Itaconic Acid Cross-Linked Biomolecule Immobilization Approach on Amine-Functionalized Silica Nanoparticles for Highly Sensitive Enzyme-Linked Immunosorbent Assay (ELISA).

Biomolecule immobilization on nanomaterials is attractive for biosensors since it enables the capture of a higher concentration of bioreceptor units while also serving as a transduction element. The technique could enhance the accuracy, specificity, and sensitivity of the analytical measurements of biomolecules. However, it was found that the limitation in chemically binding biomolecules on nanoparticle surfaces could only cross-link between the C-terminal and N-terminal. Here, we report the facile one-step synthesis of amine-functionalized silica nanoparticles (AFSNPs). (3-Aminopropyl)triethoxysilane was used as a precursor to modify the functional surface of nanoparticles via the Stöber process. The biomolecules were immobilized to the AFSNPs through itaconic acid, a novel cross-linker that binds between the N-terminal and N-terminal and potentially improves proteins and nucleic acid immobilization onto the nanoparticle surface. The newly developed immobilization approach on AFSNPs for biomolecular detection enhanced the efficiency of ELISA, resulting in increased sensitivity. It might also be easily used to identify different pathogens for clinical diagnostics.

Grey Wolf Optimizer with Behavior Considerations and Dimensional Learning in Three-Dimensional Tooth Model Reconstruction.

Three-dimensional registration with the affine transform is one of the most important steps in 3D reconstruction. In this paper, the modified grey wolf optimizer with behavior considerations and dimensional learning (BCDL-GWO) algorithm as a registration method is introduced. To refine the 3D registration result, we incorporate the iterative closet point (ICP). The BCDL-GWO with ICP method is implemented on the scanned commercial orthodontic tooth and regular tooth models. Since this is a registration from multi-views of optical images, the hierarchical structure is implemented. According to the results for both models, the proposed algorithm produces high-quality 3D visualization images with the smallest mean squared error of about 7.2186 and 7.3999 µm2, respectively. Our results are compared with the statistical randomization-based particle swarm optimization (SR-PSO). The results show that the BCDL-GWO with ICP is better than those from the SR-PSO. However, the computational complexities of both methods are similar.

Signal Acquisition-Independent Lossless Electrocardiogram Compression Using Adaptive Linear Prediction.

In this paper, we propose a lossless electrocardiogram (ECG) compression method using a prediction error-based adaptive linear prediction technique. This method combines the adaptive linear prediction, which minimizes the prediction error in the ECG signal prediction, and the modified Golomb-Rice coding, which encodes the prediction error to the binary code as the compressed data. We used the PTB Diagnostic ECG database, the European ST-T database, and the MIT-BIH Arrhythmia database for the evaluation and achieved the average compression ratios for single-lead ECG signals of 3.16, 3.75, and 3.52, respectively, despite different signal acquisition setup in each database. As the prediction order is very crucial for this particular problem, we also investigate the validity of the popular linear prediction coefficients that are generally used in ECG compression by determining the prediction coefficients from the three databases using the autocorrelation method. The findings are in agreement with the previous works in that the second-order linear prediction is suitable for the ECG compression application.

Fuzzy K-Nearest Neighbor Based Dental Fluorosis Classification Using Multi-Prototype Unsupervised Possibilistic Fuzzy Clustering via Cuckoo Search Algorithm.

Dental fluorosis in children is a prevalent disease in many regions of the world. One of its root causes is excessive exposure to high concentrations of fluoride in contaminated drinking water during tooth formation. Typically, the disease causes undesirable chalky white or even dark brown stains on the tooth enamel. To help dentists screen the severity of fluorosis, this paper proposes an automatic image-based dental fluorosis segmentation and classification system. Six features from red, green, and blue (RGB) and hue, saturation, and intensity (HIS) color spaces are clustered using unsupervised possibilistic fuzzy clustering (UPFC) into five categories: white, yellow, opaque, brown, and background. The fuzzy k-nearest neighbor method is used for feature classification, and the number of clusters is optimized using the cuckoo search algorithm. The resulting multi-prototypes are further utilized to create a binary mask of teeth and used to segment the tooth region into three groups: white-yellow, opaque, and brown pixels. Finally, a fluorosis classification rule is created based on the proportions of opaque and brown pixels to classify fluorosis into four classes: Normal, Stage 1, Stage 2, and Stage 3. The experimental results on 128 blind test images showed that the average pixel accuracy of the segmented binary tooth mask was 92.24% over the four fluorosis classes, and the average pixel accuracy of segmented teeth into white-yellow, opaque, and brown pixels was 79.46%. The proposed method correctly classified four classes of fluorosis in 86 images from a total of 128 blind test images. When compared with a previous work, this result also indicates 10 out of 15 correct classifications on the blind test images, which is equivalent to a 13.33% improvement over the previous work.

