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IEEE Transactions on Neural Systems and Rehabilitation Engineering

Institute of Electrical and Electronics Engineers (IEEE)

Preprints posted in the last 7 days, ranked by how well they match IEEE Transactions on Neural Systems and Rehabilitation Engineering's content profile, based on 40 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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Reliability and Concurrent Validity of a Computer Vision-Based Tool for Quantitative Finger Movement Analysis

Maharshi, A.; Ladha, B.; Malani, R.; Palaskar, P.

2026-06-01 rehabilitation medicine and physical therapy 10.64898/2026.05.21.26353446 medRxiv
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Background: Accurate evaluation of fine motor abilities is a key aspect of neurological rehabilitation. However, conventional approaches like goniometry are limited by variations among raters and their difficulty in detecting active movement. On the other hand, computer vision-based software delivers non-invasive and quantitative analysis of hand movements. An innovative computer-vision-based software tool, F.A.I.R. Chance(C), was developed to track and analyze individual finger joint movements on a camera-equipped laptop and give real-time numerical feedback. However, its metrics require validation in a healthy population before the tool can be used for clinical purposes. Objective: To assess the reliability and validity of finger movement assessment by the F.A.I.R. Chance computer vision-based tool in healthy adult participants. Methods: An observational cross-sectional study was done at MGM School of Physiotherapy, comprising 30 healthy participants between 18 and 60 years of age. Finger movements like flexion, extension, abduction, and adduction were measured with a standard handheld goniometer. These same finger movements were then measured with the tool at two time points separated by a 30-minute interval to determine the test-retest reliability. The tool's measurements were compared with the goniometric measurements to determine its concurrent validity. Test retest reliability was checked by the Intra-class Correlation Coefficient ICC (2,1), while concurrent validity was tested through Pearson's correlation coefficients. Results: Metacarpophalangeal and proximal interphalangeal joint motions demonstrated moderate to good test-retest reliability (ICC: 0.716-0.953) for the F.A.I.R. Chance tool. However, distal interphalangeal joint movements had lower consistency. Good reliability (ICC: 0.754-0.908) was seen for movements of abduction and adduction in the fingers. Strong concurrent validity for extension movements of the metacarpophalangeal joints (r=0.760-0.914) and moderate concurrent validity for flexion movements of the metacarpophalangeal joints (r=0.427-0.604) was demonstrated for all fingers for the F.A.I.R. Chance tool. Concurrent validity for adduction and abduction movements demonstrated a low to fair correlation with goniometric measurements (r=0.210-0.440). This is consistent with previous research showing poor agreement between goniometry and adduction-abduction movements of the fingers. Conclusion: The F.A.I.R. Chance tool shows good reliability and acceptable concurrent validity to assess fine motor movements in the healthy adult population. This sets a basis for further clinical study of the tool in the target population with fine motor impairments. Keywords: artificial intelligence; assistive technology; computer vision; fine motor evaluation; hand function;

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Exploring Auditory Biofeedback Paradigms for Gait Training in Children with Cerebral Palsy: A User-Centered Design Study

Kantan, P. R.; Hansen, M. B.; Foldager, J. J.; Fjeldgaard, F. S.; Dahl, S.; Spaich, E. G.

2026-05-29 rehabilitation medicine and physical therapy 10.64898/2026.05.29.26353852 medRxiv
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Purpose: To identify, through iterative user-centered design, the auditory biofeedback requirements and sound preferences supporting gait training in children with cerebral palsy (CP), and to determine which feedback variables, sound mappings, and sound types yield clinically viable and movement-interpretable paradigms. Methods: The iterative process spanned two prototype phases. Prototype A comprised seven paradigms demonstrated to two experienced physiotherapists (Workshop 1A). Two of these were subsequently discarded owing to poor sound-movement interpretability and two were modified. Six paradigms were added to Prototype B, demonstrated to four children, five parents, and one therapist (Workshop 1B) and two therapists (Workshop 2B). Data were analyzed using systematic text condensation. Results: Within-child sound preferences varied with energy level and sensory state on a given day. Sound-movement interpretability tended to suffer for paradigms with greater acoustic complexity (e.g. computer-generated music). Therapists endorsed a repertoire spanning both movement quality and movement quantity targets. Participants independently proposed paradigms rewarding restrained and controlled movement, a feedback category absent from the current prototype. Conclusions: Session-level calibration is preferable to fixed sound profiles, requiring real-time interface support for paradigm adjustment. Acoustic complexity must remain subordinate to movement-sound interpretability. Paradigms targeting movement restraint are a development priority unaddressed in the literature.

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Preliminary Reliability and Validity of SynapTrack, a Smartphone-Based Digital Biomarker Platform for Remote Assessment of Cervical Spondylotic Myelopathy

Yakdan, S.; Singh, P.; Arkam, F.; Chen, E.; Lewis, A.; Steel, B.; Becker, I.; Guo, W.; Naveed, H.; Wang, C.; Yang, D.; Wang, Z.; Ray, W. Z.; Hassenstab, J.; Steinmetz, M. P.; Ghogawala, Z.; Kelleher, C.; Greenberg, J.

