulating CRP and hs-CRP concentrations were associated with lumbar disc pathology, with CRP showing a consistent independent association across the combined disease, LDH and LDHD multivariable models, whereas E-selectin showed no significant association. Multivariable models incorporating inflammatory and clinical variables demonstrated greater discriminatory performance than individual biomarkers. These findings support a potential systemic inflammatory component in lumbar disc pathology, although the cross-sectional nature of the measurements does not establish causality or a local inflammatory response within the disc.

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An interpretable, formally verified point-of-care ultrasound risk equation for difficult videolaryngoscopy: development and internal validation

Oyarzun-Silva, R. A.; Hernandez-Hernandez, P.; Fernandez-Vaquero, M. A.; De Luis-Cabezon, N.

2026-09-02 anesthesia 10.64898/2026.08.28.26361621 medRxiv
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Background. Videolaryngoscopy still requires adjuncts or hyperangulated rescue in a clinically important minority, and bedside screening discriminates modestly. Point-of-care ultrasound (POCUS) of the anterior airway is a promising alternative, but existing prediction models are opaque or assume a pre-specified functional form. We developed and internally validated a parsimonious, fully disclosed POCUS risk equation whose form is recovered from data and whose structural properties are machine-checked by formal proof - to our knowledge the first formally verified clinical risk predictor - following TRIPOD+AI 2024. Methods. In a prospective single-centre, single-operator cohort of 259 adults undergoing elective videolaryngoscopy (no-Easy airway 68/259, 26.3%), Sequentially Thresholded Least Squares with bootstrap stability selection (B=300) screened a 71-term library of nine POCUS features and retained a seven-term logistic equation; a two-term bootstrap-stable model was pre-specified as robustness analysis. Internal validation used 5x10 repeated cross-validation plus temporal and device hold-outs, with pre-specified overfitting and optimism assessments. Five behavioural properties of the deployed equation were machine-checked in Lean 4. Results. Two interactions met the |c|/sigma_c>2 stability criterion: skin-to-epiglottis x skin-to-hyoid-bone distance and tongue volume x sagittal tongue area. The seven-term equation reached a 5x10 cross-validated C-statistic of 0.966 (optimism-corrected 0.968) and held across temporal and device hold-outs (0.94-0.97). Calibration-in-the-large matched prevalence, with cross-validated slope 0.90 attenuating to 0.625 out-of-time; standard recalibration restored 0.92 without loss of discrimination. The pre-specified two-term robustness model reproduced this performance (C-statistic 0.964-0.968; events-per-parameter 34; shrinkage 0.99), confirming the result is not an artefact of the screening stage. Net benefit over a clinical baseline was positive across 10-50% thresholds. All five Lean 4 theorems compiled without sorry. Conclusions. A sparse, formally verified POCUS equation predicts difficult videolaryngoscopy with high internally validated discrimination and quantified, modest overfitting. Because the equation was developed in a single-operator cohort and its inputs are operator-dependent, external validation requires prior harmonisation of the measurement protocol and operator credentialing.

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Identifying patients with a phenotype consistent with chronic postsurgical pain after hip and knee arthroplasty using robust, scalable k-medoids clustering analysis

Gillam, L.; Doleman, B.; Knaggs, R.; Williams, J.

