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Food Research International

Elsevier BV

Preprints posted in the last 7 days, ranked by how well they match Food Research International's content profile, based on 11 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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Compatibility of National Food Composition Databases with USDA FoodData Central: A Seven-Country LLM-Based Analysis

Nakagawa, S.; Yamamoto, A.

2026-06-01 nutrition 10.64898/2026.05.23.26353942 medRxiv
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To evaluate the international interoperability of food composition databases, we assessed the compatibility of seven national food composition tables with USDA FoodData Central (FDC) using the LLM-based matching method reported previously (Nakagawa and Yamamoto, 2026). Databases from four English-speaking countries (Canada, United Kingdom, Australia, and New Zealand), South Korea, and Japan were compared with 8,158 USDA FDC entries (SR Legacy and Foundation Foods, excluding Survey/FNDDS). Match rates varied by country (62.0-89.7%) and food category. After excluding six USDA categories unsuitable for cross-national comparison, 45.2% of the remaining 6,290 entries were not matched by any country. Canada showed the highest concordance, reflecting shared North American food supply. Japan and South Korea showed similar low coverage for vegetables and spices. These findings suggest that while USDA FDC represents a practical foundation for a globally comprehensive food composition database given its breadth, systematic incorporation of country-specific foods and classification schemes will be necessary to achieve true international interoperability.

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Polyphenol Estimator: A New Tool to Estimate Dietary Polyphenol Intake from ASA24 and NHANES Dietary Data

Wilson, S. M. G.; Oliver, A.; Lemay, D. G.

2026-05-29 nutrition 10.64898/2026.05.27.26353727 medRxiv
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Background: Recent food-based recommendations for flavan-3-ols highlight a growing need to understand the breadth of our dietary polyphenol exposure. However, estimation of dietary polyphenol intake remains challenging, requiring custom computational tools that are often difficult to implement or not fully reproducible. Objective: We aimed to an automated, user-friendly tool to estimate polyphenol intake from diet recalls and records. Methods: We developed Polyphenol Estimator, a tool that processes dietary data from the Automated Self-Administered 24-Hour (ASA24) Dietary Assessment Tool or the Automated Multiple-Pass Method from the National Health and Examination Survey (NHANES). Polyphenol Estimator disaggregates foods using the FDA Food Disaggregation Database into ingredients, matches these ingredients to FooDB, and estimates polyphenol intake at the total, class, and compound level. Optionally, these polyphenol estimates can be used to calculate the Dietary Inflammatory Index (DII). Polyphenol Estimator is freely available online (https://swi1.github.io/polyphenol_estimator) with a tutorial for users with limited programming experience. Results: To illustrate Polyphenol Estimator, we applied it to two days of diet recalls from adults ([≥] 20 years) in NHANES 2021-2023 (n = 2778). For 97.7% of participants, less than 2.5% of reported foods went unmapped, with 75.7% of participants having complete mappings. Total polyphenol intake was 517 +/- 439 (mean +/- SD) mg/1000 kcal, largely from green tea, coffee, black tea, apples, wine, oranges, and blueberries. At the class level, polyphenols classified as organooxygen compounds, flavonoids, and cinnamic acids and derivatives were top intake contributors. At the compound level, cyptochlorogenic acid, neocholorogenic acid, and caffeic acid were top contributors. Lastly, the DII was 1.4 +/- 1.9, indicating the average diet had proinflammatory potential. Conclusions: Polyphenol Estimator offers an automated method to obtain total, class, and compound-level polyphenol estimates from dietary data to aid future efforts to understand polyphenol intake exposures and their biological impact on health.

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Comparative Study on Image Quality of Deep Learning and Adaptive Statistical Iterative Reconstruction-V in Thin Layer CT of liver Lesions

Yang, J.; Li, L.; Cao, J.; Zhang, J.

