Revisiting miRNA Association with Melanoma Recurrence and Metastasis from a Machine Learning Point of View.

The diagnostic and prognostic value of miRNAs in cutaneous melanoma (CM) has been broadly studied and supported by advanced bioinformatics tools. From early studies using miRNA arrays with several limitations, to the recent NGS-derived miRNA expression profiles, an accurate diagnostic panel of a comprehensive pre-specified set of miRNAs that could aid timely identification of specific cancer stages is still elusive, mainly because of the heterogeneity of the approaches and the samples. Herein, we summarize the existing studies that report several miRNAs as important diagnostic and prognostic biomarkers in CM. Using publicly available NGS data, we analyzed the correlation of specific miRNA expression profiles with the expression signatures of known gene targets. Combining network analytics with machine learning, we developed specific non-linear classification models that could successfully predict CM recurrence and metastasis, based on two newly identified miRNA signatures. Subsequent unbiased analyses and independent test sets (i.e., a dataset not used for training, as a validation cohort) using our prediction models resulted in 73.85% and 82.09% accuracy in predicting CM recurrence and metastasis, respectively. Overall, our approach combines detailed analysis of miRNA profiles with heuristic optimization and machine learning, which facilitates dimensionality reduction and optimization of the prediction models. Our approach provides an improved prediction strategy that could serve as an auxiliary tool towards precision treatment.

Clinical implications of the anatomical position of the urethra meatus in women with recurrent post-coital cystitis: a case-control study.

INTRODUCTION AND HYPOTHESIS: Recurrent post-coital urinary infection (rUTI)-usually cystitis-is a common entity among otherwise healthy young women. However, little is known about the possible influence of genital anatomical variations. Only a shorter urethral meatus-anus distance has been described as a risk factor. The aim of this study was to evaluate our hypothesis that a shorter urethra-vagina distance is involved in the etiology of post-coital urinary infection. METHODS: In this prospective case-control study, 61 young women aged between 18 and 40 years with an acute post-coital UTI and a history of intercourse-related rUTI were consecutively recruited between January 2013 and February 2018. Fifty-six age-matched, sexually active women with no history of UTI served as controls. Perineal measurements included the distances between the clitoris-urethra (C-U), urethra-vagina (U-V), urethra-anus (U-A) and perineum. Demographic and sexual behavior characteristics and the morphology of the urethral meatus were also noted. Univariate analysis compared variables between groups. ROC analysis was used to define the efficiency of perineal measurements in predicting outcome. Odds ratios and 95% confidence intervals for UTI-predisposing variables were estimated using logistic regression analysis. RESULTS: The U-V and U-A distance was shorter in patients compared with controls [median (interquatile range): 16 mm (14-18) vs. 21 mm (19-23) and 51 mm (47-53) vs. 59 mm (55-62), respectively, p < 0.001]. The U-V performed better in ROC analysis than the U-A distance (AUC 0.952 vs. 0.875, p = 0.023). The only statistically significant parameters in multivariate analysis influencing UTI were BMI (OR: 0.702; 0.510-0.967, p = 0.030) and U-V (OR: 0.297; 0.161-0.549, p < 0.001). CONCLUSIONS: Our results indicate an association between shorter urethra-vagina distance and post-coital rUTIs.

Distinct Roles of Apolipoproteins A1 and E in the Modulation of High-Density Lipoprotein Composition and Function.

