Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenotypic performance of nine genotypes of Cry1A.105/Cry2Ab2 dual-gene resistant fall armyworm on non-Bt and MON 89034 maize.

BACKGROUND The fall armyworm, Spodoptera frugiperda (J.E. Smith), is the first target pest that has developed resistance to Bt crops across several countries. Leaf tissue and whole plant assays were employed to determine the survival, development, progeny production, and net reproductive rate of all nine possible genotypes of Cry1A.105/Cry2Ab2-dual gene resistant S. frugiperda on non-Bt and MON 89034 maize expressing the Cry1A.105/Cry2Ab2 proteins. RESULTS The homozygous resistant genotype was highly resistant to Bt plants. Genotypes possessing only Cry2Ab2 resistance alleles (RAs) or two Cry1A.105 RAs only were susceptible to MON 89034 with a functional dominance level (DML ) of 0.0-0.07 on MON 89034 plants. In contrast, genotypes containing two Cry1A.105 plus one Cry2Ab2 RA performed well on Bt plants, with a DML of 0.11-0.78. Significant numbers of survivors on Bt plants were also observed for genotypes containing a single Cry1A.105 RA, or a Cry1A.105 plus one or two Cry2Ab2 RAs, with a DML of 0.0-0.47. CONCLUSIONS The fitness of individual resistant genes on pyramided Bt plants varied in the dual-gene resistance system. Genotypes containing more Cry1A.105 RAs performed better than those possessing more Cry2Ab2 RAs. The functional dominance level of an individual resistant gene in this system is related to the DML level in its corresponding single-gene system. Data generated from this study should fill gaps in understanding dual-/multiple-gene Bt resistance, as well as providing useful information for refining resistance modeling, improving resistance risk assessment, and developing management strategies for the sustainable use of pyramided Bt maize technology. © 2019 Society of Chemical Industry.
Evaluation of salivary and plasma microRNA expression in patients with Sjögren's syndrome, and correlations with clinical and ultrasonographic outcomes.

OBJECTIVES To correlate the expression of microRNAs (miRNAs) 146a/b, 16, the 17-92 cluster and 181a in salivary and plasma samples taken from primary Sjögren's syndrome (pSS) patients with clinical, laboratory and ultrasound findings. METHODS Plasma and salivary samples were collected from 28 patients with pSS according to 2012 ACR and/or 2016 ACR/EULAR criteria (27 females, mean age 64.4±10.1 years, mean disease duration 10.7±6.9 years), and from 23 healthy subjects used as controls. The following patient data were recorded: ESSDAI and ESSPRI scores, anti-SSA and anti-SSB antibody status and laboratory data, Schirmer's test, ultrasound scores of the four major salivary glands according to Cornec et al., and concomitant treatments. The retro-transcribed and quantified miRNAs were: miR16-5p, miR17-5p, miR18a-5p, miR19a-5p, miR19b-1-5p, miR20a, miR92-5p, miR146a-5p, miR146b-5p, miR181a-5p. RESULTS SS patients had higher expression of salivary miR146a than gender- and age-matched controls (p=0.01). Spearman's regression analysis revealed that salivary miR146b was significantly more expressed in the patients with worse ESSPRI scores (p=0.02), whereas salivary miR17 and 146b and plasma miR17 expression was lower in the patients with higher ultrasound scores (respectively p=0.01, p=0.01 and p=0.04). Salivary miR18a expression was significantly increased in the patients who were anti-La/SSB positive (p=0.04). Neither salivary nor plasma miRNAs correlated with disease duration or concomitant therapies. CONCLUSIONS Our data show that salivary mi146a may represent a marker of the disease, and that the expression of salivary miR17, 18a and 146b may be altered in patients with pSS, and associated with worse ultrasound and ESSPRI scores and anti-La/SSB positivity.
Futurist Machine Art, Constructivism and the Modernity of Mechanization

This volume, Futurism and the Technological Imagination, results from a conference of the International Society for the Study of European Ideas in Helsinki. It contains a number of re-written conference contributions as well as several specially commissioned essays that address various aspects of the Futurists’ relationship to technology both on an ideological level and with regard to their artistic languages. In the early twentieth century, many art movements vied with each other to overhaul the aesthetic and ideological foundations of arts and literature and to make them suitable vehicles of expression in the new Era of the Machine. Some of the most remarkable examples came from the Futurist movement, founded in 1909 by Filippo Tommaso Marinetti. By addressing the full spectrum of Futurist attitudes to science and the machine world, this collection of 14 essays offers a multifaceted account of the complex and often contradictory features of the Futurist technological imagination. The volume will appeal to anybody interested in the history of modern culture, art and literature.
The effects of genetic variants related to insulin metabolism pathways and the interactions with lifestyles on colorectal cancer risk.

