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MethodsX

○ Elsevier BV

Preprints posted in the last 7 days, ranked by how well they match MethodsX's content profile, based on 16 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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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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Cardiac MRI at 3.0T in the presence of implantable cardioverter defibrillators (ICDs)

Reiter, T.; Weber, O. M.; Weiss, i.; Kraus, N.; Kress, S.; Bauer, W. R.

2026-10-21 cardiovascular medicine 10.64898/2026.10.16.26364740 medRxiv
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Patients with implantable cardioverter-defibrillators (ICDs) often are excluded from receiving CMR scans at 3.0T due to ICD-induced image artifacts. This work aims to transfer sequence protocols established for CMR imaging in the presence of ICDs at 1.5T to a first human application at 3.0T. All measurements were performed on a clinical 3T MRI scanner. Phantom measurements were used to establish and optimize wideband PSIR LGE imaging at 3.0T. Volunteer measurements with externally placed ICDs were used for optimization of CINE imaging and wideband PSIR imaging. Thirdly, patients with implanted ICD were examined with the optimized protocols. Human measurements showed that SA stacks obtained with spoiled GRE after contrast agent showed a markedly lower artifact burden than the conventional approach. For scar imaging, a wideband PSIR with a bandwidth of 3kHz and a frequency offset of +750Hz allowed a sufficient suppression of relevant artifacts in the majority of scans. No strong correlation between the image quality and the distance between the cardiac silhouette and the device was detected. The presented work shows the feasibility of clinical cardiac MRI at 3.0T including GRE-CINE and wideband PSIR-LGE for patients with ICDs.

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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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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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Hidden in Plain Sight: Clinical Profile, Diagnosis, and Outcomes of Cardiac Amyloidosis in Cali, Colombia

Barbosa-Balaguera, S.; Castano, O.; Echeverry, E. J.; Llano, C. D. M.; Muriel Ruiz, A. J.; Diaz, J. B.; Cordoba, A. M. T.; Ayala-Zapata, S.; Velasquez-Trujillo, L. A.; Escandon, A. H.

2026-10-20 cardiovascular medicine 10.64898/2026.10.15.26365704 medRxiv
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Background Cardiac amyloidosis is an increasingly recognized cause of heart failure in older adults, yet Colombian data, and data from the southwest of the country in particular, remain scarce. We describe the clinical, diagnostic, imaging and outcome profile of patients with cardiac amyloidosis at two high-complexity institutions in Cali. Methods Observational, descriptive, retrospective, two-center study. Patients were identified in the institutional registries of both centers using ICD-10 codes for amyloidosis, and clinical data were abstracted manually from medical records. Continuous variables are reported as median (interquartile range) and categorical variables as counts and percentages over the number of patients with available data. Results Thirty-two patients were analyzed (median age 77 years; 68.8% men). Heart failure (90.6%), atrial fibrillation (46.9%) and carpal tunnel syndrome (31.2%) were frequent. The etiological classification depended on the test considered: bone scintigraphy was positive (Perugini 2-3) in 23 of 26 patients studied (88.5%), but a monoclonal protein was screened for in only 22, and the full non-invasive criteria for ATTR were met in 16 of 32 (50.0%). Genetic testing was positive in 9 of 18 tested, and the variant was Val142Ile in all 8 patients in whom it was characterized. The working diagnosis was ATTR in 26 patients (81.2%) and AL in 6 (18.8%). Tafamidis was used in 37.5%. Eleven of the 31 patients with known vital status died (35.5%), and NT-proBNP was markedly higher among those who died (6640 vs 1186 pg/mL; p=0.003). Conclusions In this southwestern Colombian cohort, cardiac amyloidosis presented as the classic transthyretin phenotype, with the Val142Ile variant in all 8 patients in whom it was characterized. Bone scintigraphy was frequently positive, but screening for a monoclonal protein was often omitted, so only half the cohort met the full non-invasive criteria for ATTR. Mortality was high and closely associated with NT-proBNP.

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Heart rate variability and electrocardiographic parameters among workers exposed to chronic intermittent hypobaric hypoxia in the Peruvian Andes: A cross-sectional study Cardiac autonomic function in Andean workers

Montes-Madariaga, E. S.; Ortiz-Saavedra, J. B.; Mamani Castillo, J. S.; Valencia-Pacheco, A. I.; Ballon Echegaray, J. A.; Paz Torres, I. L.; Leon Vasquez, R. A. J.

