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Translational Vision Science & Technology

● Association for Research in Vision and Ophthalmology (ARVO)

Preprints posted in the last 7 days, ranked by how well they match Translational Vision Science & Technology's content profile, based on 39 papers previously published here. The average preprint has a 0.05% match score for this journal, so anything above that is already an above-average fit.

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Beyond the Index: Association of AI-CO Central Image Area with Central Visual Field Damage in Glaucoma

KORA, Y.; Kora, H.; Kora, T.

2026-10-21 ophthalmology 10.64898/2026.10.18.26365818 medRxiv
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Purpose: To evaluate the associations of the numerical AI-CO center index and visually classified central dark-area extent with Humphrey 10-2 mean deviation (MD). Methods: This single-center retrospective study included 320 eyes of 169 patients with AI-CO imaging, broad-field 24-2F or 30-2 testing, and 10-2 testing. Both visual field examinations were performed within 365 days before or after AI-CO imaging. Two ophthalmologists independently classified central dark-area extent into five Levels (0-4). Analyses assessed Spearman correlations, areas under the receiver operating characteristic curve (AUCs), distributions across final central dark-area Levels, and interrater reliability. Patient-cluster bootstrap confidence intervals and a one-eye-per-patient sensitivity analysis addressed inclusion of both eyes. Results: AI-CO center correlated with 10-2 MD (rho=0.829; 95% CI, 0.773-0.873). AUCs for 10-2 MD below -2, -6, and -12 dB were 0.902, 0.939, and 0.961, respectively. The numbers of eyes in Levels 0-4 were 66, 57, 94, 53, and 50; median 10-2 MD values were -0.59, -1.48, -3.54, -6.24, and -18.15 dB, respectively. Quadratic-weighted kappa was 0.970 (95% CI, 0.958-0.981). Sensitivity analyses yielded broadly similar findings. Conclusions: The numerical AI-CO center index and visually classified central dark-area extent were associated with central visual field damage. Assessing the extent of dark regions in the central image alongside the numerical index may provide useful information for interpreting central visual field status from the AI-CO display.

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Association of Adduction-Induced Optic Nerve Head Strain with Visual Field Loss Progression in Myopic Normal-Tension Glaucoma: The Wenzhou Glaucoma Progression Study

Chen, D.-F.; Xiong, Z.; Zhang, J.; Deng, C.; Li, J.; Liu, G.; Wang, T.; Huang, Q.; Jonas, J.; Girard, M. J. A.; Wang, X.; Liang, Y.

2026-10-19 ophthalmology 10.64898/2026.10.15.26365686 medRxiv
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Purpose: To characterize the biomechanical response of the optic nerve head (ONH) in myopic versus non-myopic individuals with normal-tension glaucoma (NTG), and to evaluate the association between ONH strains and the rate of visual field (VF) progression. Design: Retrospective clinical cohort study. Participants: A total of 118 NTG eyes from 77 patients with [&ge;] 2 years of follow-up and 5 VF tests were enrolled, including 66 eyes with myopia and 52 eyes without. Methods: Each participant underwent three-dimensional (3D) optical coherence tomography (OCT) imaging of the ONH under three mechanical loading conditions: 20{degrees} adduction, 30{degrees} abduction and acute intraocular pressure (IOP) elevation by applying a 0.80 N force to the lower eyelid. Effective strains across the global ONH complex and within specific segmented tissues (pre-lamina, lamina cribrosa, choroid, and sclera) were quantified using a validated 3D strain-mapping algorithm. Results: Myopic NTG eyes exhibited significantly higher ONH strains compared to non-myopic eyes under acute IOP elevation (10.1{+/-}2.7% vs. 9.3{+/-}1.8%, P = 0.044) and abduction (9.2{+/-}2.3% vs. 8.4{+/-}2.1%, P = 0.048). In the non-myopic group, ONH strains varied significantly across conditions (P < 0.001), with adduction (9.9{+/-}2.0%) and acute IOP elevation (9.3{+/-}1.8%) eliciting greater strains than abduction (8.4{+/-}2.1%). These condition-dependent variations were less pronounced in the myopic group (10.1{+/-}2.7% vs. 9.8{+/-}2.7% vs. 9.2{+/-}2.3%, P = 0.07). Multivariable linear mixed-effects analysis revealed that in myopic NTG, higher ONH strains induced by adduction were significantly associated with faster MD decline (estimate: -0.139 dB/year per 1% increase, P = 0.03, adjusted for age, spherical equivalent and baseline perimetric mean defect). Conversely, larger strains during acute IOP elevation were associated with slower progression (estimate: 0.184 dB/year per 1% increase, P = 0.004). Tissue-specific analysis confirmed that adduction-induced strains in the choroid and pre-lamina tissue as well as IOP-induced strains across all ONH tissues were significantly correlated with the rate of perimetric progression in myopic eyes (all P < 0.05). Conclusions: In this cohort, greater adduction-induced ONH strain was associated with faster perimetric deterioration in myopic NTG. These findings support further investigation of gaze-related optic nerve traction as a potential non-IOP-related biomechanical factor in myopic NTG. Keywords: Normal tension glaucoma, Myopia, Optic nerve head, Ocular biomechanics, Visual field Progression, adduction.

