Artificial Intelligence and Machine Learning in Computational Nanotoxicology: Unlocking and Empowering Nanomedicine.

AbstractAdvances in nanomedicine, coupled with novel methods of creating advanced materials at the nanoscale, have opened new perspectives for the development of healthcare and medical products. Special attention must be paid toward safe design approaches for nanomaterial‐based products. Recently, artificial intelligence (AI) and machine learning (ML) gifted the computational tool for enhancing and improving the simulation and modeling process for nanotoxicology and nanotherapeutics. In particular, the correlation of in vitro generated pharmacokinetics and pharmacodynamics to in vivo application scenarios is an important step toward the development of safe nanomedicinal products. This review portrays how in vitro and in vivo datasets are used in in silico models to unlock and empower nanomedicine. Physiologically based pharmacokinetic (PBPK) modeling and absorption, distribution, metabolism, and excretion (ADME)‐based in silico methods along with dosimetry models as a focus area for nanomedicine are mainly described. The computational OMICS, colloidal particle determination, and algorithms to establish dosimetry for inhalation toxicology, and quantitative structure–activity relationships at nanoscale (nano‐QSAR) are revisited. The challenges and opportunities facing the blind spots in nanotoxicology in this computationally dominated era are highlighted as the future to accelerate nanomedicine clinical translation

Genome-wide microRNA screening in Nile tilapia reveals pervasive isomiRs’ transcription, sex-biased arm switching and increasing complexity of expression throughout development

MicroRNAs (miRNAs) are key regulators of gene expression in multicellular organisms. The elucidation of miRNA function and evolution depends on the identification and characterization of miRNA repertoire of strategic organisms, as the fast-evolving cichlid fishes. Using RNA-seq and comparative genomics we carried out an in-depth report of miRNAs in Nile tilapia (Oreochromis niloticus), an emergent model organism to investigate evo-devo mechanisms. Five hundred known miRNAs and almost one hundred putative novel vertebrate miRNAs have been identified, many of which seem to be teleost-specific, cichlid-specific or tilapia-specific. Abundant miRNA isoforms (isomiRs) were identified with modifications in both 5p and 3p miRNA transcripts. Changes in arm usage (arm switching) of nine miRNAs were detected in early development, adult stage and even between male and female samples. We found an increasing complexity of miRNA expression during ontogenetic development, revealing a remarkable synchronism between the rate of new miRNAs recruitment and morphological changes. Overall, our results enlarge vertebrate miRNA collection and reveal a notable differential ratio of miRNA arms and isoforms influenced by sex and developmental life stage, providing a better picture of the evolutionary and spatiotemporal dynamics of miRNAs

Tackling Complex Analytical Tasks: An ISO/TS-Based Validation Approach for Hydrodynamic Chromatography Single Particle Inductively Coupled Plasma Mass Spectrometry

Nano-carrier systems such as liposomes have promising biomedical applications. Nevertheless, characterization of these complex samples is a challenging analytical task. In this study a coupled hydrodynamic chromatography-single particle-inductively coupled plasma mass spectrometry (HDC-spICP-MS) approach was validated based on the technical specification (TS) 19590:2017 of the international organization for standardization (ISO). The TS has been adapted to the hyphenated setup. The quality criteria (QC), e.g., linearity of the calibration, transport efficiency, were investigated. Furthermore, a cross calibration of the particle size was performed with values from dynamic light scattering (DLS) and transmission electron microscopy (TEM). Due to an additional Y-piece, an online-calibration routine was implemented. This approach allows the calibration of the ICP-MS during the dead time of the chromatography run, to reduce the required time and enhance the robustness of the results. The optimized method was tested with different gold nanoparticle (Au-NP) mixtures to investigate the characterization properties of HDC separations for samples with increasing complexity. Additionally, the technique was successfully applied to simultaneously determine both the hydrodynamic radius and the Au-NP content in liposomes. With the established hyphenated setup, it was possible to distinguish between different subpopulations with various NP loads and different hydrodynamic diameters inside the liposome carriers

Differentiation of Early from Advanced Coronary Atherosclerotic Lesions: Systematic Comparison of CT, Intravascular US, and Optical Frequency Domain Imaging with Histopathologic Examination in ex Vivo Human Hearts

Purpose:To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques.Materials and Methods:All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic.Results:Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both P < .0001), while mixed plaque at coronary CT angiography, calcified plaque at intravascular US, and lipid-rich plaque at OFDI were associated with advanced lesions (OR: 2.49, P = .0003; OR: 2.60, P = .002; and OR: 31.2, P < .0001, respectively). OFDI had higher accuracy for discriminating early from advanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, P < .0001). Interobserver agreement was excellent for OFDI and coronary CT angiography (κ = 0.87 and 0.85, respectively) and was good for intravascular US (κ = 0.66).Conclusion:Systematic and standardized comparison between invasive and noninvasive modalities for coronary plaque characterization in ex vivo specimens demonstrated that coronary CT angiography and intravascular US are reasonably associated with plaque composition and lesion grading according to histopathologic findings, while OFDI was strongly associated. These data may help to develop initial concepts of sequential imaging strategies to identify patients with advanced coronary plaques.© RSNA, 2012Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12111891/-/DC1