Miracle-dz/UniFAR-FTUs huggingface dataset:
Extending the time window for intravenous thrombolysis in acute ischemic stroke using magnetic resonance imaging-based patient selection

Background Intravenous thrombolysis with alteplase within a time window up to 4.5 h is the only approved pharmacological treatment for acute ischemic stroke. We studied whether acute ischemic stroke patients with penumbral tissue identified on magnetic resonance imaging 4.5–9 h after symptom onset benefit from intravenous thrombolysis compared to placebo. Methods Acute ischemic stroke patients with salvageable brain tissue identified on a magnetic resonance imaging were randomly assigned to receive standard dose alteplase or placebo. The primary end point was disability at 90 days assessed by the modified Rankin scale, which has a range of 0–6 (with 0 indicating no symptoms at all and 6 indicating death). Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results The trial was stopped early for slow recruitment after the enrollment of 119 (61 alteplase, 58 placebo) of 264 patients planned. Median time to intravenous thrombolysis was 7 h 42 min. The primary endpoint showed no significant difference in the modified Rankin scale distribution at day 90 (odds ratio alteplase versus placebo, 1.20; 95% CI, 0.63–2.27, P = 0.58). One symptomatic intracranial hemorrhage occurred in the alteplase group. Mortality at 90 days did not differ significantly between the two groups (11.5 and 6.8%, respectively; P = 0.53). Conclusions Intravenous alteplase administered between 4.5 and 9 h after the onset of symptoms in patients with salvageable tissue did not result in a significant benefit over placebo. (Supported by Boehringer Ingelheim, Germany; ISRCTN 71616222).
Targeting p53-MDM2 interaction using small molecule inhibitors and the challenges needed to be addressed.

MDM2 protein is the core negative regulator of p53 that maintains the cellular levels of p53 at a low level in normal cells. Mutation of the TP53 gene accounts for 50% of all human cancers. In the remaining malignancies with wild-type TP53, p53 function is inhibited through other mechanisms. Recently, synthetic small molecule inhibitors have been developed which target a small hydrophobic pocket on MDM2 to which p53 normally binds. Given that MDM2-p53 antagonists have been undergoing clinical trials for different types of cancer, this review illustrates different aspects of these new cancer targeted therapeutic agents with the focus on the major advances in the field. It emphases on the p53 function, regulation of p53, targeting the p53-MDM2 interaction for cancer therapy, p53-dependent and -independent effects of inhibition of p53-MDM2 interaction. Then, representatives of small molecule MDM2-p53 binding antagonists are introduced with focus on those entered into clinical trials. Furthermore, the review discusses the gene signatures in order to predict sensitivity to MDM2 antagonists, potential side effects and the reasons for the observed hematotoxicity, mechanisms of resistance to these drugs, their evaluation as monotherapy or in combination with conventional chemotherapy or with other targeted therapeutic agents. Finally, it highlights the certainly intriguing questions and challenges which would be addressed in future studies.
Influence of Manuring on Growth and Yield of Tomato Varieties in Akure, a Rain Forest Zone of South West Nigeria

