Automated identification of normoblast cell from human peripheral blood smear images.

In this paper, we have presented a new computer-aided technique for automatic detection of nucleated red blood cells (NRBCs) or normoblast cell from peripheral blood smear image. The proposed methodology initiates with the localization of the nucleated cells by adopting multilevel thresholding approach in smear images. A novel colour space transformation technique has been introduced to differentiate nucleated blood cells [white blood cells (WBCs) and NRBC] from red blood cells (RBCs) by enhancing the contrast between them. Subsequently, special fuzzy c-means (SFCM) clustering algorithm is applied on enhanced image to segment out the nucleated cell. Finally, nucleated RBC and WBC are discriminated by the random forest tree classifier based on first-order statistical-based features. Experimentally, we observed that the proposed technique achieved 99.42% accuracy in automatic detection of NRBC from blood smear images. Further, the technique could be used to assist the clinicians to diagnose a different anaemic condition.

An Ensemble Rule Learning Approach for Automated Morphological Classification of Erythrocytes.

The analysis of pathophysiological change to erythrocytes is important for early diagnosis of anaemia. The manual assessment of pathology slides is time-consuming and complicated regarding various types of cell identification. This paper proposes an ensemble rule-based decision-making approach for morphological classification of erythrocytes. Firstly, the digital microscopic blood smear images are pre-processed for removal of spurious regions followed by colour normalisation and thresholding. The erythrocytes are segmented from background image using the watershed algorithm. The shape features are then extracted from the segmented image to detect shape abnormality present in microscopic blood smear images. The decision about the abnormality is taken using proposed multiple rule-based expert systems. The deciding factor is majority ensemble voting for abnormally shaped erythrocytes. Here, shape-based features are considered for nine different types of abnormal erythrocytes including normal erythrocytes. Further, the adaptive boosting algorithm is used to generate multiple decision tree models where each model tree generates an individual rule set. The supervised classification method is followed to generate rules using a C4.5 decision tree. The proposed ensemble approach is precise in detecting eight types of abnormal erythrocytes with an overall accuracy of 97.81% and weighted sensitivity of 97.33%, weighted specificity of 99.7%, and weighted precision of 98%. This approach shows the robustness of proposed strategy for erythrocytes classification into abnormal and normal class. The article also clarifies its latent quality to be incorporated in point of care technology solution targeting a rapid clinical assistance.

Web-Enabled Distributed Health-Care Framework for Automated Malaria Parasite Classification: an E-Health Approach.

Web-enabled e-healthcare system or computer assisted disease diagnosis has a potential to improve the quality and service of conventional healthcare delivery approach. The article describes the design and development of a web-based distributed healthcare management system for medical information and quantitative evaluation of microscopic images using machine learning approach for malaria. In the proposed study, all the health-care centres are connected in a distributed computer network. Each peripheral centre manages its' own health-care service independently and communicates with the central server for remote assistance. The proposed methodology for automated evaluation of parasites includes pre-processing of blood smear microscopic images followed by erythrocytes segmentation. To differentiate between different parasites; a total of 138 quantitative features characterising colour, morphology, and texture are extracted from segmented erythrocytes. An integrated pattern classification framework is designed where four feature selection methods viz. Correlation-based Feature Selection (CFS), Chi-square, Information Gain, and RELIEF are employed with three different classifiers i.e. Naive Bayes', C4.5, and Instance-Based Learning (IB1) individually. Optimal features subset with the best classifier is selected for achieving maximum diagnostic precision. It is seen that the proposed method achieved with 99.2% sensitivity and 99.6% specificity by combining CFS and C4.5 in comparison with other methods. Moreover, the web-based tool is entirely designed using open standards like Java for a web application, ImageJ for image processing, and WEKA for data mining considering its feasibility in rural places with minimal health care facilities.

Near-set Based Mucin Segmentation in Histopathology Images for Detecting Mucinous Carcinoma.

