Miracle-dz/UniFAR-FTUs huggingface dataset:
Septoria tritici Blotch Development as Affected by Temperature, Duration of Leaf Wetness, Inoculum Concentration, and Host.

The effects of incubation temperature, leaf-wetness duration, inoculum concentration, and interaction between leaf-wetness duration and inoculum concentration on the development of Septoria tritici blotch were evaluated at the seedling stage in two bread wheats (Katepwa and 6 Lacos-78) and two durum wheats (AC Melita and Kyle). The study was conducted to assess if bread and durum cultivars widely grown in Manitoba and a resistant cultivar from South America react differently to the disease at temperatures characteristic of Manitoba summers, and to obtain information on conditions that would be used in differentiating resistant and susceptible cultivars under controlled conditions. The experiments were carried out under three temperature regimes. Factors that evaluated included inoculum concentration and duration of leaf wetness. Increasing incubation temperature, duration of leaf wetness, and inoculum concentration resulted in an increase in disease severity. There were significant (P < 0.05) differences for duration of leaf wetness and inoculum concentration within each cultivar. Pycnidia were observed 4 days earlier when incubation temperature increased from 18°C day/15°C night to 22°C day/15°C night or when inoculum concentration increased from 1 × 106 spores/ml to 1 × 107 spores/ml. There were more pycnidia when duration of leaf wetness was 72 h as opposed to 48 h and 60 h. The cultivar that was presumed to be resistant maintained its resistance under environmental conditions that are characteristic of Manitoba summers. We found that the optimal conditions for screening spring wheats for Septoria tritici blotch reaction were incubation temperatures of 18°C day/15°C night, and 22°C day/15°C night. Leaf wetness duration of 48 or 72 h and inoculum concentration of 1 × 107 spores/ml consistently produced a susceptible reaction on Katepwa, AC Melita, and Kyle the three cultivars that were susceptible to Septoria tritici blotch.
Baicalein inhibits matrix metalloproteinase 1 expression via activation of TRPV1‐Ca‐ERK pathway in ultraviolet B–irradiated human dermal fibroblasts

Increased matrix metalloproteinase 1 (MMP‐1) expression is a feature of photo‐aged skin. We investigated the effects of baicalein and sulphoraphane on ultraviolet B (UVB) irradiation–induced MMP‐1 expression and apoptosis using human dermal fibroblasts. UVB irradiation not only increased MMP‐1 expression, but also caused apoptosis. Both baicalein and sulphoraphane protected cells from UVB irradiation–induced apoptosis, but only baicalein inhibited MMP‐1 expression. UVB irradiation activated 12‐lipoxygenase, and its product, 12‐hydroxyeicosatetraenoic acid, activated TRPV1 channels. The resulting UVB irradiation–induced Ca2+ increase was blocked by the 12‐lipoxygenase inhibitor baicalein and the TRPV1 blocker capsazepine, but not by the Nrf2 inducer sulphoraphane. UVB irradiation also increased ROS generation and decreased Nrf2 protein levels. UVB irradiation–induced MMP‐1 expression was blocked by the Ca2+ chelator BAPTA, by capsazepine and by TRPV1 silencing. However, induction was unaffected by the antioxidant N‐acetylcysteine. ERK phosphorylation and JNK phosphorylation were induced by UVB irradiation, but only ERK phosphorylation was Ca2+ sensitive. Increased MMP‐1 expression was blocked by PD98059, but not by SP600125. Thus, increased MMP‐1 expression is mediated by increased cytosolic Ca2+ and ERK phosphorylation. UVB irradiation–induced ROS generation is also Ca2+ sensitive, and UVB irradiation–induced apoptosis is caused by increased ROS. Thus, baicalein, by blocking the UVB irradiation–induced cytosolic Ca2+ increase, protects cells from UVB irradiation–induced MMP‐1 expression and apoptosis. In contrast, sulphoraphane, by decreasing cellular ROS, protects cells from only UVB‐induced apoptosis. Thus, targeting 12‐lipoxygenase may provide a therapeutic approach to improving the health of photo‐aged human skin.
Differential Modulation of Word Recognition by Semantic and Spatial Orienting of Attention

