Exploring the Impact of Evolutionary Computing based Feature Selection in Suicidal Ideation Detection

© 2019 IEEE. The ubiquitous availability of smartphones and the increasing popularity of social media provide a platform for users to express their feelings, including suicidal ideation. Suicide prevention by suicidal ideation detection on social media lights the path to controlling the rapidly increasing suicide rates amongst youth. This paper proposes a diverse set of features and investigates into feature selection using the Firefly algorithm to build an efficient and robust supervised approach to classifying tweets with suicidal ideation. The development of a suicidal language to create three diverse, manually annotated datasets leads to the validation of the proposed model. An in-depth result and error analysis lead to an accurate system for monitoring suicidal ideation on social media along with the discovery of optimal feature subsets and selection methods using a penalty based Firefly algorithm

Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

From DNA sequence to application: possibilities and complications

The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

Dose escalation of a curcuminoid formulation

BACKGROUND: Curcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed. METHODS: A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C(3 )Complex™, Sabinsa Corporation). Healthy volunteers were administered escalating doses from 500 to 12,000 mg. RESULTS: Seven of twenty-four subjects (30%) experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg. CONCLUSION: The tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent

Effect of clopidogrel discontinuation at 1 year after drug eluting stent placement on soluble CD40L, P-selectin and C-reactive protein levels: DECADES (Discontinuation Effect of Clopidogrel After Drug Eluting Stent): a multicenter, open-label study

Antiplatelet therapy with clopidogrel has been shown to reduce major adverse cardiac events in acute coronary syndromes and after percutaneous interventions. This effect is not only due to its anti-platelet effect but also possibly due to an anti-inflammatory effect. The effect of clopidogrel cessation after one year of therapy on markers of inflammation has been investigated in diabetics and showed an increase in platelet aggregation as well as hsCRP and surface P-selectin levels. This was an exploratory multicenter prospective open-label single arm study of 98 non-diabetic patients who had received one or more drug eluting stents and were coming to the end of their 12 months course of clopidogrel therapy. The effect of clopidogrel cessation on expression of biomarkers: sCD40L, soluble P-selectin and hsCRP was measured right before clopidogrel cessation (day 0), and subsequently at 1, 2, 3 and 4 weeks after drug withdrawal. A median increase in sCD40L expression from 224 to 324.5 pg/ml was observed between baseline and 4 weeks after clopidogrel cessation, which corresponded to a 39% mean percent change based on an ANCOVA model (P < 0.001). Over the 4 weeks observation period the change in sCD40L expression correlated weakly with soluble P-selectin levels (at 4 weeks Spearman’s correlation coefficient = 0.32; P = 0.0024). Increase in P-selectin expression from baseline was statistically significant at week 1 and 2. Conversely, hsCRP level decreased by 21% at 1 week (P = 0.008) and was still reduced by 18% by 4 weeks (P = 0.062). The change in sCD40L expression appeared to vary with the type of drug eluting stent. Patients treated with drug eluting stents at 1 year after implantation display significant increase in sCD40L and decrease in hsCRP after clopidogrel cessation. Further studies should elucidate if this increase in sCD40L levels reflects solely the removal of the inhibitory effects of clopidogrel on platelet activity or rather an increase in pro-inflammatory state. The latter hypothesis may be less likely given decrease in hsCRP levels. Randomized studies are urgently needed to establish potential link of clopidogrel discontinuation and vascular outcomes

TRAIL sensitisation by arsenic trioxide is caspase-8 dependent and involves modulation of death receptor components and Akt

The majority of leukaemic cells are resistant to apoptosis induced by tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, we show that sublethal concentrations of arsenic trioxide (ATO) specifically enhanced TRAIL-induced apoptosis in leukaemic but not in other tumour cell lines. The combination of ATO and TRAIL synergistically enhanced cleavage of caspase-8, which was blocked by the caspase inhibitor IETD.fmk as well as in cells deficient for caspase-8, suggesting a requirement for the death-inducing signalling complex. Arsenic trioxide led to increased cell surface expression of DR5 (death receptor 5), inhibition of the serine/threonine kinase Akt and downregulation of the short isoform of FLIP (FLICE-inhibitory protein, FLIPS). Inhibition of the phosphatidylinositol 3 kinase (PI3K) was equally efficient in sensitising leukaemic cells to TRAIL with similar effects on DR5 and FLIPS expression, suggesting that ATO may in part act through inhibition of the PI3K/Akt signalling pathway. These results indicate that the enhancement in TRAIL-mediated apoptosis induced by ATO is due to alteration in the levels of multiple components and regulators of the death receptor-mediated pathway. These findings offer a promising and novel strategy involving a combination of TRAIL and ATO, or more specific Akt inhibitors in the treatment of various haematopoietic malignancies