In addition to high-density lipoprotein cholesterol (HDL-C) levels, HDL quality also appears to be very important for atheroprotection. Analysis of various clinical paradigms suggests that the lipid and apolipoprotein composition of HDL defines its size, shape, and functions and may determine its beneficial effects on human health. Previously, we reported that like apolipoprotein A-I (Apoa1), apolipoprotein E (Apoe) is also capable of promoting the de novo biogenesis of HDL with the participation of ATP binding cassette A lipid transporter member 1 (Abca1) and plasma enzyme lecithin:cholesterol acyltransferase (Lcat), in a manner independent of a functional Apoa1. Here, we performed a comparative analysis of the functions of these HDL subpopulations. Specifically, Apoe and Apoa1 double-deficient (Apoe(-/-) × Apoa1(-/-)) mice were infected with APOA1- or APOE3-expressing adenoviruses, and APOA1-containing HDL (APOA1-HDL) and APOE3-containing HDL (APOE3-HDL), respectively, were isolated and analyzed by biochemical and physicochemical methods. Western blot and lipidomic analyses indicated significant differences in the apolipoprotein and lipid composition of the two HDL species. Moreover APOE3-HDL presented a markedly reduced antioxidant potential and Abcg1-mediated cholesterol efflux capacity. Surprisingly, APOE3-HDL but not APOA1-HDL attenuated LPS-induced production of TNFα in RAW264.7 cells, suggesting that the anti-inflammatory effects of APOA1 are dependent on APOE expression. Taken together, our data indicate that APOA1 and APOE3 recruit different apolipoproteins and lipids on the HDL particle, leading to structurally and functionally distinct HDL subpopulations. The distinct role of these two apolipoproteins in the modulation of HDL functionality may pave the way toward the development of novel pharmaceuticals that aim to improve HDL functionality.

Microscopy image analysis of p63 immunohistochemically stained laryngeal cancer lesions for predicting patient 5-year survival.

The aim of the present study was to design a microscopy image analysis (MIA) system for predicting the 5-year survival of patients with laryngeal squamous cell carcinoma, employing histopathology images of lesions, which had been immunohistochemically (IHC) stained for p63 expression. Biopsy materials from 42 patients, with verified laryngeal cancer and follow-up, were selected from the archives of the University Hospital of Patras, Greece. Twenty six patients had survived more than 5 years and 16 less than 5 years after the first diagnosis. Histopathology images were IHC stained for p63 expression. Images were first processed by a segmentation method for isolating the p63-expressed nuclei. Seventy-seven features were evaluated regarding texture, shape, and physical topology of nuclei, p63 staining, and patient-specific data. Those features, the probabilistic neural network classifier, the leave-one-out (LOO), and the bootstrap cross-validation methods, were used to design the MIA-system for assessing the 5-year survival of patients with laryngeal cancer. MIA-system accuracy was about 90 % and 85 %, employing the LOO and the Bootstrap methods, respectively. The image texture of p63-expressed nuclei appeared coarser and contained more edges in the 5-year non-survivor group. These differences were at a statistically significant level (p < 0.05). In conclusion, this study has proposed an MIA-system that may be of assistance to physicians, as a second opinion tool in assessing the 5-year survival of patients with laryngeal cancer, and it has revealed useful information regarding differences in nuclei texture between 5-year survivors and non-survivors.

Scavenger Receptor Class B Type I Regulates Plasma Apolipoprotein E Levels and Dietary Lipid Deposition to the Liver.

Scavenger receptor class B type I (SR-BI) is primarily responsible for the selective uptake of cholesteryl esters (CE) of high-density lipoprotein (HDL) by the liver and other tissues. In the present study, we show that SR-BI-deficient (scarb1(-/-)) mice are resistant to diet-induced obesity, hepatic lipid deposition, and glucose intolerance after 24 weeks of being fed a western-type diet. No differences in energy expenditure or mitochondrial function could account for the observed phenotype. Kinetic and gene expression analyses suggested reduced de novo fatty acid synthesis in scarb1(-/-) mice. Furthermore, adenosine monophosphate-activated protein kinase (AMPK)-stimulated hepatic FFA catabolism was reduced in these mice, leaving direct dietary lipid uptake from plasma as the major modulator of hepatic lipid content. Analysis of the apolipoprotein composition of plasma lipoproteins revealed a significant accumulation of apolipoprotein E (ApoE)-containing HDL and TG-rich lipoproteins in scarb1(-/-) mice that correlated with reduced plasma LpL activity. Our data suggest that scarb1(-/-) mice fed a western-type diet for 24 weeks accumulate CE- and ApoE-rich HDL of abnormal density and size. The elevated HDL-ApoE levels inhibit plasma LpL activity, blocking the clearance of triglyceride-rich lipoproteins and preventing the shuttling of dietary lipids to the liver.

In vitro evaluation of ureteral contractility: a comparative assessment of human, porcine and sheep ureteral response to vardenafil.