In the present study, we investigated the ability to orient attention to abstract associative features of complex stimuli, more specifically, to the semantic categories of visual word stimuli. We compared the behavioral and electrophysiological effects of semantic orienting with those elicited by spatial orienting to word stimuli. Two parallel, cued lexical-decision tasks, with semantic- or spatial-orienting cues, were used. Results showed that both semantic and spatial orienting facilitated behavioral performance. The event-related potential analysis revealed different and non-overlapping patterns of modulation of word processing by semantic and spatial orienting. Modulation by semantic orienting started later, affecting only the potentials linked to conceptual or semantic processing (N300 and N400). The pattern of N300/N400 modulation in the semantic-orienting condition was similar to that observed in semantic-priming tasks, and was compatible with the operation of controlled semantic processes. Spatial orienting significantly enhanced the amplitude of the early visual potential P1 as well as the language-related N400 potential. These findings showed that the similar end-result of behavioral facilitation by semantic and spatial orienting is achieved through largely distinct mechanisms acting upon separate levels of stimulus analysis.
FGF2 induces breast cancer growth through ligand‐independent activation and recruitment of ERα and PRBΔ4 isoform to MYC regulatory sequences

Progression to hormone‐independent growth leading to endocrine therapy resistance occurs in a high proportion of patients with estrogen receptor alpha (ERα) and progesterone receptors (PR) positive breast cancer. We and others have previously shown that estrogen‐ and progestin‐induced tumor growth requires ERα and PR interaction at their target genes. Here, we show that fibroblast growth factor 2 (FGF2)‐induces cell proliferation and tumor growth through hormone‐independent ERα and PR activation and their interaction at the MYC enhancer and proximal promoter. MYC inhibitors, antiestrogens or antiprogestins reverted FGF2‐induced effects. LC–MS/MS identified 700 canonical proteins recruited to MYC regulatory sequences after FGF2 stimulation, 397 of which required active ERα (ERα‐dependent). We identified ERα‐dependent proteins regulating transcription that, after FGF2 treatment, were recruited to the enhancer as well as proteins involved in transcription initiation that were recruited to the proximal promoter. Also, among the ERα‐dependent and independent proteins detected at both sites, PR isoforms A and B as well as the novel protein product PRBΔ4 were found. PRBΔ4 lacks the hormone‐binding domain and was able to induce reporter gene expression from estrogen‐regulated elements and to increase cell proliferation when cells were stimulated with FGF2 but not by progestins. Analysis of the Cancer Genome Atlas data set revealed that PRBΔ4 expression is associated with worse overall survival in luminal breast cancer patients. This discovery provides a new mechanism by which growth factor signaling can engage nonclassical hormone receptor isoforms such as PRBΔ4, which interacts with growth‐factor activated ERα and PR to stimulate MYC gene expression and hence progression to endocrine resistance.
Randomised controlled trial of a Calcium Channel or Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker Regime to Reduce Blood Pressure Variability following Ischaemic Stroke (CAARBS): a protocol for a feasibility study

Introduction Raised blood pressure (BP) is common after stroke and is associated with a poor prognosis, yet trials of BP lowering in the immediate poststroke period have not demonstrated a benefit. One possible explanation for this may be that BP variability (BPV) rather than absolute levels predicts outcome, as BPV is increased after stroke and is associated with poor outcomes. Furthermore, there is evidence of distinct antihypertensive class effects on BPV despite similar BP-lowering effects. However, whether BPV in the immediate poststroke period is a therapeutic target has not been prospectively investigated. The objectives of this trial are to assess the feasibility and safety of recruiting patients following an acute ischaemic stroke or transient ischaemic attack (TIA) to an interventional randomised controlled trial comparing the effects of two different antihypertensive drug classes on BPV. Secondary exploratory objectives are to assess if different therapeutic strategies have diverse effects on levels of BPV and if this has an impact on outcomes. Methods 150 adult patients with first-ever ischaemic stroke or TIA who require antihypertensive therapy for secondary prevention will be recruited within 7 days of the event from stroke services across three sites. After baseline assessments they will be randomly assigned to treatment with a calcium channel blocker or ACE inhibitor/angiotensin receptor blocker-based regimen and followed up for a period of three months. Ethics and dissemination Ethical and regulatory approvals have been granted. Dissemination is planned via publication in peer-reviewed medical journals and presentation at relevant conferences. Trial registration number ISRCTN10853487.
Replacement of miR-155 Elicits Tumor Suppressive Activity and Antagonizes Bortezomib Resistance in Multiple Myeloma