2026-10-16 cardiovascular medicine 10.64898/2026.10.15.26365599 medRxiv
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Chronic intermittent hypobaric hypoxia is an occupational exposure experienced by workers who alternate between high-altitude worksites and lower-altitude resting locations. Its effects on cardiac autonomic modulation and electrocardiographic parameters remain insufficiently characterized in Andean workers. This study aimed to compare heart rate variability and electrocardiographic parameters between workers exposed to chronic intermittent hypobaric hypoxia and controls working permanently at lower altitude in Arequipa, Peru. An observational cross-sectional study was conducted in 96 male workers aged 20-60 years. The exposed group included 53 workers performing rotational shifts at altitudes [&ge;]3,000 m above sea level with rest periods at <2,500 m, while the control group included 43 workers working permanently at <2,500 m. Heart rate variability was assessed during the morning rest period in Arequipa, at approximately 2,300 25 m above sea level, using a Polar(R) H10 heart rate sensor after 15 minutes of rest. Participants also underwent standard 12-lead electrocardiography. Vital signs were clinically similar between groups. No statistically significant differences were observed in PR interval, corrected QT interval, time-domain heart rate variability parameters, or frequency-domain heart rate variability parameters. In this sample of apparently healthy male workers evaluated during their rest period at moderate altitude, exposure to chronic intermittent hypobaric hypoxia was not associated with significant differences in resting heart rate variability or standard electrocardiographic parameters.

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Teaching an ECG model where to look does not make it more robust to missing leads: a pre-registered comparison of guideline-based attention guidance with random lead masking

BOU ALI, M. N.; Mahmoud, M.

2026-10-19 cardiovascular medicine 10.64898/2026.10.17.26365795 medRxiv
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Background. Real-world 12-lead electrocardiograms (ECGs) often have missing or corrupted leads. A deep-learning classifier can be prepared for this by random lead masking during training, or by injecting clinical knowledge, for example by pulling its attention towards the leads that guidelines use for each diagnosis. Whether this knowledge adds robustness beyond masking is unknown. Methods. Pre-registered comparison of three arms sharing one network (per-lead 1D-ResNet encoder and per-diagnosis attention over the 12 leads): standard training (M0); random whole-lead masking (M1); masking plus a Kullback-Leibler penalty pulling attention towards a fixed guideline-derived key-lead map (M2, guideline-based attention guidance). Six diagnoses; five seeds per arm. Development on PTB-XL (21,799 ECGs); single sealed evaluation on PTB-XL fold 10 (2,198 ECGs) and on CODE-15% (233,204 exams, external validation). Primary endpoint: AUROC difference M2 - M1, averaged over first-degree AV block, right and left bundle branch block and atrial fibrillation and over 1 to 6 lost (zeroed) leads, with a patient-level paired BCa bootstrap 95% confidence interval. Results. The guidance did not change robustness: {Delta}AUROC -0.0010 (95% CI -0.0033 to +0.0006), an interval entirely within the pre-specified +-0.02 margin; the result was unchanged with another bootstrap seed, other interval methods and leave-one-diagnosis-out analyses. Masking improved AUROC: M1 - M0 = +0.0134 (95% CI +0.0102 to +0.0172) when one key lead was lost, and the number of lost leads tolerated before AUROC fell by more than 0.02 rose from 7 (M0) to 10 (M1). M2 attention matched the map and M2 was non-inferior on intact ECGs, but its calibration slope was lower for all six diagnoses in both datasets. M2 lost slightly more when all key leads were lost together (-0.0067) and gained only when one to three leads remained (exploratory; AUROC 0.9408 vs 0.9210 with 11 leads lost). CODE-15% reproduced every pattern (primary -0.0007, 95% CI -0.0011 to -0.0003). Conclusions. Random lead masking suffices to make an ECG classifier robust to missing leads; adding guideline knowledge aligns attention with clinical criteria but adds no robustness and worsens calibration. Guideline-aligned attention should not be taken as evidence of robustness.