OBJECTIVES: Basic science studies of ureteral physiology and pathophysiology are commonly performed on animal ureters due to several limitations associated with human ureteral sampling. In this work we question whether animal ureters are good replicas of human ureteral behavior for pharmacological studies. MATERIALS AND METHODS: Ureteral rings from human, porcine and ovine ureters underwent the same organ bath protocol. After stimulation with KCl, ureters were subjected to different doses of vardenafil. Basic contractility and ureteral response to vardenafil were analyzed. RESULTS: A different pattern of basic contractility was evidenced between species. Vardenafil administration induced a dose-dependent reduction in KCl-induced amplitude increase in human ureters and a dose-dependent reduction in autonomic contractile rhythm of porcine and ovine ureters. Although animal ureters could predict the relaxant response of human samples to vardenafil, its effect would have been overestimated using only animal models. CONCLUSIONS: Human ureteral investigations cannot entirely be replaced by existing animal models since results of the latter will vary significantly according to the tested pharmaceutical agent.

Novice surgeons: do they benefit from 3D laparoscopy?

In this study, the impact of two-dimensional (2D) and three-dimensional (3D) vision on laparoscopic performance of novice surgeons is examined. Twenty-five novice surgeons were directed to complete four basic tasks from European Training in Basic Laparoscopic Urological Skills (E-BLUS) with both 2D and 3D systems in a random order: task 1: needle guidance, task 2: cutting a circle, task 3: laparoscopic suturing, and task 4: pegs transfer. Quality and quantity scores for each task were measured. Participants completed all of the tasks in one modality of vision and than switched to the other. NASA Task Load Index was used for subjective workload assessment. Statistically significant differences in favor of 3D vision were detected in tasks 1 and 4 both in terms of quality and quantity. In task 2 and task 3, a significantly better performance was observed with the 3D vision only in quantity assessment. The participants who started the tasks in the 3D vision were better in performing the skills in 2D when compared to the participants who started with 2D vision. Overall, the participants reported a better perception of depth and spatial orientation with the 3D mode. Subjective work load was also lower for the tasks performed in 3D. Novice surgeons tended to perform better and felt much more comfortable with 3D in comparison to 2D laparoscopy. Even though previous task experience seemed to have an important impact on laparoscopic performance regardless of imaging modality, 3D laparoscopy seemed to facilitate the learning for novice surgeons.

Modified pericostal suture technique to reduce postoperative pain and provide optimum anatomic restoration after conversion of minimally invasive thoracic surgery to thoracotomy.

Minimally invasive thoracic techniques often need to be converted to open thoracotomy. Thoracotomy is associated with severe postoperative pain in 50% of the patients, and this situation can be maintained for a prolonged period. Many efforts have been made to avoid this complication. We propose an easy and fast thoracotomy closure technique to avoid nerve entrapment at the time of chest closure suitable for cases of conversion to thoracotomy after a minimally invasive attempt. The proposed method effectively avoids interference with the intercostal nerve, which remains intact and restores the anatomy of the intercostal space. Efforts to decrease postoperative pain are vital. Thoracic surgeons are the principal health professionals able to deal with operative factors and postoperative pain management. We believe that the use of this easy and fast technique can facilitate excellent anatomic repositioning of the ribs alongside nerve sparing.

Comparison of early and late complications after various bariatric procedures: incidence and treatment during 15 years at a single institution.

