Miracle-dz/UniFAR-FTUs huggingface dataset:
Steps towards implementation of protocolized dose reduction of adalimumab, etanercept and ustekinumab for psoriasis in daily practice

Abstract Background Dose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients. Objectives To evaluate the implementation of protocolized biologic DR in daily practice. Methods A pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review. Results The implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR. Conclusion Additional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR.
MGAE-DC: Predicting the synergistic effects of drug combinations through multi-channel graph autoencoders

Accurate prediction of synergistic effects of drug combinations can reduce the experimental costs for drug development and facilitate the discovery of novel efficacious combination therapies for clinical studies. The drug combinations with high synergy scores are regarded as synergistic ones, while those with moderate or low synergy scores are additive or antagonistic ones. The existing methods usually exploit the synergy data from the aspect of synergistic drug combinations, paying little attention to the additive or antagonistic ones. Also, they usually do not leverage the common patterns of drug combinations across different cell lines. In this paper, we propose a multi-channel graph autoencoder (MGAE)-based method for predicting the synergistic effects of drug combinations (DC), and shortly denote it as MGAE-DC. A MGAE model is built to learn the drug embeddings by considering not only synergistic combinations but also additive and antagonistic ones as three input channels. The later two channels guide the model to explicitly characterize the features of non-synergistic combinations through an encoder-decoder learning process, and thus the drug embeddings become more discriminative between synergistic and non-synergistic combinations. In addition, an attention mechanism is incorporated to fuse each cell-line’s drug embeddings across various cell lines, and a common drug embedding is extracted to capture the invariant patterns by developing a set of cell-line shared decoders. The generalization performance of our model is further improved with the invariant patterns. With the cell-line specific and common drug embeddings, our method is extended to predict the synergy scores of drug combinations by a neural network module. Experiments on four benchmark datasets demonstrate that MGAE-DC consistently outperforms the state-of-the-art methods. In-depth literature survey is conducted to find that many drug combinations predicted by MGAE-DC are supported by previous experimental studies. The source code and data are available at https://github.com/yushenshashen/MGAE-DC.
BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility

Abstract The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1.
Travel for later abortion in the USA: lived experiences, structural contributors and abortion fund support

Abstract As abortion restrictions expand in the USA, pregnant people will continue to experience delays and be forced to travel for abortion. The study aims to describe later abortion travel experiences, understand structural factors influencing travel, and identify strategies to improve travel. This qualitative phenomenological study analyses data from 19 interviews with people who travelled at least 25 miles for abortion after the first trimester. Framework analysis used a structural violence lens. More than two-thirds of participants travelled interstate, and half received abortion fund support. Key considerations of travel include logistics, challenges during the journey, and physical and emotional recovery during and after travel. Restrictive laws, financial insecurity and anti-abortion infrastructure are forms of structural violence that created challenges and delays. Reliance on abortion funds facilitated access but also entailed uncertainty. Better resourced abortion funds could organise travel in advance, facilitate the travel of accompanying escorts, and tailor emotional support to reduce stress for those travelling. Clinical and practical support systems must be prepared to support people travelling for abortion, as later abortion and forced travel is increasing since the constitutional right to abortion in the USA was overturned. Findings can inform interventions to support the increasing number of people travelling for abortion.
Empirical modeling of single‐wake advection and expansion using full‐scale pulsed lidar‐based measurements

In the present paper, single-wake dynamics have been studied both experimentally and numerically. The use of pulsed lidar measurements allows for validation of basic dynamic wake meandering modeling assumptions. Wake center tracking is used to estimate the wake advection velocity experimentally and to obtain an estimate of the wake expansion in a fixed frame of reference. A comparison shows good agreement between the measured average expansion and the Computational Fluid Dynamics (CFD) large eddy simulation–actuator line computations. Frandsen's expansion model seems to predict the wake expansion fairly well in the far wake but lacks accuracy in the outer region of the near wake. An empirical relationship, relating maximum wake induction and wake advection velocity, is derived and linked to the characteristics of a spherical vortex structure. Furthermore, a new empirical model for single-wake expansion is proposed based on an initial wake expansion in the pressure-driven flow regime and a spatial gradient computed from the large-scale lateral velocities, and thus inspired by the basic assumption behind the dynamic wake meandering model. Copyright © 2014 John Wiley & Sons, Ltd.
Lithium dilution through main-sequence mass loss