An Ensemble Semantic Textual Similarity Measure Based on Multiple Evidences for Biomedical Documents.

With the increasing volume of the published biomedical literature, the fast and effective retrieval of the literature on the sequence, structure, and function of biological entities is an essential task for the rapid development of biology and medicine. To capture the semantic information in biomedical literature more effectively when biomedical documents are clustered, we propose a new multi-evidence-based semantic text similarity calculation method. Two semantic similarities and one content similarity are used, in which two semantic similarities include MeSH-based semantic similarity and word embedding-based semantic similarity. To fuse three different similarities more effectively, after, respectively, calculating two semantic and one content similarities between biomedical documents, feedforward neural network is applied to integrate the two semantic similarities. Finally, weighted linear combination method is used to integrate the semantic and content similarities. To evaluate the effectiveness, the proposed method is compared with the existing basic methods, and the proposed method outperforms the existing related methods. Based on the proven results of this study, this method can be used not only in actual biological or medical experiments such as protein sequence or function analysis but also in biological and medical research fields, which will help to provide, use, and understand thematically consistent documents.

Discovering Thematically Coherent Biomedical Documents Using Contextualized Bidirectional Encoder Representations from Transformers-Based Clustering.

The increasing expansion of biomedical documents has increased the number of natural language textual resources related to the current applications. Meanwhile, there has been a great interest in extracting useful information from meaningful coherent groupings of textual content documents in the last decade. However, it is challenging to discover informative representations and define relevant articles from the rapidly growing biomedical literature due to the unsupervised nature of document clustering. Moreover, empirical investigations demonstrated that traditional text clustering methods produce unsatisfactory results in terms of non-contextualized vector space representations because that neglect the semantic relationship between biomedical texts. Recently, pre-trained language models have emerged as successful in a wide range of natural language processing applications. In this paper, we propose the Gaussian Mixture Model-based efficient clustering framework that incorporates substantially pre-trained (Bidirectional Encoder Representations from Transformers for Biomedical Text Mining) BioBERT domain-specific language representations to enhance the clustering accuracy. Our proposed framework consists of main three phases. First, classic text pre-processing techniques are used biomedical document data, which crawled from the PubMed repository. Second, representative vectors are extracted from a pre-trained BioBERT language model for biomedical text mining. Third, we employ the Gaussian Mixture Model as a clustering algorithm, which allows us to assign labels for each biomedical document. In order to prove the efficiency of our proposed model, we conducted a comprehensive experimental analysis utilizing several clustering algorithms while combining diverse embedding techniques. Consequently, the experimental results show that the proposed model outperforms the benchmark models by reaching performance measures of Fowlkes mallows score, silhouette coefficient, adjusted rand index, Davies-Bouldin score of 0.7817, 0.3765, 0.4478, 1.6849, respectively. We expect the outcomes of this study will assist domain specialists in comprehending thematically cohesive documents in the healthcare field.

Automatic Programmable Bioreactor with pH Monitoring System for Tissue Engineering Application.

Tissue engineering technology has been advanced and applied to various applications in the past few years. The presence of a bioreactor is one key factor to the successful development of advanced tissue engineering products. In this work, we developed a programmable bioreactor with a controlling program that allowed each component to be automatically operated. Moreover, we developed a new pH sensor for non-contact and real-time pH monitoring. We demonstrated that the prototype bioreactor could facilitate automatic cell culture of L929 cells. It showed that the cell viability was greater than 80% and cell proliferation was enhanced compared to that of the control obtained by a conventional cell culture procedure. This result suggests the possibility of a system that could be potentially useful for medical and industrial applications, including cultured meat, drug testing, etc.

AUTOMATIC ICD-10 CODING USING PRESCRIBED DRUGS DATA.