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Plantar Thermography for Longitudinal Remote Monitoring of Chronic Heart Failure

Esposito, M. L.; Xuan, L.; Zemp, E.; Zile, M. R.; Tedford, R. J.; Linders, D.; Prins, K. W.

2026-10-21 cardiovascular medicine 10.64898/2026.10.20.26364428 medRxiv
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Rural patients with heart failure (HF) have poor access to care, worse outcomes, and may benefit from at-home monitoring. We evaluated whether foot temperature measured using a thermographic floor mat was associated with invasively measured cardiac output and whether longitudinal temperature changes preceded HF events. We conducted a two-part prospective, observational single-center study using the SmartMat (Podimetrics, Somerville, MA), which acquires plantar thermograms and ambient temperature. In the acute study, patients undergoing clinically indicated right heart catheterization completed 4 scans on the same day. In the chronic study, patients with a HF hospitalization in the past year and New York Heart Association Class II-III symptoms were instructed to use the device and a scale daily for 6 months. A HF event was defined as receiving at least one dose of intravenous or subcutaneous diuretic. Thirty patients were enrolled in the acute study. Mean right hallux temperature positively correlated with thermodilution cardiac output (r=0.63, p<0.001). 42 patients were enrolled in the chronic study. Among patients experiencing an HF event, ambient-adjusted hallux temperature declined in the 15 days immediately preceding the event compared with days 15-30 before the event. Plantar thermograms are associated with invasively measured cardiac output and may detect subclinical worsening before HF events. Foot temperature may provide complementary information regarding HF decompensation, supporting further evaluation of plantar thermography for remote HF monitoring.

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Narrow Is Slow: CT-Derived Anatomic Isthmus 3 Width and Arrhythmogenic Substrate in Repaired Tetralogy of Fallot

Kosmopoulos, M.; Liskov, S.; Amir, R.; Berger, R. D.; Cedars, A.; Chehab, O.; Chrispin, J.; Fisher, S.; Fuller, S.; Fraint, H.; Armstrong, A. K.; Ziakas, I.; Aronis, K. N.

2026-10-19 cardiovascular medicine 10.64898/2026.10.16.26365751 medRxiv
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Background: Anatomic isthmus 3 (AI 3) is defined as the myocardium between the pulmonary valve annulus and the ventricular septal defect patch that persists after tetralogy of Fallot (ToF) repair. Ventricular tachycardia (VT) propagated through slow conducting AI 3 (SCAI 3) represents a significant cause of morbidity in ToF. There is an unmet need for non-invasive identification of SCAI 3 in patients with ToF. Objectives: To assess whether the anatomic features of AI 3 as derived from cardiac computed tomography (CT) can predict slow conduction velocity during EP study. Methods: This retrospective single-center study included patients with ToF who underwent an electrophysiologic study and had AI 3 width measured from the pre-procedure cardiac CT. All patients underwent programmed ventricular stimulation, and electroanatomic. Logistic regression was performed to assess the relationship between AI 3 width and the presence of SCAI 3. Results: Of 27 consecutive patients with ToF, twelve patients were found to have SCAI 3, and ten patients were found to have SCAI 3 mediated VT. The AI 3 was significantly narrower in patients with SCAI 3 compared to those with normal AI 3 conduction (18.4 +/- 6.6 mm vs. 29.2 +/- 9.0 mm; p = 0.001). An AI 3 width above 21.5 mm carried a negative predictive value of 80.0%. Conclusion: In adults with repaired ToF referred for electrophysiology study, a narrower CT-derived AI 3 width was associated with SCAI 3 identification. AI 3 width measured on a CT obtained before PV replacement could help guide invasive risk stratification.

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Deep learning-based electrocardiographic differentiation of Takotsubo syndrome from acute anterior myocardial infarction: explainability, human-AI interaction, and a utilization bias hypothesis

Kagawa, E.; Kato, M.; Hidaka, T.; Kunita, E.; Hironobe, N.; Matsui, S.; Kobayashi, Y.; Uotani, Y.; Teramoto, T.; Yoshii, K.; Okumoto, T.; Tani, M.; Dote, K.