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Normative Temperature, Demographic Categories, and the Limits of Infrared Thermometry

Lohier, A.; Campbell, A. G.; Chartash, D.

2026-10-21 health informatics 10.64898/2026.10.19.26365925 medRxiv
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Objective. Temperature readings are routinely stratified by race and ethnicity, though significant group differences may reflect physiology, instrument noise, or categorization rather than biology. This study tests whether these categories partition facial infrared thermography measurements beyond individual variation and baseline device noise. Approach. A secondary analysis of thermography data (n = 951 adults) compares inner-canthus maximum (TCEmax) and full-face maximum (Tmax) temperatures across five administrative categories via one-way analysis of variance (ANOVA), mixed-effects modeling, Bland-Altman analysis against oral reference, and Monte Carlo sensitivity analysis. Main results. ANOVA returns significant group differences (p < 0.001; eta-squared = 0.04 for TCEmax, 0.03 for Tmax), but the total spread (0.2 to 0.3 degrees Celsius) is comparable to device accuracy and within-subject variability. Individual variation accounts for 95% of TCEmax variance, and adding simulated Gaussian noise to participant-level temperatures (sigma = 0.10 to 0.30 degrees Celsius) preserves the complete group-mean rank order in as few as 37.5% of iterations. Significance. Testing whether a group difference survives perturbation at the scale of instrument accuracy offers a check against treating significance alone as evidence of physiology. Here, observed group differences are small relative to measurement variability, and their physiological interpretation remains uncertain, with implications for clinical tools that treat administrative categories as biologically meaningful.

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Feasibility of Distributed Wearable Ultrasound for Detecting Neuromuscular Coordination Differences After Knee Injury

King, E. L.; Lamarre, M. A.; Bashatah, A.; Aher, A.; Gibson, G.; Hajialiyan, T.; Brown, F. S. A.; Wei, Q.; Sikdar, S.; Jones, M. T.; Chitnis, P. V.

2026-10-20 rehabilitation medicine and physical therapy 10.64898/2026.10.18.26365835 medRxiv
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Objective: The aim of the current study was to evaluate the feasibility of a multi-channel distributed wearable ultrasound (D-WUS) system capable of simultaneously probing dynamic muscle activity across multiple anatomical sites to assess neuromuscular coordination during physical activity. Methods: Twenty NCAA Division I women athletes (8 with prior knee injury) performed countermovement jumps (CMJs) on dual force plates while wearing a four-channel D-WUS system targeting the vastus lateralis (VL) and vastus medialis oblique (VMO) in both limbs. Real-time M-mode ultrasound data were processed using a composite factorization approach integrating nonnegative matrix factorization and principal component analysis (CF-PCA) to extract dominant muscle-contraction patterns. Correlation and timing metrics between VL and VMO were compared across injury status. Results: CMJ performance metrics (jump height, RSImod) did not differ between groups (p > 0.05). However, D-WUS revealed significant differences in muscle coordination in the right limb: VL-VMO correlation (p = 0.029) and timing symmetry (p = 0.019) were reduced in participants with prior knee injury; left-limb differences were not significant. Right-limb timing symmetry was negatively correlated with SMFA score (rho = -0.48, p = 0.033). Functional survey scores (SMFA) also differed significantly (p = 0.001), while VISA-P scores did not. Conclusion: These preliminary findings provide feasibility-level evidence that distributed wearable ultrasound can detect limb-specific neuromuscular coordination differences not reflected in force-plate biomechanics, motivating larger prospective studies to establish reliability and clinical utility. Significance: With further validation, this approach may offer a scalable, objective means of monitoring muscle contraction during rehabilitation.

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Performance of Contemporary Large Language Models on the National Prosthodontic Resident Examination: A Multi-Year Comparative Study

Chen, Y.-w.; Bhunyanaphakul, V.; Kosago, P.; Finkelman, M.; Lee, D. J.

