Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis

Abstract Aims Levels of growth differentiation factor 15 (GDF-15), a cytokine secreted in response to cellular stress and inflammation, have been associated with multiple types of cardiovascular (CV) events. However, its comparative prognostic performance across different presentations of atherosclerotic cardiovascular disease (ASCVD) remains unknown. Methods and results An individual patient meta-analysis was performed using data pooled from eight trials including 53 486 patients. Baseline GDF-15 concentration was analyzed as a continuous variable and using established cutpoints (<1200 ng/L, 1200–1800 ng/L, > 1800 ng/L) to evaluate its prognostic performance for CV death/hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE), and their components using Cox models adjusted for clinical variables and established CV biomarkers. Analyses were further stratified on ASCVD status: acute coronary syndrome (ACS), stabilized after recent ACS, and stable ASCVD. Overall, higher GDF-15 concentration was significantly and independently associated with an increased rate of CV death/HHF and MACE (P < 0.001 for each). However, while GDF-15 showed a robust and consistent independent association with CV death and HHF across all presentations of ASCVD, its prognostic association with future myocardial infarction (MI) and stroke only remained significant in patients stabilized after recent ACS or with stable ASCVD [hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.17–1.31 and HR: 1.16, 95% CI: 1.05–1.28 for MI and stroke, respectively] and not in ACS (HR: 0.98, 95% CI: 0.90–1.06 and HR: 0.87, 95% CI: 0.39–1.92, respectively). Conclusion Growth differentiation factor 15 consistently adds prognostic information for CV death and HHF across the spectrum of ASCVD. GDF-15 also adds prognostic information for MI and stroke beyond clinical risk factors and cardiac biomarkers but not in the setting of ACS.
Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans

Abstract The increasing resistance of fungi to conventional antifungal drugs has prompted worldwide the search for new compounds. In this work, we investigated the antifungal properties of acylated Temporin L derivatives, Pent-1B and Dec-1B, against Candida albicans, including the multidrug-resistant strains. Acylated peptides resulted to be active both on reference and clinical strains with MIC values ranging from 6.5 to 26 µM, and they did not show cytotoxicity on human keratinocytes. In addition, we also observed a synergistic or additive effect with voriconazole for peptides Dec-1B and Pent-1B through the checkerboard assay on voriconazole-resistant Candida strains. Moreover, fluorescence-based assays, NMR spectroscopy, and confocal microscopy elucidated a potential membrane-active mechanism, consisting of an initial electrostatic interaction of acylated peptides with fungal membrane, followed by aggregation and insertion into the lipid bilayer and causing membrane perturbation probably through a carpeting effect. Graphical abstract
The effects of yoga on mental health in school-aged children: A Systematic Review and Narrative Synthesis of Randomised Control Trials

It is becoming increasingly common for frontline clinicians to see children and teenagers struggle with their mental health. Since mental health issues have increased over the past ten years in the UK, they are now the leading cause of disability and cost the British economy £105 billion annually. The review discusses the evidence base underpinning the effect of yoga on children’s mental health and summarises the results of 21 research papers. The Cumulative Index to Nursing and Allied Health Literature, PsycINFO, ERIC, Web of Science, PubMed, Medline and Cochrane Library were searched through Ovid from January 2008 until May 2022. The keywords 'yoga OR mindfulness – AND school AND children OR child OR youth OR adolescent' were used. The search was limited to studies in the English language. The quality of each study was rated against Version 2 of the Cochrane risk-of-bias tool for randomised control trials and a set of inclusion and exclusion criteria. The evidence for yoga therapies in children is encouraging, although studies include methodological flaws such as small sample sizes and sparse information on interventions. This review has highlighted that yoga interventions may be implemented in schools as a preventative and therapeutic measure for mental health issues.
An integrated SAGA and TFIID PIC assembly pathway selective for poised and induced promoters