BACKGROUND: Bariatric procedures are effective in the life-long treatment of clinically severe obesity, but they are technically demanding and have known complications. The present study presents mortality and morbidity with different procedures from the prospective 15-year bariatric database of the University Hospital of Patras in Greece. METHODS: From June 1994 through December 2008, 1,162 morbidly obese patients underwent various bariatric procedures at our institution (35 vertical banded gastroplasties, 151 laparoscopic sleeve gastrectomies, 90 open and 137 laparoscopic Roux-en-Y gastric bypasses, 699 biliopancreatic diversions with long limbs, and 50 reoperations). Postoperative metabolic deficiencies and causes of early and late morbidity for various bariatric procedures were compared by using the z-test for the comparison of proportions. Logistic regression analysis was used to model the occurrence of early and late death and complications. RESULTS: Total mortality was 1.81% (early 0.6%, intermediate 0.26%, late 0.95%). No significant predictors for early death were found, but age (odds ratio (OR), 1.077; 95% confidence interval (CI), 1.024-1.133; P = 0.004) and BMI (OR, 1.156; 95% CI, 1.023-1.306; P = 0.02) were predictors for late death. Early and late morbidity were 8% and 27.71%, respectively. The total leakage incidence was 1.98% and was significantly higher (P < 0.05) after reoperation. Fifteen of the 23 leaks were successfully treated conservatively. Most late complications were incisional hernias (18.85%)--almost all after open procedures. Hypoalbuminemia incidence was significantly higher after biliopancreatic diversion with long limbs (3.58%) and reoperation (8%). CONCLUSIONS: Bariatric procedures, even in specialized centers, may have serious complications because of their technical complexity in a high-risk population. Almost all can be managed successfully.

Therapeutic Equivalence of a New Preparation of Liquid Levothyroxine with Tablets in Patients with Overt Primary Hypothyroidism.

BACKGROUND: A new liquid levothyroxine (LT4) dissolved in glycerol and water has recently been developed by a Greek pharmaceutical company (Uni-Pharma, Athens, Greece). OBJECTIVES: To evaluate the therapeutic equivalence of this new liquid LT4 preparation versus the already existing tablet formulation of the same manufacturer, in order to obtain approval by the Greek National Organization for Medicines. METHODS: This was a prospective, randomized, cross-over phase III study. The study included 50 patients (9 men and 41 non-pregnant women, with a mean age of 42.5 ± 12.5 years), with documented overt primary hypothyroidism. All subjects were well controlled on substitution therapy with various LT4 formulations. None of the patients had known LT4 malabsorption. The patients were randomized into 2 groups (A and B). The individuals of group A initially received T4® tablets for 10 ± 2 weeks and subsequently switched to T4® drops (100 µg/mL solution) at the same dose for another 10 ± 2 weeks. In group B, the reverse procedure was followed. Total T3 (T3), free T4 (fT4), and TSH were measured in all participants at enrollment and at the end of each 10 ± 2-week trial period. RESULTS: Out of the 50 recruited patients, 6 were lost to follow-up and 5 were excluded due to non-compliance with the study protocol. In the 39 patients who completed the study, the serum TSH levels after 10 ± 2 weeks of treatment either with T4® tablets or with T4® drops did not differ (1.759 ± 1.104 vs. 2.076 ± 1.334 mIU/L, mean ± SD). CONCLUSIONS: In hypothyroid patients, the new liquid LT4 preparation (T4® drops) is therapeutically equivalent to the tablet form (T4® tablets).

Employing machine learning and microscopy images of AIB1-stained biopsy material to assess the 5-year survival of patients with colorectal cancer.

Our purpose was to employ microscopy images of amplified in breast cancer 1 (AIB1)-stained biopsy material of patients with colorectal cancer (CRC) to: (a) find statistically significant differences (SSDs) in the texture and color of the epithelial gland tissue, between 5-year survivors and non-survivors after the first diagnosis and (b) employ machine learning (ML) methods for predicting the CRC-patient 5-year survival. We collected biopsy material from 54 patients with diagnosed CRC from the archives of the University Hospital of Patras, Greece. Twenty-six of the patients had survived 5 years after the first diagnosis. We selected regions of interest containing the epithelial gland at different microscope lens magnifications. We computed 69 textural and color features. Furthermore, we identified features with SSDs between the two groups of patients and we designed a supervised ML system for predicting the CRC-patient 5-year survival. Additionally, we employed the VGG16 pretrained convolution neural network to extract deep learning (DL) features, the support vector machines classifier, and the bootstrap cross-validation method for boosting the accuracy of predicting 5-year survival. Fourteen features sustained SSDs between the two groups of patients. The supervised ML system achieved 87% accuracy in predicting 5-year survival. In comparison, the DL system, using images from all magnifications, gave 97% classification accuracy. Glandular texture in 5-year non-survivors appeared to be of lower contrast, coarseness, roughness, local pixel correlation, and lower AIB1 variation, all indicating loss of textural definition. The supervised ML system revealed useful information regarding features that discriminate between 5-year survivors and non-survivors while the DL system displayed superior accuracy by employing DL features.