This paper introducesnear-set based segmentation method for extraction and quantification of mucin regions for detecting mucinouscarcinoma (MC which is a sub type of Invasive ductal carcinoma (IDC)). From histology point of view, the presence of mucin is one of the indicators for detection of this carcinoma. In order to detect MC, the proposed method majorly includes pre-processing by colour correction, colour transformation followed by near-set based segmentation and post-processing for delineating only mucin regions from the histological images at 40×. The segmentation step works in two phases such as Learn and Run.In pre-processing step, white balance method is used for colour correction of microscopic images (RGB format). These images are transformed into HSI (Hue, Saturation, and Intensity) colour space and H-plane is extracted in order to get better visual separation of the different histological regions (background, mucin and tissue regions). Thereafter, histogram in H-plane is optimally partitioned to find set representation for each of the regions. In Learn phase, features of typical mucin pixel and unlabeled pixels are learnt in terms of coverage of observed sets in the sample space surrounding the pixel under consideration. On the other hand, in Run phase the unlabeled pixels are clustered as mucin and non-mucin based on its indiscernibilty with ideal mucin, i.e. their feature values differ within a tolerance limit. This experiment is performed for grade-I and grade-II of MC and hence percentage of average segmentation accuracy is achieved within confidence interval of [97.36 97.70] for extracting mucin areas. In addition, computation of percentage of mucin present in a histological image is provided for understanding the alteration of such diagnostic indicator in MC detection.

Spectral Clustering for Unsupervised Segmentation of Lower Extremity Wound Beds Using Optical Images.

Chronic lower extremity wound is a complicated disease condition of localized injury to skin and its tissues which have plagued many elders worldwide. The ulcer assessment and management is expensive and is burden on health establishment. Currently accurate wound evaluation remains a tedious task as it rely on visual inspection. This paper propose a new method for wound-area detection, using images digitally captured by a hand-held, optical camera. The strategy proposed involves spectral approach for clustering, based on the affinity matrix. The spectral clustering (SC) involves construction of similarity matrix of Laplacian based on Ng-Jorden-Weiss algorithm. Starting with a quadratic method, wound photographs were pre-processed for color homogenization. The first-order statistics filter was then applied to extract spurious regions. The filter was selected based on the performance, evaluated on four quality metrics. Then, the spectral method was used on the filtered images for effective segmentation. The segmented regions were post-processed using morphological operators. The performance of spectral segmentation was confirmed by ground-truth pictures labeled by dermatologists. The SC results were additionally compared with the results of k-means and Fuzzy C-Means (FCM) clustering algorithms. The SC approach on a set of 105 images, effectively delineated targeted wound beds yielding a segmentation accuracy of 86.73 %, positive predictive values of 91.80 %, and a sensitivity of 89.54 %. This approach shows the robustness of tool for ulcer perimeter measurement and healing progression. The article elucidates its potential to be incorporated in patient facing medical systems targeting a rapid clinical assistance.

Telemedicine Supported Chronic Wound Tissue Prediction Using Classification Approaches.

Telemedicine helps to deliver health services electronically to patients with the advancement of communication systems and health informatics. Chronic wound (CW) detection and its healing rate assessment at remote distance is very much difficult due to unavailability of expert doctors. This problem generally affects older ageing people. So there is a need of better assessment facility to the remote people in telemedicine framework. Here we have proposed a CW tissue prediction and diagnosis under telemedicine framework to classify the tissue types using linear discriminant analysis (LDA). The proposed telemedicine based wound tissue prediction (TWTP) model is able to identify wound tissue and correctly predict the wound status with a good degree of accuracy. The overall performance of the proposed wound tissue prediction methodology has been measured based on ground truth images. The proposed methodology will assist the clinicians to take better decision towards diagnosis of CW in terms of quantitative information of three types of tissue composition at low-resource set-up.

Modulation of ERK5 is a novel mechanism by which Cdc42 regulates migration of breast cancer cells.

