Optimized model architectures for deep learning on genomic data.

The success of deep learning in various applications depends on task-specific architecture design choices, including the types, hyperparameters, and number of layers. In computational biology, there is no consensus on the optimal architecture design, and decisions are often made using insights from more well-established fields such as computer vision. These may not consider the domain-specific characteristics of genome sequences, potentially limiting performance. Here, we present GenomeNet-Architect, a neural architecture design framework that automatically optimizes deep learning models for genome sequence data. It optimizes the overall layout of the architecture, with a search space specifically designed for genomics. Additionally, it optimizes hyperparameters of individual layers and the model training procedure. On a viral classification task, GenomeNet-Architect reduced the read-level misclassification rate by 19%, with 67% faster inference and 83% fewer parameters, and achieved similar contig-level accuracy with ~100 times fewer parameters compared to the best-performing deep learning baselines.

The Role of Innate and Adaptive Immune System in the Pathogenesis of Schizophrenia.

Schizophrenia is one of the most severely debilitating mental disorders that affects 1.1% of the world's population. The exact cause of the disease is not known, but genetics, environmental factors (such as infectious agents, season and region of birth, exposure to viruses, low birth weight, advanced paternal age, and tobacco), and immune system dysfunction can all contribute to the development of schizophrenia. Recently, the role of the immune system in schizophrenia has received much attention. Both acquired and innate immune systems are involved in the pathogenesis of schizophrenia and facilitate the disease's progression. Almost all cells of the immune system including microglia, B cells, and T cells play an important role in the blood-brain barrier damage, inflammation, and in the progression of this disease. In schizophrenia, the integrity of the blood-brain barrier is reduced and then the immune cells are recruited into the endothelium following an increase in the expression of cell adhesion molecules. The entry of immune cells and cytokines leads to inflammation and antibody production in the brain. Accordingly, the results of this study strengthen the hypothesis that the innate and acquired immune systems are involved in the pathogenesis of schizophrenia.

Bayesian uncertainty estimation for detection of long-tailed and unseen conditions in medical images.

Purpose: Deep supervised learning provides an effective approach for developing robust models for various computer-aided diagnosis tasks. However, there is often an underlying assumption that the frequencies of the samples between the different classes of the training dataset are either similar or balanced. In real-world medical data, the samples of positive classes often occur too infrequently to satisfy this assumption. Thus, there is an unmet need for deep-learning systems that can automatically identify and adapt to the real-world conditions of imbalanced data. Approach: We propose a deep Bayesian ensemble learning framework to address the representation learning problem of long-tailed and out-of-distribution (OOD) samples when training from medical images. By estimating the relative uncertainties of the input data, our framework can adapt to imbalanced data for learning generalizable classifiers. We trained and tested our framework on four public medical imaging datasets with various imbalance ratios and imaging modalities across three different learning tasks: semantic medical image segmentation, OOD detection, and in-domain generalization. We compared the performance of our framework with those of state-of-the-art comparator methods. Results: Our proposed framework outperformed the comparator models significantly across all performance metrics (pairwise t-test: p<0.01) in the semantic segmentation of high-resolution CT and MR images as well as in the detection of OOD samples (p<0.01), thereby showing significant improvement in handling the associated long-tailed data distribution. The results of the in-domain generalization also indicated that our framework can enhance the prediction of retinal glaucoma, contributing to clinical decision-making processes. Conclusions: Training of the proposed deep Bayesian ensemble learning framework with dynamic Monte-Carlo dropout and a combination of losses yielded the best generalization to unseen samples from imbalanced medical imaging datasets across different learning tasks.

A self-supervised deep learning method for data-efficient training in genomics.

Deep learning in bioinformatics is often limited to problems where extensive amounts of labeled data are available for supervised classification. By exploiting unlabeled data, self-supervised learning techniques can improve the performance of machine learning models in the presence of limited labeled data. Although many self-supervised learning methods have been suggested before, they have failed to exploit the unique characteristics of genomic data. Therefore, we introduce Self-GenomeNet, a self-supervised learning technique that is custom-tailored for genomic data. Self-GenomeNet leverages reverse-complement sequences and effectively learns short- and long-term dependencies by predicting targets of different lengths. Self-GenomeNet performs better than other self-supervised methods in data-scarce genomic tasks and outperforms standard supervised training with ~10 times fewer labeled training data. Furthermore, the learned representations generalize well to new datasets and tasks. These findings suggest that Self-GenomeNet is well suited for large-scale, unlabeled genomic datasets and could substantially improve the performance of genomic models.