OBJECTIVES Genetic variants in metabolic signaling pathways may interact with lifestyle factors, such as dietary fatty acids, influencing postmenopausal colorectal cancer (CRC) risk, but these interrelated pathways are not fully understood. METHODS In this study, we examined 54 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I/insulin traits and their signaling pathways and lifestyle factors in relation to postmenopausal CRC, using data from 6,539 postmenopausal women in the Women's Health Initiative Harmonized and Imputed Genome-Wide Association Studies. By employing a two-stage random survival forest analysis, we evaluated the SNPs and lifestyle factors by ranking them according to their predictive value and accuracy for CRC. RESULTS We identified four SNPs (IRS1 rs1801123, IRS1 rs1801278, AKT2 rs3730256, and AKT2 rs7247515) and two lifestyle factors (age and percentage calories from saturated fatty acids) as the top six most influential predictors for CRC risk. We further examined interactive effects of those factors on cancer risk. In the individual SNP analysis, no significant association was observed, but the combination of the four SNPs, age, and percentage calories from saturated fatty acid (≥11% per day) significantly increased the risk of CRC in a gene and lifestyle dose-dependent manner. CONCLUSIONS Our findings provide insight into gene-lifestyle interactions and will enable researchers to focus on individuals with risk genotypes to promote intervention strategies. Our study suggests the careful use of data on potential genetic targets in clinical trials for cancer prevention to reduce the risk for CRC in postmenopausal women.
An intervention to improve pneumococcal vaccination uptake in high risk 50-64 year olds vs. expanded age-based recommendations: an exploratory cost-effectiveness analysis

ABSTRACT In the U.S., pneumococcal polysaccharide vaccine (PPSV23) uptake among high-risk adults aged <65 years is consistently low and improvement is needed. One barrier to improved vaccine coverage is the complexity of the adult vaccination schedule. This exploratory analysis compared the cost-effectiveness of strategies to increase pneumococcal vaccine uptake in high-risk adults aged 50–64 years. We used a Markov model to compare strategies for non-immunocompromised 50–64 year olds: 1) current pneumococcal polysaccharide vaccine (PPSV23) recommendations; 2) current recommendations enhanced by an intervention; 3) PPSV23 plus pneumococcal conjugate vaccine (PCV13) for high-risk patients with no intervention; or 4) both vaccines for all 50-year-olds with no intervention. Parameters included CDC data and other US data, varied extensively in sensitivity analyses. In the analysis, vaccinating high-risk individuals with PPSV23/PCV13 was the least costly strategy, with total costs of $424/person. Vaccinating all 50 year olds with PPSV23/PCV13 cost $40 more and gained 0.00068 quality-adjusted life years (QALY), or $57,786/QALY gained. Current recommendations with or without an intervention program were more expensive and less effective than other strategies. In multi-way sensitivity analyses, the current recommendations/intervention program strategy was favored at a $100,000/QALY threshold only if non-bacteremic pneumococcal pneumonia rate or PCV13 serotype coverage were substantially lower than base case values. Thus, an intervention program to improve pneumococcal vaccine uptake among high-risk 50–64 year-olds was not cost-effective in most scenarios. High-risk individuals receiving both PCV13 and PPSV23 could be economically favorable, and vaccinating all 50-year-olds with both vaccines could be considered.
Identification of Therapeutically Active Molecules against Anthrax through Structure and Ligand based Drug Design.

