Miracle-dz/UniFAR-FTUs huggingface dataset:
Isochorismate-based salicylic acid biosynthesis confers basal resistance to Fusarium graminearum in barley.

Salicylic acid (SA) plays an important role in signal transduction and disease resistance. In Arabidopsis, SA can be made by either of two biosynthetic branches, one involving isochorismate synthase (ICS) and the other involving phenylalanine ammonia-lyase (PAL). However, the biosynthetic pathway and the importance of SA remain largely unknown in Triticeae. Here, we cloned one ICS and seven PAL genes from barley, and studied their functions by their overexpression and suppression in that plant. Suppression of the ICS gene significantly delayed plant growth, whereas PAL genes, both overexpressed and suppressed, had no significant effect on plant growth. Similarly, suppression of ICS compromised plant resistance to Fusarium graminearum, whereas similar suppression of PAL genes had no significant effect. We then focused on transgenic plants with ICS. In a leaf-based test with F. graminearum, transgenic plants with an up-regulated ICS were comparable with wild-type control plants. By contrast, transgenic plants with a suppressed ICS lost the ability to accumulate SA during pathogen infection and were also more susceptible to Fusarium than the wild-type controls. This suggests that ICS plays a unique role in SA biosynthesis in barley, which, in turn, confers a basal resistance to F. graminearum by modulating the accumulation of H2 O2 , O2- and reactive oxygen-associated enzymatic activities. Although SA mediates systemic acquired resistance (SAR) in dicots, there was no comparable SAR response to F. graminearum in barley. This study expands our knowledge about SA biosynthesis in barley and proves that SA confers basal resistance to fungal pathogens.
Using recurrent neural network models for early detection of heart failure onset

Objective: We explored whether use of deep learning to model temporal relations among events in electronic health records (EHRs) would improve model performance in predicting initial diagnosis of heart failure (HF) compared to conventional methods that ignore temporality. Materials and Methods: Data were from a health system’s EHR on 3884 incident HF cases and 28 903 controls, identified as primary care patients, between May 16, 2000, and May 23, 2013. Recurrent neural network (RNN) models using gated recurrent units (GRUs) were adapted to detect relations among time-stamped events (eg, disease diagnosis, medication orders, procedure orders, etc.) with a 12- to 18-month observation window of cases and controls. Model performance metrics were compared to regularized logistic regression, neural network, support vector machine, and K-nearest neighbor classifier approaches. Results: Using a 12-month observation window, the area under the curve (AUC) for the RNN model was 0.777, compared to AUCs for logistic regression (0.747), multilayer perceptron (MLP) with 1 hidden layer (0.765), support vector machine (SVM) (0.743), and K-nearest neighbor (KNN) (0.730). When using an 18-month observation window, the AUC for the RNN model increased to 0.883 and was significantly higher than the 0.834 AUC for the best of the baseline methods (MLP). Conclusion: Deep learning models adapted to leverage temporal relations appear to improve performance of models for detection of incident heart failure with a short observation window of 12–18 months.
The effect of obstructive sleep apnea treatment on cardiovascular outcomes.

