Purpose: The aims of our study were to elucidate the role of methylation of a large panel of genes during multistage pathogenesis
of bladder cancer and to correlate our findings with patient age and ...other clinicopathologic features.
Experimental Design: We studied the methylation status of 21 genes by quantitative methylation-specific PCR in an evaluation
set of 25 tumor and 5 normal samples. Based on methylation frequency in tumors and normals in gene evaluation set, we selected
7 candidate genes and tested an independent set of 93 tumors and 26 normals. The presence or absence of methylation was evaluated
for an association with cancer using cross-tabulations and χ 2 or Fisher's exact tests as appropriate. All statistical tests were two-sided.
Results: Most primary tumors (89 of 93, 96%) had methylation of one or more genes of independent set; 53 (57%) CCNA1 , 29 (31%) MINT1 , 36 (39%) CRBP , 53 (57%) CCND2 , 66 (71%) PGP9.5 , 60 (65%) CALCA , and 78 (84%) AIM1 . Normal uroepithelium samples from 26 controls revealed no methylation of the CCNA1 and MINT1 genes, whereas methylation of CRBP, CCND2, PGP9.5 , and CALCA was detected at low levels. All the 7 genes in independent set were tightly correlated with each other and 3 of these genes
showed increased methylation frequencies in bladder cancer with increasing age. PGP9.5 and AIM1 methylation correlated with primary tumor invasion.
Conclusion: Our results indicate that the methylation profile of novel genes in bladder cancers correlates with clinicopathologic
features of poor prognosis and is an age-related phenomenon. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2786–94)
Hierarchical Multi-Label Classification is a classification task where the classes to be predicted are hierarchically organized. Each instance can be assigned to classes belonging to more than one ...path in the hierarchy. This scenario is typically found in protein function prediction, considering that each protein may perform many functions, which can be further specialized into sub-functions. We present a new hierarchical multi-label classification method based on multiple neural networks for the task of protein function prediction. A set of neural networks are incrementally training, each being responsible for the prediction of the classes belonging to a given level.
The method proposed here is an extension of our previous work. Here we use the neural network output of a level to complement the feature vectors used as input to train the neural network in the next level. We experimentally compare this novel method with several other reduction strategies, showing that it obtains the best predictive performance. Empirical results also show that the proposed method achieves better or comparable predictive performance when compared with state-of-the-art methods for hierarchical multi-label classification in the context of protein function prediction.
The experiments showed that using the output in one level as input to the next level contributed to better classification results. We believe the method was able to learn the relationships between the protein functions during training, and this information was useful for classification. We also identified in which functional classes our method performed better.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Coronavirus disease (COVID-19) survivors exhibit multisystemic alterations after hospitalization. Little is known about long-term imaging and pulmonary function of hospitalized patients intensive ...care unit (ICU) who survive COVID-19. We aimed to investigate long-term consequences of COVID-19 on the respiratory system of patients discharged from hospital ICU and identify risk factors associated with chest computed tomography (CT) lesion severity.
A prospective cohort study of COVID-19 patients admitted to a tertiary hospital ICU in Brazil (March-August/2020), and followed-up six-twelve months after hospital admission. Initial assessment included: modified Medical Research Council dyspnea scale, SpO2 evaluation, forced vital capacity, and chest X-Ray. Patients with alterations in at least one of these examinations were eligible for CT and pulmonary function tests (PFTs) approximately 16 months after hospital admission. Primary outcome: CT lesion severity (fibrotic-like or non-fibrotic-like). Baseline clinical variables were used to build a machine learning model (ML) to predict the severity of CT lesion.
In total, 326 patients (72%) were eligible for CT and PFTs. COVID-19 CT lesions were identified in 81.8% of patients, and half of them showed mild restrictive lung impairment and impaired lung diffusion capacity. Patients with COVID-19 CT findings were stratified into two categories of lesion severity: non-fibrotic-like (50.8%-ground-glass opacities/reticulations) and fibrotic-like (49.2%-traction bronchiectasis/architectural distortion). No association between CT feature severity and altered lung diffusion or functional restrictive/obstructive patterns was found. The ML detected that male sex, ICU and invasive mechanic ventilation (IMV) period, tracheostomy and vasoactive drug need during hospitalization were predictors of CT lesion severity(sensitivity,0.78±0.02;specificity,0.79±0.01;F1-score,0.78±0.02;positive predictive rate,0.78±0.02; accuracy,0.78±0.02; and area under the curve,0.83±0.01).
