Alzheimer's disease (AD) is the most common type of neurodegenerative disorder, typically causing dementia along aging. AD is mainly characterized by a pathological extracellular accumulation of ...amyloid-beta peptides that affects excitatory and inhibitory synaptic transmission, inducing aberrant patterns in neuronal circuits. Growing evidence shows that AD targets cortical neuronal networks related to cognitive functions including episodic memory and visuospatial attention. This is partially reflected by the abnormal mechanisms of cortical neural synchronization and coupling that generate resting state electroencephalographic (EEG) rhythms. The cortical neural synchronization is typically indexed by EEG power density. The EEG coupling between electrode pairs probes functional (inter-relatedness of EEG signals) and effective (casual effect from one over the other electrode) connectivity. The former is typically indexed by synchronization likelihood (linear and nonlinear) or spectral coherence (linear), the latter by granger causality or information theory indexes. Here we reviewed literature concerning EEG studies in condition of resting state in AD and mild cognitive impairment (MCI) subjects as a window on abnormalities of the cortical neural synchronization and functional and effective connectivity. Results showed abnormalities of the EEG power density at specific frequency bands (<12Hz) in the MCI and AD populations, associated with an altered functional and effective EEG connectivity among long range cortical networks (i.e. fronto-parietal and fronto-temporal). These results suggest that resting state EEG rhythms reflect the abnormal cortical neural synchronization and coupling in the brain of prodromal and overt AD subjects, possibly reflecting dysfunctional neuroplasticity of the neural transmission in long range cortical networks.
The aim of the present review is to discuss how the promising field of biobanking can support health care research strategies. As the concept has evolved over time, biobanks have grown from simple ...biological sample repositories to complex and dynamic units belonging to large infrastructure networks, such as the Pan-European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI). Biobanks were established to support scientific knowledge. Different professional figures with varied expertise collaborate to obtain and collect biological and clinical data from human subjects. At same time biobanks preserve the human and legal rights of each person that offers biomaterial for research.
A literature review was conducted in April 2019 from the online database PubMed, accessed through the Bibliosan platform. Four primary topics related to biobanking will be discussed: (i) evolution, (ii) bioethical issues, (iii) organization, and (iv) imaging.
Most biobanks were founded as local units to support specific research projects, so they evolved in a decentralized manner. The consequence is an urgent needing for procedure harmonization regarding sample collection, processing, and storage. Considering the involvement of biomaterials obtained from human beings, different ethical issues such as the informed consent model, sample ownership, veto rights, and biobank sustainability are debated. In the face of these methodological and ethical challenges, international organizations such as BBMRI play a key role in supporting biobanking activities. Finally, a unique development is the creation of imaging biobanks that support the translation of imaging biomarkers (identified using a radiomic approach) into clinical practice by ensuring standardization of data acquisition and analysis, accredited technical validation, and transparent sharing of biological and clinical data.
Modern biobanks permit large-scale analysis for individuation of specific diseases biomarkers starting from biological or digital material (i.e., bioimages) with well-annotated clinical and biological data. These features are essential for improving personalized medical approaches, where effective biomarker identification is a critical step for disease diagnosis and prognosis.
Whole-body attenuation correction (AC) is still challenging in combined PET/MR scanners. We describe Dixon-VIBE Deep Learning (DIVIDE), a deep-learning network that allows synthesizing pelvis ...pseudo-CT maps based only on the standard Dixon volumetric interpolated breath-hold examination (Dixon-VIBE) images currently acquired for AC in some commercial scanners.
We propose a network that maps between the four 2-dimensional (2D) Dixon MR images (water, fat, in-phase, and out-of-phase) and their corresponding 2D CT image. In contrast to previous methods, we used transposed convolutions to learn the up-sampling parameters, we used whole 2D slices to provide context information, and we pretrained the network with brain images. Twenty-eight datasets obtained from 19 patients who underwent PET/CT and PET/MR examinations were used to evaluate the proposed method. We assessed the accuracy of the μ-maps and reconstructed PET images by performing voxel- and region-based analysis comparing the SUVs (in g/mL) obtained after AC using the Dixon-VIBE (PET
), DIVIDE (PET
), and CT-based (PET
) methods. Additionally, the bias in quantification was estimated in synthetic lesions defined in the prostate, rectum, pelvis, and spine.
