Geometric tree kernels: Classification of COPD from airway tree geometry

Methodological contributions: This paper introduces a family of kernels for analyzing (anatomical) trees endowed with vector valued measurements made along the tree. While state-of-the-art graph and tree kernels use combinatorial tree/graph structure with discrete node and edge labels, the kernels presented in this paper can include geometric information such as branch shape, branch radius or other vector valued properties. In addition to being flexible in their ability to model different types of attributes, the presented kernels are computationally efficient and some of them can easily be computed for large datasets (N of the order 10.000) of trees with 30-600 branches. Combining the kernels with standard machine learning tools enables us to analyze the relation between disease and anatomical tree structure and geometry. Experimental results: The kernels are used to compare airway trees segmented from low-dose CT, endowed with branch shape descriptors and airway wall area percentage measurements made along the tree. Using kernelized hypothesis testing we show that the geometric airway trees are significantly differently distributed in patients with Chronic Obstructive Pulmonary Disease (COPD) than in healthy individuals. The geometric tree kernels also give a significant increase in the classification accuracy of COPD from geometric tree structure endowed with airway wall thickness measurements in comparison with state-of-the-art methods, giving further insight into the relationship between airway wall thickness and COPD. Software: Software for computing kernels and statistical tests is available at http://image.diku.dk/aasa/software.php.Comment: 12 page

A Database and Evaluation for Classification of RNA Molecules Using Graph Methods

In this paper, we introduce a new graph dataset based on the representation of RNA. The RNA dataset includes 3178 RNA chains which are labelled in 8 classes according to their reported biological functions. The goal of this database is to provide a platform for investigating the classication of RNA using graph-based methods. The molecules are represented by graphs representing the sequence and base-pairs of the RNA, with a number of labelling schemes using base labels and local shape. We report the results of a number of state-of-the-art graph based methods on this dataset as a baseline comparison and investigate how these methods can be used to categorise RNA molecules on their type and functions. The methods applied are Weisfeiler Lehman and optimal assignment kernels, shortest paths kernel and the all paths and cycle methods. We also compare to the standard Needleman-Wunsch algorithm used in bioinformatics for DNA and RNA comparison, and demonstrate the superiority of graph kernels even on a string representation. The highest classication rate is obtained by the WL-OA algorithm using base labels and base-pair connections

Pediatric acute lymphoblastic leukemia treatment protocols improvement: emphasis on minimal residual disease

Treatment of acute lymphoblastic leukemia (ALL) in children during the last 50 years has changed significantly, which has increased the survival of patients from 10–15 % in the early 60s to 80–85 % by the mid-2000s. Such results have been achieved through the development of new polychemotherapy regimens, the introduction of neuroleukemia prophylaxis, the strengthening of standard chemotherapy by increasing the dose and / or frequency of chemotherapeutic drugs administration, and the definition of criteria for patient stratification into prognostic risks groups and the development of principles of risk-adopted therapy.However, inspite of the overall success of pediatric acute lymphoblastic leukemia therapy, some variants of acute lymphoblastic leukemia associated with poor prognosis, especially acute lymphoblastic leukemia with BCR-ABL1 and MLL rearrangements. Besides the prolonged persistence of minimal residual disease is also an unfavorable prognostic factor requiring therapy intensification.In the current issue we present the main steps in the evolution of programmed chemotherapy of children with acute lymphoblastic leukemia. Great attention was paid for modern risk-stratifying criteria with an emphasis on minimal residual disease

INTERTEXTUAL GAME IN THE NOVEL “ULYSSES” BY JAMES JOYCE

The article is devoted to the description of intertextual game in the novel “Ulysses” by James Joyce. The features of the Joyce’s poetics are explored with the aim of interpretational limits’ determination in the text. The authors carry out analyses of the first episode in which synthesis of characters, applying of details, allusions and oppositions are revealed as the main mechanisms of combination for various plans of narration

Treatment results of pediatric acute myeloid leukemia with epigenetic drugs addition

Background. Currently, overall survival rate for pediatric patients with acute myeloid leukemia (AML) do not exceed 70 %. The intensity of modern AML chemotherapeutic programs has reached its limit, and further chemotherapy dose escalation for treatment results improvement is impossible, because it fraught with life-threatening complications. It is investigating a new ways of tumor treatment for improvement of AML patient’s survival level: therapeutic efficacy of targeted and epigenetic drugs.Objective: to evaluate the efficacy of epigenetic drugs (azacitidine, decitabine, all-trans-retinoid acid and valproic acid) in combination with AML-BFM 2004 protocol for treatment of pediatric AML.Materials and methods. 80 patients with primary AML diagnosis were enrolled the study. Age was ranged from 8 months to 17 years (median 6.7 ± 0.6 years). From June 2012 to January 2018 all patients were subdivided in two treatment groups. 1st group included 34 patients treated with NII POH AML 2012 protocol, 2nd group – 46 patients treated by AML-BFM 2004 protocol.Results. 3-year relapse-free survival in 1st group, regardless of prognostic risk group, was 66.7 ± 11.7 %, 2nd group – 68.9 ± 9.9 %. Eventfree survival (EFS) for patients from 1st group was 66.7 ± 11.7 %, form 2nd group – 50.4 ± 10.2 %. Overall survival in 1st group was 66.7 ± 14.3 %, 2nd group – 66.9 ± 7.5 %. For patients with unfavorable risk from 1st treatment group 3-year relapse-free survival was 69.1 ± 11.9 %, 2nd – 64.9 ± 11.3 % (p = 0,8). EFS – 69.1 ± 11.9 and 44.8 ± 11.3 % respectively (p = 0,13). 3-year overall survival for patients with unfavorable risk group was 69.4 ± 14.6 and 64.4 ± 7.9 % in 1st and 2nd treatment groups respectively.Conclusion. The efficacy of decitabine in “window” regimen was higher in contrast to azacitidine; epigenetic therapy with AML-BFM 2004 protocol allow us to achieve a higher EFS, because of induction mortality and infection-related death decrease – EFS in 1st group was 16 % higher than in 2nd. Besides, EFS in unfavorable risk group, who treated with epigenetic drugs, was 25 % higher – 69.1 ± 11.9 % and 44.8 ± 11.3 % in 1st and 2nd groups respectively (p = 0.13). Nevertheless, overall survival in both groups was the same – 66 % (1st – 66.7 ± 14.3 % and 2nd – 66.9 ± 7.5 %)