An Increase in Mitochondrial DNA Promotes Nuclear DNA Replication in Yeast

Coordination between cellular metabolism and DNA replication determines when cells initiate division. It has been assumed that metabolism only plays a permissive role in cell division. While blocking metabolism arrests cell division, it is not known whether an up-regulation of metabolic reactions accelerates cell cycle transitions. Here, we show that increasing the amount of mitochondrial DNA accelerates overall cell proliferation and promotes nuclear DNA replication, in a nutrient-dependent manner. The Sir2p NAD+-dependent de-acetylase antagonizes this mitochondrial role. We found that cells with increased mitochondrial DNA have reduced Sir2p levels bound at origins of DNA replication in the nucleus, accompanied with increased levels of K9, K14-acetylated histone H3 at those origins. Our results demonstrate an active role of mitochondrial processes in the control of cell division. They also suggest that cellular metabolism may impact on chromatin modifications to regulate the activity of origins of DNA replication

HBV Infection in Relation to Consistent Condom Use: A Population-Based Study in Peru

Data on hepatitis B virus (HBV) prevalence are limited in developing countries. There is also limited information of consistent condom use efficacy for reducing HBV transmission at the population level. The study goal was to evaluate the prevalence and factors associated with HBV infection in Peru, and the relationship between anti-HBc positivity and consistent condom use.Data from two different surveys performed in 28 mid-sized Peruvian cities were analyzed. Participants aged 18-29 years were selected using a multistage cluster sampling. Information was collected through a validated two-part questionnaire. The first part (face-to-face) concerned demographic data, while the second part (self-administered using handheld computers) concerned sexual behavior. Hepatitis B core antibody (anti-HBc) was tested in 7,000 blood samples. Prevalences and associations were adjusted for sample strata, primary sampling units and population weights. Anti-HBc prevalence was 5.0% (95%CI 4.1%-5.9%), with the highest prevalence among jungle cities: 16.3% (95%CI 13.8%-19.1%). In the multivariable analysis, Anti-HBc positivity was directly associated with geographic region (highlands OR = 2.05; 95%CI 1.28-3.27, and jungle OR = 4.86; 95%CI 3.05-7.74; compared to coastal region); and inversely associated with age at sexual debut (OR = 0.90; 95%CI 0.85-0.97). Consistent condom use, evaluated in about 40% of participants, was associated with reduced prevalence (OR = 0.34; 95%CI 0.15-0.79) after adjusting for gender, geographic region, education level, lifetime number of sex partners, age at sexual debut and year of survey.Residence in highlands or jungle cities is associated with higher anti-HBc prevalences, whereas increasing age at sexual debut were associated with lower prevalences. Consistent condom use was associated with decreased risk of anti-HBc. Findings from this study emphasize the need of primary prevention programs (vaccination) especially in the jungle population, and imply that condom use promotion might be a potential strategy to prevent HBV infection

Polymorphisms of the endothelial nitric oxide synthase (NOS3) gene in preeclampsia: a candidate-gene association study

<p>Abstract</p> <p>Background</p> <p>The endothelial nitric oxide synthase gene (<it>NOS3</it>) has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the <it>NOS3 </it>gene in a population of Caucasian origin.</p> <p>Methods</p> <p>We examined the association of three common variants of the <it>NOS3 </it>gene (4b/a, T-786C and G894T) and their haplotypes in a case-control sample of 102 patients with preeclampsia and 176 women with a history of uncomplicated pregnancies. Genotyping for the <it>NOS3 </it>variants was performed and odds ratios and 95% confidence intervals were obtained to evaluate the association between <it>NOS3 </it>polymorphisms and preeclampsia.</p> <p>Results</p> <p>The single locus analysis for the three variants using various genetic models and a model-free approach revealed no significant association in relation to clinical status. The analysis of haplotypes also showed lack of significant association.</p> <p>Conclusions</p> <p>Given the limitations of the candidate-gene approach in investigating complex traits, the evidence of our study does not support the major contributory role of these common <it>NOS3 </it>variants in preeclampsia. Future larger studies may help in elucidating the genetics of preeclampsia further.</p