2026-06-01 surgery 10.64898/2026.05.29.26354454 medRxiv
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Background and Objectives: Cervical spondylotic myelopathy (CSM) is a leading cause of neurological disability in older adults. However, validated, scalable tools to quantify disease severity and changes over time are lacking. Recent advances in smartphone technology have opened new avenues for longitudinal, objective, and remote monitoring of neurological conditions. We performed a preliminary evaluation of the reliability and validity of SynapTrack, a smartphone-based digital platform for objective remote CSM assessments. Methods: In this single-center prospective cohort study, 265 participants (151 with CSM, 114 healthy controls) completed in-person SynapTrack assessments related to tapping, pinching, and vibratory detection, along with reference laboratory measures of dexterity (Box and Block Test, 9-Hole Peg Test) and vibratory sensation (tuning fork). A subset completed repeated home-based testing to assess test-retest reliability. We evaluated convergent validity, construct validity against the modified Japanese Orthopedic Association (mJOA) score, known-groups validity, and test-retest reliability (intraclass correlation coefficient, ICC). Results: Smartphone-derived metrics demonstrated good-to-excellent test-retest reliability, with the strongest stability for vibratory detection threshold (ICC = 0.92), overall and non-dominant tapping speed (ICC = 0.90 each), and pinching successful targets (ICC = 0.90). Convergent validity was supported by moderate-to-strong correlations between digital metrics and reference laboratory dexterity tests ({rho} up to 0.60 for tapping speed; up to -0.65 for the vibratory threshold). Construct validity against the mJOA was strongest for the vibratory threshold ({rho} = -0.53 to -0.54) and Level 2 non-dominant pinching errors ({rho} = -0.45). Selected metrics distinguished CSM patients from controls with good discrimination, including non-dominant tapping speed (AUROC = 0.76, 95% CI 0.68-0.85), Level 2 dominant pinching successful targets (AUROC = 0.78, 95% CI 0.62-0.94), and the non-dominant vibratory threshold (AUROC = 0.77, 95% CI 0.64-0.90). Conclusions and Relevance: A smartphone-based battery of upper-extremity sensorimotor tasks demonstrated preliminary reliability and validity in CSM. Furthermore, to our knowledge, the novel vibratory detection task represents the first smartphone-based sensory assessment used for CSM. Collectively, these findings position SynapTrack as a scalable platform for objective, remote neurological monitoring of CSM.

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Quantifying longitudinal gait changes in ALS using wearable digital health technology metrics

Burke, K. M.; Calcagno, N.; Mandepudi, S.; Premasiri, A.; Hall, K. C.; Vieira, F. G.; Berry, J. D.; Straczkiewicz, M.

2026-05-28 neurology 10.64898/2026.05.27.26354200 medRxiv
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Wearable digital health technologies may complement traditional gait assessments in amyotrophic lateral sclerosis (ALS) by sensitively capturing real-world mobility changes. In this study, we validated six digital gait metrics derived from ankle-worn sensors in a natural history cohort of 182 individuals with ALS. Investigated metrics correspond to various aspects of gait, including volume, speed, intensity, similarity, variability, and fragmentation. Longitudinal analyses showed significant declines in step count, peak cadence, stride intensity, and stride similarity, with increasing stride duration variability and walking fragmentation over 52 weeks. Many participants exhibited greater relative change in the gait metrics than the self-reported ALS Functional Rating Scale-Revised (ALSFRS-RSE). Stratified analyses revealed that digital metrics captured significant functional decline even in participants with stable walking scores on the ALSFRS-RSE. These findings support the potential utility of these metrics for disease monitoring in ALS clinical care and trials.

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Weight-Guided Constraints for Body Model and Lead Selection in Pediatric CIED MRI Safety Simulations

Hameed, S.; Henry, K.; Jiang, F.; Bhusal, B.; Dillenbeck, H.; Gakenheimer-Smith, L.; Webster, G.; Golestani Rad, L.

2026-05-30 radiology and imaging 10.64898/2026.05.26.26354162 medRxiv
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Pediatric patients with cardiac implantable electronic devices (CIEDs) face limited MRI access due to RF-induced heating, and computational modeling is increasingly used to characterize this risk. The validity of these simulations, however, depends on pairing body models with clinically realistic lead configurations, guidance that is currently lacking. We retrospectively analyzed 302 CIED surgeries in 281 pediatric patients to derive weight-based constraints for simulation design. Weight alone discriminated epicardial from endocardial lead implantation with AUC = 0.90, and adding age and height yielded no improvement, supporting weight as a sufficient single-parameter selection metric. The probabilistic crossover between approaches occurred at 44~kg, substantially higher than the 10 to 15~kg threshold commonly cited in the literature, with a broad transition zone of 21 to 66~kg in which both lead types were routinely used. Lead length was likewise weight-constrained: only 25~cm leads were observed in patients below 6~kg, and leads of 45~cm or longer were uncommon below 50~kg. These findings yield a three-tier framework, with epicardial-only configurations below 21~kg, dual configurations within 21 to 66~kg, and weight-thresholded lead lengths throughout, enabling MRI safety simulations to focus on clinically realizable anatomy and device combinations.