2026-10-21 dentistry and oral medicine 10.64898/2026.10.19.26365937 medRxiv
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Purpose: To compare the performance of three large language models (LLMs), ChatGPT-o1, Grok 3, and Gemini 2.0 Pro, on the American College of Prosthodontists' National Prosthodontic Resident Examination (NPRE). Materials and Methods: Official NPRE examinations from years 2015-2024 were retrieved from the American College of Prosthodontists website and used to prompt each LLM. Paid access tiers and advanced reasoning were enabled. Responses from LLMs were recorded and compared against the official answer keys for accuracy, variability across years, and consistency of responses. Duplicate questions were retained for the primary analysis and removed in a sensitivity analysis. Accuracy (percent correct) was compared using generalized estimating equations binary logistic regression (primary); Cochran's Q with Bonferroni-adjusted McNemar tests (sensitivity). Year-to-year variability (SD of annual accuracy) was compared using weighted Levene tests. Consistency across duplicate items was quantified as the percentage of perfect matches and compared using Cochran's Q with Bonferroni-adjusted McNemar tests. Results: Across 1,487 questions, overall accuracy differed among models (global P < 0.001). ChatGPT-o1 achieved 78.4% correct, Grok 3 76.4%, and Gemini 2.0 Pro 73.2%; ChatGPT-o1 and Grok 3's accuracy significantly exceeded Gemini 2.0 Pro (both P [&le;] 0.016), with no significant difference between ChatGPT-o1 and Grok 3 (P = 0.099). After removing duplicates (n = 1,200), results were similar: ChatGPT-o1, Grok 3, and Gemini 2.0 Pro were 77.1%, 76.6%, and 71.5% correct, respectively; ChatGPT-o1 and Grok 3's accuracy was significantly higher than Gemini 2.0 Pro (both P < 0.001). Variability across years did not differ significantly (P [&ge;] 0.097). Grok 3 showed significantly higher perfect-match consistency (79.2%) than ChatGPT-o1 (69.4%) and Gemini 2.0 Pro (64.5%) (P [&le;] 0.010). Conclusions: Contemporary LLMs showed 70-80% accuracy on postgraduate prosthodontic multiple-choice content. While promising for educational support, residual error and inconsistency warrant human oversight and transparent methods reporting before curricular adoption.

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Development of a Communication Characteristics Module for Autistic Adults and the Creation of a Communication Profile Variable

Kripke-Ludwig, R.; Vera, J. W.; Moura, I.; Kapp, S. K.; Siddeek, Z.; Maslak, J.; Wallington, A. F.; Rosa, S. D. R.; Kripke, C. C.; Nicolaidis, C.

2026-10-19 rehabilitation medicine and physical therapy 10.64898/2026.10.15.26365687 medRxiv
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Purpose Autistic adults have diverse communication characteristics that are not well captured by standard demographic measures. Communication affects self-determination, relationships, access to healthcare, and services. Characterizing communication differences may improve research and intervention targeting for meaningful subgroups of autistic adults. Methods The Academic Autism Spectrum Partnership in Research and Education (AASPIRE) Outcomes Project team used a community based participatory research (CBPR) approach to develop a self- or caregiver-report module to characterize communication among autistic adults. The 10-item module asks about receptive and expressive communication, literacy, speech reliability, usage of digital communication, use of alternatives to speech, and communication fluency. It can be completed directly, with or without support, or via a caregiver. We used baseline survey data from 844 autistic adults to evaluate the module and derived a five-level variable, Communication Profile, from selected module items to stratify participants. We examined completion feasibility, response consistency, and construct validity. We also assessed test-retest reliability in a 15% random subsample who completed a 2-week retest following the 6-month survey, with oversampling of caregiver-report respondents. Results The Communication Characteristics module demonstrated high completion feasibility, minimal systematic error, and strong construct validity. The Communication Profile variable stratified participants into five meaningful communication profiles and demonstrated strong construct validity and substantial test-retest reliability ({kappa} = .69). Conclusion The Communication Characteristics module and Communication Profile variable provide a valid approach for characterizing communication diversity among autistic adults for research, clinical, and service settings. The full AASPIRE Measurement Toolkit is available at https://aaspire.org/measurement. Lay Summary Autistic people communicate in many different ways, and their communication may change in different situations. We developed and tested a set of survey questions to describe an individuals communication. We also used the results to describe 5 groups of autistic people based on how they communicate, without treating these groups as different types of autism.

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Self-supervised pretraining for dermoscopic lesion segmentation with limited labels: A controlled comparison of initialisation strategies

Hamda, H. K. H.; Mustafa, S.; Khalili Moghaddam, G.

2026-10-15 dermatology 10.64898/2026.10.14.26365443 medRxiv
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Background: Self-supervised learning may improve segmentation when labelled data are limited, but its benefit may depend on model and initialisation strategy. This study evaluated in-domain masked-reconstruction pretraining across limited annotation budgets. Methods: The International Skin Imaging Collaboration (ISIC) 2016 development set was partitioned into 765 images for self-supervised pretraining, 94 for fine-tuning and 41 for validation. Five nested annotation budgets (12-94 images) and five seeds were evaluated on the 379-image test set. A custom U-Net compared random and in-domain self-supervised initialisation; a ResNet-34 U-Net compared random, ImageNet, in-domain self-supervised and sequential ImageNet-to-self-supervised initialisation. Models trained with 94 labelled images were evaluated without adaptation on ISIC 2017. A separate experiment examined restoration-based pretraining. Results: In the custom U-Net, self-supervised pretraining achieved higher mean Dice than random initialisation at all five budgets, including 0.664 versus 0.615 with 12 labels and 0.811 versus 0.768 with 94 labels. Seed-level 95% confidence intervals for paired differences excluded zero at 47 and 94 labels but not at the other budgets. With 47 labels, the self-supervised model achieved mean Dice of 0.789, compared with 0.768 for random initialisation with 94 labels. In ResNet-34, ImageNet initialisation achieved higher mean Dice than in-domain self-supervised pretraining at all five budgets, and adding self-supervised pretraining after ImageNet reduced mean Dice at four of five budgets. All six 94-label configurations achieved lower mean Dice on ISIC 2017 than ISIC 2016. In the restoration experiment, mean Dice was 0.686 with random initialisation and 0.638-0.642 following pretraining. Conclusions: In-domain masked-reconstruction pretraining improved mean Dice relative to random initialisation in the custom U-Net, but not consistently in the ResNet-34 U-Net, where ImageNet initialisation performed better at every budget. Adding self-supervised pretraining after ImageNet provided no consistent gain. These findings are specific to the dermoscopic lesion-segmentation experiments and do not establish melanoma-specific diagnostic or clinical performance.