BACKGROUND People suffer from fatal diseases which are responsible for mortality. Potent devices and medicines are being developed to fight diseases caused by the microorganism for saving the lives of individuals. Highly pathogenic viruses and bacteria are being incorporated into biological warfare, which has become a major threat to mankind and causes the destruction of lives in a short span of time. OBJECTIVE The pathogen Bacillus anthracis, which is the causative of anthrax, is used in bioterrorism. Efforts are therefore being made to study the progress of biodefense drug discovery research in combating anthrax-based bioterrorism. METHODS This review describes the present status of the studies ontherapeutic measurement of anthrax toxin inhibitors towards inhibition of protective antigen, lethal and edema factors using chemometric and drug design tools to explore essential structural features for further design of active congeneric compounds. RESULTS The inhibitors estimated to show high activity through different models may be proposed for further synthesis and testing of biological activity in terms of anthrax toxin inhibition and cytotoxicity testing by in vitro and in vivo assays. CONCLUSION Such an attempt is an insight of biodefense drug design against the dreadful threat to the nation due to anthrax-based terrorism and biological warfare.
Methods and Current Trends in Determination of Neuraminidase Activity and Evaluation of Neuraminidase Inhibitors

Abstract This review focuses on the methods and current trends in determination of neuraminidases (NAs) activity and evaluation of neuraminidase inhibitors (NAIs) by means of biochemical assays. These methods can be used, in principle, for any type of sialidase, with regard to substrate specificity and optimal conditions for enzymatic reaction. Considering the range of organisms producing sialidases, this review omits cell-based assays (plaque assays and study of cytopathic effect) and animal model studies, which are reviewed elsewhere concerning specific organisms. The present review also provides the brief introductory survey of role of sialic acids and neuraminidases, but main focus is on the methods of determining neuraminidase activity and evaluating neuraminidase inhibitors. The future prospect of improvement in analytical techniques regarding the enzymatic activity of sialidases is briefly outlined.
Plasma Sulphur-Containing Amino Acids, Physical Exercise and Insulin Sensitivity in Overweight Dysglycemic and Normal Weight Normoglycemic Men

Plasma sulphur-containing amino acids and related metabolites are associated with insulin sensitivity, although the mechanisms are unclear. We examined the effect of exercise on this relationship. Dysglycemic (n = 13) and normoglycemic (n = 13) men underwent 45 min cycling before and after 12 weeks exercise intervention. We performed hyperinsulinemic euglycemic clamp, mRNA-sequencing of skeletal muscle and adipose tissue biopsies, and targeted profiling of plasma metabolites by LC-MS/MS. Insulin sensitivity increased similarly in dysglycemic and normoglycemic men after 12 weeks of exercise, in parallel to similar increases in concentration of plasma glutamine, and decreased concentrations of plasma glutamate, cysteine, taurine, and glutathione. Change in plasma concentrations of cysteine and glutathione exhibited the strongest correlations to exercise-improved insulin sensitivity, and expression of a cluster of genes essential for oxidative phosphorylation and fatty acid metabolism in both skeletal muscle and adipose tissue, as well as mitochondria-related genes such as mitofilin. Forty-five min of cycling decreased plasma concentrations of glutamine and methionine, and increased plasma concentrations of glutamate, homocysteine, cystathionine, cysteine, glutathione, and taurine. Similar acute responses were seen in both groups before and after the 12 weeks training period. Both acute and long-term exercise may influence transsulphuration and glutathione biosynthesis, linking exercise-improved insulin sensitivity to oxidative stress and mitochondrial function.
Cystatin C for predicting all-cause mortality and rehospitalization in patients with heart failure: a meta-analysis

Circulating cystatin C (cys-C/CYC) has been identified as an independent predictor of all-cause mortality in patients with coronary artery disease and the general population. This meta-analysis aimed to systematically evaluate the association between elevated cys-C level and all-cause mortality and rehospitalization risk amongst patients with heart failure (HF). PubMed and Embase databases were searched until December 2017. All prospective observational studies that reported a multivariate-adjusted risk estimate of all-cause mortality and/or rehospitalization for the highest compared with lowest cys-C level in HF patients were included. Ten prospective studies involving 3155 HF patients were included. Meta-analysis indicated that the highest compared with lowest cys-C level was associated with an increased risk of all-cause mortality (hazard ratio (HR): 2.33; 95% confidence intervals (CI): 1.67–3.27; I2 = 75.0%, P<0.001) and combination of mortality/rehospitalization (HR: 2.06; 95%CI: 1.58–2.69; I2 = 41.6%, P=0.181). Results of stratified analysis indicated that the all-cause mortality risk was consistently found in the follow-up duration, cys-C cut-off value or type of HF subgroup. Elevated cys-C level is possibly associated with an increased risk of all-cause mortality and rehospitalization in HF patients. This increased risk is probably independent of creatinine or estimated glomerular filtration rate (eGFR).
EduCan trial: study protocol for a randomised controlled trial on the effectiveness of pain neuroscience education after breast cancer surgery on pain, physical, emotional and work-related functioning