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Evaluating the sensitivity of heart rate variability fractal correlation properties to training load variations: Implications for monitoring training readiness and durability

van Rassel, C. R.; Rummel, M.; MacInnis, M. J.

2026-05-30 sports medicine 10.64898/2026.05.27.26354281 medRxiv
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This study examined the utility of HRV detrended fluctuation analysis alpha-1 (DFA1) to assess readiness-to-train and exercise durability under varying acute training loads. Nineteen trained cyclists completed two 20-minute time-trials (TT) under rested and fatigued conditions. DFA1 was measured during a standardized warm-up (WU), 20-min TT, and standardized cool-down (CD). Power output (PO) and DFA1 responses were compared across conditions, and associations with performance and fitness (W/kg) were examined. DFA1 values declined with increasing WU and CD exercise intensity (p<0.001) and were significantly attenuated following the 20-min TT (p<0.001). While DFA1 profiles did not differ significantly between rested and fatigued conditions, lower pre-TT DFA1 was associated with reduced TT performance (p=0.022; r=0.55), suggesting relevance to training readiness. Additionally, an 18% decline in DFA1 between 10- and 20-min during the TT (p=0.031), and lower post-TT values at matched intensities were observed (p<0.001), indicating physiological perturbation from the 20-min TT. Fitter participants exhibited lower DFA1 values during the 20-min TT (p<0.001; r=-0.77), suggesting a greater capacity to sustain physiological stress. While DFA1 is responsive to exercise intensity and stress, offering potential to assess training readiness and durability, more robust fatigue protocols are needed to validate DFA1 as training load monitoring tool.

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Application of SinoPlan in Trajectory Planning for Robot-Assisted Intracerebral Hematoma Puncture

Zhang, F. y.; Yao, J.; Zhou, Q. y.; fang, Y. c.; Hu, A.; Wang, Y.; Ding, W.; Wu, X.; Gu, Y.

2026-05-27 surgery 10.64898/2026.05.24.26353998 medRxiv
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Robot-assisted hematoma puncture has seen significant development in primary hospitals across the country. Sino Plan software system is the core of the intelligent surgical robot, independently developed by Sinovation.We conducted a comparative study of imaging indicators, such as residual hematoma volume and hematoma clearance rate, as well as prognostic indicators, in patients who underwent hematoma puncture at our hospital over a 9-year period, before and after the introduction of Sino Plan.The results indicated that following the application of Sino Plan, the hematoma clearance rate was significantly enhanced, and the residual hematoma volume was markedly reduced. Regarding patient prognosis, there was no significant difference in GCS scores between the two groups, but the incidence of adverse prognostic events was lower in patients where Sino Plan was utilized.In conclusion, this 9-year retrospective analysis at our hospital reveals that Sino Plan offers distinct advantages. However, its application in certain special cases suggests that further improvements to the software are warranted to better meet the demands of more specific clinical scenarios.

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Validation of Gait Tasks in SynapTrack Mobile App for Cervical Spondylotic Myelopathy

Lewis, A.; Arkam, F.; Steel, B.; Chen, E.; Singh, P.; Yakdan, S.; Becker, I.; Guo, W.; Shahrabani, A.; Payne, P. R.; Ghogawala, Z.; Steinmetz, M. P.; Neuman, B.; Ray, W. Z.; Duncan, R.; Greenberg, J.

2026-05-29 surgery 10.64898/2026.05.27.26354225 medRxiv
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Background Gait impairment is a central sign of cervical spondylotic myelopathy (CSM) that is typically evaluated through subjective patient-reported questionnaires or objective in-clinic measures. These systems require substantial resources to administer and are poorly suited for longitudinal monitoring, however, emerging smartphone applications present an efficient alternative. We developed and assessed the validity of a data processing framework based on the SynapTrack smartphone application to assess gait function in individuals with CSM. Methods Participants completed walking tasks which were recorded on both the SynapTrack app and a gold standard gait mat. Acceleration data extracted from the smartphone by the app were filtered and processed to produce gait cycle features including velocity, step time, waveform features and frequency domain features. Standard gait features were compared across the two methods by correlation and Bland-Altman plots to assess validity. App-based gait features were then compared to the standard modified Japanese Orthopedic Assessment (mJOA) assessment to determine construct validity through correlation and ability to discriminate between individuals with CSM and healthy controls. Finally, intraclass correlation coefficients and coefficients of variation were used to measure test-retest reliability and standard variation across app features. Results A total of 110 participants were included in this study, of which 55 (50%) had CSM, 24 (22%) had peripheral neuropathy, and 31 (28%) were healthy controls. SynapTrack gait measures including velocity, step time, and double support showed strong validity as indicated through Bland-Altman plots and high correlation (>0.8) with mat features. In addition to the gait features, acceleration root mean square, acceleration crest, spectral entropy, and dominant frequency showed strong construct validity compared to the mJOA across correlation (0.2-0.54), trend test (p < 0.001), and AUROC (0.62-0.79) analyses. ICCs showed moderate test-retest reliability (0.52-0.67). Discussion The proposed framework for processing gait data showed strong validity compared to the gold standard mat and high construct validity compared to the mJOA suggesting the utility of the SynapTrack app as an efficient alternative to existing methods. The confirmation of gait metrics related to CSM severity and identification of relevant waveform and frequency domain features present opportunities to use smartphone apps to develop ecologically valid data driven markers of CSM severity.

