Artificial intelligence (AI) aims to mimic human cognitive functions. It is bringing a paradigm shift to healthcare, powered by increasing availability of healthcare data and rapid progress of analytics techniques. We survey the current status of AI applications in healthcare and discuss its future. AI can be applied to various types of healthcare data (structured and unstructured). Popular AI techniques include machine learning methods for structured data, such as the classical support vector machine and neural network, and the modern deep learning, as well as natural language processing for unstructured data. Major disease areas that use AI tools include cancer, neurology and cardiology. We then review in more details the AI applications in stroke, in the three major areas of early detection and diagnosis, treatment, as well as outcome prediction and prognosis evaluation. We conclude with discussion about pioneer AI systems, such as IBM Watson, and hurdles for real-life deployment of AI.

https://svn.bmj.com/content/svnbmj/2/4/230.full.pdf

Artificial intelligence in healthcare: past, present and future

Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling is one of the most important intracellular pathways, which can be considered as a master regulator for cancer. Enormous efforts have been dedicated to the development of drugs targeting PI3K signaling, many of which are currently employed in clinical trials evaluation, and it is becoming increasingly clear that PI3K inhibitors are effective in inhibiting tumor progression. PI3K inhibitors are subdivided into dual PI3K/mTOR inhibitors, pan-PI3K inhibitors and isoform-specific inhibitors. In this review, we performed a critical review to summarize the role of the PI3K pathway in tumor development, recent PI3K inhibitors development based on clinical trials, and the mechanisms of resistance to PI3K inhibition.

/pdf/targeting-pi3k-in-cancer-mechanisms-and-advances-in-clinical-4ituoao2ez.pdf

Targeting PI3K in cancer: mechanisms and advances in clinical trials

Noncoding RNAs (ncRNAs) constitute the majority of the human transcribed genome. This largest class of RNA transcripts plays diverse roles in a multitude of cellular processes, and has been implicated in many pathological conditions, especially cancer. The different subclasses of ncRNAs include microRNAs, a class of short ncRNAs; and a variety of long ncRNAs (lncRNAs), such as lincRNAs, antisense RNAs, pseudogenes, and circular RNAs. Many studies have demonstrated the involvement of these ncRNAs in competitive regulatory interactions, known as competing endogenous RNA (ceRNA) networks, whereby lncRNAs can act as microRNA decoys to modulate gene expression. These interactions are often interconnected, thus aberrant expression of any network component could derail the complex regulatory circuitry, culminating in cancer development and progression. Recent integrative analyses have provided evidence that new computational platforms and experimental approaches can be harnessed together to distinguish key ceRNA interactions in specific cancers, which could facilitate the identification of robust biomarkers and therapeutic targets, and hence, more effective cancer therapies and better patient outcome and survival.

Noncoding RNA:RNA Regulatory Networks in Cancer.

Nano-titanium dioxide (TiO2) is one of the most commonly used materials being synthesized for use as one of the top five nanoparticles. Due to the extensive application of TiO2 nanoparticles and their inclusion in many commercial products, the increased exposure of human beings to nanoparticles is possible. This exposure could be routed via dermal penetration, inhalation and oral ingestion or intravenous injection. Therefore, regular evaluation of their potential toxicity and distribution in the bodies of exposed individuals is essential. Keeping in view the potential health hazards of TiO2 nanoparticles for humans, we reviewed the research articles about studies performed on rats or other mammals as animal models. Most of these studies utilized the dermal or skin and the pulmonary exposures as the primary routes of toxicity. It was interesting that only very few studies revealed that the TiO2 nanoparticles could penetrate through the skin and translocate to other tissues, while many other studies demonstrated that no penetration or translocation could happen through the skin. Conversely, the TiO2 nanoparticles that entered through the pulmonary route were translocated to the brain or the systemic circulation from where these reached other organs like the kidney, liver, etc. In most studies, TiO2 nanoparticles appeared to have caused oxidative stress, histopathological alterations, carcinogenesis, genotoxicity and immune disruption. Therefore, the use of such materials in humans must be either avoided or strictly managed to minimise risks for human health in various situations.

Toxicity of Nano-Titanium Dioxide (TiO2-NP) Through Various Routes of Exposure: a Review.

Contemporary methods for dispersion of carbon nanotubes in water and non-aqueous media are discussed. Most attention is paid to ultrasonic and plasma techniques and other physical techniques, as well as to the use of surfactants, functionalizing and debundling agents of distinct nature (elemental substances, metal and organic salts, mineral and organic acids, oxides, inorganic and organic peroxides, organic sulfonates, polymers, dyes, natural products, biomolecules, and coordination compounds). Special studies on CNTs solubilization are examined.