2026-08-12 orthopedics 10.64898/2026.08.11.26360161 medRxiv
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Background Chronic postsurgical pain (CPSP) affects between 7-23% and 13-44% of patients after hip and knee arthroplasty, respectively. Standardised methods of pain assessment provide superior evaluation of pain, including the Oxford Joint Score Pain Subscale (OJS-PS). We aim to estimate the proportion of patients with a phenotype consistent with CPSP through a k-medoids clustering technique and identify a threshold on the OJS-PS to highlight such patients at a population level. Methods In this cross-sectional study Patient Reported Outcomes Measures data 6-months after hip and knee arthroplasty from 2017 to 2025 were examined. An adapted k-medoid clustering technique utilising subsampling, batch assignment and probabilistic consensus allocated clusters. A receiver operator characteristic analysis identified a threshold on the OJS-PS noting the lowest scoring cluster. Our categorisation was compared to self-reported severe or moderate pain; sensitivity, specificity and accuracy of this categorisation were calculated. Results We analysed 109,542 hip and 113,799 knee arthroplasty patients; three clusters were used in each analysis. After hip arthroplasty: 14.4% of patients were assigned to the cluster with the lowest median OJS-PS of 11 [IQR 8 - 13]. A threshold of 15.5 classified patients as severe or moderate pain with 60.6% sensitivity, 91.0% specificity and 85.7% accuracy. Similarly, after knee arthroplasty, 25.3% were assigned to the cluster with the lowest median OJS-PS of 14 [IQR 11 - 16]. A threshold of 18.5 on the OJS-PS had an 85.4% sensitivity, 88.4% specificity and 87.8% accuracy for classifying patients with self-reported severe or moderate pain. Conclusions This robust and scalable clustering technique on ordinal clinical data estimates the proportion of patients reporting a phenotype consistent with CPSP. On a population level the thresholds identified on the OJS-PS could aid screening for potential CPSP patients 6 months after hip and knee arthroplasties.

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Optimising scan body enhances accuracy of full-arch implant scan using a smartphone video with deep learning model: An in vitro study

Lu, Y.; Yu, J.; Liu, F.; Joda, T.; Li, J.

2026-08-12 dentistry and oral medicine 10.64898/2026.08.10.26360076 medRxiv
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Objective. A deep learning (DL) model was used to convert smartphone videos of a complete arch implant cast into 3D scans. The aim of current study was to determine if a custom scan body (SB) with geometric features and coating would outperform regular PEEK stock SB in this DL scenario. The DL-derived scan outcomes were compared with those obtained from a conventional splinted open-tray impression and from photogrammetry. Materials and Methods. A maxillary edentulous model with six implants and multi-unit abutment analogs was scanned using four protocols: conventional splinted open-tray impression (CO), photogrammetry (PG; Icam4D), DL using stock SBs (DLS) and DL using custom SBs (DLC). Each protocol was repeated for 10 times. The DL scans were produced from smartphone videos with a high-fidelity, multi-view 3D construction AI model (Neuralangelo). The custom designed SB incorporated geometric features and was fabricated via 3D printing followed by a spray coating. Accuracy (trueness and precision) was assessed using three measurements: Root Mean Square (RMS), linear deviation, and angular deviation. Results. DLC outperformed DLS in both trueness and precision regarding RMS and linear measurements (p<0.001). CO and PG demonstrated the highest RMS and linear trueness, with no significant difference between them (RMS: p=0.93; linear: p=0.663). PG achieved the best precision across RMS, linear and angular measurements. Conclusion. The optimised SB significantly improves the accuracy of DL-based approach for full-arch implant scan comparing to regular PEEK stock scan bodies. While early stage, neural surface reconstruction has potential as a viable option for full-arch implant rehabilitation.

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Diagnostic Accuracy of Dynamic Supine-to-Sitting Radiography for Acute Osteoporotic Vertebral Fractures. A Preliminary Single-Center Diagnostic Accuracy Study

Kimura, R.; Yamamoto, N.; Doi, K.

