Citations

Importance In vivo biomarkers for detecting neuropathologies from repetitive head impacts (RHI), including chronic traumatic encephalopathy (CTE), are needed. Objective To evaluate the utility of plasma phosphorylated tau 217 (p-tau217), assess its performance as a beta-amyloid (Aβ) biomarker in participants with RHI exposure at risk for CTE, and explore concordance with CTE neuropathology in a postmortem subsample. Design, Setting, and Participants This longitudinal, multicenter, case-control study used data from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of CTE (DIAGNOSE CTE) Research Project, collected from September 2016 to October 2023. Participants were former American football players (case participants) and asymptomatic men unexposed to RHI (control participants). A subsample had available neuropathologic data. Exposures RHI, traumatic encephalopathy syndrome (TES) diagnoses, and levels of CTE certainty. Main Outcomes and Measures Plasma p-tau217 (classified as positive [≥0.63 pg/mL], intermediate [0.40-0.62 pg/mL], and negative [<0.40 pg/mL]), Aβ–positron emission tomography (PET; 18 F-florbetapir; with Aβ-positive defined as a standardized uptake value ratio [SUVR] ≥1.10), and tau-PET ( 18 F-flortaucipir). TES diagnoses were assigned by multidisciplinary consensus conference. Analyses of postmortem brains controlled for age, race, and APOE ε4 status. Results Among 231 participants (mean [SD] age, 57.75 [8.25] years), 177 were former football players (117 professional and 60 college) and 54 were unexposed participants. Former football players had higher baseline mean (SD) p-tau217 concentrations than unexposed participants (0.35 [0.26] pg/mL vs 0.27 [0.14] pg/mL; P = .008), although this was driven by a higher proportion of Aβ-PET–positive participants among former players. Plasma p-tau217 increased over time across the sample (B = 0.207 [95% CI, 0.117-0.298]; P < .001), with no significant time × exposure group interactions. Among football players, p-tau217 showed no time × group interactions with TES diagnosis, TES-CTE certainty, or RHI metrics. Higher p-tau217 concentration correlated with higher global Aβ-PET SUVR (B = 0.058 [95% CI, 0.053-3.501; P = .01), with a few discordant cases (5 participants were p-tau217–negative and Aβ-PET–positive; 7 participants were p-tau217–positive and Aβ-PET–negative). P-tau217 had similar areas under the curve for projecting Aβ-PET positivity as cerebrospinal fluid (CSF) p-tau181/Aβ42 and CSF Aβ40/42 measures (p-tau217: AUC, 0.88 [95% CI, 0.80-0.96]; CSF p-tau181/Aβ42: AUC, 0.89 [95% CI, 0.79-1.00]; CSF Aβ40/42: AUC, 0.85 [95% CI, 0.72-0.98]). Among 9 brain donors, 6 had CTE (stages II-IV; none with Alzheimer disease). Seven had negative or intermediate p-tau217, concordant with Aβ-PET. Two p-tau217 outliers with stage III CTE had normal concentrations upon additional testing. Conclusions and Relevance The findings of this study suggest that plasma p-tau217 concentration is unlikely to be useful for the detection of CTE, but it does show utility for ruling out Aβ pathology in participants at risk for CTE.

Importance Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. Objective To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. Evidence Review PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. Findings The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. Conclusions and Relevance The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

Abstract Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

Background Children's media both reflects and shapes societal attitudes toward physical disability. Despite its potential impact on self-concept and stigma, longitudinal, data-driven analysis of these portrayals remains scarce. This study aimed to quantify longitudinal trends in the tone and framing of physical disability representation in children's media and to explore implications for pediatric rehabilitation. Methods A quantitative content analysis was conducted on 68 children's media productions (1933–2025) sourced from the Vanderbilt Peabody database. Content was filtered to age-appropriate ratings (G, PG, PG-13, TV-14). Three trained reviewers classified depictions of physical disability by clinical category (e.g., spinal cord injury, limb difference) and tone (Positive, Neutral, Negative) and coded for the presence of rehabilitation themes. Inter-rater reliability (κ = 0.83) was achieved. Statistical testing included Mann-Kendall trend analysis and Fisher's exact tests to compare pre-2000 vs post-2000 portrayals. Results Positive portrayals increased significantly from pre-2000 (63%) to post-2000 (90%) (p = 0.01). A consistent upward trend across decades was confirmed (Z = 3.47, p < 0.01). Spinal cord injury was the most frequently depicted disability (40%); rehabilitation themes appeared in 24% of productions, more commonly post-2000. Productions with rehabilitation content were more likely to feature positive portrayals (94% vs 89%). Conclusions Over nine decades, children's media has shifted toward more affirming representations of physical disability, particularly after 2000. Findings suggest that pediatric rehabilitation providers can use positive media examples to reinforce therapeutic engagement, normalize assistive devices, and address stigma in age-appropriate ways.