2026-10-19 cardiovascular medicine 10.64898/2026.10.15.26365116 medRxiv
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Background: Artificial intelligence (AI) may improve electrocardiographic differentiation of Takotsubo syndrome from acute anterior ST-segment elevation myocardial infarction (STEMI), but its impact on human diagnostic performance, the added value of visual explanations, and differences by reader background and experience remain uncertain. Methods: Using 12-lead electrocardiogram (ECG) images from two hospitals, we developed and externally validated an ensemble of three deep learning models after self-supervised pretraining and fine-tuning. The diagnostic task used ECGs recorded within 14 days after symptom onset, regardless of reperfusion status. We conducted a four-phase reader study. Phases 1-3 compared unaided interpretation, a reference sheet, and additional AI assistance. In Phase 4, readers evaluated a new ECG set after randomization to reference-sheet support alone, with AI predictions, or with AI predictions plus gradient-weighted class activation mapping (Grad-CAM) heatmaps. Diagnostic correctness was analyzed using generalized linear mixed-effects models. Exploratory analyses examined differences by cardiologist status and experience. Results: Development and external-validation cohorts, including healthy controls, comprised 832 and 95 participants, respectively. For Takotsubo-STEMI discrimination, external-validation accuracy was 0.914, with areas under the receiver operating characteristic and precision-recall curves of 0.970 and 0.984. Seventy healthcare providers completed the reader study. The estimated probability of correct diagnosis increased from 0.632 without assistance to 0.864 with AI assistance (odds ratio [OR], 3.71; P<0.001). In randomized Phase 4, AI assistance improved accuracy vs reference-sheet support alone (OR, 4.28; 95% CI, 3.08-5.95; P<0.001), and Grad-CAM provided additional benefit (OR, 1.53; 95% CI, 1.04-2.25; P=0.033). Exploratory analyses showed greater improvement among less experienced readers; with AI assistance, non-cardiologists outperformed cardiologists. AI-assisted readers remained less accurate overall than the model alone. Conclusions: An ECG image-based ensemble differentiated Takotsubo syndrome from anterior STEMI and improved reader accuracy. Visual explanations provided additional benefit, while experience-related differences highlight the importance of effective human-AI interaction.

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Fully Automated Multi-Chamber Strain Profiling in Consecutive Patients Undergoing Transthoracic Echocardiography: Feasibility, Functional Clustering, and Prognostic Implications

Noh, S. A.; Park, J.; Yoon, Y. E.; Jeon, J.; Jang, Y.; Lee, S.-A.; Bak, M.; Choi, H.-M.; Hwang, I.-C.; Cho, G.-Y.

2026-10-21 cardiovascular medicine 10.64898/2026.10.20.26365880 medRxiv
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Aims: Myocardial strain enables sensitive assessment of cardiac function, but its clinical application has largely focused on individual chambers or selected patient populations. We evaluated the feasibility and clinical relevance of fully automated multi-chamber strain assessment in consecutive patients undergoing routine transthoracic echocardiography (TTE). Methods and results: This retrospective study included 8,350 consecutive adults undergoing TTE. A hospital-wide artificial intelligence (AI)-based system automatically measured left ventricular (LV) global longitudinal strain (LVGLS), left atrial (LA) reservoir strain (LASr), and right ventricular (RV) free-wall strain (RVFWS). AI-derived LVGLS was available from at least one apical view in 97.1% of patients and from all three views in 94.8%; LASr and RVFWS were available in 94.1% and 94.5%, respectively, resulting in complete multi-chamber strain assessment in 90.3%. Strain measures showed modest correlations with conventional chamber-specific echocardiographic parameters and differential associations with clinical outcomes. Gaussian mixture modeling identified three distinct clusters characterized by preserved multi-chamber function, RV-dominant dysfunction, and pan-chamber dysfunction. Compared with the preserved cluster, pan-chamber dysfunction was associated with the highest risk of all-cause death or heart failure hospitalization (adjusted hazard ratio, 3.44; 95% CI, 2.43-4.88; P<0.001). Prognostic associations remained evident in patients with LV ejection fraction (LVEF) [&ge;]50%, and cluster assignment provided incremental prognostic information beyond clinical factors, LVEF, and RV fractional area change. Conclusions: Fully automated multi-chamber strain assessment was feasible in a large consecutive TTE cohort. Integrating strain across cardiac chambers may provide complementary functional characterization and identify clinically relevant clusters with prognostic information beyond conventional assessment.