Introduction Over the past decades, awareness on the importance of educational interventions in cancer pain management has increased. However, education is often restricted to biomedical pain management instructions. A more modern educational approach, also known as pain neuroscience education (PNE), explains pain from a biopsychosocial perspective. We hypothesise that this more comprehensive educational approach in the early treatment phase of breast cancer will lead to more beneficial effects for cancer pain management. Therefore, the aim of the present study is to investigate the effectiveness of this PNE intervention, in addition to best evidence physical therapy modalities for treatment and prevention of pain, physical, emotional and work-related functioning after breast cancer surgery, compared with a traditional biomedical educational intervention. Methods A double-blinded randomised controlled trial has been started in November 2017 at the University Hospitals of Leuven. Immediately after breast cancer surgery, all participants (n=184) receive a 12-week intensive standard physical therapy programme. They receive three additional refresher sessions at 6, 8 and 12 months postsurgery. In addition, participants receive three educational sessions during the first-month postsurgery and three ‘booster sessions’ at 6, 8 and 12 months postsurgery. In the intervention group, the content of the education sessions is based on the modern PNE approach. Whereas in the control group, the education is based on the traditional biomedical approach. The primary outcome parameter is pain-related disability 1 year after surgery. Secondary outcomes related to other dimensions of pain, physical, emotional and work-related functioning at 1-week, 4, 6, 8, 12 and 18 months postsurgery. Ethics and dissemination The study will be conducted in accordance with the Declaration of Helsinki. This protocol has been approved by the ethical committee of the University Hospitals of Leuven. Results will be disseminated via peer-reviewed scientific journals and presentations at congresses. Trial registration number NCT03351075.
Characterizing and ranking computed metabolic engineering strategies

Abstract Motivation The computer-aided design of metabolic intervention strategies has become a key component of an integrated metabolic engineering approach and a broad range of methods and algorithms has been developed for this task. Many of these algorithms enforce coupling of growth with product synthesis and may return thousands of possible intervention strategies from which the most suitable strategy must then be selected Results This work focuses on how to evaluate and rank, in a meaningful way, a given pool of computed metabolic engineering strategies for growth-coupled product synthesis. Apart from straightforward criteria, such as a preferably small number of necessary interventions, a reasonable growth rate and a high product yield, we present several new criteria useful to pick the most suitable intervention strategy. Among others, we investigate the robustness of the intervention strategies by searching for metabolites that may disrupt growth coupling when accumulated or secreted and by checking whether the interventions interrupt pathways at their origin (preferable) or at downstream steps. We also assess thermodynamic properties of the pathway(s) favored by the intervention strategy. Furthermore, strategies that have a significant overlap with alternative solutions are ranked higher because they provide flexibility in implementation. We also introduce the notion of equivalence classes for grouping intervention strategies with identical solution spaces. Our ranking procedure involves in total ten criteria and we demonstrate its applicability by assessing knockout-based intervention strategies computed in a genome-scale model of E.coli for the growth-coupled synthesis of l-methionine and of the heterologous product 1,4-butanediol. Availability and implementation The MATLAB scripts that were used to characterize and rank the example intervention strategies are available at http://www2.mpi-magdeburg.mpg. de/projects/cna/etcdownloads.html. Supplementary information Supplementary data are available at Bioinformatics online.
PepQuery enables fast, accurate, and convenient proteomic validation of novel genomic alterations

