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Neurofibrillary tau tangles are a hallmark pathology of Alzheimer's disease (AD) and are more closely associated with AD-related cortical atrophy and symptom severity than amyloid-beta (Aβ). However, studies regarding the effect of tau on longitudinal cortical thinning, particularly in healthy aging and preclinical AD, have been limited in number due to the relatively recent introduction of in vivo PET tracers for imaging tau pathology. Here, we investigate [18F]-flortaucipir (FTP, a marker of paired helical filament tau) PET as a predictor of atrophy in healthy aging and preclinical AD. We examine longitudinal structural MRI brain imaging data, retrospectively and prospectively relative to FTP imaging, using piecewise linear mixed-effect models with time centered at each participant's FTP-PET session. Participants include 111 individuals from the Harvard Aging Brain Study who underwent at least three MRI sessions over an average of 4.46 years and one FTP-PET at the approximate midpoint of the observation period. Our primary analyses focus on inferior temporal (IT) FTP standardized uptake value ratios and longitudinal FreeSurfer defined cortical regions of interest. Relationships were also explored using other regional FTP measures (entorhinal, composite, and local), within high and low Pittsburgh compound-B (PiB) PET groups, and with longitudinal subcortical volume. Strong associations between IT FTP and cortical thinning were found, most notably in temporal, midline, and prefrontal regions, with stronger effects generally observed in the prospective as compared to retrospective time frame. Significant differences between prospective and retrospective rates of thinning were found in the inferior and middle temporal gyri, cingulate areas, as well as pars orbitalis such that higher IT FTP was associated with greater prospective rates of thinning. Within the high PiB group, significant differences between prospective and retrospective rates of thinning were similarly observed. However, no consistent pattern of tau-related change in cortical thickness within the low PiB group was discerned. These results provide support for the hypothesis that tau pathology is a driver of future atrophy as well as provide additional evidence for tau-PET as an effective AD biomarker for interventional clinical trials. •Tau positron emission tomography images were acquired for 111 individuals.•Magnetic resonance data were longitudinally collected (nscans = 386).•Prospective structural changes were observed with higher inferior temporal tau.•Lateral temporal regions may represent an inflection point in preclinical AD.•Findings are consistent with the hypothesis that tau is a driver of atrophy.

Cortical thinning occurs throughout the entire life and extends to late-life neurodegeneration, yet the neurobiological substrates are poorly understood. Here, we used a virtual-histology technique and gene expression data from the Allen Human Brain Atlas to compare the regional profiles of longitudinal cortical thinning through life (4004 magnetic resonance images [MRIs]) with those of gene expression for several neuronal and non-neuronal cell types. The results were replicated in three independent datasets. We found that inter-regional profiles of cortical thinning related to expression profiles for marker genes of CA1 pyramidal cells, astrocytes and, microglia during development and in aging. During the two stages of life, the relationships went in opposite directions: greater gene expression related to less thinning in development and vice versa in aging. The association between cortical thinning and cell-specific gene expression was also present in mild cognitive impairment and Alzheimer’s Disease. These findings suggest a role of astrocytes and microglia in promoting and supporting neuronal growth and dendritic structures through life that affects cortical thickness during development, aging, and neurodegeneration. Overall, the findings contribute to our understanding of the neurobiology underlying variations in MRI-derived estimates of cortical thinning through life and late-life disease.

Hydrogels are highly cross-linked polymer networks that are heavily swollen with water. Hydrogels have been used as dynamic, tunable, degradable materials for growing cells and tissues. Zhang and Khademhosseini review the advances in making hydrogels with improved mechanical strength and greater flexibility for use in a wide range of applications. Science , this issue p. eaaf3627 Hydrogels are formed from hydrophilic polymer chains surrounded by a water-rich environment. They have widespread applications in various fields such as biomedicine, soft electronics, sensors, and actuators. Conventional hydrogels usually possess limited mechanical strength and are prone to permanent breakage. Further, the lack of dynamic cues and structural complexity within the hydrogels has limited their functions. Recent developments include engineering hydrogels that possess improved physicochemical properties, ranging from designs of innovative chemistries and compositions to integration of dynamic modulation and sophisticated architectures. We review major advances in designing and engineering hydrogels and strategies targeting precise manipulation of their properties across multiple scales.

We review science-based adaptation strategies for western North American (wNA) forests that include restoring active fire regimes and fostering resilient structure and composition of forested landscapes. As part of the review, we address common questions associated with climate adaptation and realignment treatments that run counter to a broad consensus in the literature. These include the following: (1) Are the effects of fire exclusion overstated? If so, are treatments unwarranted and even counterproductive? (2) Is forest thinning alone sufficient to mitigate wildfire hazard? (3) Can forest thinning and prescribed burning solve the problem? (4) Should active forest management, including forest thinning, be concentrated in the wildland urban interface (WUI)? (5) Can wildfires on their own do the work of fuel treatments? (6) Is the primary objective of fuel reduction treatments to assist in future firefighting response and containment? (7) Do fuel treatments work under extreme fire weather? (8) Is the scale of the problem too great? Can we ever catch up? (9) Will planting more trees mitigate climate change in wNA forests? And (10) is post-fire management needed or even ecologically justified? Based on our review of the scientific evidence, a range of proactive management actions are justified and necessary to keep pace with changing climatic and wildfire regimes and declining forest heterogeneity after severe wildfires. Science-based adaptation options include the use of managed wildfire, prescribed burning, and coupled mechanical thinning and prescribed burning as is consistent with land management allocations and forest conditions. Although some current models of fire management in wNA are averse to short-term risks and uncertainties, the long-term environmental, social, and cultural consequences of wildfire management primarily grounded in fire suppression are well documented, highlighting an urgency to invest in intentional forest management and restoration of active fire regimes.