Absolute mean relative change values relative to CT AC were lower than 2% on average for the DIVIDE method in every region of interest except for bone tissue, where it was lower than 4% and 6.75 times smaller than the relative change of the Dixon method. There was an excellent voxel-by-voxel correlation between PET
and PET
(
= 0.9998,
< 0.01). The Bland-Altman plot between PET
and PET
showed that the average of the differences and the variability were lower (mean PET
-PET
SUV, 0.0003; PET
-PET
SD, 0.0094; 95% confidence interval, -0.0180,0.0188) than the average of differences between PET
and PET
(mean PET
-PET
SUV, 0.0006; PET
-PET
SD, 0.0264; 95% confidence interval, -0.0510,0.0524). Statistically significant changes in PET data quantification were observed between the 2 methods in the synthetic lesions, with the largest improvement in femur and spine lesions.
The DIVIDE method can accurately synthesize a pelvis pseudo-CT scan from standard Dixon-VIBE images, allowing for accurate AC in combined PET/MR scanners. Additionally, our implementation allows rapid pseudo-CT synthesis, making it suitable for routine applications and even allowing retrospective processing of Dixon-VIBE data.
Although recent successes in clinical trials are strengthening research focused on cancer immunology, the poor immunogenicity and off-target side effects of immunotherapeutics remain major challenges ...in translating these promising approaches to clinically feasible therapies in the treatment of a large range of tumors. Nanotechnology offers target-based approaches, which have shown significant improvements in the rapidly advancing field of cancer immunotherapy. Here, we first discuss the chemical and physical features of nanoparticulate systems that can be tuned to address the anticancer immune response, and then review recent, key examples of the exploited strategies, ranging from nanovaccines to NPs revising the tumor immunosuppressive microenvironment, up to immunotherapeutic multimodal NPs. Finally, the paper concludes by identifying the promising and outstanding challenges the field of emerging nanotechnologies is facing for cancer immunotherapy.
Breast cancer is the most common cancer amongst women worldwide. Recently, owing to screening programs and new technologies, the survival rate has increased significantly. Breast cancer can ...potentially develop metastases, and, despite them, lung metastases generally occur within five years of breast cancer diagnosis. In this study, the objective was to analyze the effect of breast cancer-derived EVs on a lung epithelial cell line. BEAS-2B cells were treated with extracellular vesicles (EVs) derived from triple-negative breast cancer cells (TNBCs), e.g., MDA-MB-231 and HS578T, separated using differential ultracentrifugation. We observed an increased growth, migration, and invasiveness of normal epithelial lung cells over time in the presence of TNBC EVs compared to the control. Therefore, these data suggest that EVs released by tumor cells contain biological molecules capable of influencing the pro-tumorigenic activity of normal cells. Exploring the role of EVs in oncology research and their potential cargo may be novel biomarkers for early cancer detection and further diagnosis.
Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, ...and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on β-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.
Highlights • ECoG activity was recorded in drug-resistant epileptic patients during movement execution and observation. • ECoG desynchronization and synchronization was lower during movement ...observation than movement execution. • This data support the existence of a mirror system in humans.
Epigenetic-sensitive mechanisms may be correlated both to pathogenesis and prognosis of coronary heart disease (CHD). We prospectively investigated some plasma circulating microRNA levels in patients ...undergoing cardiac computed tomography for suspected CHD (n = 95).
