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Clinically normal females exhibit higher F-flortaucipir (FTP)-PET signal than males across the cortex. However, these sex differences may be explained by neuroimaging idiosyncrasies such as off-target extracerebral tracer retention or partial volume effects (PVEs). 343 clinically normal participants (female = 58%; mean[SD]=73.8[8.5] years) and 55 patients with mild cognitive impairment (female = 38%; mean[SD] = 76.9[7.3] years) underwent cross-sectional FTP-PET. We parcellated extracerebral FreeSurfer areas based on proximity to cortical ROIs. Sex differences in cortical tau were then estimated after accounting for local extracerebral retention. We simulated PVE by convolving group-level standardized uptake value ratio means in each ROI with 6 mm Gaussian kernels and compared the sexes across ROIs post-smoothing. Widespread sex differences in extracerebral retention were observed. Although attenuating sex differences in cortical tau-PET signal, covarying for extracerebral retention did not impact the largest sex differences in tau-PET signal. Differences in PVE were observed in both female and male directions with no clear sex-specific bias. Our findings suggest that sex differences in FTP are not solely attributed to off-target extracerebral retention or PVE, consistent with the notion that sex differences in medial temporal and neocortical tau are biologically driven. Future work should investigate sex differences in regional cerebral blood flow kinetics and longitudinal tau-PET.
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http://dx.doi.org/10.1177/0271678X231196978 | DOI Listing |
AAPS J
September 2025
Gene Transfer and Immunogenicity Branch, Division of Gene Therapy 2, Office of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, WO52 RM3124, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-0002, USA.
As the field of gene therapy advances and as the importance of sex as a biological variable in shaping viral immune responses is recognized, the impact of sex on adeno-associated virus (AAV) vectors mediated gene therapies remain largely unexplored. Here we review current understanding of the immune response against AAV gene therapy as well as the knowledge of sex differences observed in viral responses. We discuss sex differences in innate immune mechanisms such as Toll-like receptor recognition and complement activation, as well as the functional responses of key immune cells such as dendritic cells, macrophages, and T/B cells that are involved in AAV immunogenicity.
View Article and Find Full Text PDFMol Syst Biol
September 2025
Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.
The complex interplay between circulating metabolites and immune responses, which is pivotal to disease pathophysiology, remains poorly understood and understudied in systematic research. Here, we performed a comprehensive analysis of the immune response and circulating metabolome in two Western European cohorts (534 and 324 healthy individuals) and one from sub-Saharan Africa (323 healthy donors). At the metabolic level, our analysis revealed sex-specific differences in the correlation between phosphatidylcholine and cytokine responses following ex vivo stimulation.
View Article and Find Full Text PDFKeio J Med
September 2025
Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan.
In Japan, many schools include kendo as part of the school physical education program. Farther afield, kendo also serves as a life-long method to improve and retain physical fitness and mental skills for adults of all ages around the world. Therefore, kendo has the potential to be an inexpensive public health modality if proven safe.
View Article and Find Full Text PDFMethods Cell Biol
September 2025
Department of Basic Sciences, Faculty of Medicine and Sciences, Universidad San Sebastián, Santiago, Chile. Electronic address:
Obesity is a multifactorial disease characterized by excessive accumulation of adipose tissue, resulting from an imbalance between energy intake and expenditure. Mouse models have emerged as invaluable tools for elucidating the complex genetic, environmental, and physiological mechanisms driving to obesity. This chapter provides an overview of the methodologies employed to establish and study obesity in mice, highlighting their relevance to human disease.
View Article and Find Full Text PDFJ Safety Res
September 2025
Faculty of Economics, UNED, Madrid, Spain. Electronic address:
Introduction: In this paper, we examine the relationship between sex and injury severity in car accidents in Spain from 2014 to 2021 using discrete choice models.
Method: We differentiate between no injuries, minor injuries, severe injuries, and fatalities, finding significant gender differences. These results hold even after controlling for vehicle dimensions.