Members of Rho family GTPases including Cdc42 are known to play pivotal roles in cell migration. Cell migration is also known to be regulated by many protein kinases. Kinetworks KPSS 11.0 phospho-site screening of Cdc42-silenced Hs578T breast cancer cells revealed most dramatic change in ERK5 MAP kinase. In the present study, we set out to determine the relationship between Cdc42 and ERK5 and its significance in breast cancer cell migration and invasion. Specific siRNAs were used for knocking down Cdc42 or ERK5 in breast cancer cells. Increased ERK5 phosphorylation in breast cancer cells was achieved by infection of constitutively active MEK5 adenovirus. The cells were then subjected to cell migration or invasion assay without the presence of serum or any growth factor. We found that Cdc42 negatively regulated phosphorylation of ERK5, which in turn exhibited an inverse relationship with migration and invasiveness of breast cancer cells. To find out some in vivo relevance of the results of our in vitro experiments we also examined the expression of ERK5 in the breast cancer tissues and their adjacent normal control tissues by real-time RT-PCR and immunocytochemistry. ERK5 expression was found to be reduced in breast cancer tissues as compared with their adjacent uninvolved mammary tissues. Therefore, Cdc42 may promote breast cancer cell migration and invasion by inhibiting ERK5 phosphorylation and ERK5 expression may be inversely correlated with the progression of some breast tumors.

Handloomed fabrics recognition with deep learning.

Every nation treasures its handloom heritage, and in India, the handloom industry safeguards cultural traditions, sustains millions of artisans, and preserves ancient weaving techniques. To protect this legacy, a critical need arises to distinguish genuine handloom products, exemplified by the renowned "gamucha" from India's northeast, from counterfeit powerloom imitations. Our study's objective is to create an AI tool for effortless detection of authentic handloom items amidst a sea of fakes. Six deep learning architectures-VGG16, VGG19, ResNet50, InceptionV3, InceptionResNetV2, and DenseNet201-were trained on annotated image repositories of handloom and powerloom towels (17,484 images in total, with 14,020 for training and 3464 for validation). A novel deep learning model was also proposed. Despite respectable training accuracies, the pre-trained models exhibited lower performance on the validation dataset compared to our novel model. The proposed model outperformed pre-trained models, demonstrating superior validation accuracy, lower validation loss, computational efficiency, and adaptability to the specific classification problem. Notably, the existing models showed challenges in generalizing to unseen data and raised concerns about practical deployment due to computational expenses. This study pioneers a computer-assisted approach for automated differentiation between authentic handwoven "gamucha"s and counterfeit powerloom imitations-a groundbreaking recognition method. The methodology presented not only holds scalability potential and opportunities for accuracy improvement but also suggests broader applications across diverse fabric products.

Epithelio-mesenchymal transitional attributes in oral sub-mucous fibrosis.

Evaluating molecular attributes in association with its epithelial and sub-epithelial changes of oral sub-mucous fibrosis is meaningful in exploring the plausibility of an epithelio-mesenchymal transition (EMT) and malignant potentiality of this pathosis. In this study histopathological and histochemical attributes for basement membrane and connective tissue in biopsies of oral sub-mucous fibrosis (n = 55) and normal oral mucosa (n = 16) were assessed and expressions of p63, E-cadherin, ß-catenin, N-cadherin and TWIST were analyzed immunohistochemically. The p63 and its isoforms (TA and ∆N), PARD3, E-cadherin and ß-catenin were also assessed transcriptomically by q-PCR and EMT players like TWIST1, ZEB1, MMP9 and micro-RNA 205 were searched in gene expression microarrays. Oral epithelium demonstrating impairment in progressive maturation in oral sub-mucous fibrosis concomitantly experienced an increase in basement membrane thickness and collagen deposition along with alteration in target molecular expressions. In comparison to non-dysplastic conditions dysplastic stages exhibited significant increase in p63 and p63∆N expressions whereas, E-cadherin and ß-catenin exhibited loss from the membrane with concurrent increase in cytoplasm. Further the N-cadherin and TWIST were gained remarkably along with the appearance of nuclear accumulation features of ß-catenin. The microarray search had noticed the up-regulation of TWIST1, ZEB1 and MMP9 along with down regulation of micro-RNA 205. The simultaneous increase in basement membrane thickness and sub-epithelial collagen deposition were the plausible indicators for increased matrix stiffness with expected impact on oral epithelial functional homoeostasis. This was corroborated with the increase in expressions of epithelial master regulator p63 and its oncogenic isoform (∆N) along with membranous loss of E-cadherin (EMT hallmark) and its associate ß-catein and gain of mesenchymal markers like N-cadherin and TWIST. These also became indicative for the induction of epithelial to mesenchymal transitional mechanism in oral sub-mucous fibrosis when connoted here with the relevant modulation in expressions of EMT regulators.

