Speed and efficiency: evaluating pulmonary nodule detection with AI-enhanced 3D gradient echo imaging.

Objectives: Evaluating the diagnostic feasibility of accelerated pulmonary MR imaging for detection and characterisation of pulmonary nodules with artificial intelligence-aided compressed sensing.

Materials And Methods: In this prospective trial, patients with benign and malignant lung nodules admitted between December 2021 and December 2022 underwent chest CT and pulmonary MRI. Pulmonary MRI used a respiratory-gated 3D gradient echo sequence, accelerated with a combination of parallel imaging, compressed sensing, and deep learning image reconstruction with three different acceleration factors (CS-AI-7, CS-AI-10, and CS-AI-15).

Measuring nanoscale forces with living probes.

Optical trapping techniques have been used to investigate fundamental biological processes ranging from the identification of the processive mechanisms of kinesin and myosin to understanding the mechanics of DNA. To date, these investigations have relied almost exclusively on the use of isotropic probes based on colloidal microspheres. However, there are many potential advantages in utilizing more complex probe morphologies: use of multiple trapping points enables control of the interaction volume; increasing the distance between the optical trap and the sample minimizes photodamage in sensitive biological materials; and geometric anisotropy introduces the potential for asymmetric surface chemistry and multifunctional probes.

The challenge of testing chemicals for potential carcinogenicity using multiple short-term assays: an analysis of a proposed test battery for hair dyes.

Recent reports of the association of hair dyes usage with increased bladder cancer risk in women with the slow NAT-2 acetylator phenotype have resulted both in attempts to identify the putative carcinogen as well as in devising batteries of tests that could be used to screen for such putative carcinogens in hair dye formulations, their intermediates and final products. Analytical studies have reported the presence of traces ( approximately 0.5 ppm) of the carcinogen 4-aminobiphenyl in some hair dye preparations.

Lack of predictivity of the rat lethality (LD50) test for ecological and human health effects.

The relationship between acute toxicity in rats (LD50 values) and indicators of potential health hazards in humans was investigated, based on a chemical population-based paradigm (i.e. the "chemical diversity approach").

SAR modelling of complex phenomena: probing methodological limitations.

The increased acceptance of the use of structure-activity relationship (SAR) approaches to toxicity modelling has necessitated an evaluation of the limitations of the methodology. In this study, the limit of the capacity of the MULTICASE SAR program to model complex biological and toxicological phenomena was assessed. It was estimated that, provided the data set consists of at least 300 chemicals, divided equally between active and inactive compounds, the program is capable of handling phenomena that are even more "complex" than those modelled up to now (for example, allergic contact dermatitis, Salmonella mutagenicity, biodegradability, inhibition of tubulin polymerisation).

Structure-activity approach to the identification of environmental estrogens: the MCASE approach.

A sizable number of environmental contaminants and natural products have been found to possess hormonal activity and have been termed endocrine-disrupting chemicals. Due to the vast number (estimated at about 58,000) of environmental contaminants, their potential to adversely affect the endocrine system, and the paucity of health effects data associated with them, the U.S.

SAR modeling of genotoxic phenomena: the consequence on predictive performance of deviation from a unity ratio of genotoxicants/non-genotoxicants.

SAR approaches to the study of genotoxic phenomena are finding increased applications. However, the data being modeled are frequently not considered optimal due to the small size of the dataset and an uneven distribution of genotoxicants and non-genotoxicants in the dataset. The effects of such imbalances on the performance of one SAR approach were investigated with respect to the modeling of the induction of unscheduled DNA synthesis in rat hepotocytes and of sister chromatid exchanges and chromosomal aberrations in cultural CHO cells.

Synergy between systemic toxicity and genotoxicity: relevance to human cancer risk.

The health risk manager and policy analyst must frequently make recommendations based upon incomplete toxicity data. This is a situation which is encountered in the evaluation of human carcinogenic risks as animal cancer bioassay results are often not available. In this study, in order to assess the relevance of other possible indicators of carcinogenic risks, we used the "chemical diversity approach" to estimate the magnitude of the human carcinogenic risk based upon Salmonella mutagenicity and systemic toxicity data of the "universe of chemicals" to which humans have the potential to be exposed.

Environmental odors and health hazards.

Using the recently developed and validated 'chemical diversity approach', the potential of chemicals, to be detected by the human olfactory system and to cause adverse health effects, was investigated. The analyses found no significant association between odor perceptibility and potential for inducing health effects.

SAR: flavonoids and COX-2 inhibition.

An analysis based upon structure-activity relationships (SAR) of the COX-2-inhibiting properties of flavonoids, a group of potential cancer chemopreventative agents, reveals that there is a dual structural basis for these activities. Each of these structural determinants (pharmacophores) alone is sufficient for activity. One of the pharmacophores is a 2D 6.

Environmental persistence of chemicals and their carcinogenic risks to humans.

A "chemical population"-based investigation of xenobiotics (i.e. a sample of 10,000 chemicals representative of agents in commerce, industry, and the environment, both synthetic and natural) that have the potential for ecotoxicity because of their persistence in the environment and their potential association with carcinogenic risks to humans was undertaken.

A substructure-based SAR model for odor perception in humans relevant to health risk assessments.

The ability of human to perceive odors is a very complex phenomenon involving the selective binding of molecules to approximately 1000 olfactory receptors. Accordingly, the derivation of a substructure-based SAR model can be expected to be problematic. Yet, based upon published data on odor thresholds of volatile organic chemicals, we were able to derive such an SAR model.

A data mining approach for the elucidation of the action of putative etiological agents: application to the non-genotoxic carcinogenicity of genistein.