2026-08-10 orthopedics 10.64898/2026.08.06.26359902 medRxiv
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Background: Acute osteoporotic vertebral fractures (OVFs) may be difficult to detect on conventional radiographs, particularly before substantial vertebral collapse occurs. Comparing supine and sitting lateral radiographs may reveal load-dependent vertebral mobility. This preliminary study evaluated the diagnostic accuracy of supine to sitting dynamic radiography for detecting MRI confirmed acute OVFs. Methods: This retrospective, single center diagnostic accuracy study included consecutive patients who underwent paired supine and sitting lateral radiography and MRI of the same spinal region between April 2024 and July 2026. Dynamic radiographs were interpreted by a board certified orthopedic and spine surgeon who was blinded to the MRI findings. MRI was independently interpreted by a second board certified orthopedic surgeon and served as the reference standard. The primary outcome was patient-level sensitivity and specificity. Vertebra level diagnostic accuracy was evaluated secondarily, with patient cluster bootstrap confidence intervals used to account for within patient correlation. Results: Sixty three patients (mean age, 80.6 years; 51 women [81.0%]) and 490 evaluable vertebrae were analyzed. MRI identified acute OVFs in 34 patients and 36 vertebrae. At the patient level, dynamic radiography yielded 31 true positive, no false-positive, three false negative, and 29 true negative results. Sensitivity was 91.2% (95% confidence interval [CI], 76.3%-98.1%), specificity was 100.0% (95% CI, 88.1%-100.0%), positive predictive value was 100.0%, negative predictive value was 90.6%, and overall accuracy was 95.2%. At the vertebral level, sensitivity was 91.7% (33/36; patient cluster bootstrap 95% CI, 81.3%-100.0%) and specificity was 100.0% (454/454). The three missed fractures involved T9, L2, and L3. No false-positive vertebrae were observed. Conclusions: Supine to sitting dynamic radiography demonstrated high patient level sensitivity and no observed false positive findings for MRI confirmed acute OVFs. It may provide a practical complementary diagnostic option when MRI is not immediately available. However, a negative dynamic radiographic examination does not exclude an acute fracture, and the apparent perfect specificity requires validation in larger, prospective multi-reader studies.

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Protocol for: mixed methods study on diversity of children with cochlear implants and their families engaging with the BEARS (Both Ears) virtual reality training games: improving clinical trial diversity and scale-up inclusiveness

Cullington, H. E.; Driver, S.; Nightingale, R.; Somerset, S.; Corbett, F.; Jepson, M.; Conefrey, C.; Chauhan, T.; Vickers, D.

2026-08-06 otolaryngology 10.64898/2026.08.04.26359667 medRxiv
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Introduction We are currently working on the BEARS (Both Ears) virtual reality (VR) Randomised Controlled Trial. We are recruiting 272 deaf children and young people who use bilateral (both ears) cochlear implants (CI) to examine if using the BEARS VR games helps their hearing in background noise and ultimately their quality of life. Clinical trial participants should be representative of the population with the health condition, although this is rarely achieved in practice as people from ethnic minorities or those from more deprived areas may face barriers to participation. Study Design Mixed methods design Objectives Use a literature review and collection of data from cochlear implant centres to establish the sociodemographic characteristics of deaf children aged 8 to 16 years with bilateral cochlear implants in the United Kingdom (UK). a. Establish the sociodemographic characteristics of the families recruited to the BEARS clinical trial in the first six months, and compare with the age-matched population of deaf children with bilateral cochlear implants in the UK. b. Analyse the BEARS clinical trial pre-screening diversity data. c. Implement an established recruitment intervention method in a workshop to explore and optimise recruitment number and diversity. d. Compare the final six months of recruitment data diversity with the initial six months. Use interviews and focus groups to collect qualitative data from children and their families who chose not to take part in BEARS, clinicians, and family representatives (e.g. teachers) to explore barriers and facilitators to families taking part in BEARS. Amend the BEARS scale-up plan based on new learning. Methods Literature and scoping reviews, quantitative analysis of BEARS recruitment data, in-depth interviews, paired interviews, focus groups Sample size Qualitative sample: 10-15 children aged 8-16 with bilateral CI, 10-15 parents/carers of children with bilateral CI, 10-12 clinicians and 10-12 family representatives. Significance This work will evaluate how diverse the BEARS clinical trial recruitment is and whether it is representative of the UK population of children with bilateral cochlear implants. We will investigate recruitment barriers and implement measures to try to improve recruitment diversity.