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Upright Participation for Learners with Physical Disabilities: A Pilot Randomized Crossover Effectiveness-Implementation Trial of Robot-assisted Walking in Schools

Hilderley, A.; Diot, C.; Morgan, B.; Byrne, E.; Chu, E.; Gosselin, A.; Sheldon, K.; McCormick, A.; Wright, F. V.; Pritchard, L.; Shen, H.; Kirton, A.; Condliffe, E.

2026-10-21 rehabilitation medicine and physical therapy 10.64898/2026.10.16.26365549 medRxiv
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Background: School-based implementation of robot-assisted walking may support increased physical and social participation for children with physical disabilities, but evidence from an adequately powered trial is needed. This pilot study evaluated implementation strategies and study procedures to inform a future definitive trial. Methods: Participants were randomized to 12-weeks of robot-assisted walking or control, with subsequent crossover to the other condition. In the intervention arm, targeted dose was 75 minutes of robot-assisted walking, spread across three days/week. Implementation strategies for the child's classroom team included educational materials, centralized technical assistance, school champions, and on-going training. Implementation strategy evaluation focused on intervention protocol feasibility (i.e., weekly device use, troubleshooting) and fidelity (documentation of implementation strategy modifications). Preliminary estimates participation goal changes were obtained using the Canadian Occupational Performance Measure (COPM) 'Performance' scale (/10). Results: Eight children with neurodevelopmental physical disabilities participated (mean age 3.5, SD 0.5 years). Device use varied from 2.1 to 4.3 days/week (median 3.3) with a range of 48 to 96 minutes/week (median 80). Target use of >= 3 days/week was achieved for 66% of weeks and met the >=75-minute target for 33% of weeks. Troubleshooting occurred in 18.5% of sessions. Two implementation strategies were modified to improve feasibility. COPM mean change was 3.56 (SD 1.07) for robot-assisted walking and 2.11 (SD 2.41) for control (dz=0.74). Conclusions: This pilot study provided preliminary evidence regarding both the feasibility of robot-assisted walking implementation in schools and its potential effectiveness for children with physical disabilities. Findings support progression to a definitive trial.

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AI-Assisted Interpretation of Neurologic Autoantibody Cell-Based Assays

Qi, Z.; Cao, Z.; Tan, H.; Tang, B.; Shi, S. X.; Jia, R.; Yao, Y.; Chen, J.; Zhang, Z.; Wan, J.; Zheng, P.

2026-10-19 neurology 10.64898/2026.10.16.26365578 medRxiv
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Neurologic autoantibody cell-based assay images are difficult to interpret when fluorescence is weak, focal or dominated by background signal. We developed a visual artificial intelligence overlay that transfers detected cell boundaries from the structural channel to the antibody-staining image and evaluated standalone model concordance and its association with reader classifications. The analysis used 2 763 records for model development and 499 held-out records spanning 14 antibody targets. Four readers assessed the held-out records first without assistance and then with the boundary overlay and model category available. The selected model agreed with the reader-derived three-class reference in 85.2% of records, but recall was lowest for weak-positive or equivocal records. Reader agreement increased in the assisted session, and almost all revised ratings moved towards the model category. The combined display may support consistent visual review while also creating a risk of model-directed anchoring; its role as a second-read aid requires independent validation.

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Quality and transcript-grounded clinical-risk error burden of AI-generated vs allied health professional clinical notes: a paired simulation study across four disciplines

Bergman, H. I.; Liu, V.; Ali, S.

2026-10-19 health informatics 10.64898/2026.10.16.26365719 medRxiv
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Background: Ambient artificial-intelligence (AI) scribes are being deployed beyond medicine into allied-health practice, but comparative evidence mainly concerns physician documentation. Objective: To compare quality and transcript-grounded clinical-risk error burden of AI-generated and allied health professional notes from identical simulated consultations. Methods: Paired simulation across dietetics, physiotherapy, occupational therapy and speech and language therapy (five consultations each; 20 pairs; 40 notes). Heidi generated an unedited first-draft note and a professional documented each encounter. Professionals rated PDQI-9 quality. Professional and automated review identified unsupported statements and omissions; two language models graded clinical risk. Co-primary outcomes were PDQI-9 score and Critical+High error density. Results: Mean PDQI-9 scores were 38.45 and 35.05 for AI and professional notes (paired difference +3.40, 95% CI +0.01 to +6.79; Wilcoxon p=0.042; dz=0.47). The Bayesian estimate was +3.47 (94% equal-tailed credible interval +0.66 to +6.30; P[AI>professional]=0.989). Automated-reviewer all-error density was 3.35 vs 8.55 per note (professional-minus-AI difference 5.20, 95% CI 3.85 to 6.55); omission density was 1.45 vs 5.20 (difference 3.75, 2.80 to 4.65). Critical+High density was 0.35 vs 0.75 (difference 0.40, -0.10 to 1.00). The pooled quality result was driven principally by dietetics. Conclusions: AI-generated notes achieved modestly higher pooled quality and fewer transcript-grounded errors, chiefly omissions; serious-error evidence was inconclusive. Small discipline samples and incomplete ground truth preclude safety or discipline-wide superiority claims.

