Hybrid EANN-EA System for the Primary Estimation of Cardiometabolic Risk

The most important part of the early prevention of atherosclerosis and cardiovascular diseases is the estimation of the cardiometabolic risk (CMR). The CMR estimation can be divided into two phases. The first phase is called primary estimation of CMR (PE-CMR) and includes solely diagnostic methods that are non-invasive, easily-obtained, and low-cost. Since cardiovascular diseases are among the main causes of death in the world, it would be significant for regional health strategies to develop an intelligent software system for PE-CMR that would save time and money by extracting the persons with potentially higher CMR and conducting complete tests only on them. The development of such a software system has few limitations - dataset can be very large, data can not be collected at the same time and the same place (eg. data can be collected at different health institutions) and data of some other region are not applicable since every population has own features. This paper presents a MATLAB solution for PE-CMR based on the ensemble of well-learned artificial neural networks guided by evolutionary algorithm or shortly EANN-EA system. Our solution is suitable for research of CMR in population of some region and its accuracy is above 90 %.     

Impact of treatment on survival of patients with secondary glioblastoma

Data concerning treatment of secondary glioblastoma evolving from previously treated WHO II or III grade tumors are very scarce. The aim of this study was to evaluate the impact of surgical resection and adjuvant treatment on survival in patients with secondary glioblastoma. Thirty-nine patients with secondary glioblastoma evolving from previously treated lower grade gliomas between 2004 and 2015 were included. We evaluated the extent of resection, pathological parameters, adjuvant treatment, as well as survival after malignant transformation. The primary tumor grade was WHO II in 16 (41.0%) and WHO III in 23 (59.0%) patients. Median age was 43 years (range 23–67). Median KPS was 80 (range 60–100) before surgery, and 70 (range 50–100) after surgery. Gross total resection (GTR) of contrast-enhancing disease was achieved in 19 (48.7%) patients. Adjuvant treatment was radio-chemotherapy in 23 (59.0%), radiotherapy in three (7.7%), chemotherapy in five (12.8%) and none in eight (20.5%) patients. Median survival was 11 months (range 1–35) in the entire group. Time since initial diagnosis and previous treatment did not correlate with survival after glioblastoma. Failed GTR, poor KPS after surgery, and no adjuvant treatment were prognostic factors for shorter survival in univariate analysis (p?<?0.0001, p?=?0.028 and p?=?0.003). In selected patients, complete resection and adjuvant treatment may prolong survival in spite of multiple previous therapies.     

Clinical value of monoclonal antibodies and tyrosine kinase inhibitors in the treatment of head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of malignant tumours that affects over 500,000 patients per year. Treatment failure is generally due to the heterogeneity of these tumours and to the serious adverse effects associated with treatment. Immunological system impairment, which is common in HNSCC, further contributes to treatment failure by mediating tumour escape mechanisms. To date, the only clinically approved targeted therapy agent is cetuximab, a monoclonal antibody (mAb) that binds to, and inhibits, epidermal growth factor receptor, which is widely overexpressed in HNSCC. Cetuximab has been proven to induce antibody-dependent cellular cytotoxicity, further magnifying its therapeutic effect. DNA sequencing of HNSCC cells has identified the presence of mutated genes, thus making their protein products potential targets for therapeutic inhibition. Immune mechanisms have been found to have a significant impact on carcinogenesis, thus providing the rationale to support efforts to identify anticancer compounds with immunomodulatory properties. In the context of the rapid development of novel targeted agents, the aim of the present paper is to review our current understanding of HNSCC and to review the novel anticancer agents (mAbs and TKIs) introduced in recent years, including an assessment of their efficacy and mechanisms of action.     

Secondary haemophagocytic lymphohistiocytosis triggered by postnatally acquired cytomegalovirus infection in a late preterm infant

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition with impairment of cytotoxic T-cells and natural killer cells. Causes in infants are mostly hereditary immune defects as well as various infectious triggering factors, amongst these cytomegalovirus (CMV). Vertical CMV transmission may occur in utero, during birth, and by breast feeding. Usually, a CMV infection transmitted via breast milk is symptomatic only in very immature preterm infants. We report on a late preterm infant born after 35 + 5 weeks of gestation with a birth weight of 1840 g, being admitted to our intensive care unit at the age of 9 weeks with acute enteritis and severe dehydration. After a prolonged recovery, the infant developed a sepsis-like condition with hyperpyrexia, hepatosplenomegaly, and pancytopenia. Combination with high ferritin levels (2809 μg/l), hypertriglyceridaemia (481 mg/dl), elevated soluble IL-2 receptor (sCD25, 9120 U/ml), and reduced perforin expression allowed diagnosis of HLH, caused by an acute CMV infection. Since connatal CMV infection had been ruled out earlier, we report the rare case of secondary HLH triggered by a postnatally acquired symptomatic CMV infection in an immunocompetent infant, most likely transmitted via breast milk. The infant was successfully treated with ganciclovir without need for immunosuppressive therapy.     

AU-1 from Agavaceae plants causes transient increase in p21/Cip1 expression in renal adenocarcinoma ACHN cells in an miR-34-dependent manner

Here, we show that AU-1, spirostanol saponin isolated from Agavaceae plants, causes a transient increase in cyclin-dependent kinase inhibitor (CDKI) p21/Cip1 through the upregulation of miRNAs, miR-34 and miR-21. AU-1 stimulated p21/Cip1 expression without exerting cytotoxicity against different types of carcinoma cell lines. In renal adenocarcinoma ACHN cells, AU-1 transiently elevated the expression level of p21/Cip1 protein without marked increases in p21/Cip1 mRNA levels. Rapid and transient increases in miR-34 and miR-21, both of which are known to upregulate p21/Cip1, were observed in AU-1-treated cells. Inhibitor for miR-34 and for miR-21 significantly blocked the AU-1-caused increase in p21/Cip1, indicating that elevation of p21/Cip1 protein by AU-1 is dependent on these microRNAs. We further clarified that NAD-dependent deacetylase SIRT1, a direct target of miR-34, is decreased by the treatment with AU-1. Furthermore, we found that SIRT1-knockdown increases p21/Cip1 protein levels in an miR-21-dependent manner. On the other hand, ectopic expression of p21/Cip1 resulted in the lowered expression of miR-34 and miR-21, suggesting that reciprocal regulation exists between p21/Cip1 and these miRNAs. We propose that the following feedback network composed of miR-34/SIRT1/miR-21/p21 is triggered by the treatment with AU-1: in cells treated with AU-1, transient elevation of miR-34 leads to the downregulation of SIRT1, thereby miR-21 is freed from SIRT1-dependent suppression. Then, elevated miR-21 upregulates p21/Cip1 protein, followed by the suppression of miR-34 expression.