Obstructive sleep apnea (OSA) is widely prevalent [1]. Central sleep apnea (CSA) is another common form of sleep-disordered breathing, comorbid with heart failure. Both chronic conditions often require lifelong care and are associated with increased cardiovascular risk. A meta-analysis of prospective studies (n = 25,760) showed that OSA was associated with cardiovascular disease (CVD), coronary disease, stroke and mortality [2]. Those with OSA have increased sympathetic activity as demonstrated by microneurography and catecholamine levels, which is one mechanism linking OSA to CVD [3]. Positive airway pressure (PAP) is the treatment of choice for OSA of any severity, and can be administered as continuous (CPAP), bilevel (BPAP) or autotitrating (APAP) forms [4]. CPAP is indicated for treatment of moderate-to-severe OSA (American Academy of Sleep Medicine [AASM] standard level of recommendation, reflecting a high degree of clinical certainty) and mild OSA (option level of recommendation, reflecting a moderate degree of clinical certainty). BPAP or APAP can be considered for OSA management in CPAP intolerant patients. Alternative therapies can be offered in addition or if the patient is intolerant or declines CPAP. These include behavioral (i.e., weight loss, exercise, positional therapy, avoidance of sedatives), oral appliances, surgical procedures (i.e., uvulopalatopharyngoplasty) and adjunctive therapies (i.e., oxygen therapy and/or pharmacologic agents). Observational studies suggest that the use of CPAP is associated with lower cardiovascular adverse events and mortality [5], however, randomized trial evidence is lacking. Recent studies provide insight into the therapeutic efficacy of positive pressure therapy on cardiovascular outcomes, although findings are inconsistent and the benefit remains unproven [5–8]. The SAVE study randomly assigned 2717 adults with moderate to severe OSA and coronary or cerebrovascular disease to usual care with or without CPAP (mean follow-up: 3.7 years). CPAP significantly reduced snoring and daytime sleepiness. There was no significant difference between groups in individual or composite
Effect of mechanical strain on the pluripotency of murine embryonic stem cells seeded in a collagen‐I scaffold

The use of embryonic stem cells (ESC) in regenerative medicine is restricted due to the possibility of tumorigenicity after inefficient or incomplete differentiation. Studies from our group, and others, suggest that mechanical stimuli may have a suppressive effect on the pluripotency/tumorigenesis of murine ESC (mESC). Furthermore, we have demonstrated that mESC seeded in a type I collagen scaffold, and transplanted into a murine bone fracture model, demonstrated repair without tumor formation. However, it remains unknown if mechanical factors were involved in blocking tumorigenicity of the mESC. Therefore, the aims of the current study were: (i) to characterize the mechanical environment within the transplanted construct (mESC‐Col I) in an in vivo murine fracture model using computational analyses; and (ii) to reproduce this mechanical environment in vitro to elucidate the role of these mechanical factors on mESC pluripotent gene expression. It was predicted that the mESC‐Col I construct was subjected to an average octahedral shear strain of ∼3.8% and a compressive strain of ∼3.1% within the fracture in vivo when the murine tibia was subjected to an axial compression load of 4 N (1 Hz). When a similar strain environment was replicated experimentally in vitro, the expression patterns of marker genes for pluripotency (Oct 4, Sox 2, Nanog, Rex 1, and oncogene ERas) were significantly down‐regulated. This suggests that the local micro‐mechanical environment within the fracture site in vivo may be involved in regulating stem cell fate after transplantation, and that these physical factors should be considered when developing regenerative medicine strategies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:799–807, 2018.
IL-10 expression defines an immunosuppressive dendritic cell population induced by antitumor therapeutic vaccination

Vaccination induces immunostimulatory signals that are often accompanied by regulatory mechanisms such as IL-10, which control T-cell activation and inhibit vaccine-dependent antitumor therapeutic effect. Here we characterized IL-10-producing cells in different tumor models treated with therapeutic vaccines. Although several cell subsets produced IL-10 irrespective of treatment, an early vaccine-dependent induction of IL-10 was detected in dendritic cells (DC). IL-10 production defined a DC population characterized by a poorly mature phenotype, lower expression of T-cell stimulating molecules and upregulation of PD-L1. These IL-10+ DC showed impaired in vitro T-cell stimulatory capacity, which was rescued by incubation with IL-10R and PD-L1-inhibiting antibodies. In vivo IL-10 blockade during vaccination decreased the proportion of IL-10+ DC and improved their maturation, without modifying PD-L1 expression. Similarly, PD-L1 blockade did not affect IL- 10 expression. Interestingly, vaccination combined with simultaneous blockade of IL-10 and PD-L1 induced stronger immune responses, resulting in a higher therapeutic efficacy in tumor-bearing mice. These results show that vaccine-induced immunoregulatory IL- 10+ DC impair priming of antitumor immunity, suggesting that therapeutic vaccination protocols may benefit from combined targeting of inhibitory molecules expressed by this DC subset.
Temperature effect on the mechanical parameters of a clayey compacted soil

