Citations

Abstract Positron emission tomography (PET)-based molecular imaging is a clinically important tool for the evaluation of dementia and other neurodegenerative disorders, using radiotracers that target specific molecular and pathophysiological processes. Fluorodeoxyglucose brain PET has historically supported neurodegenerative disorder evaluation through detection of characteristic patterns of regional glucose hypometabolism. In recent years, the molecular imaging of protein aggregates has taken on an increasingly important role. This is evident with the widespread clinical adoption of amyloid PET and early use of tau PET to provide diagnostic and prognostic information for patients with suspected Alzheimer’s disease. Additional classes of radiotracers relevant to neurodegenerative diseases are under active investigation, including those targeting neuroinflammation, synaptic density, and α-synuclein aggregates. We review the major classes of PET radiotracers for neurodegenerative diseases, describing their molecular mechanisms, diagnostic performance, and their current and emerging clinical roles in dementia evaluation. Case examples for clinically used tracers illustrate imaging features relevant to diagnosis and characterization of prognosis and treatment effect. Finally, we discuss early developments and current challenges in the development of theranostic approaches and novel radiotracers for neurodegenerative diseases.

Introduction The World Health Organization (WHO) endorses male circumcision as an effective human immunodeficiency virus (HIV) prevention intervention in settings where the expected impact is greatest, including Sub-Saharan Africa. Data on cost implications of early infant male circumcision (EIMC) are limited. The ShangRing (SR) is a WHO pre-qualified device for circumcision. We sought to perform a comprehensive cost assessment alongside a randomized controlled trial (RCT) of the SR versus the standard of care Mogen clamp (MoC) for EIMC to enable future scale-up towards a cost-effective HIV prevention strategy. Methods We collected resource utilization and economic data as part of an RCT of infants aged 0–60 days old undergoing EIMC in Kenya, Tanzania, and Uganda. Cost data for both the SR and MoC included baseline facility costs, direct costs, and indirect costs. The Decision Makers Program Planning Tool v1.0 was used to perform a direct cost comparison of these two devices. The Goals model was used to compare the costs of EIMC in 2023 using the present value of money to circumcise an adolescent male 15 years from now. Results A total of 1,378 infant males underwent circumcision, 689 via SR and 689 via MoC. The overall cost of a single EIMC in Kenya, Tanzania, and Uganda were 61.30 United States Dollars ($), $47.14, and $64.59 respectively for the SR, and $56.38, $50.43, and $58.57 respectively for the MoC. In Kenya, EIMC would be less expensive based on nominal present costs in 2023 compared to waiting for adolescent circumcision at age 15 years in 2038. This finding is reversed in Tanzania and Uganda. Conclusions The overall cost of EIMC via SR versus MoC is comparable in an RCT. With scale-up utilizing lower level personnel, the cost of SR may be further reduced. The SR is an attractive alternative for future EIMC initiatives in Sub-Saharan Africa to further reduce HIV burden.

The bone marrow immune microenvironment (BMME) is a critical factor in multiple myeloma (MM) pathogenesis. Despite higher incidence of MM among self-identified African Americans, the relationship between African genetic similarity and the BMME remains unclear. We present the largest analysis to date assessing the impact of Ancestry on the BMME in myeloma (N=320, including 64 with ≥50% African genetic similarity, AFR-High) leveraging our recently generated Immune Atlas. AFR-High was associated with enrichment of late T-effector cells, driven by rare cytotoxic CD4⁺ T cells, suggesting a distinct adaptive BMME. AFR-High exhibited expansion of late-differentiated adaptive NK cells with high cytotoxic GNLY and GZMH expression. AFR-High depicted reduced CD14⁺ monocytes, increased CD16⁺ non-classical monocytes, and expansion of macrophage-like monocyte populations with enrichment of metabolic adaptation, efferocytosis and phagocytic clearance programs, and immunoregulatory pathways. These findings reveal a shift from an innate inflammatory immune landscape toward adaptive cytotoxic and immunoregulatory remodeling associated with African genetic similarity in MM.

