Citations

Abstract Introduction Burnout among healthcare professionals remains a critical public health issue linked to impaired cognition, emotional exhaustion, and diminished clinical performance. Structured breathing practices have demonstrated promise in improving autonomic regulation and cerebral oxygenation, yet their feasibility and acceptability in real-world healthcare settings remain underexplored. Objectives This single-arm pilot feasibility trial aims to evaluate the feasibility, acceptability, and implementation appropriateness of a structured breathing-based intervention for healthcare professionals across community-based Mayo Clinic Health System (MCHS) sites. Secondary objectives include assessing usability and engagement with the mobile breathing platform, while exploratory analyses will examine preliminary signals of change in psychological well-being and cerebral hemodynamics. Methods and Analysis A total of 40 physicians and nurses reporting moderate or greater burnout will be enrolled across four MCHS sites. Participants will complete a four-month structured breathing program delivered primarily online, supported by a mobile application for practice tracking. Assessments will occur at baseline, 2 months, and 4 months, with optional functional near-infrared spectroscopy (fNIRS) measures of cerebral oxygenation collected at baseline and 4 months in a subset. Primary outcomes include (1) recruitment yield, retention, and adherence rates; (2) acceptability and participant satisfaction (survey and qualitative feedback); and (3) implementation appropriateness measured by the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Secondary outcomes assess digital engagement and usability through mobile analytics and the System Usability Scale (SUS). Exploratory outcomes evaluate psychological indicators—burnout, depression, anxiety, perceived stress, sleep, fatigue, professional fulfillment, and resilience—and physiological endpoints (fNIRS). Analyses will be descriptive, summarizing feasibility metrics with 95% confidence intervals. Progression criteria (recruitment ≥75%, retention ≥80%, adherence ≥70%, AIM/IAM/FIM ≥4.0) will determine readiness for a definitive hybrid effectiveness–implementation trial. Ethics and Dissemination The study is approved by the Mayo Clinic Institutional Review Board (IRB # 25-009320). All participants will provide informed consent. Study procedures ensure confidentiality, cultural sensitivity, and participant safety. Data will be securely stored in REDCap and disseminated through peer-reviewed publications and scientific conference ClinicalTrials.gov ID The study has been prospectively registered at ClinicalTrials.gov (Identifier NCT07218458 ). Strengths and Limitations Evaluates a structured breathing-based intervention using both subjective and objective indicators of feasibility, including recruitment, retention, adherence, and implementation appropriateness. Integrates mobile application analytics with standardized implementation measures (AIM, IAM, FIM) to capture digital engagement and real-world usability. Incorporates functional near-infrared spectroscopy (fNIRS) to explore physiological mechanisms underlying burnout recovery, linking cerebral oxygenation to behavioral outcomes. Conducted across diverse community-based Mayo Clinic Health System sites, enhancing ecological validity and relevance to decentralized clinical settings. Limitations include the single-arm, region-restricted design, modest sample size, and reliance on volunteer participants, which constrain generalizability and preclude causal inference; exploratory outcomes are intended to guide future trial refinement.

PURPOSE Manual extraction of treatment outcomes from unstructured oncology clinical notes is a significant challenge for real-world evidence (RWE) generation. This study aimed to develop and evaluate a robust natural language processing (NLP) system to automatically extract cancer treatments and their associated RECIST-based response categories (complete response, partial response, stable disease, and progressive disease) from non–small cell lung cancer (NSCLC) clinical notes. METHODS This retrospective NLP development and validation study used a corpus of 250 NSCLC oncology notes from University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, annotated by physician experts. An end-to-end NLP pipeline was designed, integrating a rule-based module for entity extraction (treatments and responses) and a machine learning module using biomedical clinical bidirectional encoder representations from transformers for relation classification. The system's performance was evaluated on a held-out test set, with partial external validation for relation extraction on a Mayo Clinic data set. RESULTS The NLP system achieved high overall accuracy. On the UPMC test set (64 notes), the relation classification model attained an area under the receiver operating characteristic curve of 0.94 and an F1 score of 0.92 for linking treatments with documented responses. The rule-based entity extraction demonstrated a macro-averaged F1 score of 0.87 (precision 0.98, recall 0.81). Although precision was high for chemotherapy and most response types (1.00), recall for cancer surgery was 0.45. External validation at Mayo Clinic showed moderate relation extraction F1 scores (range: 0.51-0.64). CONCLUSION The proposed NLP system can reliably extract structured treatment and response information from unstructured NSCLC oncology notes with high accuracy. This automated approach can assist in abstracting critical cancer treatment outcomes from clinical narrative text, thereby streamlining real-world data analysis and supporting the generation of RWE in oncology.