Dispersion of carbon nanotubes in water and non-aqueous solvents

Abnormal expression of long non-coding RNAs (lncRNAs) have been shown to play an important role in tumor biology. The Cancer Genome Atlas (TCGA) platform is a large sample sequencing database of lncRNAs, and further analysis of the associations between these data and patients' clinical related information can provide new approaches to find the functions of lncRNA. In the present study, 361 RNA sequencing profiles of gastric cancer (GC) patients were selected from TCGA. Then, we constructed the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network of GC. There were 25 GC specific lncRNAs (fold change >2, p<0.05) identified, 19 of them were included in ceRNA network. Subsequently, we selected these 19 key lncRNAs and analyzed the correlations with clinical features and overall survival, 14 of them were discriminatively expressed with tumor size, tumor grade, TNM stage and lymphatic metastasis (p<0.05). In addition, eight lncRNAs (RPLP0P2, FOXD2-AS1, H19, TINCR, SLC26A4-AS1, SMIM10L2A, SMIM10L2B and SNORD116-4) were found to be significantly associated with overall survival (log-rank p<0.05). Finally, two key lncRNAs HOTAIR and UCA1 were selected for validation of their expression levels in 82 newly diagnosed GC patients by qRT-PCR. Results showed that the fold changes between TCGA and qRT-PCR were 100% in agreement. In addition, we also found that HOTAIR was significantly correlated with tumor size and lymphatic metastasis (p<0.05), and UCA1 was significantly correlated with tumor size, TNM stage and lymphatic metastasis (p<0.05). The clinical relevance of the two lncRNAs and the bioinformatics analysis results were almost the same. Overall, our study showed the GC specific lncRNAs expression patterns and a ceRNA network in GC. Clinical features related to GC specific lncRNAs also suggested these lncRNAs are worthwhile for further study as novel candidate biomarkers for the clinical diagnosis of GC and potential indicators for prognosis.

/pdf/integrated-analysis-of-long-non-coding-rna-competing-rb78qe3dm9.pdf

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer

The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated during disease occurrence and to play an important role in the progression of several cancers. However, the biological role and potential regulation mechanism of UCA1 in the carcinogenesis of gastric cancer remain unclear. In the present study, we found that UCA1 was aberrantly upregulated in gastric cancer tissues and gastric cancer cell lines, and was associated with TNM stage and metastasis. UCA1 silencing significantly inhibited gastric cancer BGC-823 cell proliferation and increased its apoptosis. We also found that UCA1 played an important role in the migration and invasion of gastric cancer cells in vitro and in vivo. The molecular mechanism of UCA1 suggested that UCA1 regulates the PI3K-Akt-mTOR signaling proteins and their downstream mediators, to alter gastric cancer progression in vitro and in vivo. Collectively, the results showed a pivotal role of UCA1 in the tumorigenesis of gastric cancer. In addition, the study characterized a novel lncRNA-mRNA regulatory network, which may lead to a better understanding of the pathogenesis of gastric cancer and assist in lncRNA-directed diagnosis and therapy for this malignancy.

/pdf/dysregulated-lncrna-uca1-contributes-to-the-progression-of-428n9esxol.pdf

Dysregulated lncRNA-UCA1 contributes to the progression of gastric cancer through regulation of the PI3K-Akt-mTOR signaling pathway

Lung cancer is one of the most lethal malignancies worldwide. To reduce the high morbidity and mortality of the disease, sensitive and specific biomarkers for early detection are urgently needed. Tumor-specific microRNAs (miRNAs) seem to be potential biomarkers for the early diagnosis and treatment of cancer. In this study, the microarray of miRNAs and mRNAs on the same samples was performed and the intersection taken with The Cancer Genome Atlas (TCGA) lung cancer miRNA/RNAseq dataset. Then, miRNA-mRNA regulatory network was constructed to identify miRNA candidates associated with lung cancer through integrating gene expression and miRNA-target prediction. Furthermore, the expression levels of miRNA candidates were validated by stem-loop real-time reverse transcription PCR (qRT-PCR) in larger lung cancer population. The relationship between signature miRNAs and the risk of lung cancer were assessed by conditional logistic regression analysis. Diagnostic value of these miRNAs was determined by areas under receiver operating characteristic curves (ROC). The Affymetrix microarray analysis identified a total of 116 miRNAs and 502 mRNAs that could distinguish lung tumor tissues from adjacent non-tumor tissues, of which 70 miRNAs and 136 mRNAs were upregulated, while 46 miRNAs and 366 mRNAs were downregulated, respectively. In combination with TCGA analysis, we identified 32 miRNAs and 377 mRNAs related to lung cancer. Then, 28 key miRNAs related to 61 inter-section mRNAs were identified by miRNA-mRNA network analysis. The miRNA function analysis was indicative of that 18 upregulated and 10 downregulated miRNAs involved in signaling pathways related to Environmental Information Processing and Human Diseases. Population result showed that the expression of 7 miRNAs (miR-205-5p, miR-3917, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p and miR-27a-5p) was consistent with the analysis result of microarray and TCGA. In addition, upregulation of miR-205-5p, miR-3917 and downregulation of miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p, miR-27a-5p increased the risk of lung cancer by conditional logistic regression analysis. The diagnostic accuracy of miR-205-5p, miR-3917, miR-27a-5p, miR-30a-3p, miR-30a-5p, miR-30c-2-3p, miR-30d-5p showed that their corresponding AUCs were 0.728, 0.661, 0.637, 0.758, 0.772, 0.734, 0.776, respectively. Therefore, there are a set of signature miRNAs which may be promising biomarkers for the early screening of high-risk populations and early diagnosis of lung cancer.