2026-05-26 radiology and imaging 10.64898/2026.05.23.26353923 medRxiv
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Objective:This study aims to compare the advantages and disadvantages of DLIR and adaptive statistical iterative reconstruction-V (ASIR-V) in thin-slice (2.5 mm) CT images of hepatic lesions characterized by high and low contrast. Additionally, the study seeks to determine the optimal DLIR strength for the evaluation of liver lesions. Methods:A retrospective analysis was performed on 90 patients who underwent abdominal contrast-enhanced CT scans. Group A comprised 48 patients with low-contrast lesions, while Group B included 42 patients with high-contrast lesions. The acquired images were reconstructed using post-processing DLIR at low (DLIR-L), medium (DLIR-M), and high (DLIR-H) strengths, all with a slice thickness of 2.5 mm (subgroups A1-A3, B1-B3). Furthermore, images were reconstructed with ASIR-V at 50% strength at slice thicknesses of 2.5 mm and 5 mm (subgroups A4/B4 and A5/B5, respectively). CT values and standard deviations (SD) of the liver and lesions were measured, and the corresponding signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The edge rise slope (ERS) was determined using ImageJ software by measuring CT values along a line from the liver parenchyma to the lesion. Objective metrics were compared using one-way ANOVA, with independent samples t-tests applied for inter-group differences. Subjective scoring, which encompassed noise level, diagnostic confidence, and lesion margin delineation, was conducted by two radiologists, with differences analyzed using the Kappa test. Results: Objective evaluation revealed a progressive decrease in lesion SD and a progressive increase in SNR and CNR from subgroups A1/B1 to A3/B3. The SD of Group A2 decreased by 57.4% compared to A4, while the SNR and CNR of A2 icreased by 19.3% and 24.6% compared to A4. Although subgroup B2 had a lower SNR than B5, the difference was not statistically significant. SNR and CNR in B2 increased by 24.1% and 11.9%, respectively, compared to B4. ERS gradually decreased from A1/B1 to A3/B3. ERS values in A2 and B2 increased by 27.0% and 39.4%, respectively, relative to A5 and B5. Although A3 had a lower ERS than A1 and A2, all DLIR subgroups exhibited higher ERS than A5; similar trends were observed in Group B. Subjective evaluation indicated good inter-reader agreement (Kappa > 0.61, p < 0.05). As DLIR strength increased, noise scores rose progressively in both groups. However, noise in A2 and B2 was lower than in A4/A5 and B4/B5. Diagnostic confidence and lesion margin delineation scores were highest in A2 and B2, while all subjective scores were lowest in A5 and B5. Discussion: Most prior studies evaluated the liver, vessels, or confirmed that image quality can be guaranteed at low doses. However, there are few studies on specific individual lesions. Therefore, this study aims to investigate specific individual lesions. The details and detection rate were analyzed separately to confirm the clinical acceptability of 2.5-mm DLIR image in different contrast lesions. Conclusion: For both high- and low-contrast hepatic lesions, DLIR provides superior image quality compared to ASIR-V, with the 2.5mm DLIR-M setting being optimal. DLIR-M reduces image noise, improves spatial resolution, and produces images more suitable for diagnostic purposes.

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Hospital Waste Management Readiness in Urban Bangladesh: A Knowledge, Attitudes, and Practices Assessment

Bhuiyan, N. N.; Bhuiyan, K. N.; Aktar, S.; Biswas, R. S. R.; Rakib, T. M.; Hossain, M. A.

2026-05-28 health systems and quality improvement 10.64898/2026.05.25.26354076 medRxiv
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Healthcare waste (HCW) management is a critical determinant of occupational safety, infection control, and environmental protection, particularly in low- and middle-income settings. Using the knowledge-attitude-practice (KAP) framework, this study assessed cognitive, behavioral, and institutional dimensions of HCW management among healthcare workers in urban Bangladesh. A cross-sectional survey was conducted among 342 cleaners and nurses in hospitals in the Chattogram Metropolitan Area (CMA) and Cumilla City Corporation (CuCC). Marked disparities were observed across professional groups. Training coverage was significantly lower among nurses than cleaners in CMA (22.5% vs. 48.7%; p = 0.002), whereas in CuCC nurses showed higher coverage (69.0% vs. 52.3%; p < 0.01). Knowledge of color-coded waste segregation was generally inadequate, with only 39.3% of CMA cleaners correctly identifying pharmaceutical waste bins compared with 60.0% of nurses (p < 0.01); CuCC nurses demonstrated substantially higher awareness (82.8%). Attitudinal indicators favored nurses, with strong hygiene and environmental risk awareness (95-100%) compared with cleaners (66-87.3%; p < 0.001). Despite this, compliance with segregation practices remained low across both sites (<30%). Several institutional support indicators were more favorable among nurses, particularly in CuCC. These findings indicate a significant knowledge-practice gap, emphasizing that effective HCW management requires not only training but also strengthened institutional structures and enforcement mechanisms to reduce public health and environmental risks.

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Resting energy expenditure and thermic effect of a high-fat meal in the early follicular and mid-luteal phases of the menstrual cycle: a crossover trial protocol

Goulet, N.; Lyndon, S.; Beauregard, N.; McInnis, K.; Mauger, J.-F.; Doucet, E.; Imbeault, P.

2026-05-30 nutrition 10.64898/2026.05.25.26354032 medRxiv
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Introduction: Menstrual cycle phase has been proposed as a source of intra-individual variability in resting energy expenditure and the thermic effect of food in premenopausal females, yet studies examining the thermic effect of food across menstrual cycle phases report conflicting findings. Methods: This protocol describes a secondary analysis of prespecified outcomes from a non-randomized, two-period crossover trial primarily designed to assess postprandial plasma triglyceride concentrations across menstrual cycle phases (ClinicalTrials.gov: NCT07459465) in 12 premenopausal females aged 18-30 years, free of chronic disease and hormonal contraceptive use, recruited in Ottawa, Canada. Participants complete two experimental sessions: one in the early follicular phase and one in the mid-luteal phase, each involving consumption of a high-fat meal. Eleven secondary outcomes will be reported: fasting resting energy expenditure, thermic effect of food, respiratory exchange ratio, carbohydrate oxidation rate, lipid oxidation rate, desire to eat, hunger, fullness, prospective food consumption, serum beta-estradiol, and serum progesterone. Masked outcome analyses are performed using linear mixed-effects models. Results: Recruitment began on 26 March 2026; results will be reported in the Stage 2 manuscript. Discussion: Findings from this trial may help clarify whether menstrual cycle phase constitutes a meaningful source of intra-individual variability in energy metabolism, with implications for the design of metabolic research in premenopausal females.

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Nutritional, behavioral and anthropometric factors associated with colorectal cancer in Nouakchott, Mauritania: a case-control study

Tolba, N.; Najdi, A.; El Hfid, M.; Hmeied Maham, M.; Mohamed Brahim, S.; Tolba, A.; Sellal, N.

2026-05-26 epidemiology 10.64898/2026.05.23.26353931 medRxiv
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Background Colorectal cancer is a growing public health concern in low- and middle-income countries, particularly in the context of nutritional transition and changing lifestyles. In Mauritania, evidence on factors associated with colorectal cancer remains limited. This study sought to identify nutritional, behavioral and anthropometric factors associated with colorectal cancer among adults living in Nouakchott. Methods A case-control study was conducted in Nouakchott between January and April 2026. The study included 50 confirmed colorectal cancer cases and 100 controls with no personal history of cancer. Data were collected using a standardized questionnaire covering sociodemographic characteristics, dietary habits, behavioral factors and anthropometric measurements. Crude and adjusted odds ratios with 95% confidence intervals were calculated using binary logistic regression. Results Low educational level was more frequent among cases than controls, 70.0% versus 27.0%, and remained independently associated with case status after adjustment (aOR = 4.98; 95% CI: 1.81-13.70; p = 0.002). Being married or living with a partner was also associated with case status (aOR = 3.72; 95% CI: 1.19-11.66; p = 0.024). Abdominal obesity was associated with colorectal cancer in bivariate analysis but not after adjustment. High consumption of salty foods remained associated with case status in the multivariate model (aOR = 47.45; 95% CI: 4.83-466.40; p = 0.001). However, this estimate should be interpreted with caution given the wide confidence interval and the limited sample size (n=50 cases). Refined sugars and canned foods were associated with case status only in bivariate analysis. Inverse associations observed for coffee and sugar-sweetened beverages should be interpreted cautiously because of possible reverse causality. Conclusion Low educational level and high consumption of salty foods were the most defensible factors associated with colorectal cancer in this study. These findings support strengthening nutrition-related prevention and health education interventions in Nouakchott. Larger studies with more detailed dietary assessment are needed to confirm these associations.

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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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Vaginal Antisepsis for Major Gynecologic Surgeries Using Chlorhexidine Gluconate versus Povidone Iodine: A Systematic Review and Meta-Analysis

Dias, Y.; Gebrekidan, F.; Lowder, J.; Sutcliffe, S.; Yaeger, L.