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BanglaDiaHallu: Hallucinations of large language models and the effect of guideline-grounded retrieval-augmented generation in Bangla diabetes question answering

Nahid, K.; Anam, M.; Saon, M. T. H.; Any, O. H.; Hassan, K. M. R.; Anwar, M. M.

2026-10-16 health informatics 10.64898/2026.10.14.26365587 medRxiv
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Large language models (LLMs) are increasingly consulted for health advice, but they can produce fluent statements that are false or unsupported, known as hallucinations, and this risk is poorly characterised in low-resource languages such as Bangla. We measured hallucinations of locally deployable open-weight LLMs in Bangla diabetes question answering and tested whether retrieval-augmented generation (RAG) grounded in Bangladeshs National Guideline on Diabetes Mellitus reduces them. Forty patient questions spanning six clinical sub-domains were each answered twice, under zero-shot prompting, by Qwen3.5-9B, TigerLLM-9B, Qwen3.6-35B-A3B and Gemma-4-26B-A4B, and by BanglaDiaRAG, which adds hybrid dense (BGE-M3) and sparse (BM25) retrieval from a physician-reviewed Bangla guideline knowledge base to Qwen3.5-9B. Two physicians rated the 400 de-identified responses by consensus for medical accuracy, completeness, safety, readability and reliability on a 0-1 scale, and responses with accuracy below 0.70 were classified as hallucinated. Hallucination rates were 2.5% for Gemma-4-26B-A4B, 3.8% for TigerLLM-9B, 22.5% for Qwen3.6-35B-A3B and 77.5% for Qwen3.5-9B. Guideline grounding lowered the rate of Qwen3.5-9B to 11.3% (difference -66.3 percentage points; 95% CI -76.3 to -55.0) and raised every criterion by 0.24 to 0.38 points (Holm-adjusted p < 0.001). BanglaDiaRAG outscored Qwen3.6-35B-A3B on all five criteria and matched or exceeded TigerLLM-9B, but it remained below Gemma-4-26B-A4B in safety, readability and reliability, and its residual errors were specific, confident and potentially harmful. Guideline grounding can turn a weak general-purpose model into a much safer Bangla diabetes assistant, but the choice of base model mattered as much as retrieval and no configuration was free of hallucination, so clinical oversight remains essential before patient-facing use.

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Deep Learning-Based Anatomical Level Classification of Craniofacial CT Slices: Comparison of CNN Architectures and Ensemble Methods

Nishimoto, S.; Nakajima, K.; Yoshiike, H.; Ishise, H.; Saito, T.; Kawai, K.

2026-10-19 radiology and imaging 10.64898/2026.10.16.26365710 medRxiv
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Computed tomography (CT) interpretation requires recognition of the anatomical level of each slice. Classification may facilitate preprocessing and AI-assisted fracture diagnosis. We developed deep learning models to classify craniofacial CT slices into six anatomical categories. A total of 11,769 images were collected from a multicenter database involving 10 Japanese university hospitals and the public Head-Neck-Radiomics-HN1 dataset. Patients were divided into training (70%) and evaluation (30%) sets. Five CNN architectures were trained from scratch, and hard- and soft-voting ensembles were evaluated. Individual-model accuracy ranged from 94.72% to 96.09%; the hard-voting ensemble achieved 96.46% accuracy (Cohen's k = 0.954). Although performance differed among individual models (Cochran's Q = 99.29, p < 0.001), the ensemble did not significantly outperform EfficientNetV2B1 (McNemar's p = 0.163). Errors occurred mainly between adjacent anatomical regions. Deep learning can classify craniofacial CT slices accurately and may support automated dataset organization and AI-assisted fracture diagnosis. External validation is needed.

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Network representations of digital clock drawings for cognitive impairment detection

Pinheiro, A.; Cheng, H.; Karjadi, C.; Gifford, K.; Demissie, S.; Lunetta, K. L.; Liu, C.; Au, R.; Mohammed, S.