the elastic domain The objectives of this work were to improve the understanding and quantify the impact of temperature variation on soil bearing capacity. Calculation of the bearing capacity of foundations is based on the results of pressuremeter tests or penetrometer tests. Experimental methods have been developed to enable the conduction of these tests in the laboratory conditions. ABSTRACT: Energetic geostructures consist in establishing a thermal exchange with the ground directly through building foundations or structures. Adapting the whole or part of foundation piles into energy piles brings questions on the impact of the temperature variations on the geotechnical parameters of the sensitive soils (illite, smectite …). The estimation of bearing capacity of deep foundations is actually based on pressuremeter or penetrometer test results. In this study, these tests, adapted to the laboratory, were carried out on compacted materials submitted to different thermal variations. Firstly, a set of mini-penetration tests were performed at different temperature. The results showed that the measured parameters namely the cone resistance ( q c ) and the sleeve friction resistance ( f s ) are affected by temperature at low water contents. Secondly, mini-pressuremeter tests were conducted on an illitic soil compacted in a cylindrical container, submitted to 20 and 40 °C. An impact of the temperature variation on the limit pressure ( p l ) and the creep pressure ( p f ) was detected.
eHealth Literacy: Predictors in a Population With Moderate-to-High Cardiovascular Risk

Background Electronic health (eHealth) literacy is a growing area of research parallel to the ongoing development of eHealth interventions. There is, however, little and conflicting information regarding the factors that influence eHealth literacy, notably in chronic disease. We are similarly ill-informed about the relationship between eHealth and health literacy, 2 related yet distinct health-related literacies. Objective The aim of our study was to investigate the demographic, socioeconomic, technology use, and health literacy predictors of eHealth literacy in a population with moderate-to-high cardiovascular risk. Methods Demographic and socioeconomic data were collected from 453 participants of the CONNECT (Consumer Navigation of Electronic Cardiovascular Tools) study, which included age, gender, education, income, cardiovascular-related polypharmacy, private health care, main electronic device use, and time spent on the Internet. Participants also completed an eHealth Literacy Scale (eHEALS) and a Health Literacy Questionnaire (HLQ). Univariate analyses were performed to compare patient demographic and socioeconomic characteristics between the low (eHEALS<26) and high (eHEALS≥26) eHealth literacy groups. To then determine the predictors of low eHealth literacy, multiple-adjusted generalized estimating equation logistic regression model was used. This technique was also used to examine the correlation between eHealth literacy and health literacy for 4 predefined literacy themes: navigating resources, skills to use resources, usefulness for oneself, and critical evaluation. Results The univariate analysis showed that patients with lower eHealth literacy were older (68 years vs 66 years, P=.01), had lower level of education (P=.007), and spent less time on the Internet (P<.001). However, multiple-adjusted generalized estimating equation logistic regression model demonstrated that only the time spent on the Internet (P=.01) was associated with the level of eHealth literacy. Regarding the comparison between the eHEALS items and HLQ scales, a positive linear relationship was found for the themes “usefulness for oneself” (P=.049) and “critical evaluation” (P=.01). Conclusions This study shows the importance of evaluating patients’ familiarity with the Internet as reflected, in part, by the time spent on the Internet. It also shows the importance of specifically assessing eHealth literacy in conjunction with a health literacy assessment in order to assess patients’ navigational knowledge and skills using the Internet, specific to the use of eHealth applications.
Conceptualization of Relational Assurance Mechanisms - A Literature Review on Relational Assurance Mechanisms, Their Antecedents and Effects