In this study, Mittal et al. report that sequence-specific transcription factors and their tethered cofactors (e.g., SAGA, Mediator, TUP, NuA4, SWI/SNF, and RPD3-L) are generally bound to promoters prior to induction (“poised”), rather than recruited upon induction, whereas induction recruits the preinitiation complex (PIC) to DNA. Their findings suggest that inducible systems, where present, evolved on top of constitutive systems.
A dataset of ant colonies’ motion trajectories in indoor and outdoor scenes to study clustering behavior

Abstract Background The motion and interaction of social insects (such as ants) have been studied by many researchers to understand clustering mechanisms. Most studies in the field of ant behavior have focused only on indoor environments (a laboratory setup), while outdoor environments (natural environments) are still underexplored. Findings In this article, we collect 10 videos of 3 species of ant colonies from different scenes, including 5 indoor and 5 outdoor scenes. We develop an image sequence marking software named VisualMarkData, which enables us to provide annotations of the ants in the videos. (i) It offers comprehensive annotations of states at the individual-target and colony-target levels. (ii) It provides a simple matrix format to represent multiple targets and multiple groups of annotations (along with their IDs and behavior labels). (iii) During the annotation process, we propose a simple and effective visualization that takes the annotation information of the previous frame as a reference, and then a user can simply click on the center point of each target to complete the annotation task. (iv) We develop a user-friendly window-based GUI to minimize labor and maximize annotation quality. In all 5,354 frames, the location information and the identification number of each ant are recorded for a total of 712 ants and 114,112 annotations. Moreover, we provide visual analysis tools to assess and validate the technical quality and reproducibility of our data. Conclusions We provide a large-scale ant dataset with the accompanying annotation software. It is hoped that our work will contribute to a deeper exploration of the behavior of ant colonies.
GOAL ATTAINMENT AFTER TREATMENT WITH ABOBOTULINUMTOXINA AND A TAILORED HOME THERAPY PROGRAMME IN CHILDREN WITH UPPER LIMB SPASTICITY: DESCRIPTIVE, EXPLORATORY ANALYSIS OF A LARGE RANDOMIZED, CONTROLLED STUDY

Objective This exploratory analysis of a large, randomized, double-blind study (NCT02106351) describes the effect of treatment with abobotulinumtoxinA followed by a tailored home exercises therapy programme in enabling children with upper limb spasticity due to cerebral palsy to achieve their functional goals using goal attainment scaling (GAS). Methods Children with cerebral palsy and spasticity in ≥ 1 upper limb received up to 4 injection cycles of abobotulinumtoxinA (2 U/kg (cycle 1 only), 8U/kg and 16U/kg) into the elbow and wrist flexors and other upper limb muscles selected to support individual treatment goals. Children followed a home exercises therapy programme, which included stretches and exercises specifically chosen to facilitate goal achievement and engagement in activities. Results For cycle 1, most children had active function goals set as their primary goal (69.7% vs 19.2% passive function goals). GAS T-scores and goal responder rates at week 16 indicated that most types of primary goal were achieved at least as expected during cycle 1 (all groups). Primary goal GAS T-scores were generally maintained for the first 3 abobotulinumtoxinA treatment cycles. Conclusion Most children with upper limb spasticity treated with repeat cycles of abobotulinumtoxinA supported by an individualized home exercises therapy programme achieved their functional goals. LAY ABSTRACT Treatment with botulinum toxins (such as abobotulinumtoxinA; aboBoNT-A) is often recommended to treat spasticity of the upper limb to help children with cerebral palsy improve their hand skills. In this large study, children with cerebral palsy were treated with up to 4 aboBoNT-A injection cycles followed by a home exercises programme that was specifically made for each child to help them meet their treatment goals. This study aimed to explore the types of goals the children wanted to achieve with this treatment and the factors that influence goal attainment. Most children in this study had “active function” goals set, including “involving the affected arm more in daily activities” and improving “reaching”, “use of limb as a helping hand” and “grasp and release”. Combined treatment with aboBoNT-A and the exercise programme helped most children achieve their goals, but it was difficult to discern any differences in efficacy between the aboBoNT-A doses used in the study. The authors suggest that the high rates of goal achievement in this study indicate that botulinum toxin should not usually be given without a physiotherapy programme.
Seeing an Auditory Object: Pupillary Light Response Reflects Covert Attention to Auditory Space and Object