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Randomised Trial of a Multilingual Conversational AI for Preoperative Education

Ke, Y.; Niu, C.; Liao, J.; Sim, J.; Abdullah, H. R.; Jin, L.; An, J.; Ho, H. S. S.; Tung, J. Y. M.; Tan, H. K.; Sng, B. L.; Ting, D. S. W.; Ong, M. E. H.; Liu, N.

2026-05-26 anesthesia 10.64898/2026.05.24.26353997 medRxiv
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Background Informed consent depends on patients' understanding of anaesthesia risk, yet comprehension remains poor despite routine preoperative consultation. Conversational artificial intelligence (AI) could establish patient-reported understanding before clinician contact, but whether such systems can achieve patient-reported understanding comparable to clinician-delivered education remains unknown. Methods We conducted a randomised equivalence trial (n = 130) of PEAR (Preoperative Education of Anaesthesia Risks), a multilingual retrieval-augmented conversational AI grounded in institutional consent materials, versus standard preoperative consultation in adults undergoing elective surgery. Results A total of 130 adults (mean age 52.4 +/- 14.5 years) were enrolled. Post-consultation understanding scores in the PEAR group met the pre-specified equivalence criterion compared with standard consultation across all three primary measures. Patients who interacted with PEAR before clinician contact achieved understanding scores comparable to those receiving standard face-to-face consultation alone. PEAR reduced documentation and consultation time, corresponding to a projected annual net benefit of approximately SGD 0.99 million (USD 0.78 million) at a single tertiary centre. Conclusions A retrieval-augmented conversational AI achieved patient-reported understanding of anaesthesia risk equivalent to standard preoperative consultation while substantially improving workflow efficiency. These findings support supervised deployment of conversational AI within perioperative care pathways while preserving clinician oversight for verification and patient-specific decision-making.

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Optical coherence tomography as a biomarker for frontotemporal dementia: a systematic review & meta-analysis

Wang, E.; Kohli, A.; Taha, H. B.

2026-05-27 neurology 10.64898/2026.05.19.26353366 medRxiv
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Background: Frontotemporal dementia (FTD) lacks widely accessible disease-specific biomarkers. Optical coherence tomography (OCT) and OCT angiography (OCTA) may provide non-invasive measures of retinal changes associated with neurodegeneration. We conducted a systematic review and meta-analysis evaluating retinal biomarkers in FTD compared with Alzheimer disease (AD) and controls. Methods: A systematic search of PubMed and Embase was conducted through April 25, 2026 according to PRISMA guidelines. Studies evaluating OCT/OCTA biomarkers in FTD with comparator groups were included. Inverse weighted random-effects models, publication bias assessments, and meta-regressions were performed. Results: Ten studies involving 139 individuals with FTD, 87 with AD, 29 with mild cognitive impairment, 14 with TDP-43 proteinopathy, 5 with tauopathy, and 255 controls were included in the systematic review; five studies were eligible for meta-analysis. Compared with AD, individuals with FTD demonstrated significantly thinner retinal nerve fiber layer (RNFL) thickness (SMD = -0.61, 95% CI -0.98, -0.24). Compared with controls, individuals with FTD exhibited significantly thinner ganglion cell layer-inner plexiform layer (GCL-IPL) thickness (SMD = -0.55, 95% CI -1.02, -0.08), whereas pooled analyses across multiple retinal biomarkers were non-significant (SMD = -0.19, 95% CI -0.52, 0.14). RNFL thickness correlated negatively with female % in FTD and positively with age in both AD and controls. Conclusions: Individuals with FTD exhibit lower RNFL thickness than AD and lower GCL-IPL thickness than controls, suggesting retinal alterations may reflect neurodegeneration. However, larger longitudinal studies with standardized OCT/OCTA protocols are needed to determine the diagnostic and prognostic utility of retinal biomarkers in FTD

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An ECG foundation model for generalizable cardiac function prediction across the lifespan

Yang, Y.; Peracchio, L.; Mayourian, J.; Miller, T.; La Cava, W.