Abstract Background Plasma biomarkers show promise as a noninvasive method for measuring Alzheimer's disease pathology and neurodegeneration throughout the lifecourse. However, the relationship between longitudinal changes in these biomarkers and late‐life brain morphology in community‐dwelling populations requires further investigation. Method Between 2011 and 2013, 1,977 participants from the Atherosclerosis Risk in Communities Study received an adjudicated cognitive diagnosis and underwent 3 Tesla magnetic resonance imaging scans. Whole‐brain cortical thickness was quantified by Freesurfer. Stored plasma samples collected in midlife (1993‐95, mean age 59.0 years) and late‐life (2011‐13, mean age 76.8 years) from a subsample of 1,515 participants were assayed in 2022 using Quanterix SiMoA. The assay quantified amyloid‐β (Aβ)42/40, phosphorylated tau at threonine 181 ( p ‐Tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). Linear regression models estimated the association of plasma biomarkers from midlife, late‐life, and the change from midlife to late‐life with cortical thickness in late‐life. Interactions and effect modification by age were examined in exploratory analyses. Result The sample (Table 1) included 920 (60.7%) women, 387 (25.5%) Black participants, 513 (33.9%) participants with mild cognitive impairment, and 85 (5.6%) participants with dementia. The average age in late‐life was 76.8 (5.3 SD) years and the average cortical thickness was 2.27 (0.11 SD) millimeters. Cortical thickness was lower in individuals with adjudicated mild cognitive impairment or dementia compared to individuals without cognitive impairment (2.25 mm versus 2.29 mm, p <0.0001). In models adjusted for demographics, lifestyle factors, cardiovascular factors, and the presence of APOE ε4 alleles, higher midlife measures of p ‐Tau181 and increases from midlife to late‐life in NfL and GFAP were associated with lower cortical thickness in late‐life (Table 2). Concurrent measures of plasma biomarkers in late‐life were associated with lower cortical thickness (Table 2) and exhibited a stronger association among participants ≥75 years compared to <75 years (Table 3). Conclusion Plasma biomarkers of Alzheimer's disease pathology and neurodegeneration obtained in midlife and late‐life were associated with late‐life differences in cortical thickness. Additional longitudinal research is needed to determine whether plasma biomarkers predict cortical thinning over time and may serve as an early indicator of accelerated brain atrophy.

Abstract Dr. Petersen will be a panelist.

Abstract Background Research on gender and ethnic differences in white matter tracts yields mixed results. Although men show larger global corpus callosum (CC) in absolute values, women have demonstrated larger splenium and isthmus. Additionally, men have shown greater white matter and fractional anisotropy (FA) in multiple regions than women. This study investigates sex and ethnic differences in the corpus callosum and transcallosal white matter tissue microstructure of older individuals with normal cognition and memory disorders. Method 191 participants (Female n = 120; Hispanics n = 115; Non‐Hispanics n = 76; Age mean = 71.07; SD = 7.75) were included in the sample from the 1Florida ADRC with cognitively normal ( n = 75), MCI ( n = 88), and dementia ( n = 28) diagnoses. Corpus callosum volumes were collected using a Siemens Skyra 3T MRI scanner and were divided into anterior, mid‐anterior, central, mid‐posterior, and posterior regions. Also, MRI‐based free water diffusion tensor imaging (FW‐DTI) measured FW‐corrected FA (fwcFA) to assess and compare the integrity of transcallosal tract templates (TCATT) across motor, temporal, parietal, and occipital regions across males and females and ethnic groups. Result Univariate ANCOVAs controlling for age and clinical diagnosis were performed; females had larger normalized CC volumes in the posterior, F (1, 184) = 8.92, p = .003, η p 2 = .046, mid‐anterior, F (1,184)= 5.68, p = .018, η p 2 = .030, and anterior, F (1,184)= 14.54, p < .001, η p 2 = .073, regions, which all survived FDR corrections, with no ethnic differences observed. For transcallosal tracts, females had higher fwcFA in the inferior temporal gyrus, η p 2 Hispanics had higher fwcFA in the premotor cortex, η p 2 η p 2 Conclusion Sex and ethnicity influence white matter changes during aging independently of age and cognitive diagnosis. However, the effect explained by these demographic variables was very small, suggesting the influence of additional factors.