Tomato a highly nutritious and income relevance crop. The optimum productivity is constrained by a number of factors such as soil fertility management. A field experiment was conducted at Teaching and Research Farm, Federal University of Technology, Akure, Nigeria between December 2012 to April 2013 (irrigated) and March – August 2013 (rainfed) to investigate the effect manuring on the growth and yield of tomato varieties. Four manuring sources (Organic, Organo-mineral, Urea and No fertilizer) and four tomato varieties (Beske, Ibadan local, Roma and UC) laid out as a randomized complete block design in a factorial arrangement and replicated three times. Results showed that manuring influenced on set of flowering in tomato, organic fertilizer prolonged day to anthesis (22.72 day) closely followed by organomineral (22.49 days) while control (no fertilizer) was earliest (20.88 days). Beske significantly showed earliness to flowering, Ibadan local and Roma were delayed but had similar flowering dates (P≤ 0.05). The varieties had distinct fruit yield responses to fertilizer application, fruit produced were in order of Beske, Ibadan local and UC (721.9;626.4) g;(683.6; 696.2) g; (550.0; 463.6) g (384.4; 431.5) g for rainfed and irrigation respectively. Varietal effect was significant on fruit yields for irrigated, Beske recorded heaviest fruit yield (6.03g) followed by Ibadan local (4.72), Roma (2.6) and UC (2.14). Harvested fruit among the varieties in both seasons were (3978.5t/ha;3484.9t/ha;1229.8t/ha and 985.2 t/ha) and (3947.2t/ha; 3452.8t/ha; 1197.8t/ha; 953.2t/ha) for Beske, Ibadan local, Roma and UC respectively. Fertilizer application were significant for both season on harvested fruits weight in magnitude order of Organomineral, organic fertilizer urea and control (3535.9;3503.9t/ha),organic fertilizer (2935.2;2903.2t/ha), Urea (2078.8;2047.4t/ha) and control (1128.0;1096.5t/ha). Beske and Ibadan local varieties performed better in the rainforest zone of Nigeria. Organic fertilizer sources complimented with mineral fertilizer timely applied with good agronomic managements are measures to enhance growth and yield performance of tomato.
Proportions of interferon-γ-producing ascites lymphocytes in response to mycobacterial antigens: A help for early diagnosis of peritoneal tuberculosis in a low TB incidence country

Background Peritoneal tuberculosis (TB) remains difficult to diagnose because of its non-specific clinical features and the lack of efficient microbiological tests. As delayed diagnosis is associated with high mortality rates, new diagnostic tools are needed. Methods and findings We investigated for 24 patients prospectively enrolled with a possible diagnosis of peritoneal TB, the diagnostic value of the analysis of IFN-γ production by peritoneal fluid lymphocytes in response to a short in vitro stimulation with mycobacterial antigens. The patients were classified in two groups: non-TB and confirmed or highly probable TB. Diagnosis of TB was based on microbiological and histopathological criteria and/or a favorable response to anti-TB treatment. The IFN-γ production by peritoneal CD4+ T lymphocytes was analyzed by flow cytometry after an overnight in vitro stimulation with three different mycobacterial antigens, purified protein derivative (PPD), heparin-binding haemagglutinin (HBHA) or early-secreted-antigen-target-6 (ESAT-6). The percentages of PPD-, HBHA- or ESAT-6-induced IFN-γ-producing peritoneal fluid CD4+ T lymphocytes were higher in the TB group than in the non-TB group (p = 0.0007, p = 0.0004, and p = 0.0002 respectively). Based on cut-off values determined by ROC curve analysis of the results from TB and highly probable TB compared to those of non-TB patients, the sensitivity of these three tests was 100% with a specificity of 92%. Conclusions The analysis of mycobacterial-induced IFN-γ production by peritoneal lymphocytes is a promising tool to reliably and rapidly diagnose peritoneal TB. Further studies should be performed on larger cohorts of patients in high-TB-incidence countries to confirm the clinical value of this new diagnostic approach for peritoneal TB.
Least square support vectors machines approach to diagnosis of stator winding short circuit fault in induction motor

Various approaches have been proposed to monitor the state of machines by intelligent techniques such as the neural network, fuzzy logic, neuro-fuzzy, pattern recognition. However, the use of LS-SVM. This article presents an automatic computerized system for the diagnosis and the monitoring of faults between turns of the stator in IM applying the LS-SVM least square support vector machine. in this study for the detection of short circuit faults in the stator winding of the induction motor. Since it requires a mathematical model suitable for modelling defects, a defective IM model is presented. The proposed method uses the stator current as input and at the output decides the state of the motor, indicating the severity of the short-circuit fault.
A clinical audit of the growth of preterm infants fed predominantly pasteurised donor human milk v. those fed mother’s own milk in the neonatal intensive care unit