Background adjustment of cDNA microarray images by Maximum Entropy distributions.

Many empirical studies have demonstrated the exquisite sensitivity of both traditional and novel statistical and machine intelligence algorithms to the method of background adjustment used to analyze microarray datasets. In this paper we develop a statistical framework that approaches background adjustment as a classic stochastic inverse problem, whose noise characteristics are given in terms of Maximum Entropy distributions. We derive analytic closed form approximations to the combined problem of estimating the magnitude of the background in microarray images and adjusting for its presence. The proposed method reduces standardized measures of log expression variability across replicates in situations of known differential and non-differential gene expression without increasing the bias. Additionally, it results in computationally efficient procedures for estimation and learning based on sufficient statistics and can filter out spot measures with intensities that are numerically close to the background level resulting in a noise reduction of about 7%.

Factors affecting the long-term response to tacrolimus in renal transplant patients: pharmacokinetic and pharmacogenetic approach.

BACKGROUND: The aim of our study was to determine the impact of CYP3A5*1 and CYP3A5*3 on the kinetics of tacrolimus in renal transplant recipients. MATERIAL AND METHODS: Forty kidney recipients were selected to participate. Maintenance scheme consisted of tacrolimus, a purine inhibitor and a steroid. CYP3A5 genotyping was performed with PCR and RFLP. Pharmacokinetic model was developed with Linear Regression and General Linear Model repeated measures approach. The impact of sex, CYP3A5*1 allele, age at transplantation, hepatic and renal function on tacrolimus kinetics was examined. RESULTS: The frequency of CYP3A5*3/*3 and CYP3A5*1/*3 genotype was 35/40 and 5/40, respectively. No CYP3A5*1/*1 was detected. CYP3A5*1 variant was associated with significant lower TAC dose adjusted concentration at 3, 6, 12 and 36 months after transplantation. Hepatic and renal function showed a significant effect on tacrolimus dose adjusted concentration 3 months after transplantation (p=0.000 and 0.028, respectively). Sex did not show a significant impact on tacrolimus kinetics. Carriers of CYP3A5*1 allele had lower predicted measures for tacrolimus dose adjusted concentration and higher predicted measures for volume of distribution. CONCLUSION: We proved that CYP3A5*1 carriers need higher tacrolimus dose than CYP3A5*3 homozygotes to achieve the target blood concentration.

Postconcussion syndrome after mild traumatic brain injury in Western Greece.

BACKGROUND: The prevalence of postconcussion syndrome (PCS) in the first weeks after mild traumatic brain injury varies from 40% to 80%. However, as many as 50% of patients report symptoms for up to 3 months and 10% to 15% for more than a year. The objective of this study is to analyze the characteristics and estimate the prevalence of PCS in an adult Greek population. METHODS: This prospective study was performed in the University Hospital of Patras in Western Greece. Patients with mild traumatic brain injury (n = 539) were randomly recruited on admission between May 2006 and May 2008. Overall, 223 patients (223 of 539, 41.5%) met the Colorado Medical Society guidelines for concussion; 141 men (63%) and 82 women (37%) with a median age of 30 years (range, 18.5-57.5 years) were included in the study. Patient follow-up consisted of telephone interviews at 1 month, 3 months, and 6 months postinjury, when they were asked about experiencing common postconcussion symptoms (International Classification of Diseases-10th revision criteria). RESULTS: The rate of PCS at 1 month, 3 months, and 6 months postinjury was estimated to be 10.3%, 6%, and 0.9%, respectively. The syndrome was more frequent among women (17%) and individuals with bleeding diathesis (26%) compared with men (6.4%) and patients without clotting disorders (8.5%), respectively. In addition, higher rates of PCS affected patients who sustained assaults compared with other types of accidents. CONCLUSIONS: The prevalence of PCS was remarkably higher in previous studies. Cultural differences regarding symptom expectation and the lack of compensation might explain the low rate of chronic symptoms in Greeks.