Spatial biases are an intrinsic feature of occurrence data used in species distribution models (SDMs). Thinning species occurrences, where records close in the geographic or environmental space are removed from the modeling procedure, is an approach often used to address these biases. However, thinning occurrence data can also negatively affect SDM performance, given that the benefits of removing spatial biases might be outweighed by the detrimental effects of data loss caused by this approach. We used real and virtual species to evaluate how spatial and environmental thinning affected different performance metrics of four SDM methods. The occurrence data of virtual species were sampled randomly, evenly spaced, and clustered in the geographic space to simulate different types of spatial biases, and several spatial and environmental thinning distances were used to thin the occurrence data. Null datasets were also generated for each thinning distance where we randomly removed the same number of occurrences by a thinning distance and compared the results of the thinned and null datasets. We found that spatially or environmentally thinned occurrence data is no better than randomly removing them, given that thinned datasets performed similarly to null datasets. Specifically, spatial and environmental thinning led to a general decrease in model performances across all SDM methods. These results were observed for real and virtual species, were positively associated with thinning distance, and were consistent across the different types of spatial biases. Our results suggest that thinning occurrence data usually fails to improve SDM performance and that the use of thinning approaches when modeling species distributions should be considered carefully.

The cognitive and behavioral development of children and adolescents is closely related to the maturation of brain morphology. Although the trajectory of brain development has been depicted in detail, the underlying biological mechanism of normal cortical morphological development in childhood and adolescence remains unclear. By combining the Allen Human Brain Atlas dataset with two single‐site magnetic resonance imaging data including 427 and 733 subjects from China and the United States, respectively, we performed partial least squares regression and enrichment analysis to explore the relationship between the gene transcriptional expression and the development of cortical thickness in childhood and adolescence. We found that the spatial model of normal cortical thinning during childhood and adolescence is associated with genes expressed predominantly in astrocytes, microglia, excitatory and inhibitory neurons. Top cortical development‐related genes are enriched for energy‐related and DNA‐related terms and are associated with psychological and cognitive disorders. Interestingly, there is a great deal of similarity between the findings derived from the two single‐site datasets. This fills the gap between early cortical development and transcriptomes, which promotes an integrative understanding of the potential biological neural mechanisms. The underlying biological mechanism of early cortical morphological development remains unclear. We found linear development pattern of cortical thickness during childhood and adolescence is associated with spatially varying gene transcription, which expresses predominantly in astrocytes, microglia, excitatory and inhibitory neurons, and ontologically enriches for energy‐related and DNA‐related terms. Cortical development‐related genes are also associated with psychological and cognitive disorders.

Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models. Participants from both the NAPLS2 and NAPLS3 samples were classified as either 'long' or 'short' symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis. The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78). These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes.

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer’s disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini–Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer’s disease, which supports its potential utility as a clinically useful biomarker.In a longitudinal cohort of familial Alzheimer’s disease patients, the rate of change of blood biomarker levels identifies disease carriers much earlier than absolute levels and predicts both neurodegeneration and cognitive decline.

The deep structure of the continental collision between India and Asia and whether India’s lower crust is underplated beneath Tibet or subducted into the mantle remain controversial. It is also unknown whether the active normal faults that facilitate orogen-parallel extension of Tibetan upper crust continue into the lower crust and upper mantle. Our receiver-function images collected parallel to the India–Tibet collision zone show the 20-km-thick Indian lower crust that underplates Tibet at 88.5–92°E beneath the Yarlung-Zangbo suture is essentially absent in the vicinity of the Cona-Sangri and Pumqu-Xainza grabens, demonstrating a clear link between upper-crustal and lower-crustal thinning. Satellite gravity data that covary with the thickness of Indian lower crust are consistent with the lower crust being only ∼30% eclogitized so gravitationally stable. Deep earthquakes coincide with Moho offsets and with lateral thinning of the Indian lower crust near the bottom of the partially eclogitized Indian lower crust, suggesting the Indian lower crust is locally foundering or stoping into the mantle. Loss of Indian lower crust by these means implies gravitational instability that can result from localized rapid eclogitization enabled by dehydration reactions in weakly hydrous mafic granulites or by volatile-rich asthenospheric upwelling directly beneath the two grabens. We propose that two competing processes, plateau formation by underplating and continental loss by foundering or stoping, are simultaneously operating beneath the collision zone.

K3M: A universal algorithm for image skeletonization and a review of thinning techniques This paper aims at three aspects closely related to each other: first, it presents the state of the art in the area of thinning methodologies, by giving descriptions of general ideas of the most significant algorithms with a comparison between them. Secondly, it proposes a new thinning algorithm that presents interesting properties in terms of processing quality and algorithm clarity, enriched with examples. Thirdly, the work considers parallelization issues for intrinsically sequential algorithms of thinning. The main advantage of the suggested algorithm is its universality, which makes it useful and versatile for a variety of applications.