This article discusses the emerging trends and challenges related to automatic clinical coding. We introduce an automatic coding system, which assigns short ICD-10 codes (restricted to the first three symbols, which define the category of the disease) based only on drugs prescribed to patients. We show that even with limited input data, the accuracy levels are comparable to those achieved by entry-level clinical coders as depicted by Seyed Nouraei et al.1 We also examine the standard method for performance estimation and speculate that the actual accuracy of our coding system is even higher than estimated.

Infectious Disease Relational Data Analysis Using String Grammar Non-Euclidean Relational Fuzzy C-Means.

Statistical analysis in infectious diseases is becoming more important, especially in prevention policy development. To achieve that, the epidemiology, a study of the relationship between the occurrence and who/when/where, is needed. In this paper, we develop the string grammar non-Euclidean relational fuzzy C-means (sgNERF-CM) algorithm to determine a relationship inside the data from the age, career, and month viewpoint for all provinces in Thailand for the dengue fever, influenza, and Hepatitis B virus (HBV) infection. The Dunn's index is used to select the best models because of its ability to identify the compact and well-separated clusters. We compare the results of the sgNERF-CM algorithm with the string grammar relational hard C-means (sgRHCM) algorithm. In addition, their numerical counterparts, i.e., relational hard C-means (RHCM) and non-Euclidean relational fuzzy C-means (NERF-CM) algorithms are also applied in the comparison. We found that the sgNERF-CM algorithm is far better than the numerical counterparts and better than the sgRHCM algorithm in most cases. From the results, we found that the month-based dataset does not help in relationship-finding since the diseases tend to happen all year round. People from different age ranges in different regions in Thailand have different numbers of dengue fever infections. The occupations that have a higher chance to have dengue fever are student and teacher groups from the central, north-east, north, and south regions. Additionally, students in all regions, except the central region, have a high risk of dengue infection. For the influenza dataset, we found that a group of people with the age of more than 1 year to 64 years old has higher number of influenza infections in every province. Most occupations in all regions have a higher risk of infecting the influenza. For the HBV dataset, people in all regions with an age between 10 to 65 years old have a high risk in infecting the disease. In addition, only farmer and general contractor groups in all regions have high chance of infecting HBV as well.

Deep Learning Feature Extraction Approach for Hematopoietic Cancer Subtype Classification.

Hematopoietic cancer is a malignant transformation in immune system cells. Hematopoietic cancer is characterized by the cells that are expressed, so it is usually difficult to distinguish its heterogeneities in the hematopoiesis process. Traditional approaches for cancer subtyping use statistical techniques. Furthermore, due to the overfitting problem of small samples, in case of a minor cancer, it does not have enough sample material for building a classification model. Therefore, we propose not only to build a classification model for five major subtypes using two kinds of losses, namely reconstruction loss and classification loss, but also to extract suitable features using a deep autoencoder. Furthermore, for considering the data imbalance problem, we apply an oversampling algorithm, the synthetic minority oversampling technique (SMOTE). For validation of our proposed autoencoder-based feature extraction approach for hematopoietic cancer subtype classification, we compared other traditional feature selection algorithms (principal component analysis, non-negative matrix factorization) and classification algorithms with the SMOTE oversampling approach. Additionally, we used the Shapley Additive exPlanations (SHAP) interpretation technique in our model to explain the important gene/protein for hematopoietic cancer subtype classification. Furthermore, we compared five widely used classification algorithms, including logistic regression, random forest, k-nearest neighbor, artificial neural network and support vector machine. The results of autoencoder-based feature extraction approaches showed good performance, and the best result was the SMOTE oversampling-applied support vector machine algorithm consider both focal loss and reconstruction loss as the loss function for autoencoder (AE) feature selection approach, which produced 97.01% accuracy, 92.60% recall, 99.52% specificity, 93.54% F1-measure, 97.87% G-mean and 95.46% index of balanced accuracy as subtype classification performance measures.

XGBoost-Based Framework for Smoking-Induced Noncommunicable Disease Prediction.