AI skill development is essential in health professions education (HPE), yet this type of faculty development is complex to design and implement. While competency frameworks and AI education programs are emerging, many faculty developers are themselves still building AI literacy and confidence, and practical guidance for how to design a faculty development program on AI that is accessible, skill-oriented, and responsive to rapid technological change remains limited. Although webinars and workshops can only do so much, a well-planned faculty development program can provide a great introduction to AI, alleviate fears, and inspire participants to keep growing and learning. Drawing on our experience designing and hosting the AAMC GEA AI Skill-Building Webinar Series and the current literature in AI, this article offers twelve practical tips for faculty developers who are creating AI-focused learning opportunities for everyone involved in HPE. These tips will help readers create robust AI skill-building sessions that move participants beyond awareness of AI and shift their perspectives toward applied, reflective, and responsible use of AI in HPE.

Abstract Purpose Bibliometric indicators are widely used to evaluate faculty productivity, yet these metrics change with career stage, evolving authorship practices, and technological shifts in how science is produced. This study examines patterns of scholarly output among radiation therapy medical physics faculty at leading cancer centers and provides a framework and quantitative metrics for managing career age‐ and era‐based effects. Methods Peer‐reviewed articles (1969–2025) were collected from Scopus for 397 Ph.D. medical physics faculty at the 20 U.S. cancer centers most highly ranked by US News and World Report in 2025. The bibliometric measures included annual rates of authorships (), first/last authorships (), monograph‐equivalents (), as well as the cumulative h‐index and contribution‐normalized ha‐index. Career age was defined by year of first publication. Productivity distributions were evaluated by career age using empirical cumulative distribution functions derived from 2016–2025 data. Era‐dependent fluctuations (1990–2025) were examined using age‐normalized metrics and trends in authorship team size. Tabulated bibliometrics as a function of career age are provided for evaluation of individual performance. Results Productivity increased substantially with career age, peaking in late career. Senior faculty produced approximately two‐fold higher annual output than early‐career peers. At career ages of 1, 10, 20, 30, and 40 years, the median bibliometric rates were = (1.2, 1.6, 2.5, 2.5,1.8) year −1 , = (0.4, 0.4, 0.5, 0.5,0.2) year −1 , = (0.2, 0.2, 0.3, 0.3,0.3) year −1 , h‐index = (0, 7, 15, 23,43), and ha‐index = (0, 3.3, 6.0, 9.4,15.0). Era‐based effects were substantial. Between 1990 and 2025, median authors per paper increased from 4 to 10, inflating authorship‐based metrics. In contrast, contribution‐weighted measures (FL, ME, ha‐index) demonstrated greater temporal stability. Conclusions Scholarly productivity in radiation therapy medical physics is strongly dependent on career age, with peak output occurring near the end of a typical career before declining modestly near retirement. Career‐age‐based percentile benchmarks provide a more balanced framework for evaluating academic performance than unadjusted bibliometric comparisons, especially for early‐career investigators. Due to changes in authorship norms over time, first/last authorships, monograph equivalents, and ha‐index may provide more accurate and equitable assessments of research performance than authorships or h‐index.

Abstract Recent evidence implicates somatic mutations in disease-associated genes across multiple neurodegenerative disorders, including the identification of two somatic TARDBP variants as a putative cause of frontotemporal lobar degeneration with TDP-43 pathology type C (FTLD-TDP type C). However, these findings remain anecdotal. We performed single-nucleus amplicon sequencing of 39,800 neurons from the superior temporal gyrus of sporadic FTLD-TDP type C patients (34,738 neurons, 52 individuals) and non-demented controls (5,062 neurons, 26 individuals) using the Mission Bio Tapestri platform and investigated somatic variants in TARDBP and other FTLD-TDP-associated genes in a case-control setting. We uncovered an extensive landscape of ultra-low-frequency (<1%) somatic mutations across all analysed genes, including TARDBP . Rare somatic occurrences of known ALS/FTD-associated germline TARDBP variants, including p.N267S and p.M337V, were identified exclusively in patients. Among all targeted genes, TARDBP had the highest proportion of neurons harbouring a somatic variant, and this mutational burden was lower in individuals who died at an older age. Strikingly, the C-terminal domain of TDP-43, where most ALS/FTD germline pathogenic variants reside, exhibited a lower neuronal mutational burden than its other domains. This suggests that neurons harbouring damaging mutations may undergo progressive loss prior to autopsy, leaving only rare survivors at frequencies too low to detect by bulk or small-scale single-cell approaches. Together, our findings provide an unprecedented resolution into the somatic mutational landscape of post-mitotic neurons in FTLD-TDP type C and reveal a gene-specific layer of neuronal mosaicism that current single-cell WGS studies fail to detect.