Abstract Background Tau PET measures are inherently continuous and applying dichotomized thresholds introduces conceptual and analytical idiosyncrasies. Understanding the limitations in the transition from tau‐negative to tau‐positive classifications is crucial for the effective use of these thresholds. This study aims to determine the confidence levels of tau PET thresholds of abnormality for different tau PET tracers by characterizing their “gray zone” using the universal tau PET scale (Uniτ, www.unitau.app ). Method We evaluated 485 individuals across the aging and AD spectrum from the HEAD study, with head‐to‐head scans for MK6240 and Flortaucipir. Uniτ estimates were derived from the Meta‐Temporal ROI. Tau positivity (T+) was defined as Uniτ values exceeding the mean plus 3 SD of individuals younger than 28 years ( n = 24). Two physicians independently performed a visual assessment of tau positivity for each tracer, with agreement indicating clear tau pathology (TVR+). Logistic regression was used to estimate the probability of TVR+ across Uniτ values for each tracer ( n = 189, CU elderly Aβ‐ and CI Aβ+). Individuals were classified as negative, positive, or within a “gray zone” between the most liberal T+ threshold and varying TVR+ probability thresholds (50%, 75%, 90%, 95%, and 99%). Result The Uniτ gray zone, defined as a function of TVR+ probabilities, demonstrated consistency between the two tracers, with differences observed only in the decimal range. The most liberal Uniτ threshold for T+ was 11.0 for both MK6240 and Flortaucipir, closely matching the 50% TVR+ probability threshold (11.1 for MK6240 and 11.7 for Flortaucipir). Higher TVR+ probabilities corresponded to increased Uniτ values with MK6240 and Flortaucipir showing near‐identical values between the tracers: 14.2 and 14.8 for 75%, 17.3 and 17.9 for 90%, 19.4 and 19.9 for 95%, and 24.1 and 24.6 for 99%, respectively (Figure 1). In total, 26 participants fell within the gray zone for MK6240, compared to 47 participants for Flortaucipir. Conclusion These findings highlight the potential of Uniτ to provide a standardized approach for assessing tau positivity across tracers. By combining quantitative Uniτ measures with visual assessments, we enhance the understanding of tau positivity certainty, particularly in the transition between negative and positive classifications.

Abstract Background Sex, education and race/ethnicity are all associated with risk of Alzheimer's disease dementia. Here, we assess the effects of self‐reported sex, educational attainment and race/ethnicity on amyloid‐positivity, and tau‐PET‐positivity in 12,048 (7,394 cognitively unimpaired [CU], 2,177 MCI, and 2,477 dementia) individuals from 42 cohorts worldwide. Method Logistic generalized estimating equations were used to estimate frequency of amyloid‐positivity (using cohort‐specific thresholds for amyloid‐PET [84%] or CSF) and tau‐PET‐positivity (cohort‐specific thresholds of 2SD above mean temporal uptake in amyloid‐negative controls). We assessed: i) sex and APOEε4 ( N = 10,098) associations, to complement earlier findings of a higher frequency of tau‐positivity in females, ii) effects of lower/higher education ( N = 10,970; cohort‐specific median‐split), and iii) effects of race/ethnicity (non‐Hispanic White [hereafter: White], N = 4880; Asian, N = 116; Black or African‐American [hereafter: Black], N = 353; Hispanic, N = 356, only from Northern‐American cohorts). Outcomes were frequency of amyloid‐positivity in CU individuals only, and tau‐PET‐positivity in both amyloid‐positive (AB+) CU and cognitively impaired (CI, i.e. MCI and dementia) individuals. Interaction effects on the relationship between age and amyloid/tau‐positivity were assessed and only retained in the models when significant. Result Female sex was associated with an APOEε4 ‐independent increased frequency of amyloid‐positivity (β=0.51[0.22], p = 0.02) in CU and increase of tau‐positivity in both AB+CU (β=0.27[0.08]) and AB+CI (β=0.37[0.08], both p <0.01). Remarkably, tau‐positivity frequencies of female APOEε4 non‐carriers were equivalent to male APOEε4 carriers in AB+CI (Figure 1). No significant sex* APOE interactions were observed. In CU, higher education was associated with lower amyloid‐positivity frequency (β=‐0.12[0.05], p = 0.02). In contrast, among AB+CU, there was an age*education interaction effect that indicated more pronounced age effects on tau‐positivity in individuals with higher education (age*education:β interaction =0.03[0.01], p <0.01). There were no education effects in AB+CI (Figure 2). In CU, an age*race/ethnicity interaction effect was observed across all non‐White groups compared to White (Hispanic:β interaction =‐0.05[0.01], p <0.01; Black:‐0.04[0.01], p <0.01; Asian:‐0.02[0.01], p = 0.04). This suggests that the impact of age on amyloid‐positivity was less pronounced in non‐White groups. Furthermore, in AB+CI, Hispanic ethnicity was related to higher tau‐positivity frequency than White (β=0.51[0.22], p = 0.02; Figure 3). Conclusion In this multi‐center initiative comprised of clinical and community‐based cohorts, we observed that self‐reported sex, educational attainment and race/ethnicity were related to positivity‐frequencies of Alzheimer's disease pathology.

Radiologists are uniquely positioned to play a critical role in the detection, surveillance, and characterization of hereditary abdominal cancer syndromes.