2026-05-27 health informatics 10.64898/2026.05.26.26354128 medRxiv
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Background Artificial intelligence-enhanced electrocardiography (AI-ECG) enables scalable, low-cost cardiac dysfunction screening, but existing models are annotation-intensive and predominantly adult-derived, leaving paediatric generalizability uncertain. Paediatric cohorts exhibit highly variable cardiac morphology and function compared to adults, which may be useful for learning generalizable AI-ECG models. Methods We pretrained ECG-Fyler on a predominantly paediatric, all-age cohort at Boston Children's Hospital (1992-2023), annotated with a cardiology-specific coding system (Fyler codes), and evaluated it on assessments from echocardiography (echo) and cardiac magnetic resonance (CMR) studies. We validated on an external adult cohort from Columbia University Irving Medical Center. Performance was benchmarked against several AI-ECG foundation models by AUROC across age groups, lesion types, and limited-data scenarios. Findings The pretraining cohort comprised 782,138 ECGs from 255,271 patients (median age: 10.9 years, IQR: [2.8-16.8]). Internal evaluation included 178,495 ECG-echo pairs (median age: 10.9 [3.7-17.0]) and 8,584 ECG-CMR pairs (median age: 20.7 [15.6-29.6]). External validation included 82,543 ECG-echo pairs from adults (median age: 64.0 [52.0-74.0]). ECG-Fyler improved AUROC across biventricular dysfunction and dilation tasks, with the largest gains in low-data settings. In internal validation, ECG-Fyler detected low left ventricular ejection fraction (LVEF [&le;] 40%) from only 100 fine-tuning samples (AUROC: 0.80, 95% CI: [0.78-0.80]), outperforming other models (AUROC < 0.65) and improving with additional fine-tuning (AUROC: 0.94 [0.93-0.94]). Similar improvements were observed for CMR-derived LVEF, RVEF, and ventricular dilation. In external validation on adults, ECG-Fyler exhibited an AUROC of 0.83 (CI: [0.82-0.85]) for LVEF [&le;] 40%. After fine-tuning on less than 10% of external data, LVEF [&le;] 45% performance (AUROC: 0.87 [0.86-0.88]) outperformed a fully trained, site-specific prior model (AUROC: 0.85 [0.84-0.87]). Interpretation Pretraining on richly annotated, paediatric-dominant ECGs yields models that transfer efficiently across institutions and ages, supporting AI-ECG screening and triage when labels or imaging access are limited. Funding National Institutes of Health (R01LM012973); Kostin Innovation Fund, Boston Children's Hospital

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Patient Versus Prediction-Level Evaluation of a Dynamic Clinical Prediction Model of Sepsis

Tuttle, M.; Maas, C. C. H. M.; An, J.; Wessler, B. S.; Harvey, W. F.; Selker, H. P.; van Klaveren, D.; Kent, D. M.

2026-05-27 health systems and quality improvement 10.64898/2026.05.26.26354141 medRxiv
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The Epic Sepsis Model version 2 (ESMv2) is a prediction model embedded into the electronic medical record used to warn clinicians which hospitalized patients are at risk for sepsis. We conducted a retrospective cohort study of 31,951 hospitalizations of 25,760 patients to compare analyses conducted at the commonly used patient-level (where a maximum prediction prior to the onset of sepsis is used to measure performance) vs novel prediction-level (where each prediction is used to measure performance). Sepsis, defined by the Sepsis 3 criteria occurred during 1,049 hospitalizations (3.3%). Patient-level analyses suggested excellent discrimination AUC 0.86; [IQR 0.85, 0.87], whereas prediction-level analyses demonstrated lower performance AUC 0.62; [IQR 0.57, 0.65]. Low estimates of the positive predictive value (14.5% at the patient level vs 4% at the prediction level) imply a high number of false alerts. Common evaluation approaches may overstate the performance of dynamic prediction models and mislead clinical decision-making.

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Morphological feature remodeling of intracranial arteries in the context of inflammation and HIV-associated cognitive impairment

Hoang, N.; Yang, H.; Uddin, M. N.; Zhong, J.; Faiyaz, A.; Singh, M. V.; Boodoo, Z. D.; Sutton, K. R.; Wang, H. Z.; Sahin, B.; Khan, M. W.; Weber, M. T.; Yuan, C.; Chen, L.; Schifitto, G.