2026-10-19 health informatics 10.64898/2026.10.15.26365699 medRxiv
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INTRODUCTION: The digital clock drawing test (dCDT) is a cognitive screening tool capturing high-resolution pen-movement data. Existing approaches for classifying cognitive impairment from dCDTs rely on selected features or image-based methods. We propose representing dCDTs as structural networks to classify cognitive impairment and characterize spatial organization in clock drawings. METHODS: Weighted networks were constructed from 3,362 Framingham Heart Study participants, with and without cognitive impairment. Network representations were generated separately for command and copy conditions, with nodes representing pre-defined clock components (digits, hands, clock face) and edges capturing pairwise spatial relationships between components. Random forest models and graph convolutional networks were trained to predict cognitive impairment from the networks. Models were benchmarked against demographics-only and established summary feature baselines. RESULTS: Network-based models achieved AUC values comparable to the established summary feature baseline across command-only and copy-only conditions. Differences in spatial organization between the cognitively intact and impaired groups were greatest in the upper-right clock region, involving digits 1 and 2, the clock hands, and the surrounding clock face. Differences between the command and copy networks were larger among cognitively impaired participants. DISCUSSION: The proposed network representations provide an objective, scalable, and flexible framework for representing clock drawings for use in classification models. dCDT networks matched the predictive performance of established summary feature-based approaches and identified clock regions where spatial organization differed by cognitive status. After external validation, this approach has the potential to be incorporated within a clinical workflow to support automated and interpretable cognitive screening.

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Beyond the Scribe: Using Nominal Group Technique to Co-Design an Evaluation Framework for Patient-Held AI

DesRoches, C.; Norris, A.; Barr, J.; Vaughan, W.; Ruparel, R.; Liu, Y.; Thompson, M.; Stevens, J.

2026-10-19 health informatics 10.64898/2026.10.15.26365669 medRxiv
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The explosive growth of ambient AI scribes in healthcare has focused almost exclusively on relieving clinician documentation burdens and enhancing clinician efficiency and reducing burnout. While most research has focused on the clinician experience, these same types of tools, such as a patient held AI Personal Health Assistant, can be put in the hands of patients to facilitate communication with healthcare providers, to provide greater autonomy and activation for patients in managing their own healthcare, and to facilitate the task of receiving and retaining complex new information. However, to ensure these tools serve as more than just administrative aids, we partnered with a large technology company to conceptually codesign how such a tool might be studied in real world settings in a way that reflected outcomes of greatest importance to patients and families. We used the Nominal Group Technique and engaged thirty three patients and caregivers and ten multidisciplinary clinicians in structured virtual sessions to identify the outcomes on which subsequent studies should hinge. Our findings reveal a significant misalignment between current industry trends and patient priorities. While the market emphasizes the scribe function for billing, stakeholders overwhelmingly prioritized the AIPHAs role in longitudinal care management and post visit coordination. The most critical outcome identified was the impact on communication and respect, suggesting that patients view AI as a mechanism to improve the human to human dynamic and ensure a shared understanding of the care plan. Our findings further highlighted that the primary hurdle for the use of patient held AI is not technical utility but clinician trust and the need for formal consent processes. Importantly, as this technology is new and integration into the clinical experience is still being explored, patients cannot assume they will have access to the transcript of their own encounter when that record is created and held by the health system. This gap highlights the potential value of a patient held tool, preserving discussions from their visit and follow up steps in clearer detail than they may receive in their clinical note or traditional visit summary. From a system perspective, this transition requires a strategic shift from measuring workflow focused efficiency to measuring patient side advocacy and engagement. By centering the evaluation of AI on these patient defined metrics and fundamentally designing subsequent AI investigations using a partnership model, health systems can move beyond simple automation toward a model of care delivery that empowers patients to navigate complex clinical journeys with greater autonomy and clarity.

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Comorbidities of dementia in electronic health records: validation of a natural language processing app and comparison with data linkage

Mirza, L.; Bendayan, R.; Stewart, R.; Davis, K. A. S.

2026-10-19 health informatics 10.64898/2026.10.16.26365714 medRxiv
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Awareness of comorbidities in people with dementia is vital context for dementia research and clinical management. Natural Language Processing (NLP) applied to free text in the electronic health record (EHR) may help ascertain comorbidity presence. Our aim was to assess the validity of the MedCAT Comorbidity NLP app in a cohort of people with dementia. We used text from the EHR of South London and Maudsley NHS Mental Health Trust via Clinical Records Interactive Search (CRIS), linked to structured data from local primary care (Lambeth DataNet) and hospital admission data in a cohort of 3,543 people with dementia. We evaluated MedCAT Comorbidity, examining internal validity via manual review of text and external validity by cross-validation against linked primary care and hospital data; and comparison of the predictive value of comorbidity measures for mortality. Internal precision was highest for atrial fibrillation (100%) and lowest for diabetes (78%). Cross-validation with linked data varied substantially across conditions, with precision from 96% to 59% and recall 77% to 4%. The median number of comorbidities identified was two using any single source, or three when combined. MedCAT Comorbidity demonstrated predictive ability for mortality (HR 1.11 per condition), although the model fit was better using comorbidity from hospital admission data. In people with dementia, the MedCAT Comorbidity app showed high precision for most conditions during internal validation. The variability of precision and recall on external validity assessment partly reflects incomplete documentation. Results from the MedCAT comorbidity app can assist researchers in understanding comorbidity of cohorts, particularly when primary care or hospital data is not available. Our findings highlight the need to develop quality assurance protocols that include internal and external validity checks before deploying general data extraction apps for specific clinical subpopulations.