ICU hospitalization due to COVID-19 led to respiratory system alterations six-twelve months after hospital admission. Male sex and critical disease acute phase, characterized by a longer ICU and IMV period, and need for tracheostomy and vasoactive drugs, were risk factors for severe CT lesions six-twelve months after hospital admission.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigated the feasibility of detecting aberrant DNA methylation of some novel and known genes in the serum of lung cancer patients.
To determine the analytic sensitivity, we examined the tumor ...and the matched serum DNA for aberrant methylation of 15 gene promoters from 10 patients with primary lung tumors by using quantitative methylation-specific PCR. We then tested this 15-gene set to identify the more useful DNA methylation changes in the serum of a limited number of lung cancer patients and controls. In an independent set, we tested the six most promising genes (APC, CDH1, MGMT, DCC, RASSF1A, and AIM1) for further elucidation of the diagnostic application of this panel of markers.
Promoter hypermethylation of at least one of the genes studied was detected in all 10 lung primary tumors. In majority of cases, aberrant methylation in serum DNA was accompanied by methylation in the matched tumor samples. In the independent set, using a single gene that had 100% specificity (DCC), 35.5% (95% CI: 25-47) of the 76 lung cancer patients were correctly identified. For patients without methylated DCC, addition of a logistic regression score that was based on the five remaining genes improved sensitivity from 35.5% to 75% (95% CI: 64-84) but decreased the specificity from 100% to 73% (95% CI: 54-88).
This approach needs to be evaluated in a larger test set to determine the role of this gene set in early detection and surveillance of lung cancer.
Water pollution has generated the need to develop technologies to remove industrial pollutants. Adsorption has been recognized as one of the most effective techniques for effluent remediation. In ...this study, parts (stem and leaves) of a problematic aquatic weed, the water hyacinth (Eichhornia crassipes), were separated to produce a bioadsorbent. The objective was to evaluate the adsorption of a cationic dye, methylene blue (MB), in an aqueous solution of the biomass from different parts of the water hyacinth (Eichhornia crassipes) plants. The materials were characterized through techniques of infrared spectroscopy, scanning electron microscopy, X-ray diffractometry, and thermogravimetric analysis, before and after the material adsorption. Water hyacinth biomasses presented adsorption capacity above 89%, and the kinetics was faster for stem biomass. The kinetic study found that the adsorption process is better described by the pseudo-second-order model, and the adjustments of the isotherm experimental data indicated that both materials are favorable for adsorption. Therefore, water hyacinth bioadsorbent represents a renewable resource with potential for effluent treatment.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Inhibition of microRNA-21 (miR-21) prevents necroptosis in the mouse pancreas. Necroptosis contributes to hepatic necro-inflammation in the common bile duct ligation (BDL) murine model. We aimed to ...evaluate the role of miR-21 in mediating deleterious processes associated with cholestasis. Mechanistic studies established a functional link between miR-21 and necroptosis through cyclin-dependent kinase 2-associated protein 1 (CDK2AP1). miR-21 expression increased in the liver of primary biliary cholangitis (PBC) patients and BDL wild-type (WT) mice at both 3 and 14 days. Notably, under BDL, miR-21
mice displayed decreased liver injury markers in serum compared with WT mice, accompanied by reduced hepatocellular degeneration, oxidative stress and fibrosis. Hallmarks of necroptosis were decreased in the liver of BDL miR-21
mice, via relieved repression of CDK2AP1. Further, miR-21
mice displayed improved adaptive response of bile acid homeostasis. In conclusion, miR-21 ablation ameliorates liver damage and necroptosis in BDL mice. Inhibition of miR-21 should arise as a promising approach to treat cholestasis.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Novelty detection in data streams Faria, Elaine R.; Gonçalves, Isabel J. C. R.; de Carvalho, André C. P. L. F. ...