2026-05-27 hiv aids 10.64898/2026.05.19.26353071 medRxiv
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Background: Despite the success of combination antiretroviral therapy (cART), vascular comorbidities, including cerebrovascular disease, are more prominent in people living with HIV (PLWH) compared to people without HIV (PWOH). However, quantitative assessments of cerebrovascular morphometry and their associations with cognitive outcomes in the context of HIV are still limited. In this study, we explore this missing link. Methods: Magnetic Resonance Angiography (MRA) data, blood markers, and neurocognitive assessments were collected from 73 PWOH subjects (male: 57, female: 16; age: 53 {+/-} 16) and 99 PLWH subjects (male: 66, female: 30, age: 53 {+/-} 11). Vessel morphometric features were quantified using intraCranial Artery Feature Extraction (iCafe) to investigate associations between vessel morphometry, markers of monocytes, endothelial cell activation, and cognitive performance. Results: HIV status predicted a lower total number of branches ({beta} = -0.224, p = 0.001, d = -0.517) and shorter total distal length ({beta} = -0.173, p = 0.021, d = -0.370) with a moderate effect size. Total branch number was found to be negatively associated with plasma levels of monocyte markers (sCD14: r = -0.167, p = 0.033; sCD163: r = -0.157, p = 0.045) and positively correlated with white matter cerebral blood flow (r = 0.550; p [&le;] 0.05). HIV status was the strongest predictor of overall cognitive performance in ANCOVA model ({beta} = -0.219, p = 0.006, d = -0.453). Conclusions: Our results suggest that cognitive impairment in PLWH is associated with vessel morphology metrics. Monocyte immune activation may contribute to changes in vessel morphology.

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Can Large Language Models Diagnose Primary Immunodeficiency from Patient-Described Symptoms?

Reteig, L. C.; Woloshin, S.; Maglione, P. J.; Farmer, J. R.; Ong, M.-S.

2026-05-27 allergy and immunology 10.64898/2026.05.26.26353818 medRxiv
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Patients with primary immunodeficiency (PID) often face prolonged diagnostic delays and may increasingly turn to large language models (LLMs) to interpret their symptoms during this period. We evaluated whether an LLM could recognize PID from symptom descriptions derived from interviews with 21 PID patients. In a prior study, we showed that GPT-4o identified PID in 96% of cases when prompted with physician-written patient histories (Rider et al., JACI, 2024). Here, when prompted with symptom descriptions in patients' own words, GPT-5 identified PID in only 7 cases (33%), although it more broadly suggested immune system issues in 18 cases (81%). The gap between these findings indicates that LLMs are sensitive to the language and framing of symptom descriptions, performing substantially worse when patients describe their own symptoms in everyday language than when clinicians summarize patient histories in structured medical terms. This study underscores the need to carefully evaluate how LLMs are used in patient-facing applications.

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ERBB4 deficiency promotes atrial myopathy underlying the atrial fibrillation substrate

Yamaguchi, N.; Santucci, J.; Hong, S. J.; Ferrena, A.; Schlamp, F.; Willett, D.; Casdin, C. J.; Park, P. S.; Lin, X.; Xiao, J.; Hall, S.; Barnard, J.; Achter, J.; Kanhert, K.; Lundby, A.; Chung, M. K.; Van Wagoner, D. R.; Park, D. S.

2026-05-27 cardiovascular medicine 10.64898/2026.05.26.26354173 medRxiv
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Background Atrial fibrillation (AF) is a leading cause of stroke, cardiovascular morbidity, and mortality. Atrial myopathy, characterized by progressive metabolic, electrical, and structural changes, creates the arrhythmogenic substrate that drives AF. Defining the key drivers of atrial myopathic processes is essential for targeted therapies that can mitigate AF progression. Here we explore how reduced ERBB4 expression contributes to the development of left atrial myopathy. Methods We analyzed the Cleveland Clinic Biobank to compare left atrial ERBB4 levels in patients grouped by AF diagnosis. To investigate the impact of reduced ERBB4 levels on atrial tissue substrate, we created mouse models of cardiac-specific Erbb4 deficiency using Mlc2a (myosin light chain 2a)-Cre. Comprehensive physiological assessments were performed. Transcriptomic analyses of the left atrium were performed in an Erbb4 haploinsufficient mouse model and compared with human atrial datasets. Molecular validation of key dysregulated pathways was performed. Results We found that left atrial ERBB4 levels are reduced in patients with AF. Adult cardiomyocyte-specific Erbb4 heterozygous (Erbb4fl/+;Mlc2a-Cre) mice exhibited prolonged P-wave duration in the absence of ventricular dysfunction. Left atrial transcriptomic analysis in Erbb4 haploinsufficient mice showed upregulation of pathways related to fibrosis, apoptosis, and coagulation, and downregulation of pathways related to fatty acid metabolism and mitochondrial function, mirroring changes observed in pressure overload mouse models. A cross-species transcriptomic comparison revealed significant overlap between ERBB4-correlated gene expression and functional pathways in adult human atria and mice with Erbb4 haploinsufficiency. Validating the transcriptomic data, protein and functional assays demonstrated increased fibrosis, apoptosis, and oxidative stress in the mutant left atrial tissue. Conclusion Left atrial ERBB4 levels are reduced in AF patients. A mouse model of Erbb4 deficiency and human atrial transcriptomic analyses highlight a role for ERBB4 in supporting normal atrial metabolism while protecting against inflammation, apoptosis, and fibrosis.

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Early Life Determinants of Forward Compression Wave Intensity in Adults

Haynes, A.; Mynard, J. P.; van der Veen, M.; Carson, J.; Green, D. J.