Effects of Asparagus officinalis on immune system mediated EAE model of multiple sclerosis.

Background: About 5 to 10 percent of the population in developed countries are affected by autoimmune diseases. One of the most important autoimmune disease with high prevalence rate is Multiple sclerosis in which there is currently no definitive cure for it, and most medications such as interferons are used only to limit the disease. The present study aims to investigate the effect of using Asparagus Officinalis fractions in an immune system mediated model of multiple sclerosis. Material and Methods: Fractionation was performed by maceration using n-hexane, chloroform, chloroform-methanol (9: 1), n-Butanol and methanol solvents from aerial parts of Asparagus Officinalis. Thin layer chromatography, NMR and phenolic component measurement were done and two fractions were selected for checking in MS induced in vivo model. Results: It was observed that chloroform-methanolic and N-Butanol fractions had higher content of saponin in comparison of other extracts. Also, it was showed that the methanolic and n-Butanol extracts contains the highestportion of glycosylic steroid saponins in comparison to other fractions. Regarding experimental autoimmune encephalomyelitis (EAE) score, Butanolic and methanolic fractions with doses higher that 100mg/kg showed a potent supportive effects as long as locomotor activity protection even in lower dose in comparison to phosphate buffered saline (PBS) group. Conclusion: Considering the proved different effects of saponin compounds on the immune system we observed that those fractions altered the circulatory peripheral blood cells and also remit the clinical signs after EAE induction along with enhanced myelin sheath content in the median region of corpus callusom. It could be inferred that this fractions are promising candidates for further investigation as dose-dependent immune system regulating compounds in multiple sclerosis patients.

Correlation of miR-24-3p and miR-595 expression with CCL3, CCL4, IL1-beta, TNFalphaIP3, and NF-kappaBIalpha genes in PBMCs of patients with coronary artery disease.

Inflammation has been well recognized to play an important role in developing coronary artery disease (CAD). By regulating essential genes in this pathway post-transcriptionally, MicroRNAs (miRNAs) may help or hinder the development of atherosclerotic lesions. The aim of this study was to investigate the expression of miR-24-3p, miR-595, CCL3, CCL4, IL-1ß, TNFαIP3, and NF-κBIα in the peripheral blood mononuclear cells (PBMCs) of CAD and control groups and to examine whether any correlation exists between the expression of miRs and genes in CAD group. A total of 168 subjects (84 CAD subjects and 84 control subjects) were examined in this research. Expression levels of miR-24-3p, miR-595, CCL3, CCL4, IL-1ß, TNFαIP3, and NF-κBIα in PBMCs were measured using the real-time PCR technique. A comparison of the CAD group with the control group indicated significantly increased expression levels of CCL3, CCL4, and IL-1ß (Fold Change (FC)=4, P=0.009; FC=2.9, P=0.01; FC=1.8, P=0.019, respectively) and remarkably reduced expression levels of TNFαIP3 and NF-κBIα (FC=-1.4, P=0.03 and FC=-5.9, P=0.001, respectively). Moreover, the expression levels of miR-24-3p downregulated (FC=-2.5, P=0.005) and miR-595 upregulated (FC=1.9, P=0.009) in the CAD group. There was a statistical correlation between the number of clogged arteries with expression levels of miR-24-3p, miR-595, CCL3, CCL4, IL-1ß, TNFαIP3, and NF-κBIα in the CAD group. Also, there was a statistical correlation between expression levels of miR-24-3p and miR-595 with CCL3, CCL4, IL-1ß, TNFαIP3, and NF-κBIα gene expression in the CAD group. In CAD patients, decreased expression of miR-24-3p and increased expression of miR-595 may aid the progression of atherosclerotic plaques by regulating CCL3, CCL4, IL-1ß, TNFαIP3, and NF-κBIα gene expression.

A Study of Autoantibodies against Some Central Nervous System Antigens and the IL-35 Serum Level in Schizophrenia.