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Discrepancies in Interpretation of Japanese Radiology Report Expressions Between Radiologists and Referring Physicians

Yamaguchi, T.; Matsuo, H.; Nishio, M.; Inukai, J. I.; Matsunaga, T.; Kojita, Y.; Sofue, K.; Murakami, T.

2026-10-21 radiology and imaging 10.64898/2026.10.19.26364709 medRxiv
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Objectives To evaluate discrepancies between radiologists and referring physicians in the interpretation of diagnostic probabilities conveyed by common Japanese expressions used in radiology reports. Materials and Methods Fifteen expressions commonly used to convey diagnostic probabilities in radiology reports were selected by five attending radiologists. An anonymous online survey was distributed to 26 radiologists and 33 referring physicians at a single institution. Participants assigned a diagnostic probability (from 0% to 100% in 10% increments) to each expression. Differences in median probabilities between radiologists and referring physicians were analyzed using the Mann-Whitney U test. Variability in interpretation was assessed using interquartile range (IQR), with IQR [&ge;] 30% defined as substantial variability. Results All radiologists (26/26) and 97% of referring physicians (32/33) completed the survey. Seven of the 15 expressions showed statistically significant differences in interpretation between radiologists and referring physicians: "c/w" (80% vs. 60%; p = 0.031), the Japanese equivalents of "present" (100% vs. 100%; p = 0.024), "suspect of" (80% vs. 70%; p = 0.007), "possibly" (50% vs. 70%; p < 0.001), "unlikely" (10% vs. 10%; p = 0.022), "cannot be ruled out" (25% vs. 40%; p < 0.001), and "not inconsistent with" (80% vs. 90%; p = 0.008). Substantial variability in interpretation (IQR [&ge;] 30%) was observed for four expressions: "cannot be ruled out" (IQR, 10%-40%), "s/o" (IQR, 60%-90%), "c/w" (IQR, 50%-90%), and "not inconsistent with" (IQR, 70%-100%). Conclusion This study revealed that nearly half of the Japanese expressions commonly used to convey diagnostic probabilities were interpreted differently by radiologists and referring physicians. These discrepancies highlight the need for a standardized lexicon to improve clarity and consistency in radiology reporting.

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Pharmacovigilance and Mechanistic Analysis of Adverse Reaction Differences Across EGFR Tyrosine Kinase Inhibitor Generations in Non-Small Cell Lung Cancer

Arojo, O.; Jones, A. M.

2026-10-19 epidemiology 10.64898/2026.10.16.26364955 medRxiv
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Background: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely used for EGFR-mutated non-small cell lung cancer (NSCLC) but have distinct toxicity profiles across generations. Aims: To investigate relationships between EGFR-TKI physicochemical, pharmacokinetic and pharmacological properties and drug-specific adverse drug reactions (ADRs) using national and global pharmacovigilance data. Methods: ADRs for erlotinib, afatinib and osimertinib were extracted from the UK MHRA Yellow Card scheme and WHO VigiAccess. Disproportionality analysis used reporting odds ratios (RORs). Signals were defined as ROR >2, lower 95% confidence interval >1 and >3 cases. Drug properties were curated from ChEMBL, emc, SmPC and EMA sources. Results: VigiAccess contained 88,662 individual case safety reports (163,619 ADRs) and Yellow Card contained 752 reports (1,814 ADRs). Four System Organ Class (SOC) signals were identified in VigiAccess and three in Yellow Card, with five additional Yellow Card Preferred Term signals. Eye disorders showed the strongest consistent association with erlotinib (VigiAccess ROR 4.33; Yellow Card ROR 4.18). Osimertinib was associated with pneumonitis (ROR 7.67) and pulmonary embolism (ROR 3.94). Afatinib showed psychiatric disorder signals in both databases (ROR 3.2-3.3) and diarrhoea (ROR 2.79). Neoplasm-related signals likely reflected confounding by indication. Conclusions: EGFR-TKIs demonstrate generation-specific pharmacovigilance profiles. Integration with drug properties supports mechanistic plausibility for several signals, while the atypical afatinib psychiatric association warrants further investigation. Findings are hypothesis-generating and require confirmation in controlled observational or mechanistic studies.

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Longitudinal associations between neuropsychiatric symptoms, structural and perfusion MRI changes in older adults with Mild Cognitive Impairment

Lombardi, G.; Leung, C. C.-Y.; Burge, R.; Zelaya, F.; Bhattacharyya, S.; Velayudhan, L.