2026-05-27 cardiovascular medicine 10.64898/2026.05.26.26354176 medRxiv
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Intro: Characteristics of the pulse wave transmitted through the carotid arteries are predictive of cognitive decline and cerebrovascular health in humans. This study aimed to identify risk factor trajectories in childhood, adolescence and early adulthood that are associated with forward compression wave intensity (FCWI) in the common carotid artery in adults aged 28 years. Methods: Systolic blood pressure (SBP), body mass index (BMI) and fasting blood glucose (FBG) measured at multiple time-points when participants were aged between 8-20 years were included in a trajectory analysis. At age 28 years, FCWI was measured in 402 (M=206, F=196) participants who underwent a Duplex ultrasound assessment of the common carotid artery. Statistical analysis assessed differences in FCWI between each trajectory group for males and females separately. Results: In males, four trajectory groups were identified for BMI, three for SBP, and two for FBG. In females, three trajectory groups were identified for BMI, SBP, and FG. In males, having higher BMI (P=0.006), SBP (P=0.021) and FBG (P=0.002) from ages 8-20 years was associated with greater FCWI at age 28 years. In females, no associations were found between FCWI at age 28-years and trajectory groups for BMI (P=0.185), SBP (P=0.289) or FBG (P=0.070). Conclusion: Having high BMI, SBP and FBG throughout childhood, adolescence and early adulthood was associated with higher FCWI in the carotid artery at age 28 years in males, but not females. This may have a direct impact on the etiology of cognitive decline and cerebrovascular disease in later life.

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Dentine markers of pre/early postnatal lead exposure links with brain, cognitive, and behavioral outcomes in adolescents

Marshall, A. T.; Kan, E.; Adise, S.; König, M.; McConnell, R.; Martinez, M.; Midya, V.; Arora, M.; Sowell, E. R.

2026-05-27 pediatrics 10.64898/2026.05.26.26354134 medRxiv
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Lead is a toxic metal ubiquitous in our environment. While dramatic reductions in lead sources have paralleled equivalent decreases in lead-poisoning rates, chronic lead exposure remains a critical public health concern. Childhood lead exposure (at its lowest levels) is liked to changes in cognitive development but less is known about lead's effects on children's brain structure, especially as a result of in utero exposure. We measured prenatal and early-postnatal lead exposure in shed deciduous teeth of 448 9- and 10-year-old children (from 20 United States cities) and linked those lead levels to childhood brain structure, cognition/behavior, and neighborhood- and family-level socioeconomic characteristics. Here we show negative associations between tooth-lead levels and the thickness of the brain's cortex, particularly in regions linked to language processing. With increasing tooth-lead levels, children of lower-income (versus higher-income) families showed steeper declines in receptive vocabulary. Caregiver-reported behavioral problems exhibited similar associations. With in utero exposure linked to adverse neurodevelopmental outcomes (well before lead exposure and its risks are evaluated by healthcare professionals), prenatal screening of maternal lead levels/exposure, coupled with recommended strategies to reduce its placental transmission, may help reduce lead's effects on future generations.

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Auditable cross-instrument detection of unusual multivariate psychiatric response configurations using a semantically aligned covariance subspace

Periwal, V.

2026-05-27 psychiatry and clinical psychology 10.64898/2026.05.22.26353902 medRxiv
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Background: Conventional psychiatric screening instruments summarize symptoms within individual scales and prioritize cases with high single-instrument additive score severity. This design treats items as independent within instruments and ignores cross-instrument covariance structure, making it insensitive to respondents whose responses are distributed across multiple domains in unusual combinations that remain below threshold on every individual scale. Methods: We analyzed two cohorts spanning older and younger adults. Item prompts from depression, stress, anxiety, and sleep instruments were embedded into a shared semantic space using a pretrained sentence encoder. Principal component analysis of the item-prompt embeddings alone---with no use of respondent data at this stage---was used to construct a low-dimensional subspace retaining 80\% of variance in the item embedding matrix. Normalized participant responses were then projected into this subspace, with Jaccard-based stability analysis used as a check on dimensional robustness. Multivariate deviation from the cohort norm was quantified with Mahalanobis distance using Ledoit-Wolf covariance regularization. Candidate outliers were defined by the empirical 95th percentile of the cohort-specific distance distribution. To isolate response configurations not already captured by conventional single-instrument extreme-value logic, we excluded all outlier respondents who had endorsed any individual item at the maximum value of its Likert scale on any instrument. For the remaining outliers, anomalous components were backtracked to their original item loadings for interpretation. Results: In the older-adult Health and Retirement Study (HRS) cohort, principal component analysis of 27 item-prompt embeddings showed that a 10-dimensional subspace provided a stable representation of cross-instrument semantic structure. In the younger-adult Xinxiang cohort the corresponding stable solution was 16-dimensional. In each cohort, seven respondents remained as multivariate outliers despite falling below every single-instrument extreme-value threshold. These cases were not characterized by uniformly severe symptom scores but by unusual cross-domain response configurations that became visible only in the shared semantic covariance subspace. The response structure of the retained configurations differed across cohorts: older-adult cases more often involved weak endorsement of mood-labeled items alongside nonzero body- and sleep-related responses, whereas younger-adult cases more often involved incomplete response configurations spanning mood, sleep, stress, and self-harm-related items. Conclusions: A semantically aligned, auditable covariance subspace provides a practical tool for flagging unusual multivariate response configurations that single-instrument additive screening may not flag. The method is interpretable at the level of original item contributions. It should be understood as a hypothesis-generating screen for unusual response configurations requiring further clinical assessment, not as a diagnostic instrument. Outcome validity remains to be established by prospective study.