Schizophrenia (SCZ) is a debilitating mental disorder with various causes involving complex interactions between genetic factors and environmental agents. The immune system plays a vital role in the pathology and function of the nervous system. Interleukin 35 (IL-35) is a regulatory and anti-inflammatory cytokine that can prevent autoimmune and inflammatory diseases. This study aimed to investigate the role of autoantibodies against some central nervous system (CNS) antigens and IL-35 serum levels in patients with Schizophrenia. This case-control study involved 80 participants. The serum levels of IL-35 were measured by enzyme-linked immunosorbent assay and the autoantibodies in the CNS by indirect immunofluorescence assay (IFA). The serum levels of IL-35 were decreased in patient groups compared to healthy subjects. Autoantibodies against N-methyl-D-aspartate receptor (NMDAR) and myelin-associated glycoprotein (MAG) were positive in 15% (6/40) and 7.5% (3/40), respectively; however, no antibodies against myelin, aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), voltage-gated potassium channel (VGKC), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), γ-butyric acid receptor type B1 γ-butyric acid receptor type B1 (GABABR), antidipeptidyl peptidase-like protein-6 (DPPX), immunoglobulin-like cell adhesion molecule 5 (IgLON5), Glycine receptor (R) and acetylcholine receptor (Ach R) were detected (No statistics were computed).  We found that decreased serum IL-35 levels and the existence autoantibodies against NMDAR antigen may contribute to the pathogenesis of SCZ.

Serum levels of IL-37 and correlation with inflammatory cytokines and clinical outcomes in patients with coronary artery disease.

Coronary artery disease (CAD) due to atherosclerosis is one of the important reasons for death worldwide. Recent evidence has suggested the essential role of inflammation in the progression of atherosclerosis. Interleukin (IL)-37 is a critical anti-inflammatory member of the IL-1 family which regulates the inflammatory processes. The aim of this study was to compare the serum levels of IL-37 in patients with CAD compared with the control group and its correlation with oxidative stress, cholesterol homeostasis, and inflammation in patients with CAD. A total of 42 patients with CAD and 42 sex-matched and age- matched controls who underwent coronary angiography were included in this study. The serum levels of IL-37 were evaluated via ELISA. Serum levels of biochemical risk factors were determined by enzymatic methods. Serum levels of IL-37 in the CAD group subjects were significantly lower than in the control group and IL-37 was significantly increased in men with CAD than in women with CAD. IL-37 significantly had an inverse correlation with IL-6, tumor necrosis factor-α, IL-32, high-sensitivity C reactive protein, oxidized low-density lipoprotein, and malondialdehyde. Also, IL-37 had a significantly positive correlation with ferric-reducing antioxidant power (FRAP) assay. In addition, IL-37 has positively correlated with ATP-binding cassette transporter A1 and G1 gene expression in peripheral blood mononuclear cells and serum levels of the FRAP. A receiver operating characteristic test displayed that IL-37 level ratios were a relatively significant CAD predictor. Our results indicated that decreased serum levels of IL-37 in patients with CAD and its relationship with inflammatory cytokines and reverse cholesterol transport genes are more likely to be associated in the inflammatory process with disease pathology.

The Emerging Role of EMT-related lncRNAs in Therapy Resistance and their Applications as Biomarkers.

Cancer is the world's second-largest cause of death. The most common cancer treatments are surgery, radiation therapy, and chemotherapy. Drug resistance, epithelial-- to-mesenchymal transition (EMT), and metastasis are pressing issues in cancer therapy today. Increasing evidence showed that drug resistance and EMT are co-related with each other. Indeed, drug-resistant cancer cells possess enhanced EMT and invasive ability. Recent research has demonstrated that lncRNAs (long non-coding RNAs) are non-coding transcripts which play an important role in the regulation of EMT, metastasis, and drug resistance in different cancers. However, the relationships among lncRNAs, EMT, and drug resistance are still unclear. These effects could be exerted via several signaling pathways, such as TGF-ß, PI3K-AKT, and Wnt/ß-catenin. Identifying the crucial regulatory roles of lncRNAs in these pathways and processes leads to the development of novel targeted therapies. We review the key aspects of lncRNAs associated with EMT and therapy resistance. We focus on the crosstalk between lncRNAs and molecular signaling pathways affecting EMT and drug resistance. Moreover, each of the mentioned lncRNAs could be used as a potential diagnostic, prognostic, and therapeutic therapy resistancefor cancer. However, the investigation of lncRNAs for clinical applications still has several challenges.