The consequences of main-sequence mass loss for surface lithium abundances in stars are investigated through the use of evolving, mass-losing stellar models. In particular, we attempt to model lithium depletion observed in three areas: the Sun, the Hyades G dwarfs, and the Hyades F dwarfs. Mass loss as an explanation for lithium depletion has mixed success. It is concluded that mass loss can be a marginal explanation for the solar lithium problem
Biochar mitigates allelopathic effects in temperate trees.

Many invasive and some native tree species in North America exhibit strong allelopathic effects that may contribute to their local dominance. Pyrogenic carbon (PyC; including soot, charcoal, and black carbon) is produced by the incomplete combustion of organic matter and is widespread in forest soils. Many forms of PyC have sorptive properties that can reduce the bioavailability of allelochemicals. We investigated the potential for PyC produced by controlled pyrolysis of biomass ("biochar") to reduce the allelopathic effects of black walnut (Juglans nigra) and Norway maple (Acer platanoides), a common native tree species and a widespread invasive species in North America, respectively. Seedling growth of two native tree species (Acer saccharinum (silver maple) and Betula papyrifera (paper birch)) in response to leaf-litter-incubated soils were examined; litter incubation treatments included leaves of black walnut, Norway maple, and a non-allelopathic species (Tilia americana (American basswood)) in a factorial design with varying dosages; responses to the known primary allelochemical of black walnut (juglone) were also examined. Juglone and leaf litter of both allelopathic species strongly suppressed seedling growth. Biochar treatments substantially mitigated these effects, consistent with sorption of allelochemicals; in contrast no positive effects of biochar were observed in leaf litter treatments involving controls or additions of non-allelopathic leaf litter. Treatments of leaf litter and juglone with biochar increased the total biomass of silver maple by ~35% and in some cases more than doubled the biomass of paper birch. We conclude that biochars have the capacity to largely counteract allelopathic effects in temperate forest systems, suggesting effects of natural PyC in determining forest community structure, and also applied use of biochar as a soil amendment to mitigate allelopathic effects of invasive tree species.
Stochastic Stability in Large Populations

Most work in evolutionary game theory analyzes a deterministic adjustment process on a continuum of agents. However, both the assumption of a continuum and that of no randomness are approximations, so it is important to study the behavior of adjustment processes on a large but finite population subject to small but persistent stochastic shocks. This paper characterizes the properties of the invariant distribution of birth-death processes in the double limit as the population becomes infinitely large and the perturbation vanishingly small. We show that the order of these limits does not change the conclusions for processes with 'strong basins,' which is the case when the unperturbed process is deterministic. In contrast, the order of limits does matter for processes with 'weak basins,' where the unperturbed process is stochastic except at a finite number of points.
The comparison of decision-making in ambiguous situations and galvanic skin responses as somatic markers in patients with posterior cortex epilepsy and mesial temporal lobe epilepsy with hippocampal sclerosis

ABSTRACT Introduction Decision-making behaviors of patients with mesial temporal lobe epilepsy (MTLE) is a subject that has been studied frequently. However, determining the neuropsychological profiles of patients with different types of epilepsy is also important. Our main purpose was to examine the decision-making behaviors of patients with posterior cortex epilepsy (PCE) through the assumptions of somatic marker hypothesis (SMH) and to compare their performances with those of a MTLE group and a control group. Method Participants comprised of 13 patients with PCE (mean age 30.92 ± 9.99 years); 14 patients with MTLE with hippocampal sclerosis (MTLE-HS) (mean age 25.53 ± 7.40 years) and 15 controls (mean age 24.60 ± 8.45 years). Decision-making performances were assessed with the Iowa gambling test (IGT) and anticipatory skin responses before each choice were recorded. A comprehensive neuropsychological test battery was also given to all participants in order to examine the relationship of decision-making with other cognitive functions. Results Anticipatory responses before choosing from disadvantageous decks were significantly larger than choosing from advantageous decks in the PCE group (p = 0.00). No significant difference was found between the PCE and control group’s total net scores. IGT total net scores was significantly correlated with Stroop test interference time (p = 0.03). Conclusion The study reveals that cognitive impairments of patients with PCE are not limited to brain’s posterior areas’ functions, and provides evidence for the current paradigm which understands epilepsy as a network disorder.
Extensive Air Showers and Hadronic Interactions at High Energy

