We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.

Clinical Trials.gov number, NCT01420588 (3/11/2013).

Although colorectal cancer (CRC) screening is included in organized programs of many countries worldwide, there is still a place for better screening tools. In this study, 418 breath samples were collected from 65 patients with CRC, 22 with advanced or nonadvanced adenomas, and 122 control cases. All patients, including the controls, had undergone colonoscopy. The samples were analysed with two different techniques. The first technique relied on gas chromatography coupled with mass spectrometry (GC-MS) for identification and quantification of volatile organic compounds (VOCs). The T-test was used to identify significant VOCs (p values < 0.017). The second technique relied on sensor analysis with a pattern recognition method for building a breath pattern to identify different groups. Blind analysis or leave-one-out cross validation was conducted for validation. The GC-MS analysis revealed four significant VOCs that identified the tested groups; these were acetone and ethyl acetate (higher in CRC), ethanol and 4-methyl octane (lower in CRC). The sensor-analysis distinguished CRC from the control group with 85% sensitivity, 94% specificity and 91% accuracy. The performance of the sensors in identifying the advanced adenoma group from the non-advanced adenomas was 88% sensitivity, 100% specificity, and 94% accuracy. The performance of the sensors in identifying the advanced adenoma group was distinguished from the control group was 100% sensitivity, 88% specificity, and 94% accuracy. For summary, volatile marker testing by using sensor analysis is a promising noninvasive approach for CRC screening.Globally colorectal cancer (CRC) is the third most prevalent cancer and the fourth leading cause of death from malignant diseases. 1 The 5-year survival rate for colorectal cancer when diagnosed at an early stage before it has spread is about 90%. But only about four out of 10 colorectal cancers are found at that early stage. In advanced stages, the survival rates are substantially lower. Therefore, regular CRC screening or testing are considered as some of the most powerful tools for preventing colorectal cancer caused mortality. 2 Not only does CRC screening save lives, but it also is cost effective. Studies have shown that the cost-effectiveness of CRC screening is consistent with many other kinds of preventive services and is lower than some common interventions. 3 The laboratory-based faecal immunochemical test (FIT) is the test-of-choice currently in the EU. 4 Alternatively, several recent studies have demonstrated the ability of flexiblesigmoidoscopy to decrease the disease-specific mortality when used as a screening tool. 5-7 However, colonoscopy is considered better than sigmoidoscopy in preventing mortality. 8 Poland, Germany and Czech Republic are using colonoscopy as their primary screening tool. Nevertheless, the major problem with endoscopic methods for CRC screening is low compliance. 9 A systemic review of participation in CRC screening within trial settings after the first-time invitation has reported only...

Background:Squamous cell carcinoma of the head and neck (HNSCC) are wide-spread cancers that often lead to disfigurement and loss of important functions such as speech and ingestion. To date, HNSCC has no adequate method for early detection and screening.Methods:Exhaled breath samples were collected from 87 volunteers; 62 well-defined breath samples from 22 HNSCC patients (larynx and pharynx), 21 patients with benign tumours (larynx and pharynx) and 19 healthy controls were analysed in a dual approach: (i) chemical analysis using gas chromatography/mass spectrometry (GC–MS) and (ii) breath-print analysis using an array of nanomaterial-based sensors, combined with a statistical algorithm.Results:Gas chromatography/mass spectrometry identified ethanol, 2-propenenitrile and undecane as potential markers for HNSCC and/or benign tumours of the head and neck. The sensor-array-based breath-prints could clearly distinguish HNSCC both from benign tumours and from healthy states. Within the HNSCC group, patients could be classified according to tumour site and stage.Conclusions:We have demonstrated the feasibility of a breath test for a specific, clinically interesting application: distinguishing HNSCC from tumour-free or benign tumour states, as well as for staging and locating HNSCC. The sensor array used here could form the basis for the development of an urgently needed non-invasive, cost-effective, fast and reliable point-of-care diagnostic/screening tool for HNSCC.