Bell's palsy after Sputnik V COVID-19 (Gam-COVID-Vac) vaccination.

A possible association between Bell's palsy and COVID-19 vaccination has been suggested previously. Here, we report two cases of facial nerve hemiparalysis following the Sputnik V COVID-19 vaccination in a 27-year-old female patient and a 58-year-old male patient who were both clinically diagnosed with Bell's palsy.

PI3K/Akt/mTOR pathway: a potential target for anti-SARS-CoV-2 therapy.

Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A single-stranded RNA virus from a ß-Coronaviridae family causes acute clinical manifestations. Its high death rate and severe clinical symptoms have turned it into the most significant challenge worldwide. Up until now, several effective COVID-19 vaccines have been designed and marketed, but our data on specialized therapeutic drugs for the treatment of COVID-19 is still limited. In order to synthesis virus particles, SARS-CoV-2 uses host metabolic pathways such as phosphoinositide3-kinase (PI3K)/protein kinase B (PKB, also known as AKT)/mammalian target of rapamycin (mTOR). mTOR is involved in multiple biological processes. Over-activation of the mTOR pathway improves viral replication, which makes it a possible target in COVID-19 therapy. Clinical data shows the hyperactivation of the mTOR pathway in lung tissues during respiratory viral infections. However, the exact impact of mTOR pathway inhibitors on the COVID-19 severity and death rate is yet to be thoroughly investigated. There are several mTOR pathway inhibitors. Rapamycin is the most famous inhibitor of mTORC1 among all. Studies on other respiratory viruses suggest that the therapeutic inhibitors of the mTOR pathway, especially rapamycin, can be a potential approach to anti-SARS-CoV-2 therapy. Using therapeutic methods that inhibit harmful immune responses can open a new chapter in treating severe COVID-19 disease. We highlighted the potential contribution of PI3K/Akt/mTOR inhibitors in the treatment of COVID-19.

Prevalence and Risk Factors of Dysphagia in Patients with Multiple Sclerosis.

Dysphagia is one of the most common symptoms in multiple sclerosis (MS) patients. It can reduce the quality of life and increase the risk of mortality by developing complications such as aspiration pneumonia. The present study was conducted to estimate the prevalence of dysphagia in MS patients and investigate the associations between dysphagia and disease characteristics. The Persian version of the DYMUS questionnaire was used to assess dysphagia in 865 patients with MS, including 738 (85.3%) relapsing-remitting MS (RRMS), 106 (12.3%) secondary progressive MS (SPMS), and 21 (2.4%) primary progressive MS (PPMS). Also, demographic and clinical data, including age, sex, smoking status, Expanded Disability Status Scale (EDSS) score, disease duration, disease-modifying therapies exposure, initial symptoms of MS, were recorded. The mean (SD) age was 37.95(9.25) years, and 83.1% of the participants were female. The prevalence of dysphagia was estimated to be 25.4% among all patients. According to the DYMUS questionnaire results, the prevalence of dysphagia in RRMS, SPMS, and PPMS patients was 22.2%, 44.3%, and 42.9%, respectively. After multivariate analysis the current EDSS score (OR = 1.197, CI: 1.062, 1.350, p = 0.003), cerebellar impairment (OR = 1.335, CI: 1.450, 4.716, p = 0.004) and motor dysfunction (OR = 1.651, CI: 1.004, 2.715, p = 0.048) emerged as the risk factors for dysphagia. Since dysphagia, as previously mentioned, is a common symptom in multiple sclerosis, particularly in SPMS and PPMS courses, active screening for this condition is recommended in all patients, particularly those with identified risk factors.