A procedure designated "the virtual similarity index" (VSI) is described to determine the probability that two or more toxicants are related mechanistically. The approach is structure-activity relationship (SAR) based and generates the virtual toxicological profiles of the chemicals under investigation. It also determines the similarities between them.

SAR modeling: effect of experimental ambiguity.

The applicability of SAR (structure-activity relationship) techniques to data obtained using high throughput screening (HTS) and toxicogenomic techniques is explored. The reason for this study derives from the fact that for economical and time considerations HTS bioassays may consist of single determinations, i.e.

Structural concepts in cancer prevention.

The notion of developing cancer preventative strategies is attractive both from a public health and from a health economic viewpoint. However, as currently visualized, this may involve dietary supplementation of publicly available foods or the ingestion of specific supplements for prolonged periods of time. In view of the fact that the outcome of such preventative strategies may as yet not be known, it is essential that the strategy is devoid of risks.

A paradigm for determining the relevance of short-term assays: application to oxidative mutagenesis.

A simple substructure-based approach was developed to determine whether a short-term assay under development is related mechanistically to the endpoint it seeks to predict. Thus, substructures associated with mutagenicity in Salmonella are also present in carcinogens and agents active in other mutagenicity and genotoxicity assays. When applied to test results obtained with an Escherichia coli strain designed to identify oxidative mutagens, there was no significant association with either carcinogens or mutagens and genotoxicants detected by other systems.

Computational toxicology and the generation of mechanistic hypotheses: gamma-butyrolactone.

In this study, we use SAR approaches in an attempt to elucidate the action of gamma-butyrolactone (GBL), an illicit drug and a dietary supplement, that can cause coma and deaths in humans while exhibiting low systemic toxicity towards rodents. The lack of systemic toxicity of GBL and of its metabolite(s) was also predicted by validated SAR models. In fact using diverse SAR models, the only significant SAR prediction was that GBL had the potential for inhibiting human cytochrome P4502D6 (CYP2D6).

Prevalence of mutagens in the environment: experimental data versus simulations.

The recent availability of experimental data on the mutagenicity in Salmonella of a subset of high production volume chemicals allowed a comparison with the estimate derived from computer-based simulations. The prevalence of mutagens in the subsets was not significantly different: 20% versus 19.5% based upon experimental and simulation data, respectively.

In wounded sugar beet (Beta vulgaris L.) tap-root, hexose accumulation correlates with the induction of a vacuolar invertase isoform.

Wounding of sugar beet tap-root causes an induction of invertase activity, which contributes to post-harvest sucrose losses. In this first comprehensive monitoring of wound-induced invertase mRNAs, proteins, enzyme activities, and tissue hexose concentrations, the VI isoform responsible for wound-induced hexose accumulation in mature tap-root could be identified.

SAR modeling of unbalanced data sets.

The increased acceptance of SAR approaches to hazard identification has led us to investigate methods to improve the predictive performance of SAR models. In the present study we demonstrate that although on theoretical grounds the ratio of active to inactive chemicals in the learning set should be unity, SAR models can "tolerate" an unbalanced range in ratios from 3:1 (i.e.

Estimating the extent of the health hazard posed by high-production volume chemicals.

We used structure-activity relationship modeling to estimate the number of toxic chemicals among the high-production volume (HPV) group. We selected 200 chemicals from among the HPV chemical list and predicted the potential of each for its ability to induce a variety of adverse effects including genotoxicity, carcinogenicity, developmental, and systemic toxicity. We found a significantly less than expected proportion of toxic chemicals among the HPV sample when compared to a reference set of 10,000 chemicals representative of the universe of chemicals.

Allergic contact dermatitis and its relationship to carcinogenicity.

The relationship between allergic contact dermatitis (ACD) and carcinogenicity was investigated using a recently developed and validated simulation approach. The analyses indicated that while there are electrophilic and non-electrophilic components to ACD, these were not identical to those operating in carcinogenicity. Accordingly, with respect to carcinogenicity prediction, the results of ACD do not improve the results based upon mutagenicity testing alone, the latter being a surrogate for potential electrophilicity.

Chemical categories for health hazard identification: a feasibility study.

The use of chemical categories has been suggested in order to lower the number of chemicals tested in the High Production Volume (HPV) Chemical Challenge Program. In this investigation we examined the reliability of using organic chemical categories to classify chemicals as either toxic or nontoxic for individual toxicological effects as well as for panels of such endpoints. The analyses indicate that chemical categories are unable to consistently identify groups of chemicals with similar toxic responses either for a multiplicity of endpoints or for single effects.

SAR modeling of genotoxic phenomena: the effect of supplementation with physiological chemicals.

Structure-activity relationship (SAR) modeling of toxicological phenomena is optimal when the ratio of toxicants to non-toxicants included in the model is unity. Frequently, however, the experimental data available are enriched with toxicants, this appears to be especially true for genotoxicity data sets. It is demonstrated herein, using a Salmonella mutagenicity data set, that when there is a paucity of non-toxicants, the learning set may be augmented with physiological chemicals on the assumption that they are non-genotoxic.

A new approach to evaluate mechanistic relationships among genotoxic phenomena: validation.

In order to determine its applicability for the study of genotoxicity, a recently developed method to probe for possible mechanistic relationships among toxicological phenomena was applied to the induction of mutations in Salmonella typhimurium. Since the basis of this phenomenon is understood, this would provide a test of the applicability of the new method to DNA-based mechanisms. The results presented indicate that significant relationships are indeed found among phenomena involving damage to or modification of DNA but not between them and non-genotoxic phenomena.