We present a pilot study that aims to examine the possibility to easily and noninvasively detect and discriminate females with ovarian cancer (OC) from females that have no tumor(s) and from females that have benign genital tract neoplasia, using exhaled breath samples. The study is based on clinical samples and data from 182 females, as follows: 48 females with OC, 48 tumor-free controls and 86 females with benign gynecological neoplasia. Analysis of the breath samples with gas chromatography linked with mass spectrometry shows that decanal, nonanal, styrene, 2-butanone and hexadecane could serve as potential volatile markers for OC. Analysis of the same samples with tailor-made nanoarrays shows good discrimination between females with OC and females that have either no tumor or benign genital tract neoplasia (71% for accuracy, sensitivity and specificity). Conversely, the nanoarray output shows excellent discrimination between the OC patients and the tumorfree controls (79% sensitivity, 100% specificity and 89% accuracy). These results suggest that the nanoarray approach might be useful to avoid unnecessary complicated or expensive tests for tumor-free females in case of a negative result. In the case of positive result, the test will indicate with high probability the presence of OC.

Mutation in the SHANK3 human gene leads to different neuropsychiatric diseases including Autism Spectrum Disorder (ASD), intellectual disabilities and Phelan-McDermid syndrome. Shank3 disruption in mice leads to dysfunction of synaptic transmission, behavior, and development. Protein S-nitrosylation, the nitric oxide (NO)-mediated posttranslational modification (PTM) of cysteine thiols (SNO), modulates the activity of proteins that regulate key signaling pathways. We tested the hypothesis that Shank3 mutation would generate downstream effects on PTM of critical proteins that lead to modification of synaptic functions. SNO-proteins in two ASD-related brain regions, cortex and striatum of young and adult InsG3680(+/+) mice (a human mutation-based Shank3 mouse model), were identified by an innovative mass spectrometric method, SNOTRAP. We found changes of the SNO-proteome in the mutant compared to WT in both ages. Pathway analysis showed enrichment of processes affected in ASD. SNO-Calcineurin in mutant led to a significant increase of phosphorylated Synapsin1 and CREB, which affect synaptic vesicle mobilization and gene transcription, respectively. A significant increase of 3-nitrotyrosine was found in the cortical regions of the adult mutant, signaling both oxidative and nitrosative stress. Neuronal NO Synthase (nNOS) was examined for levels and localization in neurons and no significant difference was found in WT vs. mutant. S-nitrosoglutathione concentrations were higher in mutant mice compared to WT. This is the first study on NO-related molecular changes and SNO-signaling in the brain of an ASD mouse model that allows the characterization and identification of key proteins, cellular pathways, and neurobiological mechanisms that might be affected in ASD.

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Mutations in the MAPT gene, which encodes the tau protein, are associated with several neurodegenerative diseases, including frontotemporal dementia (FTD), dementia with epilepsy, and other types of dementia. The missense mutation in the Mapt gene in the P301S mouse model of FTD results in impaired synaptic function and microgliosis at three months of age, which are the earliest manifestations of disease. Here, we examined changes in the S-nitrosoproteome in 2-month-old transgenic P301S mice in order to detect molecular events corresponding to early stages of disease progression. S-nitrosylated (SNO) proteins were identified in two brain regions, cortex and hippocampus, in P301S and Wild Type (WT) littermate control mice. We found major changes in the S-nitrosoproteome between the groups in both regions. Several pathways converged to show that calcium regulation and non-canonical Wnt signaling are affected using GO and pathway analysis. Significant increase in 3-nitrotyrosine was found in the CA1 and entorhinal cortex regions, which indicates an elevation of oxidative stress and nitric oxide formation. There was evidence of increased Non-Canonical Wnt/Ca++ (NC-WCa) signaling in the cortex of the P301S mice; including increases in phosphorylated CaMKII, and S-nitrosylation of E3 ubiquitin-protein ligase RNF213 (RNF-213) leading to increased levels of nuclear factor of activated T-cells 1 (NFAT-1) and FILAMIN-A, which further amplify the NC-WCa and contribute to the pathology. These findings implicate activation of the NC-WCa pathway in tauopathy and provide novel insights into the contribution of S-nitrosylation to NC-WCa activation, and offer new potential drug targets for treatment of tauopathies.