2026-10-19 geriatric medicine 10.64898/2026.10.15.26364284 medRxiv
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Neuropsychiatric symptoms (NPS) are highly prevalent in Mild Cognitive Impairment (MCI), conceptualized as an intermediate clinical state between normal aging and dementia. Although neuroimaging studies have reported associations between NPS and brain alterations in MCI, longitudinal evidence on NPS and their relationship with multimodal MRI measures remains limited. We aimed to investigate (1) longitudinal changes in NPS, volumetric assessment and measurement of regional cerebral blood flow (CBF) within the medial temporal lobe (MTL); (2) associations between longitudinal changes in MRI measures and NPS; (3) whether baseline MRI measures predicted longitudinal changes in NPS. Thirty individuals with MCI aged over 65 years were recruited, of whom eighteen followed up for a mean period of 29 {+/-} 8.9 months. There were significant reductions in total grey matter and white matter volumes, together with volume loss in the bilateral hippocampus, bilateral parahippocampal gyrus and right entorhinal cortex (pFDR[&le;]0.05) over the follow up period. Volume loss in the right parahippocampal gyrus was associated with increase in aggression (pFDR<0.01), and CBF increase in the right hippocampus and parahippocampal gyrus was associated with worsening in agitation (pFDR<0.01). Furthermore, lower baseline volume of the right entorhinal cortex was associated with increase in aggression, and lower baseline CBF in the right hippocampus and parahippocampal gyrus was associated with worsening of agitation (pFDR<0.05). Our findings highlight the importance of identifying NPS in individuals with MCI and the role of structural and perfusion MRI measures as promising biomarkers for monitoring disease progression and improving risk prediction of conversion to dementia.

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Impact of air pollution and tobacco smoke on the placental small non-coding RNA landscape

Falcon-Gracia, A.; Vespalcova, H.; Peligri, D.; Aguilar-Lacasana, S.; Pantano, L.; Nurtdinov, R. N.; Garcia, Z.; Dominguez, A.; Gomez-Herrera, L.; Sanchez, O.; Gascon, M.; Foraster, M.; Guigo, R.; Llurba, E.; Gomez-Roig, M. D.; Rivas, I.; Dadvand, P.; Sunyer, J.; Bustamante, M.; Cosin-Tomas, M.

2026-10-19 public and global health 10.64898/2026.10.16.26365732 medRxiv
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Fetal development is highly sensitive to environmental influences, including maternal smoking during pregnancy (MSDP) and air pollution. The placenta may play a central role in mediating these effects through epigenetic mechanisms, including small non-coding RNAs (sncRNAs). While most studies have focused on microRNAs (miRNAs), other sncRNA classes remain poorly characterized. Here, we characterized the placental sncRNA landscape and investigated its associations with prenatal exposure to MSDP and air pollution. The sncRNA expression profile of 390 chorionic villi samples from the Barcelona Life Study Cohort (BiSC) was measured using small RNA sequencing and the seqBuster/seqCluster pipeline. MSDP was assessed via questionnaire, and prenatal exposure to black carbon (BC), particulate matter [&le;]2.5 m (PM2.5), and nitrogen dioxide (NO2) was estimated using hybrid dispersion-land-use regression (LUR) spatiotemporal models. Associations were evaluated using linear regressions adjusted for relevant covariates. We identified 979 placental sncRNA clusters, assigned primarily to miRNAs (33.2%), piRNAs (26.4%), snoRNAs (12.2%), tRFs (7.8%), and others (20.4%). MSDP was associated with the downregulation of miR-421 and the upregulation of multiple snoRNAs from the imprinted DLK1-DIO3 locus (SNORD113-4, SNORD114-2, SNORD114-3, and SNORD114-17), as well as the piR-26394. No sncRNAs remained significantly associated with air pollution after multiple-testing correction, although several miRNAs showed suggestive associations. Overall, this study provides a comprehensive characterization of placental sncRNAs and identifies previously unreported smoking-associated sncRNAs within the imprinted DLK1-DIO3 locus, expanding our understanding of placental epigenetic responses to prenatal environmental exposures.

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Cost-Effectiveness of Expanding Housing Access for People Experiencing Homelessness and Opioid Use Disorder in California

Ling, Y.; Tsung, S.; Alarid-Escudero, F.; Goldhaber-Fiebert, J. D.; Brandeau, M. L.; Reitsma, M. B.

2026-10-19 health policy 10.64898/2026.10.15.26365505 medRxiv
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People experiencing homelessness (PEH) have substantially lower quality-adjusted life expectancy and substantially higher healthcare spending compared to housed populations. California has the largest population of PEH in the United States, and an estimated ten percent of PEH have co-occurring opioid use disorder (OUD). We developed a lifetime, individual-level microsimulation of the 18,928 PEH with OUD in California to evaluate the health and economic effects of expanding access to housing through a Housing First approach, which does not require OUD treatment or abstinence. Increases in permanent housing and shelter access were based on Los Angeles County's Measure A goals, and we accounted for both housing and healthcare costs. Expanding housing access increased mean age at death by 0.34 years, reduced fatal overdoses for the cohort by 39, and produced an incremental cost-effectiveness ratio of $31,083 per quality-adjusted life-year gained, well below conventional willingness-to-pay thresholds. We provide evidence that housing is a high-value health intervention for PEH with OUD in California. Policymakers should support Housing First programs as part of integrated responses to the intertwined crises of homelessness and opioid use.