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Left Ventricular Diastolic Intraventricular Pressure Differences and Propagation Velocity with 4D-Flow MRI in Patients with Hypertrophic Cardiomyopathy

Stipechi, L. V.; Craiem, D.; Gencer, U.; Casciaro, M. E.; Hulot, J.-S.; Hagege, A.; Soulat, G.; Mousseaux, E.

2026-10-21 cardiovascular medicine 10.64898/2026.10.15.26365692 medRxiv
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Background: Transthoracic echocardiography (TTE) remains the gold standard for assessing left ventricular (LV) diastolic dysfunction (DD), but noninvasive alternatives are needed to overcome geometric and acoustic limitations. 4D-Flow MRI enables comprehensive assessment of intraventricular pressure differences (IVPDs) and flow propagation velocity (VP). We aimed to evaluate 4D-Flow-derived IVPDs and VP in patients with hypertrophic cardiomyopathy (HCM). Methods: Thirty-eight HCM patients and 38 age- and sex-matched healthy controls underwent TTE and 4D-Flow MRI. Spatiotemporal maps of velocity and IVPDs, decomposed into inertial and convective components, were derived along the main inflow streamline from the mitral valve to the apex. Peak early filling rate (PEFR) was used to normalize IVPDs and VP. Results: While absolute peak flow rates were comparable, HCM patients exhibited significantly faster VP (100.4 vs. 60.2 cm/s, p < 0.01) and higher positive early E IVPD (1.40 vs. 0.92 mmHg, p < 0.01) compared to controls. Normalizing IVPDs by PEFR amplified group differences, revealing a markedly increased flow-normalized E-IVPD (5.13 vs. 2.94 x 103 mmHg.ml1.s, p < 0.001) and deeper reverse ER IVPD (-6.06 vs. -4.61 x 103 mmHg.ml1.s, p < 0.01) in HCM. These differences were primarily driven by the inertial components. Multivariable analysis demonstrated that ER IVPD is independently determined by PEFR and the TTE E/E' ratio (r = 0.65, p < 0.001). Conclusions: 4D-Flow MRI-derived, flow-normalized IVPDs and propagation velocity provide robust, noninvasive markers of altered LV chamber stiffness and impaired diastolic filling in HCM, offering deeper 3D hemodynamic insights into diastolic dysfunction.

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Pre-Deployment Cardiovascular Risk Assessment and Outcomes among United States Antarctic Program Participants: Insights from Contemporary Risk Models

LeBlanc, D. P.; Qadeer, A.; Krishna, S. R. G.; Forrester, A.; Patel, A.; Shi, D.; Nagueh, E.; Hsu, J.; Bhobe, N.; Gaalema, D. E.; McKeith, J.; Jneid, H.; Allencherril, J.

2026-10-16 cardiovascular medicine 10.64898/2026.10.14.26365580 medRxiv
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Background: Cardiovascular (CV) screening is critical for personnel deploying to Antarctica, where geographic isolation and limited medical care make the management of acute cardiovascular events challenging. The utility of contemporary risk prediction tools such as the AHA PREVENT equations in this unique population remains uncertain. Methods: We retrospectively analyzed 154 individuals referred for enhanced CV evaluation before deployment to the U.S. Antarctic Program (USAP). Participants were evaluated across three temporal cohorts (2018-2020, 2021-2023, and 2024-2026). Demographics, CV risk factors, cardiac testing, and deployment clearance outcomes were collected. Risk was estimated using the Framingham Risk Score (FRS), AHA/ACC Pooled Cohort Equations (PCE), and AHA PREVENT risk models. Results: The cohort was predominantly male (79.9%; mean age 44.6 {+/-} 14.6 years), and abnormal ECG was the most common referral trigger (70.8%). Median 10-year risk was low by PREVENT and FRS and borderline elevated by PCE (PREVENT 2.7% [IQR 1.1-6.6], FRS 2.3% [IQR 0.5-7.1], and PCE 6.1% [IQR 2.4-9.2]). Among 72 participants with all scores, 51% were classified discordantly; PREVENT ASCVD agreed closely with FRS (=0.77) but poorly with PCE (=0.24-0.35), which consistently estimated higher risk. PCE was calculable in 52.6% versus 70.8% for PREVENT. Overall, 132 participants (85.7%) were cleared for deployment, while 8 (5.2%) were not physically qualified (NPQ); 6 of these NPQs were due to cardiovascular causes. Of 22 cardiac medical evacuations during the study period, 21 involved individuals without prior advanced cardiovascular screening. One screened individual was evacuated for symptoms subsequently found to have no cardiac cause. Conclusions: Risk calculators disagree substantially in the fitness-selected population. We recommend PREVENT as the primary risk-stratification tool as it is the most contemporary derivation, incorporates renal function, is race-agnostic, extends to heart failure, applies from age 30, and agrees closely with FRS, easing transition. Targeted imaging, including coronary artery calcium scoring, may supplement intermediate-risk candidates.