Smoking-induced noncommunicable diseases (SiNCDs) have become a significant threat to public health and cause of death globally. In the last decade, numerous studies have been proposed using artificial intelligence techniques to predict the risk of developing SiNCDs. However, determining the most significant features and developing interpretable models are rather challenging in such systems. In this study, we propose an efficient extreme gradient boosting (XGBoost) based framework incorporated with the hybrid feature selection (HFS) method for SiNCDs prediction among the general population in South Korea and the United States. Initially, HFS is performed in three stages: (I) significant features are selected by t-test and chi-square test; (II) multicollinearity analysis serves to obtain dissimilar features; (III) final selection of best representative features is done based on least absolute shrinkage and selection operator (LASSO). Then, selected features are fed into the XGBoost predictive model. The experimental results show that our proposed model outperforms several existing baseline models. In addition, the proposed model also provides important features in order to enhance the interpretability of the SiNCDs prediction model. Consequently, the XGBoost based framework is expected to contribute for early diagnosis and prevention of the SiNCDs in public health concerns.

In vitro drug sensitivity (IDS) of patient-derived primary osteosarcoma cells as an early predictor of the clinical outcomes of osteosarcoma patients.

PURPOSE: Early prediction of clinical response to conventional chemotherapy is a significant factor in determining an overall treatment strategy for osteosarcoma. METHODS: Cells were extracted from treatment-naïve biopsies from 16 osteosarcoma patients who received a doxorubicin and cisplatin-based neoadjuvant chemotherapy regimen and their sensitivities to doxorubicin and cisplatin were measured as IC50 values. Associations of in vitro drug sensitivity (IDS) levels and clinical outcomes were examined. RESULTS: Primary osteosarcoma cells responded to doxorubicin and cisplatin with IC50 values of 0.088 ± 0.032 µM and 16.7 ± 8.5 µM, respectively. The patients with a non-metastatic phenotype and surviving patients showed significantly lower IC50 values for both drugs. ROC analysis defined the optimal IC50 cut-off values for doxorubicin (IDSdox) and cisplatin (IDScpt) as 0.05 µM (AUC 0.82) and 14 µM (AUC 0.87), respectively. Survival analysis found significantly longer disease-free survival (DFS, n = 14) and overall survival (OS, n = 16) times in the patients with low IDSdox (p = 0.0064 for DFS and p = 0.0102 for OS) and low IDScpt (p = 0.0204 for DFS and p = 0.0021 for OS). Interestingly, when the patients with low IDScpt and those with low IDSdox were combined (Group 1), significant associations with prolonged DFS (p = 0.0042, C-statistic 0.78) and OS (p = 0.0010, C-statistic 0.79) were found. In this cohort, histological response to neoadjuvant chemotherapy could predict only OS. CONCLUSIONS: This study indicates that IDS analysis could potentially be a practical, rapid, and reliable technique for predicting clinical outcomes. It could also be used to identify patients for whom conventional chemotherapy is most appropriate and, in the future, help advance personalized therapy.

String Grammar Unsupervised Possibilistic Fuzzy C-Medians for Gait Pattern Classification in Patients with Neurodegenerative Diseases.

Neurodegenerative diseases that affect serious gait abnormalities include Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington disease (HD). These diseases lead to gait rhythm distortion that can be determined by stride time interval of footfall contact times. In this paper, we present a new method for gait classification of neurodegenerative diseases. In particular, we utilize a symbolic aggregate approximation algorithm to convert left-foot stride-stride interval into a sequence of symbols using a symbolic aggregate approximation. We then find string prototypes of each class using the newly proposed string grammar unsupervised possibilistic fuzzy C-medians. Then in the testing process the fuzzy k-nearest neighbor is used. We implement the system on three 2-class problems, i.e., the classification of ALS against healthy patients, that of HD against healthy patients , and that of PD against healthy patients. The system is also implemented on one 4-class problem (the classification of ALS, HD, PD, and healthy patients altogether) called NDDs versus healthy. We found that our system yields a very good detection result. The average correct classification for ALS versus healthy is 96.88%, and that for HD versus healthy is 97.22%, whereas that for PD versus healthy is 96.43%. When the system is implemented on 4-class problem, the average accuracy is approximately 98.44%. It can provide prototypes of gait signals that are more understandable to human.

Automatic cardiac T2* relaxation time estimation from magnetic resonance images using region growing method with automatically initialized seed points.