At energies greater than 1015 eV, cosmic-ray particles can be measured only indirectly by detecting the extensive showers of secondary particles they create in the Earth's atmosphere. A detailed simulation of these particle showers is needed to reconstruct the properties of the primary particles. Key to understanding extensive air showers is the modeling of hadronic multiparticle production at energies from the particle-production threshold up to 1020 eV—far beyond the reach of man-made accelerators. In this article, we introduce the relation between extensive air showers and hadronic interactions at high energy. We review air shower predictions of commonly used interaction models and discuss their uncertainties. Finally, we illustrate the importance of accelerator measurements for air shower simulation and, complementarily, the information that can be obtained from air showers on particle production.
STOPPING AT THE MAXIMUM OF GEOMETRIC BROWNIAN MOTION WHEN SIGNALS ARE RECEIVED

Consider a geometric Brownian motion X t (ω) with drift. Suppose that there is an independent source that sends signals at random times τ 1 τ 2 τ will bring a reward S τ , where S t = max(max 0≤ u ≤ t X u , s ) for some constant s ≥ X 0 . The objective is to choose an optimal stopping time to maximize the discounted expected reward E[e − r τ i S τ i | X 0 = x , S 0 = s ], where r is a discount factor. This problem can be viewed as a randomized version of the Bermudan look-back option pricing problem. In this paper, we derive explicit solutions to this optimal stopping problem, assuming that signal arrival is a Poisson process with parameter λ. Optimal stopping rules are differentiated by the frequency of the signal process. Specifically, there exists a threshold λ * such that if λ>λ * , the optimal stopping problem is solved via the standard formulation of a ‘free boundary’ problem and the optimal stopping time τ * is governed by a threshold a * such that τ * = inf{ τ n : X τ n ≤ a * S τ n }. If λ≤λ * then it is optimal to stop immediately a signal is received, i.e. at τ * = τ 1 . Mathematically, it is intriguing that a smooth fit is critical in the former case while irrelevant in the latter.
Formulation of Fuzzy Finite‐Element Methods for Solid Mechanics Problems

Accounting for uncertainties in mechanics problems has been accomplished previously by probabilistic methods that may require highly repetitive and time‐consuming computations to analyze the behavior of mathematical models. In addition to the repetitions, knowledge of the probability distribution of state variables is often incomplete. This article introduces a new treatment of uncertainties in continuum mechanics based on fuzzy set theory. Uncertainties or fuzzy numbers herein are viewed through the concept of presumption level of the uncertainty (α‐cut), α∈[0, 1]$, which gives an interval of confidence Aα = [a1(a), a2(α]. This treatment is included in a new fuzzy finite‐element formulation. The fuzzy approach to treating uncertainties in continuum mechanics is applied to load, geometric, and material uncertainties in a number of examples. Results demonstrate sharp inclusion of the fuzzy solutions in comparison with the exact solutions.
Evaluation of γ-H2AX foci distribution among different peripheral blood mononucleated cell subtypes