Application of Machine Learning and Deep Learning Techniques for COVID-19 Screening Using Radiological Imaging: A Comprehensive Review.

Lung, being one of the most important organs in human body, is often affected by various SARS diseases, among which COVID-19 has been found to be the most fatal disease in recent times. In fact, SARS-COVID 19 led to pandemic that spreads fast among the community causing respiratory problems. Under such situation, radiological imaging-based screening [mostly chest X-ray and computer tomography (CT) modalities] has been performed for rapid screening of the disease as it is a non-invasive approach. Due to scarcity of physician/chest specialist/expert doctors, technology-enabled disease screening techniques have been developed by several researchers with the help of artificial intelligence and machine learning (AI/ML). It can be remarkably observed that the researchers have introduced several AI/ML/DL (deep learning) algorithms for computer-assisted detection of COVID-19 using chest X-ray and CT images. In this paper, a comprehensive review has been conducted to summarize the works related to applications of AI/ML/DL for diagnostic prediction of COVID-19, mainly using X-ray and CT images. Following the PRISMA guidelines, total 265 articles have been selected out of 1715 published articles till the third quarter of 2021. Furthermore, this review summarizes and compares varieties of ML/DL techniques, various datasets, and their results using X-ray and CT imaging. A detailed discussion has been made on the novelty of the published works, along with advantages and limitations.

LWSNet - a novel deep-learning architecture to segregate Covid-19 and pneumonia from x-ray imagery.

Automatic detection of lung diseases using AI-based tools became very much necessary to handle the huge number of cases occurring across the globe and support the doctors. This paper proposed a novel deep learning architecture named LWSNet (Light Weight Stacking Network) to separate Covid-19, cold pneumonia, and normal chest x-ray images. This framework is based on single, double, triple, and quadruple stack mechanisms to address the above-mentioned tri-class problem. In this framework, a truncated version of standard deep learning models and a lightweight CNN model was considered to conviniently deploy in resource-constraint devices. An evaluation was conducted on three publicly available datasets alongwith their combination. We received 97.28%, 96.50%, 97.41%, and 98.54% highest classification accuracies using quadruple stack. On further investigation, we found, using LWSNet, the average accuracy got improved from individual model to quadruple model by 2.31%, 2.55%, 2.88%, and 2.26% on four respective datasets.

Cdc42 negatively regulates intrinsic migration of highly aggressive breast cancer cells.

The small GTPase Cdc42 has been implicated as an important regulator of cell migration. However, whether Cdc42 plays similar role in all cancer cells irrespective of metastatic potential remains poorly defined. Here, we show by using three different breast cancer cell lines with different metastatic potential, the role of Cdc42 in cell migration/invasion and its relationship with a number of downstream signaling pathways controlling cell migration. Small interfering RNA (siRNA)-mediated knockdown of Cdc42 in two highly metastatic breast cancer cell lines (MDA-MB-231 and C3L5) resulted in enhancement, whereas the same in moderately metastatic (Hs578T) cell line resulted in inhibition of intrinsic cellular migration/invasion. Furthermore, Cdc42 silencing in MDA-MB-231 and C3L5 but not Hs578T cells was shown to be accompanied by increased RhoA activity and phosphorylation of protein kinase C (PKC)-δ, extracellular signal regulated kinase1/2 (Erk1/2), and protein kinase A (PKA). Pharmacological inhibition of PKCδ, MEK-Erk1/2, or PKA was shown to inhibit migration of both control and Cdc42-silenced MDA-MB-231 cells. Furthermore, introduction of constitutively active Cdc42 was shown to decrease migration/invasion of MDA-MB-231 and C3L5 but increase migration/invasion of Hs578T cells. This decreased migration/invasion of MDA-MB-231 and C3L5 cells was also shown to be accompanied by the decrease in the phosphorylations of PKCδ, Erk1/2, and PKA. These results suggested that endogenous Cdc42 could exert a negative regulatory influence on intrinsic migration/invasion and some potentially relevant changes in phosphorylation of PKCδ, Erk1/2, and PKA of some aggressive breast cancer cells.

Role of Rho GTPases in human trophoblast migration induced by IGFBP1.