BACKGROUND AND OBJECTIVE: Heart failure due to iron-overload cardiomyopathy is one of the main causes of mortality. The cardiomyopathy is reversible if intensive iron chelation treatment is done in time, but the diagnosis is often delayed because the cardiac iron deposition is unpredictable and the symptoms are lately detected. There are many ways to assess iron-overload. However, the widely used and approved method is by using MRI which is performed by calculating the T2* (T2-star). In order to compute the T2* value, the region of interest (ROI) is manually selected by an expert which may require considerable time and skills. The aim of this work is hence to develop the cardiac T2* measurement by using region growing algorithm for automatically segmenting the ROI in cardiac MR images. Mathematical morphologies are also used to reduce some errors. METHODS: Thirty MR images with free-breathing and respiratory-trigger technique were used in this work. The segmentation algorithm yields good results when compared with the manual segmentation performed by two experts. RESULTS: The averages of positive predictive value, the sensitivity, the Hausdorff distance, and the Dice similarity coefficient are 0.76, 0.84, 7.78 pixels, and 0.80 when compared with the two experts' opinions. The T2* values were carried out based on the automatically segmented ROI's. The mean difference of T2* values between the proposed technique and the experts' opinion is about 1.40ms. CONCLUSIONS: The results demonstrate the accuracy of the proposed method in T2* value estimation. Some previous methods were implemented for comparisons. The results show that the proposed method yields better segmentation and T2* value estimation performances.

Automatic cervical cell segmentation and classification in Pap smears.

Cervical cancer is one of the leading causes of cancer death in females worldwide. The disease can be cured if the patient is diagnosed in the pre-cancerous lesion stage or earlier. A common physical examination technique widely used in the screening is Papanicolaou test or Pap test. In this research, a method for automatic cervical cancer cell segmentation and classification is proposed. A single-cell image is segmented into nucleus, cytoplasm, and background, using the fuzzy C-means (FCM) clustering technique. Four cell classes in the ERUDIT and LCH datasets, i.e., normal, low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC), are considered. The 2-class problem can be achieved by grouping the last 3 classes as one abnormal class. Whereas, the Herlev dataset consists of 7 cell classes, i.e., superficial squamous, intermediate squamous, columnar, mild dysplasia, moderate dysplasia, severe dysplasia, and carcinoma in situ. These 7 classes can also be grouped to form a 2-class problem. These 3 datasets were tested on 5 classifiers including Bayesian classifier, linear discriminant analysis (LDA), K-nearest neighbor (KNN), artificial neural networks (ANN), and support vector machine (SVM). For the ERUDIT dataset, ANN with 5 nucleus-based features yielded the accuracies of 96.20% and 97.83% on the 4-class and 2-class problems, respectively. For the Herlev dataset, ANN with 9 cell-based features yielded the accuracies of 93.78% and 99.27% for the 7-class and 2-class problems, respectively. For the LCH dataset, ANN with 9 cell-based features yielded the accuracies of 95.00% and 97.00% for the 4-class and 2-class problems, respectively. The segmentation and classification performances of the proposed method were compared with that of the hard C-means clustering and watershed technique. The results show that the proposed automatic approach yields very good performance and is better than its counterparts.

Relationships between serum biomarker levels and clinical presentation of human osteosarcomas.

BACKGROUND: Currently, serum biomarkers play an important role as sensitive tools for monitoring the cancer development and progression. Each biomarker represents a specific pathogenesis and has different predictive capability. In order to identify their characteristics in human osteosarcoma, multiple potential biomarkers were analyzed simultaneously with clinical presentations. MATERIALS AND METHODS: Blood samples were collected from 28 osteosarcoma patients and 30 healthy matched controls. Specific clinical presentations were recorded, including: tumor volume, estimated based on three-dimensional MRI volumetric measurement; metastasis status; and histological cell types. Serum biomarkers analyzed by ELISA-based assays were bone-specific alkaline phosphatase (BALP), vascular endothelial growth factor (VEGF), hyaluronic acid (HA) and chondroitin sulfate WF6 (WF6). Serum lactate dehydrogenase (LDH) was analyzed by a photometric-based system. RESULTS: Serum BALP, LDH and WF6 levels of osteosarcoma patients were significantly higher than those of healthy controls, whereas HA and VEGF levels were not significantly different between the two groups. Serum BALP and LDH were positively correlated with tumor volume, (correlation coefficients 0.5 and 0.4, respectively). Serum BALP from metastasis and osteoblastic subtype group had a significantly higher level than that found in non-metastasis and non-osteoblastic subtypes group, respectively. Upon multivariate analysis, tumor volume was the only factor which correlated with BALP levels. CONCLUSION: Of the biomarkers analyzed in this study, serum BALP was the most reliable and sensitive for estimating tumor volume. A high level of serum WF6 reflects alteration of the extracellular matrix component of tumors. Both serum biomarkers can be expected to be further explored for use in specific clinical monitoring.