Effect of bladder neck preservation during endoscopic extraperitoneal radical prostatectomy on urinary continence.

OBJECTIVE: The current study investigates the effect of bladder neck (BN) preservation on postoperative continence and positive surgical margins (+SMs). PATIENTS AND METHODS: 150 patients (group 1) who underwent BN-sparing endoscopic extraperitoneal radical prostatectomy (EERPE) and 90 patients treated with EERPE and BN resection (group 2) were retrospectively evaluated. RESULTS: Both groups were similar for age, prostate-specific antigen and prostate size. There was no significant difference in operative time, mean blood loss or transfusion rate. Mean catheterization time was similar. The overall +SM rates were very similar at 10.7% for group 1 and 10.0% for group 2 (group 1, pT2 = 5.1% and pT3 = 30.3%; group 2, pT2 = 2.9% and pT3 = 33.3%). One of 16 patients in group 1 and 1 of 9 in group 2 had a +SM at BN. Statistically significant differences in continence were observed 24 h after catheter removal and 3 months postoperatively between both groups. CONCLUSION: BN preservation proved to have an impact on postoperative early continence of patients undergoing EERPE. Continence of patients who underwent BN preservation was improved after catheter removal and at the 3-month follow-up in comparison to those without BN preservation, but +SMs were not affected by the BN-sparing surgery.

Assessment of HPV Risk Type in H&E-stained Biopsy Specimens of the Cervix by Microscopy Image Analysis.

OBJECTIVES: The objective of this study was (a) to identify, by computer processing of digitized images of hematoxylin and eosin (H&E)-stained biopsy material of the cervix, differences in the structure of nuclei between high-risk (HR) and low-risk (LR) human papillomavirus virus (HPV) types and (b) to assess the HPV risk type by designing a decision-support system (DSS). MATERIALS AND METHODS: Clinical material comprised H&E-stained biopsies from squamous intraepithelial lesions of 55 patients with polymerase chain reaction-verified HR-HPV (26 patients) or LR-HPV (29 patients) infection. From each patient's biopsy specimen, we digitized 1 region of interest, guided by the expert physician. After the segmentation of nuclei, we quantified from each nucleus 77 textural and morphologic features. We represented each patient by a 77-feature vector, the feature means of all nuclei, and we created 2 classes for HR-HPV and LR-HPV types. We carried out (a) a statistical analysis to determine features with statistically significant differences between the 2 classes and (b) a discriminant analysis, by designing a DSS, to estimate the HPV risk type. RESULTS: Statistical analysis revealed 40 features with between-classes statistically significant differences and discriminant analysis showed that the best DSS design achieved a high accuracy of about 93% in identifying the HPV risk type on data not used in the design of the DSS. CONCLUSIONS: Nuclei of HR-HPV types were of higher intensity, contained larger structures, had higher edges, were coarser, rougher, had higher contrast, were larger, and attained more irregular shapes. The proposed DSS indicates that discrimination of HPV risk type from images of H&E-stained biopsy material of the cervix is promising.

GPU-enabled design of an adaptable pattern recognition system for discriminating squamous intraepithelial lesions of the cervix.

The aim of the present study was to design an adaptable pattern recognition (PR) system to discriminate low- from high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively) of the cervix using microscopy images of hematoxylin and eosin (H&E)-stained biopsy material from two different medical centers. Clinical material comprised H&E-stained biopsies of 66 patients diagnosed with LSIL (34 cases) or HSIL (32 cases). Regions of interest were selected from each patient's digitized microscopy images. Seventy-seven features were generated, regarding the texture, morphology and spatial distribution of nuclei. The probabilistic neural network (PNN) classifier, the exhaustive search feature selection method, the leave-one-out (LOO) and the bootstrap validation methods were used to design the PR system and to assess its precision. Optimal PR system design and evaluation were made feasible by the employment of graphics processing unit (GPU) and Compute Unified Device Architecture (CUDA) technologies. The accuracy of the PR-system was 93% and 88.6% when using the LOO and bootstrap validation methods, respectively. The proposed PR system for discriminating LSIL from HSIL of the cervix was designed to operate in a clinical environment, having the capability of being redesigned when new verified cases are added to its repository and when data from other medical centers are included, following similar biopsy material preparation procedures.