We show that let-7c-5p, miR-765, miR-483-5p, miR-31-5p, and miR-206 were upregulated in CHD patients (n = 66) versus healthy subjects HS (n = 29); moreover, let-7c-5p, miR-765, miR- 483-5p showed higher expression in obstructive CHD (n = 36) compared to no obstructive CHD patients (n = 66). Remarkably, miR-765, miR-93-5p, and miR-433-3p showed an upregulation in patients with critical coronary stenosis. Multivariate regression analysis demonstrated that miR-765, miR-31-5p, and miR-206 were independently associated with CHD while circulating levels of miR-765 (p = 0.035), miR-433-3p (p = 0.043), and miR-93-5p (p = 0.041) were significantly higher in critical stenosis patients. Receiver operating characteristic curve analysis revealed a good performance for miR-765, miR-93-5p, and miR-433-3p on predicting CHD severity. In conclusion, our study represents a combined epigenetic/imaging approach useful to support the diagnosis and prediction of CHD.
Abstract Purpose To compare the performance of PET/MRI imaging using MR attenuation correction (MRAC) (DIXON-based 4-segment -map) in breast cancer patients with that of PET/CT using CT-based ...attenuation correction and to compare the quantification accuracy in lesions and in normal organ tissues. Methods A total of 36 patients underwent a whole-body PET/CT scan 1 h after injection and an average of 62 min later a second scan using a hybrid PET/MRI system. PET/MRI and PET/CT were compared visually by rating anatomic allocation and image contrast. Regional tracer uptake in lesions was quantified using volumes of interest, and maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) were calculated. Metabolic tumor volume (MTV) of each lesion was computed on PET/MRI and PET/CT. Tracer uptake in normal organ tissue was assessed as SUVmax and SUVmean in liver, spleen, left ventricular myocardium, lung, and muscle. Results Overall 74 FDG positive lesions were visualized by both PET/CT and PET/MRI. No significant differences in anatomic allocation scores were found between PET/CT and PERT/MRI, while contrast score of lesions on PET/MRI was significantly higher. Both SUVmax and SUVmean of lesions were significantly higher on PET/MRI than on PET/CT, with strong correlations between PET/MRI and PET/CT data ( ρ = 0.71–0.88). MTVs of all lesions were 4% lower on PET/MRI than on PET/CT, but no statistically significant difference was observed, and an excellent correlation between measurements of MTV with PET/MRI and PET/CT was found ( ρ = 0.95–0.97; p < 0.0001). Both SUVmax and SUVmean were significantly lower by PET/MRI than by PET/CT for lung, liver and muscle, no significant difference was observed for spleen, while either SUVmax and SUVmean of myocardium were significantly higher by PET/MRI. High correlations were found between PET/MRI and PET/CT for both SUVmax and SUVmean of the left ventricular myocardium ( ρ = 0.91; p < 0.0001), while moderate correlations were found for the other normal organ tissues ( ρ = 0.36–0.61; p < 0.05). Conclusions PET/MRI showed equivalent performance in terms of qualitative lesion detection to PET/CT. Despite significant differences in tracer uptake quantification, due to either methodological and biological factors, PET/MRI and PET/CT measurements in lesions and normal organ tissues correlated well. This study demonstrates that integrated whole-body PET/MRI is feasible in a clinical setting with high quality and in a short examination time.
Clinical connectome fingerprints of cognitive decline Sorrentino, Pierpaolo; Rucco, Rosaria; Lardone, Anna ...
NeuroImage (Orlando, Fla.),
September 2021, 2021-09-00, 20210901, 2021-09, 2021-09-01, Letnik:
238
Journal Article
Recenzirano
Odprti dostop
Brain connectome fingerprinting is rapidly rising as a novel influential field in brain network analysis. Yet, it is still unclear whether connectivity fingerprints could be effectively used for ...mapping and predicting disease progression from human brain data. We hypothesize that dysregulation of brain activity in disease would reflect in worse subject identification. We propose a novel framework, Clinical Connectome Fingerprinting, to detect individual connectome features from clinical populations. We show that “clinical fingerprints” can map individual variations between elderly healthy subjects and patients with mild cognitive impairment in functional connectomes extracted from magnetoencephalography data. We find that identifiability is reduced in patients as compared to controls, and show that these connectivity features are predictive of the individual Mini-Mental State Examination (MMSE) score in patients. We hope that the proposed methodology can help in bridging the gap between connectivity features and biomarkers of brain dysfunction in large-scale brain networks.
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