Abstract Attention to the relevant object and space is the brain's strategy to effectively process the information of interest in complex environments with limited neural resources. Numerous studies have documented how attention is allocated in the visual domain, whereas the nature of attention in the auditory domain has been much less explored. Here, we show that the pupillary light response can serve as a physiological index of auditory attentional shift and can be used to probe the relationship between space-based and object-based attention as well. Experiments demonstrated that the pupillary response corresponds to the luminance condition where the attended auditory object (e.g., spoken sentence) was located, regardless of whether attention was directed by a spatial (left or right) or nonspatial (e.g., the gender of the talker) cue and regardless of whether the sound was presented via headphones or loudspeakers. These effects on the pupillary light response could not be accounted for as a consequence of small (although observable) biases in gaze position drifting. The overall results imply a unified audiovisual representation of spatial attention. Auditory object-based attention contains the space representation of the attended auditory object, even when the object is oriented without explicit spatial guidance.
Near-ultraviolet transit photometry of HAT-P-32 b with the Large Binocular Telescope: Silicate aerosols in the planetary atmosphere

Broad-band exoplanet transit photometry can characterize the planetary atmosphere when observed at multiple selected filters. This observing technique can reveal gradients in the spectra of extrasolar planets, for example, the slope of decreasing opacity from short to long optical wavelengths caused by aerosol scattering. In this work, we observed a transit of the hot Jupiter HAT-P-32 b in the shortest wavelength possible from the ground using the Large Binocular Telescope (LBT). The data comprise the best quality ground-based U-band measurement taken so far of an exoplanet transit. Compared to broad-band observations of intermediate and long optical wavelengths published previously, a clear scattering slope in the planetary transmission spectrum is revealed. Most likely, the scattering particles are magnesium silicate aerosols larger than 0.1 µm. We define a spectral index to compare this scattering feature of HAT-P-32 b with published results of other exoplanets. It turns out to be very typical in amplitude within the compared sample. Furthermore, we searched for correlation in this sample of the spectral index with planetary equilibrium temperature, surface acceleration, and stellar activity indicator, but could not find any.
Integrated phylogenomic analyses unveil reticulate evolution in Parthenocissus (Vitaceae), highlighting speciation dynamics in the Himalayan-Hengduan Mountains.

Hybridization caused by frequent environmental changes can lead to both species diversification (speciation) and speciation reversal (despeciation), but the latter has rarely been demonstrated. Parthenocissus, a genus with its trifoliolate lineage in the Himalayan-Hengduan Mountains (HHM) region showing perplexing phylogenetic relationships, provides an opportunity for investigating speciation dynamics based on integrated evidence. We investigated phylogenetic discordance and reticulate evolution in Parthenocissus based on rigorous analyses of plastome and transcriptome data. We focussed on reticulations in the trifoliolate lineage in the HHM region using a population-level genome resequencing dataset, incorporating evidence from morphology, distribution, and elevation. Comprehensive analyses confirmed multiple introgressions within Parthenocissus in a robust temporal-spatial framework. Around the HHM region, at least three hybridization hotspots were identified, one of which showed evidence of ongoing speciation reversal. We present a solid case study using an integrative methodological approach to investigate reticulate evolutionary history and its underlying mechanisms in plants. It demonstrates an example of speciation reversal through frequent hybridizations in the HHM region, which provides new perspectives on speciation dynamics in mountainous areas with strong topographic and environmental heterogeneity.
Inter-epidemic Rift Valley fever virus infection incidence and risks for zoonotic spillover in northern Tanzania