Aberrant expression of microRNAs (miRNAs) has been associated to the pathogenesis of multiple myeloma (MM). While miR-155 is considered a therapeutic target in several malignancies, its role in MM is still unclear. The analysis of miR-155 expression indicates its down-regulation in MM patient-derived as compared to healthy plasma cells, thus pointing to a tumor suppressor role in this malignancy. On this finding, we investigated miR-155 replacement as a potential anti-tumor strategy in MM. The miR-155 enforced expression triggered anti-proliferative and pro-apoptotic effects in vitro. Given the lower miR-155 levels in bortezomib-resistant as compared to sensitive MM cells, we analyzed the possible involvement of miR-155 in bortezomib resistance. Importantly, miR-155 replacement enhanced bortezomib anti-tumor activity both in vitro and in vivo in a xenograft model of human MM. In primary MM cells, we observed an inverse correlation between miR-155 and the mRNA encoding the proteasome subunit gene PSMβ5, whose dysregulation has been largely implicated in bortezomib resistance, and we validated PSMβ5 3′UTR mRNA targeting, along with reduced proteasome activity, by miR-155. Collectively, our findings demonstrate that miR-155 elicits anti-MM activity, likely via proteasome inhibition, providing the framework for miR-155-based anti-MM therapeutic strategies.
Relationship Between Vitamin D Level and Bechcet's Disease Activity: A Systematic Review and Meta-Analysis.

AIM In the present study, the evidence about the association between vitamin D deficiency and Behcet's disease activity was systematically reviewed and meta-analyzed. METHOD We searched the English and Persian databases of Medline (Ovid), CINHAL, Scopus, Proquest, the Cochrane library and SID, IranDoc, Magiran, Iran Medex for articles published up until May 2018 with the keywords were related to serum vitamin D and active and inactive Behcet's disease in adults. Meta-analysis was done using the CMA software. RESULTS A total of 138 titles were retrieved and reduced to 80 titles after deletion of duplicates and finally after close assessing of titles and abstracts eight eligible studies including a total of 939 participants were identified for systematic review and meta-analysis. According to the results of the meta-analysis, the pooled effect size of the differences in the serum level of vitamin D in patients with inactive Behçet's Disease and healthy controls was [OR:-0.05; 95% CI:-2.05, 1.94; p = 0.95]. The serum vitamin D level was significantly lower in active patients compared with healthy controls [OR:1.21; 95%CI: -0.12, 2.31; p = 0.03]. The pooled effect size of the differences in the serum level of vitamin D in active and inactive Behçet's Disease was [OR:-0.71; 95%CI: -1.41, -0.007; p = 0.04] Conclusion: There is an association between vitamin D deficiency and active Behçet's Disease. Future studies investigating the association of vitamin D deficiency and Behçet's Disease needs to involve following information: dietary intake of calcium and vitamin D, measuring of sun exposure, report of drug consumption and physical activity level.
Increased dose of carbidopa with levodopa and entacapone improves “off” time in a randomized trial

Objective To investigate whether increased fixed carbidopa doses of 65 or 105 mg (ODM-101/65 and ODM-101/105) in combination with 75, 100, 125, or 150 mg of levodopa and 200 mg of entacapone might improve “off” time in fluctuating Parkinson disease (PD) compared to the standard combination of 4:1 levodopa/carbidopa with the usual 200 mg of entacapone (LCE) during a 4-week treatment period. Methods This was a randomized, double-blind, double-dummy, active-controlled, crossover, multicenter, phase II, proof-of-concept study in patients with fluctuating PD. Results One hundred seventeen patients were randomized into the study (mean age 67.0 years; daily “off” time 5.3 hours; mean daily levodopa dose 610 mg). Carryover-adjusted mean changes from baseline “off” times were during ODM-101/65, −1.53 hours (p = 0.02 vs LCE), during ODM-101/105, −1.57 hours (p = 0.01 vs LCE), and during LCE −0.91 hours. Changes in daily “on” time without dyskinesia were 1.54 hours (p = 0.005 vs LCE), 1.38 hours (p = 0.0214 vs LCE), and 0.69 hours, respectively. Changes in “on” time with troublesome dyskinesia were <0.1 hours and not significantly different between treatments. In patients with high-activity COMT genotypes Val/Met or Val/Val, “off” time was reduced more with ODM-101/65 and ODM-101/105 than with LCE (p = 0.015 and p = 0.006). No difference between the treatments was seen in safety and tolerability. The most common treatment-related adverse effects were nausea, dizziness, drug-effect decrease, and dyskinesia, which were in most cases mild or moderate in severity. Treatment-related serious adverse events were diarrhea (ODM-101/105 and LCE), and myocardial ischemia and blood creatine kinase increase (LCE). Conclusion Increasing the dose of carbidopa in combination with levodopa and entacapone should be considered in the treatment of fluctuating PD to improve daily “off” times. Genotyping patients with PD according to COMT activity may improve individual treatment strategies. ClinicalTrials.gov identifier NCT01766258. Classification of evidence This study provides Class II evidence that an increased dose of carbidopa improves motor fluctuations when administered with levodopa and entacapone.
Significance of Medication History at the Time of Entry into the COPDGene Study: Relationship with Exacerbation and CT Metrics