The 2025 Voice AI Symposium represented a transition from conceptual research to clinical implementation in vocal biomarker science. Hosted by the NIH-funded Bridge2AI-Voice consortium, the meeting convened global experts to address the methodological, ethical, and translational challenges of integrating voice-based artificial intelligence (AI) into healthcare. This mini-review synthesizes symposium insights across six domains: multimodal integration, FAIR (Findable, Accessible, Interoperable, Reusable) and CARE (Collective Benefit, Authority to Control, Responsibility, Ethics) data governance, clinical translation, interdisciplinary training, and cross-sector innovation. Research presented demonstrated voice as a latent, multimodal biomarker reflecting neurological, cardiopulmonary, and psychological states, while discussions emphasized ethical data practices and human-centered design. The implementation-focused panels underscored the importance of workflow alignment and usability for adoption in real-world care. Collectively, the symposium reflects a field advancing toward translational readiness and ethical accountability, positioning voice AI as a scalable, inclusive tool for next-generation healthcare.

Abstract Women remain underrepresented in physical medicine and rehabilitation, comprising only 36%–39% of residents despite evidence that diverse teams improve patient outcomes. Limited early exposure and systemic barriers may contribute to this disparity. In this cross-sectional study, we surveyed 1101 US premedical students from 198 colleges across 40 states and territories to assess perceptions of physical medicine and rehabilitation and identify effective early intervention strategies. While respondents included all gender identities, the analysis focused on the 870 female-identifying students (78.8%) due to the study’s primary aim of addressing gender equity in physical medicine and rehabilitation. Only 30.6% were familiar with physical medicine and rehabilitation, with exposure primarily through social media (42.6%) and personal connections (31.1%); just 9.0% had shadowed a physical medicine and rehabilitation physician. Financial concerns were prevalent, with 68.6% citing medical education costs and 66.4% citing application fees as deterrents. Despite these barriers, 60.6% expressed interest in learning more about physical medicine and rehabilitation. Preferred engagement strategies included shadowing (81.8%), interactive workshops (76.6%), mentorship programs (60.1%), and gender-specific events such as “Women in PM&R” (62.8%). These findings underscore the need for targeted, early outreach initiatives that address both informational and financial barriers, aiming to foster greater awareness and representation of women in physical medicine and rehabilitation and ultimately support a more inclusive physician workforce.