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Reporting of Pericardial Adverse Events with Immune Checkpoint Inhibitors: A Disproportionality Analysis of the FDA Adverse Event Reporting System

Balakrishna, K.; Bhatt, V.; Hammond, A.; Bawoke, M. M.; Fradley, M. G.; Zlotoff, D. A.; Neilan, T. G.

2026-10-21 cardiovascular medicine 10.64898/2026.10.19.26365946 medRxiv
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Background. Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events in almost any organ. While myocarditis has received the most attention, data on pericardial disease with ICI use are limited. We examined pericardial adverse event reporting with nine ICIs using the FDA Adverse Event Reporting System (FAERS). Methods. We combined legacy AERS and current FAERS quarterly files from January 2011 to June 2026 into 18,629,240 unique cases, deduplicated by case number, and removed cases the FDA had listed as deleted. ICI exposure was identified from generic names, brand names, development code names and the active-ingredient field. Pericardial events were defined by seven MedDRA preferred terms. We estimated reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian information components (IC) and empirical Bayes geometric means (EBGM). We also examined myocarditis co-reporting, time trends, a comparison with other antineoplastic agents, a MedDRA query-based outcome, and 14 alternative definitions. Results. The analysis included 18,514,045 cases: 277,434 involved an ICI, 34,792 carried a pericardial term, and 1,680 had both. Pericardial events were reported disproportionately with ICIs (ROR 3.35 (95% CI 3.19 to 3.52); PRR 3.34; IC025 1.62). Eight of nine agents had a ROR above 1 (3.32 to 5.63). Among the most frequently reported terms, estimates were highest for cardiac tamponade (5.59 (95% CI 4.98 to 6.28)), followed by pericardial effusion (3.83 (95% CI 3.60 to 4.07)) and pericarditis (2.09 (95% CI 1.89 to 2.31)). After removing cases that also reported myocarditis, the ROR was 3.13 (95% CI 2.98 to 3.30). Most sensitivity analyses gave similar estimates (ROR 3.13 to 3.47); defining exposure by generic drug names alone, which identified only 44% of exposed cases, gave 3.99. Compared with cases naming other L01 antineoplastic agents, the ROR was 1.13 (95% CI 1.08 to 1.19): 1.28 (95% CI 1.20 to 1.36) for ICI-only cases and 0.96 (95% CI 0.89 to 1.04) when another antineoplastic was also named. The ICI-specific reporting odds ratio fell each quarter (odds ratio 0.977 per quarter, 95% CI 0.973 to 0.980). Conclusions. In FAERS, pericardial events were reported more often with ICIs than with other drugs across most agents and terms; however, incidence and causation cannot be determined. The excess over other antineoplastic agents was small, and reporting disproportionality declined over time. These findings support clinical awareness of pericardial disease in patients receiving ICIs and warrant study in data that can measure incidence.

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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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Preoperative Systemic Immune-Inflammation Index and Clinical Outcomes After Coronary Artery Bypass Grafting: A Systematic Review and Meta-analysis

Nourian, S.; Jalalian Rad, K.; Ghasemi, M.; Mosavi Mirkalaie, M.; Tayebi, N.; Ashrafi, M. M.; Nourallahzadeh, M. H.; Norouzi, A. R.