The Artificial intelligence review,
02/2016, Volume:
45, Issue:
2
Journal Article
Peer reviewed
Open access
In massive data analysis, data usually come in streams. In the last years, several studies have investigated novelty detection in these data streams. Different approaches have been proposed and ...validated in many application domains. A review of the main aspects of these studies can provide useful information to improve the performance of existing approaches, allow their adaptation to new applications and help to identify new important issues to be addresses in future studies. This article presents and analyses different aspects of novelty detection in data streams, like the offline and online phases, the number of classes considered at each phase, the use of ensemble versus a single classifier, supervised and unsupervised approaches for the learning task, information used for decision model update, forgetting mechanisms for outdated concepts, concept drift treatment, how to distinguish noise and outliers from novelty concepts, classification strategies for data with
unknown
label, and how to deal with recurring classes. This article also describes several applications of novelty detection in data streams investigated in the literature and discuss important challenges and future research directions.
Full text
Available for:
CEKLJ, EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
The need for analytical devices for detecting cancer at early stages has motivated research into nanomaterials where synergy is sought to achieve high sensitivity and selectivity in low-cost ...biosensors. In this study, we developed a film architecture combining self-assembled monolayer (SAM) and layer-by-layer (LbL) films of polysaccharide chitosan and the protein concanavalin A, on which a layer of anti-CA19–9 antibody was adsorbed. Using impedance spectroscopy with this biosensor, we were capable of detecting low concentrations of the antigen CA19–9, an important biomarker for pancreatic cancer. The limit of detection of 0.69U/mL reached is sufficient for detecting pancreatic cancer at very early stages. The selectivity of the biosensor was inferred from a series of control experiments with samples of cell lines that were tested positive (HT29) and negative (SW620) for the biomarker CA19–9, in addition to the lack of changes in the capacitance value for other analytes and antigen that are not related to this type of cancer. The high sensitivity and selectivity are ascribed to the very specific antigen–antibody interaction, which was confirmed with PM-IRRAS and atomic force microscopy. Also significant is that used information visualization methods to show that different cell lines and commercial samples containing distinct concentrations of CA19–9 and other analytes can be easily distinguished from each other. These computational methods are generic and may be used in optimization procedures to tailor biosensors for specific purposes, as we demonstrated here by comparing the performance of two film architectures in which the concentration of chitosan was varied.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
This technical note describes a new microfluidic sensor that combines low-cost (USD $0.97) with rapid fabrication and user-friendly, fast, sensitive, and accurate quantification of a breast cancer ...biomarker. The electrodes consisted of cost-effective bare stainless-steel capillaries, whose mass production is already well-established. These capillaries were used as received, without any surface modification. Microfluidic chips containing electrical double-layer capillary capacitors (μEDLC) were obtained by a cleanroom-free prototyping that allows the fabrication of dozens to hundreds of chips in 1 h. This sensor provided the successful quantification of CA 15-3, a biomarker protein for breast cancer, in serum samples from cancer patients. Antibody-anchored magnetic beads were utilized for immunocapture of the marker, and then, water was added to dilute the protein. Next, the CA 15-3 detection (<2 min) was made without using redox probes, antibody on electrode (sandwich immunoassay), or signal amplification strategies. In addition, the capacitance tests eliminated external pumping systems and precise volumetric sampling steps, as well as presented low sample volume (5 μL) and high sensitivity using bare capillaries in a new design for double-layer capacitors. The achieved limit-of-detection (92.0 μU mL–1) is lower than that of most methods reported in the literature for CA 15-3, which are based on nanostructured electrodes. The data shown in this technical note support the potential of the μEDLC toward breast cancer diagnosis even at early stages. We believe that accurate analyses using a simple sample pretreatment such as magnetic field-assisted immunocapture and cost-effective bare electrodes can be extended to quantify other cancer biomarkers and even biomolecules by changing the biorecognition element.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Objective
We investigated and validated the presence of emotion regulation profiles in an adult sample.
Method
In a cross‐sectional study, 1165 individuals completed the Emotion Regulation ...Questionnaire (ERQ), Difficulties in Emotion Regulation Scale (DERS), Positive and Negative Affect Scale (PANAS), and Following Affective States Test (FAST). Sample was divided into three to establish and validate emotion regulation profiles using a latent profile analysis.
Results
Sample 1 (n = 375) showed three different profiles: dysregulated, adapted, and unaware regulator. Sample 2 (n = 390) shows a consistent pattern with the same number of profiles that remained stable over time. In Sample 3 (n = 400), we validate and find that cognitive reappraisal and lack of awareness were essential to differentiating profiles.
Conclusions
Three emotional regulation profiles differ due to the levels of positive/negative affect and the propensity to avoid/follow emotions, increasing the understanding of how different regulatory strategies interact and explain different outcomes with mental health.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK