Citations

Objective: This study aims to develop a contrast-free, high-sensitivity ultrasound method, denoted as Radon transform-based flow measurement (R-Flow), for in vivo mapping of microvascular flow vectors and for establishing R-Flow-derived vector-field metrics to noninvasively quantify microcirculatory patterns in liver cirrhosis. Impact Statement: R-Flow enables robust, contrast-free imaging of microvascular dynamics and demonstrates translational feasibility in the human liver. Its direction-aware indices offer pilot in vivo quantification of flow redistribution and remodeling, providing unique insights into hepatic flow dynamics. Introduction: Microvascular dysfunction is a hallmark of many diseases, yet noninvasive visualization and quantitative assessment of abnormal microcirculation remain limited. Methods: R-Flow leverages Radon transform to decode red blood cell dynamics from the spatiotemporal domain of ultrasound flow signals, reconstructing velocity vectors at microvascular scale. From these vector maps, unique direction-aware indices are further derived to characterize flow distribution and heterogeneity. Results: Validated across simulations, phantoms, and in vivo studies, R-Flow provides robust velocity estimation across a wide range (1 to 60 mm/s). Notably, it enables high-sensitivity microvascular flow vector mapping of human liver, showing strong agreement with references ( r > 0.9). In a rat model, these direction-aware indices revealed a shift from healthy multipath perfusion in control livers to directionally biased vascular pattern in cirrhotic livers, demonstrating significant correlation with pathological indicators. Conclusion: R-Flow enables noninvasive, contrast-free mapping of microvascular blood flow velocity and offers a promising approach for high-resolution assessment of microvascular flow characteristics.

Abstract Background New insights into community-acquired pleural infection microbiology may enable development of more rapid and accessible diagnostics that can streamline treatment. This study systematically compared molecular approaches for pathogen detection in pleural fluid from patients with such infections. Considering the need for rapid results with minimum hands-on time and test complexity, off-label use of the cassette-based, random-access BIOFIRE Joint Infection Panel (BF-JIP, bioMérieux) with and without supplementary in-house polymerase chain reaction (PCR) assays was evaluated. Methods Pleural fluids from 162 subjects from the Mayo Clinic (Rochester, Minnesota) and Haukeland University Hospital (Bergen, Norway), where molecular tests are routinely used for analyzing pleural fluid, were studied. The performance of the BF-JIP was compared to 16S rRNA gene PCR followed by Sanger and/or next-generation sequencing (16S rRNA gene PCR/sequencing), an in-house PCR panel specifically designed for pleural space infections, and culture. Results The BF-JIP supplemented with 3 in-house PCR assays targeting Fusobacterium nucleatum group, Streptococcus intermedius/constellatus, and Aggregatibacter aphrophilus detected 96.8% of pleural infections, providing complete microbial profiles in 70.1%. In comparison, the detection rate of 16S rRNA gene PCR/sequencing was 92.2%, providing complete microbial profiles in 87.0%. Culture detected bacteria in only 31.9% of pleural fluids, providing complete microbial profiles in 15.3%. Conclusions These results underscore the importance of molecular approaches in diagnosing pleural space infections and demonstrate the feasibility of panel-based PCR-based diagnostics for these sometimes-complex infections. The BF-JIP, designed for testing synovial fluid, could be modified to provide a useful diagnostic for testing pleural fluid.

Objective Age of symptom onset is highly variable in familial frontotemporal lobar degeneration (f‐FTLD). Accurate prediction of onset would inform clinical management and trial enrollment. Prior studies indicate that individualized maps of brain atrophy can predict conversion to dementia in f‐FTLD. We used a Bayesian linear mixed‐effect (BLME) prediction method for identifying accelerated brain volume loss to predict conversion to dementia. Methods Participants included 234 asymptomatic or prodromal carriers of C9orf72 , GRN , or MAPT mutations (including 21 dementia converters) with ≥3 longitudinal magnetic resonance imaging (MRI) T1‐weighted scans. The BLME models established individual voxel‐wise gray matter trajectories using the first 2 scans. Person‐specific clusters of accelerated volume loss were estimated in subsequent scans and tested as predictors of dementia conversion compared with other approaches in time‐varying Cox proportional hazard models covarying for age. Receiver‐operating characteristic (ROC) curves estimated utility of cluster volume in discriminating which participants converted to dementia within 24 months. Results The BLME cluster volume predicted conversion to dementia in f‐FTLD mutation carriers overall and separately in C9orf72 , GRN , and MAPT , with comparable hazard ratios observed for atrophy W‐maps and regional volumes. Within a 24‐month timeframe, BLME cluster volume discriminated dementia converters from non‐converters with larger areas under the curve (AUCs) than other approaches. Interpretation Bayesian‐modeled individualized atrophy scores predict dementia progression among asymptomatic f‐FTLD mutation carriers and may have increased utility compared with other structural imaging methods when studying individuals over shorter timeframes that align with clinical trial design. ANN NEUROL 20269999:n/a–n/a

Objective: To assess the link between retinal vascular health and cognitive performance in a diverse population, using a novel mobile laboratory platform and portable color fundus photography. Background: The retina is an accessible window into brain health. Studies that had highlighted the link between retinal vasculature and cognition included clinical populations or narrowly defined research cohorts, with limited generalizability. To address the need to expand this research to demographic and geographic diverse communities, we launched a mobile laboratory platform across rural and urban Arizona zip codes. Methods: 240 subjects were recruited in our prospective community-based study. We assessed cognition using the MindCrowd web-based testing platform and analyzed verbal paired associates (VPA) task, a validated measure of verbal associative memory sensitive to age-related cognitive decline. Non-mydriatic color fundus photographs were obtained using the portable hand-held Aurora camera (Optomed), two images per eye (disc- and macula-centered). Image processing and vascular feature quantification were automatically conducted using Automorph software. Linear regression models examined the associations between retinal vascular metrics and VPA, adjusting for age, sex, education attainment, and risk factors. Results: Our cohort’s mean age was 45 +/-16.7 years, 32.9% were male and 39.5% had a college degree. In disc-centered fundus images, fractal dimension strongly associated with chronological age (p = 1.04E-10). Greater artery tortuosity in the retinal zones B and C was associated with lower VPA (p = 0.02 and p = 0.004, respectively). In macula-centered images, fractal dimension showed the strongest association with age (p = 4.31E-11), reinforcing its utility as a robust biomarker of vascular aging. Males had wider average artery caliber in zone B (p=0.02). Zone B vein fractal dimension (p=0.002) and vein vessel density (p=0.006) were the strongest predictors of VPA. Conclusions: This study demonstrates the safety, feasibility, and utility of a mobile laboratory to collect high-quality non-mydriatic color photos and cognitive data across a geographically diverse cohort. Arterial tortuosity and venous fractal dimension and density, particularly in retinal zone B, were predictive of cognitive performance, after adjusting for vascular health covariates. Retina may become a scalable and accessible platform for studying brain aging in the general population.

Background: Periodontitis is a potential modifiable factor influencing dementia risk. We examined whether improving periodontal health via regular flossing is associated with lower dementia risk. Methods: A total of 9,766 Atherosclerosis Risk in Communities (ARIC) study participants with teeth were followed from visit 4 (1996-1998) through 2021. Cox proportional hazards regression was used to estimate associations between regular dental flossing (≥1/week) and incident dementia. Covariates included age, race, gender, hypertension, diabetes, alcohol use, smoking status, obesity, physical activity, education level, income, insurance status, brushing frequency, regular dental care use and apolipoprotein E4 (APOE4) allele status . Cumulative incidence functions were estimated using death as a competing event. Results: Participants had mean age 62.6 years (SD = 5.6), 56% female, 79% white, 21% black, 63% reported regular flossing and 29.2% participants carry at least one APOE4 allele. The cumulative incidence of dementia was 52.6 % overall over 25 years. Regular flossing was independently and significantly associated with a lower hazard of developing dementia (HR = 0.90, 95% CI: 0.82–0.98, p = 0.02) after adjustment for all the covariates. In contrast, tooth brushing frequency (p=0.55) and regular dental care visit (p=0.22) were not significantly associated with dementia risk. By 25 years of follow-up, the cumulative incidence of dementia was 50% among flossers compared with 57% among non-flossers (Gray’s test p<0.0001, Figure). This translated to an Absolute Risk Reduction of 7%, Relative Risk Reduction of 12%, Number Needed to Floss 14. Conclusion: Flossing, but not tooth brushing or regular dental care, is independently associated with a reduced hazard of incident dementia. Dental flossing may be an additional strategy to reduce dementia risk. For every 14 individuals who floss ≥1/week, one fewer person will develop dementia.

Variability and persistent gaps in reporting have been consistently observed across studies evaluating adverse events in healthcare, dating back to the early days of the patient safety movement. Incomplete descriptions—particularly missing details regarding study design, conduct, methodologies and applied definitions—impede interpretation, hinder critical appraisal and limit reproducibility. These deficiencies not only obstruct a shared understanding of findings but also diminish the overall impact such studies may have on patient safety initiatives and policy development. To address these challenges and enhance the quality of reporting, we developed the SESAME (Standard Elements in Studies of Adverse Events and Medical Error) reporting guideline. SESAME is a 44-item checklist designed to support comprehensive and standardised reporting in studies evaluating potential patient harm. The guideline was developed over a 2-year period by an international, multidisciplinary panel through a consensus-driven process aligned with Enhancing the QUAlity and Transparency Of Health Research Network standards.