Abstract Preterm infants whose mothers are unable to produce sufficient breast milk are increasingly being supplemented with pasteurised donor human milk (PDHM) instead of commercial preterm infant formula. Concerns have been raised that this practice can result in reduced growth. This retrospective clinical audit collected data from the medical records of a cohort of preterm infants (≤30 weeks gestational age) receiving either ≥28 d of PDHM (n 53) or ≥28 d of their mother’s own milk (MOM, n 43) with standard fortification supplied to both groups during admission. Weight growth velocity was assessed from regained birth weight to 34+1 weeks’ postmenstrual age (PMA); and weight, length and head circumference were compared at discharge and 12 months (corrected age). At 34+1 weeks’ PMA, the weight growth velocity (g/kg per d) was significantly lower in the PDHM group (15·4 g/kg per d, 95 % CI 14·6, 16·1) compared with the MOM group (16·9 g/kg per d, 95 % CI 16·1, 17·7, P=0·007). However, the increase was still within clinically acceptable limits (>15 g/kg per d) and no significant difference was observed in the weight between the two groups. There was no significant difference in weight between the groups at discharge or at the 12-month corrected gestational age review. Although we demonstrated a significant reduction in the weight growth velocity of preterm infants receiving PDHM at 34 weeks’ PMA, this difference is not present at discharge, suggesting that the growth deficit is reduced by supplementation before discharge.
Could canine visceral leishmaniosis take hold in the UK?

Canine visceral leishmaniosis (CVL) is a life-threatening outcome of infection with Leishmania infantum , a protozoan parasite that is found throughout the Mediterranean basin, the Middle East, Latin America and some parts of Asia.1 Reviews of veterinary records have indicated a CVL prevalence of between 0.007 and 0.04 per cent in the UK. The majority of cases have been reported in southern England, with all affected dogs having spent at least several months in endemic countries such as Spain.2,3 Leishmania is typically transmitted during the blood meal of infected sand flies. However, sand flies are not found in the UK. In the absence of sand flies, alternative routes of transmission such as vertical, venereal and receipt of infected blood transfusions have been demonstrated (Fig 1). 4-7 Additionally, it has been speculated that direct dog-to-dog transmission through bites or wounds was the likely mode of transmission in isolated CVL cases in Finland, Germany and New Caledonia in the south-west Pacific.5,8,9 Fig 1: Transmission modes that could support the introduction and propagation of Leishmania infantum infection in the UK dog population. It includes subclinically infected dogs that would not be identified by current travel history or blood donation standards. CVL Canine visceral leishmaniosis #### What you need to know
Comparative efficacy and safety of surgical and invasive treatments for adults with degenerative lumbar spinal stenosis: protocol for a network meta-analysis and systematic review

Introduction Surgical and invasive procedures are widely used in adults with degenerative lumbar spinal stenosis when conservative treatments fail. However, little is known about the comparative efficacy and safety of these interventions. To address this, we will perform a network meta-analysis (NMA) and systematic review to compare the efficacy and safety of surgical and invasive procedures for adults with degenerative lumbar spinal stenosis. Methods and analysis We will include randomised controlled trials assessing surgical and invasive treatments for adults with degenerative lumbar spinal stenosis. We will search AMED, CINAHL, EMBASE, the Cochrane Library and MEDLINE. Only English studies will be included and no restriction will be set for publication status. For efficacy, our primary outcome will be physical function. Secondary outcomes will include pain intensity, health-related quality of life, global impression of recovery, work absenteeism and mobility. For safety, our primary outcome will be all-cause mortality. Secondary outcomes will include adverse events (number of events or number of people with an event) and treatment withdrawal due to adverse effect. Two reviewers will independently select studies, extract data and assess the risk of bias (Revised Cochrane risk-of-bias tool for randomized trials) of included studies. The quality of the evidence will be evaluated through the Grading of Recommendations Assessment, Development and Evaluation framework. Random-effects NMA will be performed to combine all the evidence under the frequentist framework and the ranking results will be presented through the surface under the cumulative ranking curve and mean rank. All analyses will be performed in Stata and R. Ethics and dissemination No ethical approval is required. The research will be published in a peer-reviewed journal. PROSPERO registration number CRD42018094180.
Training Economics Students for Innovative Activities