2026-10-20 cardiovascular medicine 10.64898/2026.10.17.26365801 medRxiv
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Background: The systemic immune-inflammation index (SII) is a routinely available blood-derived marker with potential prognostic relevance after coronary artery bypass grafting (CABG). We evaluated associations between preoperative SII and postoperative outcomes. Methods: PubMed, Embase, Scopus and Web of Science were searched to 1 October 2026, with supplementary searches through 14 October 2026. Peer-reviewed observational studies evaluating preoperative SII in adults undergoing CABG were eligible. Methodological quality was assessed using the Newcastle-Ottawa Scale. Compatible categorical associations and exploratory adjusted continuous mortality effects were pooled separately using restricted maximum-likelihood random-effects models; other findings were summarized descriptively. Results: Thirty-one reports were included, with an aggregate sample of 30,976 and possible cohort overlap; five contributed to meta-analysis. Two off-pump cohorts comprising 1,378 patients and 180 atrial-fibrillation events yielded an imprecise crude association with postoperative atrial fibrillation (OR 1.60, 95%CI 0.53-4.82; I2=68%). An exploratory crude synthesis indicated greater intra-aortic balloon pump use with higher SII (OR 2.45, 95%CI 1.16-5.18; I2=51%). Two cohorts with differing follow-up yielded an exploratory adjusted mortality HR of 1.11 (95% Wald CI 1.05-1.18) per study-specific SD increase in log-SII. In one 624-patient cohort, high SII was associated with postoperative acute kidney injury after adjustment (OR 3.35, 95% CI 2.25-4.97).Apparent atrial-fibrillation discrimination varied (AUC 0.587-0.946). Conclusions: Preoperative SII showed associations with selected adverse outcomes after CABG, supporting further evaluation as an accessible prognostic marker. Its incremental value beyond established clinical risk models requires validation. Keywords: Systemic immune-inflammation index; Coronary artery bypass grafting; Atrial fibrillation; Prognosis; Systematic review

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The Effect of Regionalization of Thoracic Surgery on Blood Transfusion at the Ottawa Hospital

Smith, J.; Smith, B.; Pittman, T.

2026-10-19 health economics 10.64898/2026.10.15.26365639 medRxiv
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This paper examines the impact of Cancer Care Ontario's regionalization of lung cancer surgery on blood transfusion use for thoracic surgery at The Ottawa Hospital. Using aggregate data scraped from the paper ''Changing trends in blood transfusion: an analysis of 244,013 hospitalizations'' by Shehata et al. (2014) we estimated the effect regionalization on the log mean number of blood transfusions among thoracic surgeons (who treat lung cancer), utilizing other surgical specialties as controls. We found that the average number of blood transfusions increased significantly among thoracic surgeons following the opening of a new cancer care centre at the hospital in December 2009, while control specialties showed no parallel change. Contextualizing these results in a modified ''population level'' treatment threshold model, it is argued that the main driver of this increase in blood transfusions among thoracic surgeons was due to the influx of less skilled thoracic surgeons to The Ottawa Hospital, and the closing of thoracic surgery units at smaller hospitals which was part of the broader regionalization process.

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Disagreement between AI and Radiologists: Quantifying Direction and Fragility

El Kaddouri, B.; Gevenois, P. A.; Bankier, A. A.

2026-10-21 radiology and imaging 10.64898/2026.10.19.26364791 medRxiv
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Background: Conventional performance metrics do not indicate whether artificial intelligence (AI)-platforms and radiologists are right or wrong on the same examinations, nor whether their non-agreement is more often beneficial or harmful. Objective: To develop, illustrate, and apply directional metrics quantifying non-agreement between radiologists and AI-platforms against a common reference standard, and to adapt a fragility-based framework for quantifying the statistical robustness of these metrics. Methods: We defined Positive Non-Agreement (PNA, AI-platform correct, radiologist incorrect), Negative Non-Agreement (NNA, radiologist correct, AI-platform incorrect), and Net Non-Agreement (NENA, their difference). Metrics were illustrated in three hypothetical scenarios of 1,000 examinations each and applied to three previously published AI-radiologist studies on pulmonary embolism and mammography. Bootstrap confidence intervals were calculated, and a reclassification fragility index (FI) quantified the minimum case reclassification needed to remove statistical support for NENA's direction. Results: In illustration, NENA was positive in two scenarios and negative in one. In the three published studies, NENA ranged from -4.18% to +10.74% and decreased consistently with increasing radiologist experience (junior residents, +6.27%; consultants, +1.45%), a gradient driven primarily by declining PNA with modest increase in NNA. The reclassification FI was defined for all three illustrative scenarios (range, 0.10%-1.70%) and for six of the seven comparisons from these studies (range, 0.34%-4.31%), but not for the weakest comparison, whose confidence interval for NENA included zero. Conclusions: PNA, NNA, and NENA provide a directional, case-level complement to conventional performance metrics for AI-radiologist non-agreement. The accompanying reclassification FI offers a statistically grounded, generalizable method for quantifying their robustness.