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that has caused epidemics involving people and animals across Africa and the Arabian Peninsula. A number of studies have found evidence for the circulation of RVFV among livestock between these epidemics but the population-level incidence of infection during this inter-epidemic period (IEP) is rarely reported. General force of infection (FOI) models were applied to age-adjusted cross-sectional serological data to reconstruct the annual FOI and population-level incidence of RVFV infection among cattle, goats, and sheep in northern Tanzania from 2009 through 2015, a period without reported Rift Valley fever (RVF) cases in people or animals. To evaluate the potential for zoonotic RVFV spillover during this period, the relationship between village-level livestock RVFV FOI and human RVFV seropositivity was quantified using multi-level logistic regression. The predicted average annual incidence was 72 (95% Credible Interval [CrI] 63, 81) RVFV infections per 10,000 animals and 96 (95% CrI 81, 113), 79 (95% CrI 62, 98), and 39 (95% CrI 28, 52) per 10,000 cattle, sheep, and goats, respectively. There was variation in transmission intensity between study villages, with the highest estimated village-level FOI 2.49% (95% CrI 1.89, 3.23) and the lowest 0.12% (95% CrI 0.02, 0.43). The human RVFV seroprevalence was 8.2% (95% Confidence Interval 6.2, 10.9). Human seropositivity was strongly associated with the village-level FOI in livestock, with the odds of seropositivity in an individual person increasing by around 1.2 times (95% CrI 1.1, 1.3) for each additional annual RVFV seroconversion per 1,000 animals. A history of raw milk consumption was also positively associated with human seropositivity. RVFV has circulated at apparently low levels among livestock in northern Tanzania in the period since the last reported epidemic. Although our data do not allow us to confirm human RVFV infections during the IEP, a strong association between human seropositivity and the FOI in cattle, goats, and sheep supports the hypothesis that RVFV circulation among livestock during the IEP poses a risk for undetected zoonotic spillover in northern Tanzania. We provide further evidence for the likely role of raw milk consumption in RVFV transmission from animals to people.
Patient-Reported Quality of Life After Intravenous Alteplase for Stroke in the WAKE-UP Trial

Background and Objectives Intravenous alteplase improves functional outcome after acute ischemic stroke. However, little is known about the effects on self-reported health-related quality of life (HRQoL). Methods WAKE-UP was a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in stroke with unknown onset time. HRQoL was assessed using the EuroQol five-dimensional questionnaire (EQ-5D) at 90 days, comprising the EQ-5D index and the EQ visual analogue scale (VAS). Functional outcome was assessed by the modified Rankin Scale (mRS). We calculated the effect of treatment on EQ-5D index and EQ VAS using multiple linear regression models. Mediation analysis was performed on stroke survivors to explore the extent to which the effect of alteplase on HRQoL was mediated by functional outcome. Results Among 490 stroke survivors, the EQ-5D index was available for 452 (92.2%), of whom 226 (50%) were assigned to treatment with alteplase and 226 (50%) to placebo. At 90 days, mean EQ-5D index was higher, reflecting a better health state, in patients randomized to treatment with alteplase than with placebo (0.75 vs 0.67) with an adjusted mean difference of 0.07 (95% CI 0.02–0.12, p = 0.005). In addition, mean EQ VAS was higher with alteplase than with placebo (72.6 vs 64.9), with an adjusted mean difference of 7.6 (95% CI 3.9–11.8, p < 0.001). Eighty-five percent of the total treatment effect of alteplase on the EQ-5D index was mediated using the mRS score while there was no significant direct effect. By contrast, the treatment effect on the EQ VAS was mainly through the direct pathway (60%), whereas 40% was mediated by the mRS. Discussion Assessment of patient-reported outcome measures reveals a potential benefit of intravenous alteplase for HRQoL beyond improvement of functional outcome. Trial Registration Information ClinicalTrials.gov number, NCT01525290; EudraCT number, 2011-005906-32.
Cost-effective, high-yield production of Pyrobaculum calidifontis DNA polymerase for PCR application