Abstract Repetitive head impacts are common in contact and collision sports and are linked to structural brain changes and an elevated risk of neurodegenerative diseases such as Chronic Traumatic Encephalopathy. Identifying early in vivo structural markers remains challenging. Although diagnosis currently requires post-mortem confirmation, clinical symptoms, including cognitive impairment and behavioural changes, are reflected in the diagnosis of Traumatic Encephalopathy Syndrome. These symptoms align with dysfunction in key brain regions—amygdala, hippocampus and thalamus—which support memory, emotion and behaviour and commonly show tau pathology in Chronic Traumatic Encephalopathy. This study uses shape analysis to examine structural differences in these regions between former American football players and unexposed asymptomatic controls and evaluates the influence of age, head impact exposure and clinical diagnosis on brain structure. We analyzed brain morphology in former American football players (n = 163) and unexposed, asymptomatic controls (n = 53). Structural segmentation was performed with FreeSurfer 7.1, and the shape analysis pipeline was used to generate subregional reconstructions. Vertex-level morphometry, based on the logarithm of the Jacobian determinant and radial distance, quantified local surface area dilation and thickness. Group differences were examined with covariate-adjusted linear regression models contrasting football players and controls, as well as participants with and without a Traumatic Encephalopathy Syndrome diagnosis. Partial correlations examined the influence of age, age of first football exposure and cumulative head impact index metrics, including frequency, linear acceleration and rotational force. Models were adjusted accordingly for age, body mass index, education, race, imaging site, apolipoprotein ϵ4 status and total intracranial volume. Former football players exhibited bilateral surface area contractions in the hippocampus and amygdala, along with reduced amygdala thickness, compared to controls. Older age was associated with widespread surface contractions and thinning across all regions, except for preserved thickness in the left hippocampus. An earlier age of first exposure to football correlated with surface contractions in the thalamus and left hippocampus. Greater cumulative linear acceleration was linked to bilateral hippocampal surface contractions and reduced thickness in the left thalamus, while greater rotational force exposure was associated with hippocampal thinning. No significant structural differences were found between players with and without a diagnosis of Traumatic Encephalopathy Syndrome. These findings extend volume-based research by revealing localized alterations in surface area dilation and thickness and emphasize the roles of age and repetitive head impact exposure in long-term brain changes.

Abstract Importance Voice-based health technologies are growing rapidly, but they lack standardized terminology, which hinders interdisciplinary collaboration, research quality, and clinical translation. Objective The objective of this work is to develop universally accepted definitions in the rapidly evolving field of vocal biomarkers, as part of the VOCAL ( V ocal Biomarker Guidelines for O ntology, C lassification, A pplication, and L ogistics) initiative, a structured, international consensus-based framework that aims to provide standards, and guidelines. Design VOCAL is a rigorous, international, multi-stage consensus-building study conducted in 2024-2025. Setting Multi-institutional collaboration between representatives from the Bridge2AI-Voice Consortium (North America) and the eVoiceNet Network (European Union), culminating in an in-person workshop at the 2025 Bridge2AI Voice Symposium. Participants A group of 24 international experts in medicine, clinical research, speech and language, audio signal processing, statistics, methodology, regulation, ethics. Methods VOCAL’s iterative process involved five rounds of review, feedback, and an in-person workshop at the international 2025 Bridge2AI Voice Symposium, ensuring the incorporation of diverse perspectives and achieving a robust agreement on the proposed definitions. Main outcomes and measures Consensus-based definitions for vocal biomarkers, spanning from broad concepts (biomarker, digital biomarker, vocal biomarker) to domain-specific measures (cardio-respiratory acoustic, voice, speech/articulatory, cognitive/language). Results A hierarchical continuum model of vocal biomarkers was established. We first distinguished between the concepts of vocal measures and vocal biomarkers. We then defined terms from broad, overarching concepts (Level 0: Biomarker, Digital Biomarker, Vocal Biomarker) to more specific physiological and cognitive domains (Level 1: Cardio-Respiratory Acoustic; Level 2: Voice; Level 3: Speech/Articulatory; Level 4: Cognitive/Language, including linguistic and paralinguistic subtypes). Conclusions and Relevance This work provides a shared vocabulary that is essential for fostering communication through interdisciplinary collaboration, improving the quality and efficiency of research and development, and ensuring the ethical, reliable, and scalable deployment of future voice-based health technologies. It lays foundational groundwork for upcoming guidelines and standards, which are crucial for advancing the field of vocal biomarkers into widespread clinical utility. Key points Question Can we establish an international consensus on the definitions related to vocal biomarkers? Findings Through a multi-stage international consensus process involving expert representatives from the Bridge2AI-Voice Consortium and eVoiceNet Network, a hierarchical model of vocal biomarkers was developed, defining terms from broad concepts (biomarker, digital biomarker, vocal biomarker) to specific physiological and cognitive domains (cardio-respiratory acoustic, voice, speech/articulatory, cognitive/language). Meaning Standardized definitions for vocal biomarkers provide an essential shared vocabulary for interdisciplinary collaboration and lay the foundational groundwork for future guidelines needed to advance the implementation of voice-based health technologies into clinical practice and clinical research.