2026-05-27 obstetrics and gynecology 10.64898/2026.05.26.26353429 medRxiv
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ABSTRACT OBJECTIVE: We performed a systematic review and meta-analysis (SRMA) of post-surgical outcomes, comparing chlorhexidine gluconate (CHG) versus povidone iodine (PI) for vaginal antisepsis of major gynecologic procedures. DATA SOURCES: Ovid Medline, Embase, Scopus, Embase, Cochrane, and Clinicaltrials.gov were searched between 1986 and December 2023, for studies comparing CHG with PI for vaginal antisepsis of major gynecologic operations. STUDY ELIGIBILITY CRITERIA: We included Randomized Controlled Trials (RCTs) and non-RCTs comparing CHG to PI for vaginal antisepsis of major gynecologic operations. The primary outcome was surgical site infections (SSIs) and the secondary outcome was urinary tract infections (UTIs) and vaginal irritation. METHODS: Summary estimates were calculated by fixed effects models when I2 [&le;] 25% and by random effects models when I2 > 25%. Statistical analysis was performed using RevMan 5.4.1. The protocol for this systematic review was registered on PROSPERO (ID CRD42022378101). RESULTS: Nine studies met the inclusion criteria, four of which were randomized controlled trials (RCTs). 9538 patients were included, 4300 (45%) of whom were allocated to CHG and 5238 (55%) to PI. No statistically significant difference in SSI incidence was found for vaginal antisepsis with CHG versus PI in pooled analyses (n= 9538 patients; RR 1.20; 95% CI 0.92-1.57; I2 =0%). In contrast, a significantly higher risk of UTIs was observed for vaginal antisepsis with CHG than with PI (n=6061 patients; RR 1.48 95% CI 1.03-2.14; I2 = 0%). CONCLUSION: In our SRMA, there were no significant differences in SSI risk when either CHG or PI was utilized for antiseptic vaginal preparation. Interestingly, vaginal antisepsis with PI was associated with a lower incidence of post-operative UTIs following major gynecologic surgery. Our findings support current guidelines that form of vaginal antisepsis can be used for SSI prevention. They also suggest that PI may result in fewer postoperative UTIs but further randomized studies are needed to support these findings. Key words: surgical site infection, surgical wound infection, urinary tract infection, urogynecologic surgery, Chlorhexidine, Povidone Iodine, surgical antiseptic,

9
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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Hierarchical organ aging signatures from routine abdominal CT add incremental disease risk stratification beyond blood biomarkers

Deng, Z.; Wang, Y.; Shi, Y.; Wang, L.; Qureshi, T. A.; Gaddam, S.; Javed, S.; Hsu, Y.-C.; De Righi, D. R.; Azab, L.; Diwan, G.; Yang, J. D.; Xie, Y.; Yuan, C.; Vendrami, C. L.; Rodriguez, A.; Specht, K.; Jeon, C. Y.; Chaudhry, H.; Buxbaum, J.; Pisegna, J. R.; Yaghmai, V.; Goessling, W.; Hernandez-Barco, Y. G.; Miller, F. H.; Tirkes, T.; Espinoza, S.; Musi, N.; Dey, D.; Sung, K. H.; Pandol, S. J.; Li, D.

2026-05-27 radiology and imaging 10.64898/2026.05.19.26353206 medRxiv
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Biological aging is heterogeneous across organ systems, yet whether CT-derived abdominal aging provides prognostic value beyond routine clinical data and whether organ decomposition adds beyond a unified estimate remains untested. We developed and evaluated organ-specific and ensemble biological age models from radiomic features across five abdominal organs in 68,675 CT scans from 32,883 subjects, evaluated on alignment with chronological age of healthy subjects (nested cross validation: MAE=3.68 years, R^2=0.90). In sequential analyses restricted to adults aged 20-60 years which is the stratum of strongest BAG-disease association, ensemble biological age gaps provided incremental prognostic value beyond demographic covariates for all-cause disease and mortality (Delta C-index=0.141, 0.051) and beyond routine blood biomarkers (Delta C-index=0.048), confirming CT-derived aging captures structural information beyond laboratory markers. Organ-specific biological age added incremental prognostic value beyond ensemble selectively for focal diseases: cardiovascular (aorta, Delta C-index=0.091) and hepato-pancreatic (pancreas, Delta C-index=0.096). These findings establish a hierarchical organization of CT-derived biological aging, positioning routine CT as a source that adds prognostic value to existing clinical biomarkers.

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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.