Assurance mechanisms are an important element of relational governance and frequently used in information systems (IS) research; still missing in this field, however, is a coherent and interrelated structure to organize available knowledge. In this study, we provide a first step towards development of a conceptualization framework of relational assurance mechanisms to enable their further investigation. From our analysis of existing literature, we discover two gaps in assurance research: (1) a fragmentation of assurance research and (2) a lack of conceptual consensus on relational assurance mechanisms. We provide a theoretical framework consisting of a conceptualization of identified relational assurance mechanisms, their antecedents and effects as a means of advancing theory in this area. Several possibilities for future research are discussed.
Evolution and Spatiotemporal Dynamics of Enterovirus A71 Subgenogroups in Vietnam

Background Enterovirus A71 (EV-A71) is the major cause of severe hand, foot, and mouth disease and viral encephalitis in children across the Asia-Pacific region, including in Vietnam, which has experienced a high burden of disease in recent years. Multiple subgenogroups (C1, C4, C5, and B5) concurrently circulate in the region with a large variation in epidemic severity. The relative differences in their evolution and epidemiology were examined within Vietnam and globally. Methods A total of 752 VP1 gene sequences were analyzed (413 generated in this study combined with 339 obtained from GenBank), collected from patients in 36 provinces in Vietnam during 2003-2013, along with epidemiological metadata. Globally representative VP1 gene datasets of subgenogroups were used to coestimate time-resolved phylogenies and relative genetic diversity to infer virus origins and regional transmission network. Results Despite frequent virus migration between countries, the highest genetic diversity of individual subgenogroups was maintained independently for several years in specific Asian countries representing genogroup-specific sources of EV-A71 diversity. Conclusion This study highlights a persistent transmission network of EV-A71, with specific Asian countries seeding other countries in the region and beyond, emphasizing the need for improved EV-A71 surveillance and detailed genetic and antigenic characterization.
Oxidative stress in organophosphate poisoning: role of standard antidotal therapy

Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed. Current standardized therapy of OP intoxications comprises live‐saving administration of the anticholinergic drug atropine accompanied by oxime AChE reactivator and diazepam. The capability of these antidotes to ameliorate OP‐induced oxidative stress varies between both therapeutic groups and individual medications within the drug class. Regarding oxidative stress, atropine does not seem to have a significant effect on oxidative stress parameters in OP poisoning. In a case of AChE reactivators, pro‐oxidative and antioxidative properties could be found. It is assumed that the ability of oximes to trigger oxidative stress is rather associated with their chemical structure than reactivation efficacy. The data indicating the potency of diazepam in preventing OP‐induced oxidative stress are not available. Based on current knowledge on the mechanism of OP‐mediated oxidative stress, alternative approaches (including antioxidants or multifunctional drugs) in therapy of OP poisoning are under consideration.
Total Cerebral Small-Vessel Disease Score is Associated with Mortality during Follow-Up after Acute Ischemic Stroke

Background and Purpose The recently developed total cerebral small-vessel disease (CSVD) score might appropriately reflect the total burden or severity of CSVD. We investigated whether the total CSVD score is associated with long-term outcomes during follow-up in patients with acute ischemic stroke. Methods In total, 1,096 consecutive patients with acute ischemic stroke who underwent brain magnetic resonance imaging were enrolled. We calculated the total CSVD score for each patient after determining the burden of cerebral microbleeds (CMBs), high-grade white-matter hyperintensities (HWHs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs). We recorded the date and cause of death for all of the patients using data from the Korean National Statistical Office. We compared the long-term mortality rate with the total CSVD score using Cox proportional-hazards models. Results CMBs were found in 26.8% of the subjects (294/1,096), HWHs in 16.4% (180/1,096), HPVSs in 19.3% (211/1,096), and ALIs in 38.0% (416/1,096). After adjusting for age, sex, and variables that were significant at p<0.1 in the univariate analysis, the total CSVD score was independently associated with long-term death from all causes [hazard ratio (HR)=1.18 per point, 95% confidence interval (CI)=1.07–1.30], ischemic stroke (HR=1.20 per point, 95% CI=1.01–1.42), and hemorrhagic stroke (HR=2.05 per point, 95% CI=1.30–3.22), but not with fatal cardiovascular events (HR=1.17 per point, 95% CI=0.82–1.67). Conclusions The total CSVD score is a potential imaging biomarker for predicting mortality during follow-up in patients with acute ischemic stroke.
Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective

Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS) to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs), as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria. To interfere with QS, bacteria use quorum sensing inhibitors (QSIs) to block the action of AIs and quorum quenching (QQ) enzymes to degrade signaling molecules. Recent studies have shown that these strategies are promising routes to decrease bacterial pathogenicity and decrease biofilms, potentially enhancing bacterial susceptibility to antimicrobial agents including antibiotics and bacteriophages. The efficacy of QSIs and QQ enzymes has been demonstrated in various animal models and are now considered in the development of new medical devices against bacterial infections, including dressings, and catheters for enlarging the therapeutic arsenal against bacteria.
RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study

Background RAS mutations are currently sought for in tumor samples, which takes a median of almost 3 weeks in western European countries. This creates problems in clinical situations that require urgent treatment and for inclusion in therapeutic trials that need RAS status for randomization. Analysis of circulating tumor DNA might help to shorten the time required to determine RAS mutational status before anti-epidermal growth factor receptor antibody therapy for metastatic colorectal cancer. Here we compared plasma with tissue RAS analysis in a large prospective multicenter cohort. Patients and methods Plasma samples were collected prospectively from chemotherapy-naive patients and analyzed centrally by next-generation sequencing (NGS) with the colon lung cancer V2 Ampliseq panel and by methylation digital PCR (WIF1 and NPY genes). Tumoral RAS status was determined locally, in parallel, according to routine practice. For a minimal κ coefficient of 0.7, reflecting acceptable concordance (precision ± 0.07), with an estimated 5% of non-exploitable data, 425 subjects were necessary. Results From July 2015 to December 2016, 425 patients were enrolled. For the 412 patients with available paired plasma and tumor samples, the κ coefficient was 0.71 [95% confidence interval (CI), 0.64-0.77] and accuracy was 85.2% (95% CI, 81.4% to 88.5%). In the 329 patients with detectable ctDNA (at least one mutation or one methylated biomarker), the κ coefficient was 0.89 (95% CI, 0.84-0.94) and accuracy was 94.8% (95% CI, 91.9% to 97.0%). The absence of liver metastases was the main clinical factor associated with inconclusive circulating tumor DNA results [odds ratio = 0.11 (95% CI, 0.06-0.21)]. In patients with liver metastases, accuracy was 93.5% with NGS alone and 97% with NGS plus the methylated biomarkers. Conclusion This prospective trial demonstrates excellent concordance between RAS status in plasma and tumor tissue from patients with colorectal cancer and liver metastases, thus validating plasma testing for routine RAS mutation analysis in these patients. Clinical Trial registration Clinicaltrials.gov, NCT02502656.
Moisture sorption isotherms and isosteric heat determination in Chilean papaya (Vasconcellea pubescens)

The moisture sorption isotherms of Chilean papaya were determined at 5, 20, and 45 oC, over a relative humidity range of 10-95%. The GAB, BET, Oswin, Halsey, Henderson, Smith, Caurie and Iglesias-Chirife models were applied to the sorption experimental data. The goodness of fit of the mathematical models was statistically evaluated by means of the determination coefficient, mean relative percentage deviation, sum square error, root-mean-square error, and chi-square values. The GAB, Oswin and Halsey models were found to be the most suitable for the description of the sorption data. The sorption heats calculated using the Clausius-Clapeyron equation were 57.35 and 59.98 kJ·mol-1, for adsorption and desorption isotherms, respectively.