An objective of this study is to develop some grounds for assessing and ensuring the readiness of economics students to participate in innovative projects. Having considered the principles of innovation economics and the reflexive-activity approach to the organization of educational process, we classified the tasks set before an economist in an innovative project and developed approaches to assess relevant competences. Using the model of assessing the individual progress of school students developed by the authors, we derived a level model of an economics student’s readiness for innovative activities. We conducted a survey and collected data that manifest three types of college student attitudes towards innovative projects in different countries. The results allow us to make assumptions on the relevant differences in the national (European, Asian, Russian) higher education systems in terms of training economists for innovative activities, and to make several suggestions for professional programmes aimed to train economists to participate in innovative projects, and, in particular, in reflective-analytical gamification of education and the procedures to create a professional language for innovation teams.
Pore condensation and freezing is responsible for ice formation below water saturation for porous particles

Significance The formation of ice at relative humidity below 100% is assumed to proceed without the presence of liquid water. However, it has been shown that liquid water can exist well below water saturation in narrow cracks and pores. Here we show that the barrier for deposition nucleation of ice directly from the vapor is insurmountable in experiments; liquid water is involved in ice formation on porous particles, regardless of the ambient humidity. Thus, our results render deposition nucleation unlikely for the formation of ice clouds in the atmosphere. Ice nucleation in the atmosphere influences cloud properties, altering precipitation and the radiative balance, ultimately regulating Earth’s climate. An accepted ice nucleation pathway, known as deposition nucleation, assumes a direct transition of water from the vapor to the ice phase, without an intermediate liquid phase. However, studies have shown that nucleation occurs through a liquid phase in porous particles with narrow cracks or surface imperfections where the condensation of liquid below water saturation can occur, questioning the validity of deposition nucleation. We show that deposition nucleation cannot explain the strongly enhanced ice nucleation efficiency of porous compared with nonporous particles at temperatures below −40 °C and the absence of ice nucleation below water saturation at −35 °C. Using classical nucleation theory (CNT) and molecular dynamics simulations (MDS), we show that a network of closely spaced pores is necessary to overcome the barrier for macroscopic ice-crystal growth from narrow cylindrical pores. In the absence of pores, CNT predicts that the nucleation barrier is insurmountable, consistent with the absence of ice formation in MDS. Our results confirm that pore condensation and freezing (PCF), i.e., a mechanism of ice formation that proceeds via liquid water condensation in pores, is a dominant pathway for atmospheric ice nucleation below water saturation. We conclude that the ice nucleation activity of particles in the cirrus regime is determined by the porosity and wettability of pores. PCF represents a mechanism by which porous particles like dust could impact cloud radiative forcing and, thus, the climate via ice cloud formation.
High-Efficiency CRISPR/Cas9-Mediated Gene Editing in Honeybee (Apis mellifera) Embryos

The honeybee (Apis mellifera) is an important insect pollinator of wild flowers and crops, playing critical roles in the global ecosystem. Additionally, the honeybee serves as an ideal social insect model. Therefore, functional studies on honeybee genes are of great interest. However, until now, effective gene manipulation methods have not been available in honeybees. Here, we reported an improved CRISPR/Cas9 gene-editing method by microinjecting sgRNA and Cas9 protein into the region of zygote formation within 2 hr after queen oviposition, which allows one-step generation of biallelic knockout mutants in honeybee with high efficiency. We first targeted the Mrjp1 gene. Two batches of honeybee embryos were collected and injected with Mrjp1 sgRNA and Cas9 protein at the ventral cephalic side and the dorsal posterior side of the embryos, respectively. The gene-editing rate at the ventral cephalic side was 93.3%, which was much higher than that (11.8%) of the dorsal-posterior-side injection. To validate the high efficiency of our honeybee gene-editing system, we targeted another gene, Pax6, and injected Pax6 sgRNA and Cas9 protein at the ventral cephalic side in the third batch. A 100% editing rate was obtained. Sanger sequencing of the TA clones showed that 73.3% (for Mrjp1) and 76.9% (for Pax6) of the edited current-generation embryos were biallelic knockout mutants. These results suggest that the CRISPR/Cas9 method we established permits one-step biallelic knockout of target genes in honeybee embryos, thereby demonstrating an efficient application to functional studies of honeybee genes. It also provides a useful reference to gene editing in other insects with elongated eggs.
Assembling the adipose organ: adipocyte lineage segregation and adipogenesis in vivo