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Thalamic sonication in chronic disorders of consciousness: a mechanistic single-arm clinical trial

Monti, M. M.; Hopkins, A. R.; Spivak, N. M.; Cain, J. A.; Gumarang, J.; Patterson, D.; Rosario, E. R.; Schnakers, C.

2026-05-28 neurology 10.64898/2026.05.26.26354167 medRxiv
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Background: Thalamic low-intensity transcranial focused ultrasound (tFUS) has shown promise for increasing behavioral responsiveness in disorders of consciousness (DOC), but no study has examined whether it can causally modulate the well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC impairment. Methods: Sixteen adult patients (44% Female; Age, M=37.81, SD=15.97) with a chronic DOC (Time Since Injury, M=3.39, SD=1.94 years) secondary to severe brain injury (TBI 44%, non-TBI 56%) underwent a 10-day inpatient, longitudinal, single-arm, open-label protocol. tFUS was delivered in a single session targeting the left central thalamus. Well-known behavioral (CRS-R), electrophysiological (EEG {delta}/{beta} ratio), metabolic (18F-FDG PET), and polysomnographic outcomes were assessed at baseline and after sonication. Results: The maximum CRS-R total score increased significantly following tFUS compared to baseline (M=13.27 vs. M=10.33; t(14)=7.407, p<0.001, d=1.913), as did the global EEG {delta}/{beta} ratio (N=14; W=17, p=0.025, r=0.68), with the degree of frontal slowing positively predicting behavioral gains ({tau}b=0.51, p=0.016). Glucose metabolism decreased bilaterally in thalamus and frontal, temporal, and parietal cortices at both post-tFUS timepoints compared to baseline. Finally, N2 sleep increased by 33% following tFUS (N=11; t(10)=2.386, p=0.038, d=0.72), though this did not survive correction. No severe adverse events were observed. Conclusion: Thalamic tFUS can causally modulate well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC. The convergent inhibitory signature across these measures suggests a thalamocortical reset mechanism, complementing existing excitatory neuromodulation approaches and providing the mechanistic foundation for a large, randomized sham-controlled trial.

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Grounding Language Models in Behavioral Science to Scale Physical Activity Interventions for Hispanic/Latinx Populations

Mantena, S. D.; Johnson, A.; Schuetz, N.; Tolas, A.; Montalvo, S.; Delgado-SanMartin, J.; Ramirez Posada, M.; Du, L.; Zhang, S.; Huynh, A. D.; Oppezzo, M.; King, A. C.; Schmiedmayer, P.; Lawrie, A.; Rodriguez, F.; Ashley, E.; Kim, D. S.

2026-05-28 cardiovascular medicine 10.64898/2026.05.26.26354165 medRxiv
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Objective: Hispanic/Latinx populations in the U.S. experience higher rates of chronic disease linked to physical inactivity, yet digital health interventions remain largely inaccessible to more than 16 million Hispanic/Latinx adults with limited English proficiency. While large language models (LLMs) offer scalable personalization, their use in non-English behavioral coaching is unexplored. This study introduces MHC-Coach-ES, a Spanish-language LLM fine-tuned on the Transtheoretical Model (TTM) of behavior change. Materials and Methods: We fine-tuned Llama 3-70B-Instruct using a two-stage pipeline. First, the model was adapted to Spanish health and motivational language using a 2.21-million-token corpus. Second, it was instruction-tuned on 3,268 translated human written messages to align the model with the Transtheoretical Model (TTM) of Behavioral Change. We compared MHC-Coach-ES with Llama 3-70B-Instruct and translated human-expert messages using a forced-choice preference survey (N = 77) and blinded expert review (N = 2). Results: Spanish-speaking participants significantly preferred MHC-Coach-ES messages over translated human-expert messages (81% preference, P<0.001). Linguistic analysis showed that MHC-Coach-ES produced more temporally anchored messages than the base model (65% vs. 20%), while maintaining readability. In blinded evaluation, clinical experts rated MHC-Coach-ES higher for alignment with Transtheoretical Model stages than human-expert messages (4.83 vs. 4.38 out of 5). The base model also outperformed translated expert messages across preference and expert ratings. Conclusions: Generative AI can operationalize behavioral science frameworks in Spanish, offering a scalable approach to reducing health disparities. The strong performance of both MHC-Coach-ES and the base model highlights the promise of generative and personalized approaches over translation-based localization for theory-driven behavioral interventions.