Abstract Polymerase Chain Reaction (PCR) is widely used for cloning, genetic engineering, mutagenesis, detection and diagnosis. A thermostable DNA polymerase is required for PCR. Here we describe low-cost and high-recovery production of Pyrobaculum calidifontis DNA polymerase (Pca-Pol). The gene was cloned in pET-28a and expressed in Escherichia coli BL21CodonPlus. Gene expression conditions were optimized. Eventually, gene expression was induced with 0.1 mM IPTG for 3 hours at 37 °C. Recombinant Pca-Pol produced was purified to homogeneity by immobilized metal-ion affinity chromatography yielding around 9000 U of Pca-Pol per liter of the culture with a recovery of 92%. Stability and PCR amplification efficiency of Pca-Pol was tested under various storage conditions with highest efficiency in 25 mM Tris-Cl buffer (pH 8.5) containing 0.1% Tween 20, 0.2 mg/mL BSA and 20% glycerol. Under this condition, no loss in PCR activity of Pca-Pol was observed, even after one year of storage. Repeated freeze-thaw, however, deteriorated enzyme activity of Pca-Pol. 55% PCR amplification activity retained after 7 prolong freeze-thaw cycles (freezing overnight at −20 °C and thawing for 45 minutes at 28 °C). Purified Pca-Pol possessed 3′–5′ exonuclease (proofreading) activity and is expected to have greater fidelity as compared to Taq polymerase which does not have proofreading activity.
Conductance smearing and anisotropic suppression of induced superconductivity in a Majorana nanowire

In a recent high-quality experimental work on normal metal--superconducting nanowire junctions arXiv:1807.01940 (2018), strong anisotropic suppression of induced superconductivity has been observed in tunnel conductance measurements in the presence of applied magnetic field with variable orientation. Following this finding, we investigate theoretically the dependence of tunnel conductance on the direction of the Zeeman field in order to understand the operational mechanisms and to extract effective system parameters. Second, motivated by a generic discrepancy between experiment and theory, i.e., many in-gap and above-gap conductance features predicted by theory are barely observed in experiments, we study several mechanisms possibly responsible for the suppression of the theoretically predicted conductance features (e.g., length of the nanowire, self-energy effect due to the proximity effect, finite temperature, finite dissipation, and multiband effect). One essential finding in the current work is that only by a combined understanding of both suppression mechanisms can we extract effective system parameters from the experimental data (e.g., the effective nanowire-superconductor coupling, the effective Lande $g$ factor, and the chemical potential of the semiconducting nanowire). In addition, we consider topologically trivial Andreev bound states in hybrid nanowires in the presence of potential inhomogeneities, such as external quantum dots or potential inhomogeneities inside the nanowire. We compare the anisotropic, field-dependent features induced by these nontopological Andreev bound states with the corresponding features produced by topological Majorana zero modes in pristine nanostructures, so that we can provide guidance to differentiate between the topologically trivial and nontrivial cases.
H3.3K27M mutation is not a suitable target for immunotherapy in HLA-A2+ patients with diffuse midline glioma

Diffuse midline glioma is the leading cause of solid cancer-related deaths in children with very limited treatment options. A majority of the tumors carry a point mutation in the histone 3 variant (H3.3) creating a potential HLA-A*02:01 binding epitope (H3.3K27M26-35). Here, we isolated an H3.3K27M-specific T cell receptor (TCR) from transgenic mice expressing a diverse human TCR repertoire. Despite a high functional avidity of H3.3K27M-specific T cells, we were not able to achieve recognition of cells naturally expressing the H3.3K27M mutation, even when overexpressed as a transgene. Similar results were obtained with T cells expressing the published TCR 1H5 against the same epitope. CRISPR/Cas9 editing was used to exclude interference by endogenous TCRs in donor T cells. Overall, our data provide strong evidence that the H3.3K27M mutation is not a suitable target for cancer immunotherapy, most likely due to insufficient epitope processing and/or amount to be recognized by HLA-A*02:01 restricted CD8+ T cells.