/pdf/differential-expression-profiles-of-micrornas-as-potential-37cxwvjbow.pdf

Differential expression profiles of microRNAs as potential biomarkers for the early diagnosis of lung cancer

To investigate the potential candidate microRNA (miRNA) biomarkers for the clinical diagnosis, classification, and prognosis of gastric cancer (GC). We use bioinformatics overlapping subclasses analysis to find the tumor grade and lymphatic metastasis-related GC specific miRNAs from the Cancer Genome Atlas (TCGA) database. Then, we further investigated these GC specific miRNAs distributions in different GC clinical features and their correlations overall survival on the basis of GC patients’ information and their related RNA sequencing profile from TCGA. Finally, we randomly selected some of key miRNAs use qRT-PCR to confirm the reliability and validity. 22 GC specific key miRNAs were identified (Fold-change >2, P < 0.05), 11 of them were discriminatively expressed with tumor size, grade, TNM stage and lymphatic metastasis (P < 0.05). In addition, nine miRNAs (miR-196b-5p, miR-135b-5p, miR-183-5p, miR-182-5p, miR-133a-3p, miR-486-5p, miR-144-5p, miR-129-5p and miR-145-5p) were found to be significantly associated with overall survival (log-rank P < 0.05). Finally, four key miRNAs (miR-183-5p, miR-486-5p, miR-30c-2-3p and miR-133a-3p) were randomly selected to validation and their expression levels in 53 newly diagnosed GC patients by qRT-PCR. Results showed that the fold-changes between TCGA and qRT-PCR were 100 % in agreement. We also found miR-183-5p and miR-486-5p were significantly correlated with tumor TNM stage (P < 0.05), and miR-30c-2-3p and miR-133a-3p were associated with tumor differentiation degree and lymph-node metastasis (P < 0.05). These verified miRNAs clinically relevant, and the bioinformatics analysis results were almost the same. These key miRNAs may functions as potential candidate biomarkers for the clinical diagnosis, classification and prognosis for GC.

Identification and functional characterization of microRNAs reveal a potential role in gastric cancer progression

The potential immune effects of titanium dioxide nanoparticles (nano-TiO2) are raising concern. Our previous study verified that nano-TiO2 induce local immune response in lung tissue followed by intratracheal instillation administration. In this study, we aim to evaluate the systemic immune effects of nano-TiO2. Sprague Dawley rats were treated by intratracheal instillation with nano-TiO2 at doses of 0.5, 4, and 32 mg/kg body weight, micro-TiO2 with 32 mg/kg body weight and 0.9% NaCl, respectively. The exposure was conducted twice a week, for four consecutive weeks. Histopathological immune organs from exposed animals showed slight congestion in spleen, generally brown particulate deposition in cervical and axillary lymph node. Furthermore, immune function response was characterized by increased proliferation of T cells and B cells following mitogen stimulation and enhanced natural killer (NK) cell killing activity in spleen, accompanying by increased number of B cells in blood. No significant changes of Th1-type cytokines (IL-2 and INF-γ) and Th2-type cytokines (TNF-α and IL-6) were observed. Intratracheal exposure to nano-TiO2 may be one of triggers to be responsible for the systemic immune response. Further study is needed to confirm long-lasting lymphocyte responses and the potential mechanisms.

https://www.mdpi.com/1422-0067/15/4/6961/pdf

Yanqiu Zhang

Papers

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer

Dysregulated lncRNA-UCA1 contributes to the progression of gastric cancer through regulation of the PI3K-Akt-mTOR signaling pathway

Differential expression profiles of microRNAs as potential biomarkers for the early diagnosis of lung cancer

Identification and functional characterization of microRNAs reveal a potential role in gastric cancer progression

Systemic Immune Effects of Titanium Dioxide Nanoparticles after Repeated Intratracheal Instillation in Rat