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Quantifying the Pharyngeal Wall Thickness on Modified Barium Swallow Studies: A Scoping Review and Reliability Study

Mao, S.; McMillan, H.; Leone, J. D.; Barbon, C. E. A.; Buoy, S. N.; Brock, K. K.; Lai, S.; Naser, M. A.; Fuller, C. D.; Hutcheson, K. A.; InHANCE Research Program Working Group,

2026-10-19 radiology and imaging 10.64898/2026.10.17.26365811 medRxiv
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Purpose: Posterior pharyngeal wall (PPW) thickening is a common structural manifestation of treatment-related internal lymphedema in patients with head and neck cancer and can be evaluated using lateral videofluoroscopic images acquired during modified barium swallow (MBS) studies. However, no standardized method currently exists for quantitative measurement. Methods: This two-phase methodological study first conducted a scoping review to characterize existing approaches to PPW thickness measurement and identify the principal factors contributing to variation in PPW thickness measurement. Eight studies were identified with variation observed across these measurement factors. An empirical reliability study was then performed using 107 MBS studies from 93 Head and Neck Cancer patients. Two independent raters annotated 10 anatomical landmarks on pre-swallow and post-swallow resting frames, and a computer-assisted algorithm quantitatively generated seven candidate PPW thickness measurements based on different vertebral reference points and measurement directions. Reliability was assessed intraclass correlation coefficients (ICCs). Results: Inter-rater reliability was highest for the measurement originating from the midpoint of C3 and extending perpendicular to the anterior C3 surface (ICC, 0.78; 95% CI, 0.72-0.83). Among the normalization references, C2-C4 vertebral length demonstrated greater reliability than C3 vertebral length, with an ICC of 0.88 (95% CI, 0.85-0.91). No significant differences were observed between pre-swallow and post-swallow PPW thickness measurements across the evaluated approaches. Conclusions: These findings provide a methodological foundation for more standardized and reliable quantification of PPW thickness, with potential to expand the role of MBS from the functional evaluation of swallowing to include quantitative characterization of pharyngeal structural abnormalities.

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Compound climate extremes predict dengue risk at operational lead times across Brazil

Fletcher, C.; Mila, C.; Moirano, G.; Araujo, E.; Lührsen, D.; Codeco, C.; Codeco Coelho, F.; Lowe, R.

2026-10-19 public and global health 10.64898/2026.10.16.26365716 medRxiv
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Brazil has one of the highest dengue burdens globally, with transmission influenced by climate events. Yet, the effects of compound climate extremes on dengue risk and prediction have not been quantified to date. Using a Bayesian spatiotemporal model of monthly dengue cases across 435 health regions from 2010 to 2025, we estimated relative risk associated with interacting long-lag and short-lag drought indicators and temperature anomalies across nine Koppen-Geiger climatic zones, adjusting for absolute temperature and El Nino-Southern Oscillation. Long-lag dry, mid-lag warm and short-lag wet conditions were associated with the highest relative risk in five climatic zones, with temperature anomalies modifying hydrometeorological dynamics more strongly in temperate than tropical areas. Climate covariates improved the prediction of case counts and outbreaks compared to baseline models at lead times of 1, 3, 6 and 12 months, and for the upcoming season 5 months ahead. Improvements were greatest in the Northeast, Southeast, and Midwest. Recent dengue incidence provided the greatest improvement at the 1-month lead, whereas combining incidence with climate information performed best at 3- and 6-month leads. We extended our framework to weekly state-level predictions of the season ahead to align with national public health planning. We proposed a multi-staged dengue forecasting approach to enhance early warning and response across Brazil.