Bayesian clustering of flow cytometry data for the diagnosis of B-chronic lymphocytic leukemia.

In the rapidly advancing field of flow cytometry, methodologies facilitating automated clinical decision support are increasingly needed. In the case of B-chronic lymphocytic leukemia (B-CLL), discrimination of the various subpopulations of blood cells is an important task. In this work, our objective is to provide a useful paradigm of computer-based assistance in the domain of flow-cytometric data analysis by proposing a Bayesian methodology for flow cytometry clustering. Using Bayesian clustering, we replicate a series of (unsupervised) data clustering tasks, usually performed manually by the expert. The proposed methodology is able to incorporate the expert's knowledge, as prior information to data-driven statistical learning methods, in a simple and efficient way. We observe almost optimal clustering results, with respect to the expert's gold standard. The model is flexible enough to identify correctly non canonical clustering structures, despite the presence of various abnormalities and heterogeneities in data; it offers an advantage over other types of approaches that apply hierarchical or distance-based concepts.

Correlating Changes in the Epithelial Gland Tissue With Advancing Colorectal Cancer Histologic Grade, Using IHC Stained for AIB1 Expression Biopsy Material.

OBJECTIVE: The objective of this study was to study the textural and color changes occurring in the epithelial gland tissue with advancing colorectal cancer (CRC), utilizing immunohistochemical stain for AIB1 expression biopsy material. MATERIAL AND METHODS: Clinical material comprised biopsy specimens of 67 patients with a diagnosis of CRC. Two experienced pathologists used H&E-stained material for grading CRC lesions and immunohistochemical (IHC) stain for AIB1 expression. Twenty six patients were diagnosed with grade I, 28 with grade II, and 13 with grade III CRC. Guided by pathologists, we selected the regions of interest from AIB1-digitized images of each patient, encompassing the epithelial gland, and we computed 69 features, quantifying textural and color properties of the AIB1-stained lesions. We evaluated the statistical differences between grades by means of the Wilcoxon statistical test for each feature, and we assessed changes in feature values with advancing tumor grade by means of the Point Biserial Correlation. RESULTS: Statistical analysis revealed 14 single features, quantifying textural and color properties of the epithelial gland, which sustained statistically significant differences between LG-CRC and HG-CRC cases. These features were drawn from the gray-level image histogram, the cooccurrence matrix, the run length matrix, the discrete wavelet transform, the Tamura method, and the L*a*b color transform. CONCLUSIONS: A systematic statistical analysis of AIB1-stained biopsy material showed that high-grade CRC lesions contain higher intensity levels, appear coarser, are more homogeneous with smooth variation across the image, have lower contrast that is slowly varying across the image, have lower AIB1 staining, and have lower edges. A combination of textural and color attributes, evaluating image gray-tone distribution, textural roughness, inhomogeneity, AIB1 staining, and image coarseness should be considered in evaluating AIB1-stained CRC lesions.

A perspective for biomedical data integration: design of databases for flow cytometry.

BACKGROUND: The integration of biomedical information is essential for tackling medical problems. We describe a data model in the domain of flow cytometry (FC) allowing for massive management, analysis and integration with other laboratory and clinical information. The paper is concerned with the proper translation of the Flow Cytometry Standard (FCS) into a relational database schema, in a way that facilitates end users at either doing research on FC or studying specific cases of patients undergone FC analysis RESULTS: The proposed database schema provides integration of data originating from diverse acquisition settings, organized in a way that allows syntactically simple queries that provide results significantly faster than the conventional implementations of the FCS standard. The proposed schema can potentially achieve up to 8 orders of magnitude reduction in query complexity and up to 2 orders of magnitude reduction in response time for data originating from flow cytometers that record 256 colours. This is mainly achieved by managing to maintain an almost constant number of data-mining procedures regardless of the size and complexity of the stored information. CONCLUSION: It is evident that using single-file data storage standards for the design of databases without any structural transformations significantly limits the flexibility of databases. Analysis of the requirements of a specific domain for integration and massive data processing can provide the necessary schema modifications that will unlock the additional functionality of a relational database.