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Data Assimilation Substitutes for Biological Complexity in Hybrid Influenza Forecasting Models

Alleman, T. W.; Van Wesemael, T.; Shanker, N.; Mietchen, M. S.; Loo, S.; Ajagbe, S. O.; Baetens, J. M.; Lemaitre, J.; Hill, A. L.; Truelove, S. A.; Bento, A. I.

2026-05-27 public and global health 10.64898/2026.05.19.26353597 medRxiv
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Hybrid mechanistic-statistical models offer interpretability and adaptability for short-term seasonal epidemic forecasting, but it remains unclear whether their accuracy depends more on increased biological complexity or on the assimilation of richer data. Using eight retrospective influenza seasons in North Carolina, we evaluate whether training on historical data and assimilating auxiliary emergency department (ED) visit data improves four-week-ahead hospital admission forecasts more than adding biological complexity (multi-subtype structure and cross-season immunity). Hierarchical Bayesian training on historical data improves accuracy by 22.4 % (95 % CI: 16.4-28.1 %), and inclusion of ED visit data yields a further 5.3 % (95 % CI: 3.0-7.6 %) improvement, whereas added biological complexity produces diminishing or null gains. We further observe a substitution effect in which ED visit data partially compensates for omitted biological structure. We deployed a simplified model variant in the 2025-2026 CDC FluSight Challenge and ranked among the top ensemble performers, supporting the robustness of Bayesian hierarchical training in real time. Together, these findings indicate that short-term forecast accuracy is driven more by historical learning and assimilating auxiliary signals than by biological fidelity, with implications for how forecasting systems should balance mechanistic complexity.

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AI Adoption for NCDs in Kenya: A Qualitative Study

Rayo, J.; Cushny, W.; Mwangi, M.; Wanyee, S.; Linguraru, M. G.; Nyaga, N.; Koros, H.; Bosire, M.; Obuya, M.; Ngaruiya, C.

2026-05-27 public and global health 10.64898/2026.05.26.26354008 medRxiv
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Background: Non-communicable diseases (NCDs) represent a critical public health challenge in Kenya, responsible for over 50% of inpatient admissions and 40% of deaths. While digital health tools and artificial intelligence offer promising ways to improve prevention, diagnosis, and management, little is known about how these tools are perceived and used in practice. There is limited research exploring the views and lived experiences of young people in Kenya, who are a strategic priority for NCD prevention because behavioral risk factors are established in this window, and for Community Health Providers (CHPs) who provide health services within the community. This study aims to address this gap by examining the perspectives of the burden of non-communicable diseases and the potential role of digital health technologies, including artificial intelligence, for preventing and managing these conditions in these specific populations. Methods: A qualitative research design using focus group discussions (FGDs) was employed in Nairobi (urban) and Busia (rural) counties between March and July 2024. Eight FGDs were conducted with 60 participants purposively sampled from three stakeholder groups: community health promoters (CHPs), healthcare workers (HCWs), and youth aged 18-35 years. A semi-structured guide, co-developed with a Community Advisory Board, explored beliefs about NCDs, health-seeking behaviors, lifestyle practices, and attitudes toward digital health and AI. Audio recordings were transcribed verbatim, translated where necessary, and analyzed thematically using grounded theory principles on NVivo software (v12). Results: Six consolidated themes emerged: (1) understanding of NCDs and perceived risk; (2) barriers to NCD prevention and care; (3) the role of CHPs; (4) adoption of AI tools for NCD management; (5) trust, ethics and access concerns; and (6) community-driven recommendations for AI integration. Significant barriers including stigma, economic constraints, and barriers to care were documented alongside enthusiasm for AI tools among youth and CHPs in both urban and rural areas. Conclusion: This study shows that AI tools are being used for NCD prevention and management through spontaneous community adoption. However, it emphasizes the need for culturally relevant, equitable, and community-driven solutions. Effective scaling requires the identification and bridging of digital literacy gaps, the establishment of affordable infrastructure, the protection of data privacy, and the integration of artificial intelligence tools into existing community health frameworks. This process should involve the collaboration of trusted intermediaries, such as CHPs and community leaders, to ensure successful outcomes. Future initiatives should prioritize participatory design, policy frameworks for ethical governance, and targeted capacity building to enhance acceptance and sustainability of digital health innovations in low- and middle-income country settings.