ABSTRACT Adipose tissue is composed of anatomically distinct depots that mediate several important aspects of energy homeostasis. The past two decades have witnessed increased research effort to elucidate the ontogenetic basis of adipose form and function. In this Review, we discuss advances in our understanding of adipose tissue development with particular emphasis on the embryonic patterning of depot-specific adipocyte lineages and adipocyte differentiation in vivo. Micro-environmental cues and other factors that influence cell identity and cell behavior at various junctures in the adipocyte lineage hierarchy are also considered. Summary: This review discusses the surprisingly complex lineage hierarchy for adipocytes as well micro-environmental and cell-intrinsic factors that influence adipocyte formation in vivo.
Climates of Warm Earth-like Planets. I. 3D Model Simulations

We present a large ensemble of simulations of an Earth-like world with increasing insolation and rotation rate. Unlike previous work utilizing idealized aquaplanet configurations, we focus our simulations on modern Earth-like topography. The orbital period is the same as that of modern Earth, but with zero obliquity and eccentricity. The atmosphere is 1 bar N2-dominated with CO2 = 400 ppmv and CH4 = 1 ppmv. The simulations include two types of oceans: one without ocean heat transport (OHT) between grid cells, as has been commonly used in the exoplanet literature, and the other a fully coupled dynamic bathtub type ocean. The dynamical regime transitions that occur as day length increases induce climate feedbacks producing cooler temperatures, first via the reduction of water vapor with increasing rotation period despite decreasing shortwave cooling by clouds, and then via decreasing water vapor and increasing shortwave cloud cooling, except at the highest insolations. Simulations without OHT are more sensitive to insolation changes for fast rotations, while slower rotations are relatively insensitive to ocean choice. OHT runs with faster rotations tend to be similar with gyres transporting heat poleward, making them warmer than those without OHT. For slower rotations OHT is directed equatorward and no high-latitude gyres are apparent. Uncertainties in cloud parameterization preclude a precise determination of habitability but do not affect robust aspects of exoplanet climate sensitivity. This is the first paper in a series that will investigate aspects of habitability in the simulations presented herein. The data sets from this study are open source and publicly available.
Subversion of natural killer cell responses by a cytomegalovirus-encoded soluble CD48 decoy receptor

Throughout evolution, cytomegaloviruses (CMVs) have been capturing genes from their hosts, employing the derived proteins to evade host immune defenses. We have recently reported the presence of a number of CD48 homologs (vCD48s) encoded by different pathogenic viruses, including several CMVs. However, their properties and biological relevance remain as yet unexplored. CD48, a cosignaling molecule expressed on the surface of most hematopoietic cells, modulates the function of natural killer (NK) and other cytotoxic cells by binding to its natural ligand 2B4 (CD244). Here, we have characterized A43, the vCD48 exhibiting the highest amino acid sequence identity with host CD48. A43, which is encoded by owl monkey CMV, is a soluble molecule released from the cell after being proteolytically processed through its membrane proximal region. A43 is expressed with immediate-early kinetics, yielding a protein that is rapidly detected in the supernatant of infected cells. Remarkably, surface plasmon resonance assays revealed that this viral protein binds to host 2B4 with high affinity and slow dissociation rates. We demonstrate that soluble A43 is capable to abrogate host CD48:2B4 interactions. Moreover, A43 strongly binds to human 2B4 and prevents 2B4-mediated NK-cell adhesion to target cells, therefore reducing the formation of conjugates and the establishment of immunological synapses between human NK cells and CD48-expressing target cells. Furthermore, in the presence of this viral protein, 2B4-mediated cytotoxicity and IFN-γ production by NK cells are severely impaired. In summary, we propose that A43 may serve as a functional soluble CD48 decoy receptor by binding and masking 2B4, thereby impeding effective NK cell immune control during viral infections. Thus, our findings provide a novel example of the immune evasion strategies developed by viruses.