Bone age assessment in young children using automatic carpal bone feature extraction and support vector regression.

Boundary extraction of carpal bone images is a critical operation of the automatic bone age assessment system, since the contrast between the bony structure and soft tissue are very poor. In this paper, we present an edge following technique for boundary extraction in carpal bone images and apply it to assess bone age in young children. Our proposed technique can detect the boundaries of carpal bones in X-ray images by using the information from the vector image model and the edge map. Feature analysis of the carpal bones can reveal the important information for bone age assessment. Five features for bone age assessment are calculated from the boundary extraction result of each carpal bone. All features are taken as input into the support vector regression (SVR) that assesses the bone age. We compare the SVR with the neural network regression (NNR). We use 180 images of carpal bone from a digital hand atlas to assess the bone age of young children from 0 to 6 years old. Leave-one-out cross validation is used for testing the efficiency of the techniques. The opinions of the skilled radiologists provided in the atlas are used as the ground truth in bone age assessment. The SVR is able to provide more accurate bone age assessment results than the NNR. The experimental results from SVR are very close to the bone age assessment by skilled radiologists.

Automatic nevirapine concentration interpretation system using support vector regression.

Follow-up of human immunodeficiency virus (HIV) patients treated with Nevirapine (NVP) is a necessary process to evaluate the drug resistance and the HIV mutation. It is also usually tested by immunochromatographic (IC) strip test. However, it is difficult to estimate the amount of drug the patient gets by visually inspection of color. In this paper, we propose an automatic interpretation system using a commercialized optical scanner. Several IC strips can be placed at any direction as long as they are on the scanner plate. There are three steps in the system, i.e., light intensity normalization, image segmentation and NVP concentration interpretation. We utilized the Support Vector Regression to interpret the NVP concentration. From the results, we found out the performance of the system is promising and better than that of the linear and nonlinear regression.

Boundary detection in medical images using edge following algorithm based on intensity gradient and texture gradient features.

Finding the correct boundary in noisy images is still a difficult task. This paper introduces a new edge following technique for boundary detection in noisy images. Utilization of the proposed technique is exhibited via its application to various types of medical images. Our proposed technique can detect the boundaries of objects in noisy images using the information from the intensity gradient via the vector image model and the texture gradient via the edge map. The performance and robustness of the technique have been tested to segment objects in synthetic noisy images and medical images including prostates in ultrasound images, left ventricles in cardiac magnetic resonance (MR) images, aortas in cardiovascular MR images, and knee joints in computerized tomography images. We compare the proposed segmentation technique with the active contour models (ACM), geodesic active contour models, active contours without edges, gradient vector flow snake models, and ACMs based on vector field convolution, by using the skilled doctors' opinions as the ground truths. The results show that our technique performs very well and yields better performance than the classical contour models. The proposed method is robust and applicable on various kinds of noisy images without prior knowledge of noise properties.

Morphological granulometric features of nucleus in automatic bone marrow white blood cell classification.

The proportion of counts of different types of white blood cells in the bone marrow, called differential counts, provides invaluable information to doctors for diagnosis. Due to the tedious nature of the differential white blood cell counting process, an automatic system is preferable. In this paper, we investigate whether information about the nucleus alone is adequate to classify white blood cells. This is important because segmentation of nucleus is much easier than the segmentation of the entire cell, especially in the bone marrow where the white blood cell density is very high. In the experiments, a set of manually segmented images of the nucleus are used to decouple segmentation errors. We analyze a set of white-blood-cell-nucleus-based features using mathematical morphology. Fivefold cross validation is used in the experiments in which Bayes' classifiers and artificial neural networks are applied as classifiers. The classification performances are evaluated by two evaluation measures: traditional and classwise classification rates. Furthermore, we compare our results with other classifiers and previously proposed nucleus-based features. The results show that the features using nucleus alone can be utilized to achieve a classification rate of 77% on the test sets. Moreover, the classification performance is better in the classwise sense when the a priori information is suppressed in both the classifiers.