Air quality index variation before and after the onset of COVID-19 pandemic: a comprehensive study on 87 capital, industrial and polluted cities of the world.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic provided an opportunity for the environment to reduce ambient pollution despite the economic, social and health disruption to the world. The purpose of this study was to investigate the changes in the air quality indexes (AQI) in industrial, densely populated and capital cities in different countries of the world before and after 2020. In this ecological study, we used AQI obtained from the free available databases such as the World Air Quality Index (WAQI). Bivariate correlation analysis was used to explore the correlations between meteorological and AQI variables. Mean differences (standard deviation: SD) of AQI parameters of different years were tested using paired-sample t-test or Wilcoxon signed-rank test as appropriate. Multivariable linear regression analysis was conducted to recognize meteorological variables affecting the AQI parameters. RESULTS: AQI-PM2.5, AQI-PM10 and AQI-NO2 changes were significantly higher before and after 2020, simultaneously with COVID-19 restrictions in different cities of the world. The overall changes of AQI-PM2.5, AQI-PM10 and AQI-NO2 in 2020 were - 7.36%, - 17.52% and - 20.54% compared to 2019. On the other hand, these results became reversed in 2021 (+ 4.25%, + 9.08% and + 7.48%). In general, the temperature and relative humidity were inversely correlated with AQI-PM2.5, AQI-PM10 and AQI-NO2. Also, after adjusting for other meteorological factors, the relative humidity was inversely associated with AQI-PM2.5, AQI-PM10 and AQI-NO2 (ß = - 1.55, ß = - 0.88 and ß = - 0.10, P < 0.01, respectively). CONCLUSIONS: The results indicated that air quality generally improved for all pollutants except carbon monoxide and ozone in 2020; however, changes in 2021 have been reversed, which may be due to the reduction of some countries' restrictions. Although this quality improvement was temporary, it is an important result for planning to control environmental pollutants.

Coexistence of periorbital lichen planus pigmentosus and pemphigus vulgaris: Report of an unusual case and a rare association.

Lichen planus pigmentosus is a rare variant of lichen planus with different patterns and manifestations. The coexistence of LPP and PV suggests that there might be a relationship between these two conditions in terms of immunologic mechanisms.

Serum levels of IL-32 in patients with coronary artery disease and its relationship with the serum levels of IL-6 and TNF-α.

The coronary artery disease (CAD) is a chronic inflammatory disease caused by atherosclerosis, in which arteries become clogged due to plaque formation, fat accumulation, and various sorts of immune cells. IL-32 is a proinflammatory cytokine, which enhances inflammation through inducing the secretion of different inflammatory cytokines. The main objective of the current study was to assess the serum levels of IL-32 in subjects with obstructive CAD and its relationship with the serum levels of IL-6 and TNF-α. This study was performed on 42 subjects with obstructive CAD and 42 subjects with non-obstructive CAD. The serum levels of TNF-α, IL-6, and IL-32 were measured using the enzyme-linked immunosorbent assay (ELISA). The serum levels of TNF-α, IL-6, and IL-32 were 3.2, 3.48, and 2.7 times higher in obstructive CAD compared to non-obstructive CAD, respectively. Moreover, the serum levels of TNF-α and IL-32 in obstructive CAD with cardiac arterial stenosis in one major vessel were significantly higher than the levels in obstructive CAD with cardiac arterial stenosis in more than one major vessel. ROC curve analysis revealed that the serum levels of TNF-α, IL-6, and IL-32 were good predictors of obstructive CAD. Moreover, multiple logistic regression analyses suggested that the serum levels of TNF-α, IL-6, IL-32, LDL, and ox-LDL were independently related to the presence of obstructive CAD, while serum levels of HDL were not. TNF-α, IL-32, and IL-6 showed an increase in obstructive CAD, and the serum levels of these cytokines showed a satisfactory ability for predicting obstructive CAD.

Giant cerebriform melanocytic nevus of the scalp: A case report.

Giant melanocytic nevus is a rare condition caused by benign proliferation of melanocytes. There is a slight risk of malignancy in these lesions which should be noticed especially when they become larger. GCMN can be removed by plastic surgery.

Expression levels of miR-27a, miR-329, ABCA1, and ABCG1 genes in peripheral blood mononuclear cells and their correlation with serum levels of oxidative stress and hs-CRP in the patients with coronary artery disease.