Insulin-like growth factor binding protein 1 (IGFBP1), the main secretory product of the decidualized endometrium of a pregnant woman, has previously been shown to interact with the alpha(5)beta(1) integrin of extravillous trophoblast (EVT) cell surface to stimulate its migration in an IGF-independent manner. This migration stimulation has also been shown to require activation of extracellular signal regulated kinases 1 and 2 (ERK1/2; mitogen-activated protein kinase [MAPK] 3/1]) and focal adhesion kinase. The present study examined the roles of Rho GTPases RHOA, RHOC, RAC1, and CDC42 as well as RHO kinases ROCK1 and ROCK2 in IGFBP1-mediated migration of an immortalized EVT cell line HTR-8/SVneo. A nonselective RHO kinase inhibitor, Y27632, as well as siRNAs selective for ROCK1 and ROCK2 decreased the migration of these cells in a Transwell migration assay, and this inhibition could not be restored by IGFBP1. Clostridium difficile toxin B, which inhibits all the Rho GTPases, RAC inhibitor NSC23766, RAC1 siRNA, and CDC42 siRNA, decreased their basal migration, but none of these inhibitions except CDC42 siRNA-induced inhibition could be restored by IGFBP1. Clostridium botulinum C3 exoenzyme that inhibits RHOA, RHOB, and RHOC inhibited basal migration but not IGFBP1-induced migration. IGFBP1-induced activation of ERK1/2 (MAPK3/1), which did not require RHO proteins, might function as an alternate pathway for RHO action. However, selective siRNA-mediated downregulation of RHOA inhibited basal, but not IGFBP1-mediated, migration, whereas that of RHOC inhibited both basal and IGFBP1-mediated migration of these EVT cells. Therefore, RHO kinase, RHOC, and RAC1 are essential, but RHOA and CDC42 are not essential, for IGFBP1-induced EVT migration.

Delineating metabolic dysfunction in cellular metabolism of oral submucous fibrosis using 1H nuclear magnetic resonance spectroscopy.

OBJECTIVE: To delineate the metabolism involved in oral submucous fibrosis progression towards carcinogenesis by 1H nuclear magnetic resonance spectroscopy. METHODS: The proposed study was designed using 1H-NMR by comparing the metabolites in the serum sample of oral submucous fibrosis (n = 20) compared to the normal group (n = 20) using 1H nuclear magnetic resonance spectroscopy. Various statistical analysis like multivariate statistical analysis, Principle component analysis, Partial least squares Discriminant Analysis, Hierarchical cluster analysis was applied to analyze potential serum metabolites. RESULTS: The results generated from the principle component analysis, partial least squares discriminant analysis and hierarchical cluster analysis are sufficient to distinguish between oral submucous fibrosis group and normal group. A total of 15 significant metabolites associated with main pathways were identified, which correlated with the progression of cancer. Up-regulation of glucose metabolism-related metabolites indicated the high energy demand due to enhanced cell division rate in the oral submucous fibrosis group. A significant increase in lipid metabolism-related metabolites revealed the reprogramming of the fatty acids metabolic pathway to fulfilling the need for cell membrane formation in cancer cells. On the other hand, metabolites related to choline phosphocholine, the metabolic pathway was also altered. CONCLUSION: Our findings could identify the differentiating metabolites in the oral submucous fibrosis group. Significant alteration in metabolites in the oral submucous fibrosis group exhibited deregulation in metabolic events. The findings reported in the study can be beneficial to further explain the molecular aspects that lead to the progression of oral submucous fibrosis towards carcinogenesis.

Evaluation of oxidative stress and the microenvironment in oral submucous fibrosis.