Massively parallel or second-generation sequencing-based genomic studies continuously identify new genomic alterations that may lead to novel protein sequences, which are attractive candidates for disease biomarkers and therapeutic targets after proteomic validation. Integrative proteogenomic methods have been developed to use mass spectrometry (MS)-based proteomics data for such validation. These methods replace the reference sequence database in proteomic database searching with a customized protein database that incorporates sample- or disease-specific sequences derived from DNA or RNA sequencing, thus enabling the identification of novel protein sequences. Although useful, this spectrum-centric approach requires a full evaluation of all possible spectrum-peptide pairs, which is time-consuming, error-prone, and difficult to apply. Here, we present PepQuery, a peptide-centric approach that focuses on only novel DNA or protein sequences of interest. PepQuery allows quick and easy proteomic validation of genomic alterations without customized database construction. We demonstrated the sensitivity and specificity of the approach in validating completely novel proteins, novel splice junctions, and single amino acid variants using simulations and experimental data. Notably, enabling unrestricted modification searching in PepQuery reduced false positives by up to 95%. We implemented PepQuery as both web-based and stand-alone applications. The web version provides direct access to more than half a billion MS/MS spectra from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and other cancer proteomic studies. The stand-alone version supports batch analysis and user-provided MS/MS data. PepQuery will increase the usage of proteogenomics beyond the proteomics community and will broaden the application of proteogenomics in personalized medicine.
Revisiting Successful Aging With HIV Through a Revised Biopsychosocial Model: An Update of the Literature

Abstract The concept of successful aging was recognized only recently by HIV researchers because people living with HIV (PLWH) in the early epidemic were not expected to survive. With the introduction of antiretrovirals that block viral replication, PLWH are now aging with HIV. Given the complex nature of HIV within the social, economic, and political climates in which it occurs, a holistic model of successful aging is needed to guide researchers and clinicians. Several overarching models exist, but must be updated for rapidly advancing HIV and aging research agendas. We provide an updated, adapted, and integrated biopsychosocial model of successful aging with HIV based on the principles of Baltes and Baltes (1998) on 8 essential components of successful aging: (a) length of life, (b) biological health, (c) mental health, (d) cognitive efficiency, (e) social competence, (f) productivity, (g) personal control, and (h) life satisfaction. Clinical practice and research implications are highlighted.
Low use of long-lasting insecticidal nets for malaria prevention in south-central Ethiopia: A community-based cohort study

INTRODUCTION A decline in malaria morbidity and mortality has been documented in Ethiopia since 2005 following a scale-up of the distribution of long-lasting insecticidal nets (LLINs). However, universal access to LLINs ownership and use has not yet been achieved. This study aimed to determine ownership and use of LLINs over time in south-central Ethiopia. METHODS A cohort of 17,142 individuals residing in 3,006 households was followed-up from October 2014 to January 2017 (121 weeks). New PermaNet2.0 LLINs were given to households in October 2014. Once per week, the LLIN use status was documented for each individual. A survey was conducted after 110 weeks of LLIN distribution to determine LLIN ownership. A multilevel negative binomial regression model was fitted to identify significant predictors of LLIN use. RESULTS At baseline, the LLIN ownership was 100%. After 110 weeks only 233 (8%) of the households owned at least one LLIN. The median proportion of LLIN use per individuals during the study period was only 14%. During the first year (week 1-52) the average LLIN use per individuals was 36% and during the second year (week 53-104) it was 4.6%. More frequent LLIN use was reported among age group [5-14 years (adjusted IRR = 1.13, 95% CI 1.04-1.22), 15-24 years (adjusted IRR = 1.33, 95% CI 1.23-1.45), ≥25 years (adjusted IRR = 1.99, 95% CI 1.83-2.17)] compared to <5 years, and household head educational status [read and write (adjusted IRR = 1.17, 95% CI 1.09-1.26), primary (adjusted IRR = 1.20, 95% CI 1.12-1.27), secondary or above (adjusted IRR = 1.20, 95% CI (1.11-1.30)] compared to illiterate. Having a family size of over five persons (adjusted IRR = 0.78, 95% CI 0.73-0.84) was associated with less frequent use of LLINs compared to a family size of ≤5 persons. CONCLUSIONS The study showed a low LLIN ownership after 110 weeks and a low LLIN use during 121 weeks of follow-up, despite 100% LLIN coverage at baseline. The study highlights the need to design strategies to increase LLIN ownership and use for setting similar to those studied here.