Atherosclerosis is a chronic inflammatory disease with high mortality worldwide. The reverse cholesterol transport pathway in macrophage plays an important role in the pathogenesis of coronary artery disease (CAD) and is strongly controlled by regulatory factors. The microRNAs can promote or prevent the formation of atherosclerotic lesions by post-transcriptional regulation of vital genes in this pathway. Therefore, this study was conducted to investigate the relationship between the expression levels of miR-27a, miR-329, ABCA1, and ABCG1 genes and serum levels of hs-CRP, ox-LDL, and indices of oxidative stress in the patients with established CAD and controls. A total of 84 subjects (42 patients with CAD and 42 controls) were included in this study. Expression levels of miR-27a-3p, miR-329-3p, ABCA1, and ABCG1 genes in the peripheral blood mononuclear cells (PBMCs) and serum concentration of hs-CRP and ox-LDL were measured by real time-PCR and ELISA, respectively. Also, oxidative stress parameters in the serum were evaluated by ferric-reducing antioxidant power (FRAP) and malondialdehyde (MDA) assays. ABCA1 and ABCG1 gene expression in PBMC and serum concentration of FRAP were significantly lower in the CAD group compared to the control group. Expression levels of miR-27a and miR-329 and serum levels of hs-CRP, ox-LDL, and MDA were significantly higher in the CAD group compared to the control group. Serum levels of hs-CRP, ox-LDL, and expression level of miR-27a have inversely related to ABCA1 and ABCG1 gene expression in all the subjects. An increase in the expression levels of miR-27a and miR-329 may lead to the progression of atherosclerosis plaque by downregulating the expression of ABCA1 and ABCG1 genes.

Generative multi-adversarial network for striking the right balance in abdominal image segmentation.

Purpose The identification of abnormalities that are relatively rare within otherwise normal anatomy is a major challenge for deep learning in the semantic segmentation of medical images. The small number of samples of the minority classes in the training data makes the learning of optimal classification challenging, while the more frequently occurring samples of the majority class hamper the generalization of the classification boundary between infrequently occurring target objects and classes. In this paper, we developed a novel generative multi-adversarial network, called Ensemble-GAN, for mitigating this class imbalance problem in the semantic segmentation of abdominal images.Method The Ensemble-GAN framework is composed of a single-generator and a multi-discriminator variant for handling the class imbalance problem to provide a better generalization than existing approaches. The ensemble model aggregates the estimates of multiple models by training from different initializations and losses from various subsets of the training data. The single generator network analyzes the input image as a condition to predict a corresponding semantic segmentation image by use of feedback from the ensemble of discriminator networks. To evaluate the framework, we trained our framework on two public datasets, with different imbalance ratios and imaging modalities: the Chaos 2019 and the LiTS 2017.Result In terms of the F1 score, the accuracies of the semantic segmentation of healthy spleen, liver, and left and right kidneys were 0.93, 0.96, 0.90 and 0.94, respectively. The overall F1 scores for simultaneous segmentation of the lesions and liver were 0.83 and 0.94, respectively.Conclusion The proposed Ensemble-GAN framework demonstrated outstanding performance in the semantic segmentation of medical images in comparison with other approaches on popular abdominal imaging benchmarks. The Ensemble-GAN has the potential to segment abdominal images more accurately than human experts.

An update on long intergenic noncoding RNA p21: a regulatory molecule with various significant functions in cancer.

Long intergenic noncoding RNA p21 was mapped on the human chromosome 6p21.2. Accordingly, it was firstly described by promoting the p53-dependent apoptosis in the mouse. Also, it is a new lncRNA playing some vital roles in the cell cycle, apoptosis, cell proliferation, tumorigenesis, invasion, metastasis, and angiogenesis. In this regard, it was shown that, lincRNA-p21 regulates these biological processes involved in carcinogenesis through various signaling pathways including Notch signaling, JAK2/STAT3, and AKT/mTOR pathways. Another mechanism by that lincRNA-p21 can affect these processes is a cross-talk with different miRNAs. In vitro and in vivo studies revealed dysregulation of lincRNA-p21 in various human cancers. In addition, emerging evidence demonstrated that, lincRNA-p21 can be considered as a potential prognostic and therapeutic biomarker in cancers. Also, lincRNA-p21 enhances the response to radiotherapy for colorectal cancer. However, the molecular mechanisms of lincRNA-p21 in carcinogenesis have not been fully elucidated so far. So, this review summarizes the function of lincRNA-p21, as a tumor suppressor factor in different biological processes implicated in cancers.