BACKGROUND: Oral Submucous fibrosis (OSF) is a chronic inflammatory mucosal disease of unknown etiology. Statistics show cases of OSF which has a high rate of overall prevalence and increase the chance of malignant transformation. As we know malignant cells is situated in a very complex microenvironment with altered metabolic pathway including intermediates which participate in oxidative stress process which enhances metabolic rewiring and promotes tumor progression. This study aims to evaluate the tumor microenvironment and their role in metabolic reprogramming. METHODS: This study was conducted on the serum sample of OSF (n = 20) compared to the healthy group (n = 20) using ELISA. The serum levels of intermediate by-products of metabolic pathway and oxidative stress induced biomolecular damage products were determined. The sensitivity of results was analyzed by correlating it with markers of metabolic status (Glucose, Total cholesterol, Total protein). RESULTS: Metabolic pathway intermediates molecules like Fatty Acids (FAA), Ascorbic acid, Citrate, Oxaloacetate (OAA), levels were significantly high in the serum of OSF cases. This indicated that intermediates act as a metabolic switch that drives cells to adapt malignant transformation pathway. Markers related to oxidative DNA damage (8-hydroxy-2' -deoxyguanosine), Oxidative lipid peroxidation (8-epi-Prostaglandin F2α), and Protein carbonyl were significantly up-regulated. This significant increase in oxidative stress marker revealed the reprogramming of the metabolic pathway for fulfilling the nutritional requirement of cancer cells. A further significant correlation was observed with metabolic products confirmed altered metabolic status. CONCLUSION: Our findings could identify the differentiating intermediate pathway metabolites and oxidative damage to biomolecules that are leading to rewiring of metabolism in the OSF group. Findings described in the study can be helpful to explain further the molecular aspects that lead to the progression of OSF towards carcinogenesis.

Roles of Rho guanosine 5'-triphosphatase A, Rho kinases, and extracellular signal regulated kinase (1/2) in prostaglandin E2-mediated migration of first-trimester human extravillous trophoblast.

Prostaglandin (PG) E(2) may regulate invasiveness of human placenta because we previously reported stimulation of migration of placental trophoblasts by PGE(2) acting through PGE receptor (EP)-1 and activating calpain. RhoA GTPase and its important effector Rho kinase (ROCK) have also been previously shown to regulate trophoblast migration. Using immortalized HTR-8/SVneo trophoblast cells and first-trimester human chorionic villus explant cultures on matrigel, we further examined the role of RhoA/ROCK and MAPK (ERK1/2) pathways on PGE(2)-mediated stimulation of trophoblast migration. Migration of cytotrophoblasts was shown to be inhibited by treatment of the trophoblast cell line and chorionic villus explants with either cell-permeable C3 transferase or selective RhoA small interfering RNA. These inhibitions were significantly mitigated by the addition of PGE(2), an EP1/EP3 agonist or an EP3/EP4 agonist, suggesting that RhoA plays an important role in trophoblast migration but may not be obligatory for PGE(2) action. Treatment of HTR-8/SVneo cells with nonselective ROCK inhibitor Y27632 or ROCK small interfering RNAs inhibited migration of these cells, which could not be rescued with PGE(2) or the other two EP agonists, suggesting the obligatory role of ROCK in PGE(2)-induced migratory response. Furthermore, U0126, an inhibitor of MAPK kinases MEK1 and MEK2, abrogated PGE(2)-induced migration of trophoblasts, and PGE(2) or the other two EP agonists stimulated ERK1/2 activation in trophoblasts, which was not abrogated by pretreatment with C3 transferase, indicating that ERK signaling pathway is an efficient alternate pathway for RhoA in PGE(2)-mediated migration of trophoblasts. These results suggest that ROCK and ERK1/2 play more important roles than RhoA in PGE(2)-mediated migration stimulation of first-trimester trophoblasts.

Her2Net: A Deep Framework for Semantic Segmentation and Classification of Cell Membranes and Nuclei in Breast Cancer Evaluation.

We present an efficient deep learning framework for identifying, segmenting, and classifying cell membranes and nuclei from human epidermal growth factor receptor-2 (HER2)-stained breast cancer images with minimal user intervention. This is a long-standing issue for pathologists because the manual quantification of HER2 is error-prone, costly, and time-consuming. Hence, we propose a deep learning-based HER2 deep neural network (Her2Net) to solve this issue. The convolutional and deconvolutional parts of the proposed Her2Net framework consisted mainly of multiple convolution layers, max-pooling layers, spatial pyramid pooling layers, deconvolution layers, up-sampling layers, and trapezoidal long short-term memory (TLSTM). A fully connected layer and a softmax layer were also used for classification and error estimation. Finally, HER2 scores were calculated based on the classification results. The main contribution of our proposed Her2Net framework includes the implementation of TLSTM and a deep learning framework for cell membrane and nucleus detection, segmentation, and classification and HER2 scoring. Our proposed Her2Net achieved 96.64% precision, 96.79% recall, 96.71% F-score, 93.08% negative predictive value, 98.33% accuracy, and a 6.84% false-positive rate. Our results demonstrate the high accuracy and wide applicability of the proposed Her2Net in the context of HER2 scoring for breast cancer evaluation.