Abstract Background: Despite the importance of respiratory medication use in COPD, relatively little is known about which clinical phenotypes were associated with respiratory medications. Methods: To determine the association between respiratory medication use and exacerbations or quantitative CT metrics, we analyzed medication history from 4,484 COPD subjects enrolled in the COPDGene Study. Results: 2,941 (65.6%) subjects were receiving one or more respiratory medications; this group experienced more frequent exacerbations in the year before study entry and had increased gas trapping, emphysema, and subsegmental airway wall area, compared to the patients who were on no respiratory medication. In subgroup analysis, subjects who were on triple therapy (long-acting beta2-agonist [LABA], long-acting muscarinic antagonist [LAMA], and inhaled corticosteroids [ICS]) had the highest frequencies of exacerbations and severe exacerbations and tended to have increased quantitative measures of emphysema and gas trapping on CT compared to other five groups. After adjustment for confounding variables, the triple therapy group experienced more exacerbations and severe exacerbations compared with other five groups. In addition, the LABA+LAMA+ICS group was more likely to have emphysema and gas trapping on CT than other groups in multivariable logistic analysis. Interestingly, the total number of respiratory medications was significantly associated with not only the frequency of exacerbations but also gas trapping and airway wall thickness as assessed by CT scan in multivariable analysis. Conclusions: These results suggest that the use of respiratory medications, especially the number of medications, may identify a more severe phenotype of COPD that is highly susceptible to COPD exacerbations.
Effect of Rheumatologist Education on Systematic Measurements and Treatment Decisions in Rheumatoid Arthritis: The Metrix Study

Objective. To determine whether an educational intervention could result in changes in physicians’ practice behavior. Methods. Twenty rheumatologists performed a prospective chart audit of 50 consecutive patients with rheumatoid arthritis (RA) and again after 6 months. Ten were randomized to the educational intervention: monthly Web-based conferences on the value of systematic assessments in RA, recent evidence-based information, practice efficiency, and other topics; this group also read articles on targeting care in RA. The others were randomized to no intervention. Results. One thousand serial RA charts were audited at baseline and 1000 at 6 months, with no between-group differences in patient characteristics: mean disease duration of 10 years; 77% women; 74% rheumatoid factor– positive; mean Disease Activity Score (DAS) 3.7; and 68% taking methotrexate, 14% taking steroids, and 27% taking biologics. At 6 months the intervention group collected more global assessments (patient global 53% preintervention vs 66% postintervention, and MD global 51% vs 60%; p < 0.05) and Health Assessment Questionnaires (37% vs 42%; p > 0.05; p = nonsignificant), whereas controls had no change in outcomes collected. For the intervention group there was a 32% increase in calculable composite scores [such as DAS, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index; p < 0.05] but no change in the controls. There was more targeting to a low disease state. For those with SDAI between 3.3 and 11, the percentage of patients receiving a change in therapy was 66% in the intervention group and 36% in controls (p < 0.05). When DAS was between 2.4 and 3.6, 57% of the intervention group and 38% of controls made changes to treatment (p < 0.05). Conclusion. Small-group learning with feedback from practice audits is an inexpensive way to improve outcomes in RA.
Immunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes

Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1 axis, have altered the management of non–small cell lung cancer (NSCLC) over the last 10 years. First demonstrated to improve outcomes in second-line or later therapy of advanced disease, ICIs were shown to improve overall survival compared with chemotherapy in first-line therapy for patients whose tumors express PD-L1 on at least 50% of cells. More recently, combining ICIs with chemotherapy has been shown to improve survival in patients with both squamous and nonsquamous NSCLC, regardless of PD-L1 expression. However, PD-L1 and, more recently, tumor mutational burden have not proven to be straightforward indicative biomarkers. We describe the advances to date in utilizing these biomarkers, as well as novel markers of tumor inflammation, to ascertain which patients are most likely to benefit from ICIs. Ongoing translational work promises to improve the proportion of patients who benefit from these agents.
Developing Prediction Models for 30-Day Unplanned Readmission Among Children With Medical Complexity.

OBJECTIVES To target interventions to prevent readmission, we sought to develop clinical prediction models for 30-day readmission among children with complex chronic conditions (CCCs). METHODS After extracting sociodemographic and clinical characteristics from electronic health records for children with CCCs admitted to an academic medical center, we constructed a multivariable logistic regression model to predict readmission from characteristics obtainable at admission and then a second model adding hospitalization and discharge variables to the first model. We assessed model performance using c-statistic and calibration curves and internal validation using bootstrapping. We then created readmission risk scoring systems from final model β-coefficients. RESULTS Of the 2296 index admissions involving children with CCCs, 188 (8.2%) had unplanned 30-day readmissions. The model with admission characteristics included previous admissions, previous emergency department visits, number of CCC categories, and medical versus surgical admission (c-statistic 0.65). The model with hospitalization and discharge factors added discharge disposition, length of stay, and weekday discharge to the admission variables (c-statistic 0.67). Bootstrap samples had similar c-statistics, and slopes did not suggest significant overfitting for either model. Readmission risk was 3.6% to 4.9% in the lowest risk quartile versus 15.9% to 17.6% in the highest risk quartile (or 3.6-4.5 times higher) for both models. CONCLUSIONS Clinical variables related to the degree of medical complexity and illness severity can stratify children with CCCs into groups with clinically meaningful differences in the risk of readmission. Future research will explore whether these models can be used to target interventions and resources aimed at decreasing readmissions.
Repeated evolution of a morphological novelty: a phylogenetic analysis of the inflated fruiting calyx in the Physalideae tribe (Solanaceae)

PREMISE OF THE STUDY The evolution of novel fruit morphologies has been integral to the success of angiosperms. The inflated fruiting calyx, in which the balloon-like calyx swells to completely surround the fruit, has evolved repeatedly across angiosperms and is postulated to aid in protection and dispersal. Here we investigate the evolution of this trait in the tomatillos and their allies (Physalideae, Solanaceae), using a newly estimated phylogeny and a suite of comparative methods to infer evolutionary gains and losses. METHODS The Physalideae phylogeny was estimated using DNA sequences from four regions (ITS, LEAFY, trnL-F, waxy) using maximum likelihood and Bayesian Inference. Maximum likelihood model selection was used to determine the best fitting model of trait evolution. Using this model, we estimated ancestral states along with the numbers of gains and losses of fruiting calyx accrescence and inflation with Bayesian stochastic mapping. Also, phylogenetic signal in calyx morphology was examined with two metrics (parsimony score and Fritz and Purvis’ D). KEY RESULTS The well resolved phylogeny points to multiple taxa in need of revision, including the eight genera that are non-monophyletic as presently circumscribed. Model fitting indicated that calyx evolution has proceeded in stepwise fashion, from non-accrescent, to accrescent, to inflated. Moreover, these transitions appear to be largely irreversible. Among the 215 sampled Physalideae, we inferred 24 gains of fruiting calyx accrescence, 24 subsequent transitions to a fully inflated calyx and only two reversals. A median of 50 shifts were estimated in total across the clade from the ancestral non-accrescent calyx. Nonetheless, fruiting calyx accrescence and inflation show strong phylogenetic signal. CONCLUSIONS Our phylogeny greatly improves the resolution of Physalideae and highlights the need for taxonomic work. The analyses of trait evolution reveal that the inflated fruiting calyx has evolved many times and that the trajectory towards this phenotype is generally stepwise and directional. These results provide a strong foundation for studying the genetic and developmental mechanisms responsible for the repeated origins of this charismatic fruit trait.