Efficient deep learning model for mitosis detection using breast histopathology images.

Mitosis detection is one of the critical factors of cancer prognosis, carrying significant diagnostic information required for breast cancer grading. It provides vital clues to estimate the aggressiveness and the proliferation rate of the tumour. The manual mitosis quantification from whole slide images is a very labor-intensive and challenging task. The aim of this study is to propose a supervised model to detect mitosis signature from breast histopathology WSI images. The model has been designed using deep learning architecture with handcrafted features. We used handcrafted features issued from previous medical challenges MITOS @ ICPR 2012, AMIDA-13 and projects (MICO ANR TecSan) expertise. The deep learning architecture mainly consists of five convolution layers, four max-pooling layers, four rectified linear units (ReLU), and two fully connected layers. ReLU has been used after each convolution layer as an activation function. Dropout layer has been included after first fully connected layer to avoid overfitting. Handcrafted features mainly consist of morphological, textural and intensity features. The proposed architecture has shown to have an improved 92% precision, 88% recall and 90% F-score. Prospectively, the proposed model will be very beneficial in routine exam, providing pathologists with efficient and - as we will prove - effective second opinion for breast cancer grading from whole slide images. Last but not the least, this model could lead junior and senior pathologists, as medical researchers, to a superior understanding and evaluation of breast cancer stage and genesis.

"Omics" in oral cancer: New approaches for biomarker discovery.

OBJECTIVES: In this review paper, we explored the application of "omics" approaches in the study of oral cancer (OC). It will provide a better understanding of how "omics" approaches may lead to novel biomarker molecules or molecular signatures with potential value in clinical practice. A future direction of "omics"-driven research in OC is also discussed. METHODS: Studies on "omics"-based approaches [genomics/proteomics/transcriptomics/metabolomics] were investigated for differentiating oral squamous cell carcinoma,oral sub-mucous fibrosis, oral leukoplakia, oral lichen planus, oral erythroplakia from normal cases. Electronic databases viz., PubMed, Springer, and Google Scholar were searched. RESULTS: One eighty-one studies were included in this review. The review shows that the fields of genomics, transcriptomics, proteomics, and metabolomics-based marker identification have implemented advanced tools to screen early changes in DNA, RNA, protein, and metabolite expression in OC population. CONCLUSIONS: It may be concluded that despite advances in OC therapy, symptomatic presentation occurs at an advanced stage, where various curative treatment options become very limited. A molecular level study is essential for detecting an OC biomarker at an early stage. Modern "Omics" strategies can potentially make a major contribution to meet this need.

Serum-based diagnostic prediction of oral submucous fibrosis using FTIR spectrometry.

Oral submucous fibrosis (OSF) is found to have the highest malignant potentiality among all other pre-cancerous lesions. However, its detection prior to tissue biopsy can be challenging in clinics. Moreover, biopsy examination is invasive and painful. Hence, there is an urgent need of new technology that facilitates accurate diagnostic prediction of OSF prior to biopsy. Here, we used FTIR spectroscopy coupled with chemometric techniques to distinguish the serum metabolic signatures of OSF patients (n=30) and healthy controls (n=30). Serum biochemical analyses have been performed to further support the FTIR findings. Absorbance intensities of 45 infrared wavenumbers differed significantly between OSF and normal serum FTIR spectra representing alterations in carbohydrates, proteins, lipids and nucleic acids. Nineteen prominent significant wavenumbers (P≤0.001) at 1020, 1025, 1035, 1039, 1045, 1078, 1055, 1100, 1117, 1122, 1151, 1169, 1243, 1313, 1398, 1453, 1544, 1650 and 1725cm-1 provided excellent segregation of OSF spectra from normal using multivariate statistical techniques. These findings provided essential information on the metabolic features of blood serum of OSF patients and established that FTIR spectroscopy coupled with chemometric analysis can be potentially useful in the rapid and accurate preoperative screening/diagnosis of OSF.