Abstract Introduction The detection of γ-H2AX foci in peripheral blood mononucleated cells (PBMCs) has been incorporated as an early assay for biological dosimetry. However, overdispersion in the γ-H2AX foci distribution is generally reported. In a previous study from our group, it was suggested that overdispersion could be caused by the fact that when evaluating PBMCs, different cell subtypes are analyzed, and that these could differ in their radiosensitivity. This would cause a mixture of different frequencies that would result in the overdispersion observed. Objectives The objective of this study was to evaluate both the possible differences in the radiosensitivities of the different cell subtypes present in the PBMCs and to evaluate the distribution of γ-H2AX foci in each cell subtype. Materials and methods Peripheral blood samples from three healthy donors were obtained and total PBMCs, and CD3+, CD4+, CD8+, CD19+, and CD56+ cells were separated. Cells were irradiated with 1 and 2 Gy and incubated at 37 °C for 1, 2, 4, and 24 h. Sham-irradiated cells were also analyzed. γ-H2AX foci were detected after immunofluorescence staining and analyzed automatically using a Metafer Scanning System. For each condition, 250 nuclei were considered. Results When the results from each donor were compared, no observable significant differences between donors were observed. When the different cell subtypes were compared, CD8+ cells showed the highest mean of γ-H2AX foci in all post-irradiation time points. The cell type that showed the lowest γ-H2AX foci frequency was CD56+. The frequencies observed in CD4+ and CD19+ cells fluctuated between CD8+ and CD56+ without any clear pattern. For all cell types evaluated, and at all post-irradiation times, overdispersion in γ-H2AX foci distribution was significant. Independent of the cell type evaluated the value of the variance was four times greater than that of the mean. Conclusion Although different PBMC subsets studied showed different radiation sensitivity, these differences did not explain the overdispersion observed in the γ-H2AX foci distribution after exposure to IR.
On the Perihelion Precession of Solar Planetary Orbits

This is an article,The present letter presents an improved version of the Azimuthally Symmetric Theory of Gravitation (ASTG-model) which was presented for the first time in the present journal four years ago. We propose a solution to the standing problem of the -parameters in which effort we put the ASTG-model on a clear pedestal for falsification. As in the maiden reading, the perihelion precessional data of Solar planetary orbits is used to set the theory into motion.
Rubin-152: a massive star on the galactic fringe

Rubin-152 is spectroscopically identical with a type O4--5 main-sequence star, and the standard luminosity calibration places it at the unexpected distance of 50 kpc from the Galactic center. Although its radial velocity is inconsistent with a circular orbit, a highly eccentric one cannot be excluded. On the other hand, the data reported here are also consistent with the hypothesis that R-152 is in an advanced stage of evolution, and that it is a nearby, low-mass, low-luminosity object which by perverse coincidence exhibits the effective temperature and surface gravity of a very massive star.
Near-Infrared Images of Protoplanetary Disk Surrounding HD 142527

We discovered a unique morphology in a disk around the Herbig Ae star HD 142527 by near-infrared (H and K bands) adaptive optics imaging observations. The almost face-on disk consists of two bright arcs facing one another along the east-west direction (banana-split structure) and one spiral arm extending to the north from the western arc. The eastern arc is located at ~100-400 AU in radius from the star, and the western one is detected at ~150-490 AU. The stellar position is displaced from the center of the disk by about 20 AU to the north, and also from the center of the inner hole. The two arcs show an asymmetry in their size and brightness; the larger western arc is brighter than the east one by about 2 mag. The morphology of the disk, consisting of a banana-split structure and a spiral arm, most likely suggests the presence of an unseen eccentric binary and a recent stellar encounter.
RNAJP: enhanced RNA 3D structure predictions with non-canonical interactions and global topology sampling

Abstract RNA 3D structures are critical for understanding their functions. However, only a limited number of RNA structures have been experimentally solved, so computational prediction methods are highly desirable. Nevertheless, accurate prediction of RNA 3D structures, especially those containing multiway junctions, remains a significant challenge, mainly due to the complicated non-canonical base pairing and stacking interactions in the junction loops and the possible long-range interactions between loop structures. Here we present RNAJP (‘RNA Junction Prediction’), a nucleotide- and helix-level coarse-grained model for the prediction of RNA 3D structures, particularly junction structures, from a given 2D structure. Through global sampling of the 3D arrangements of the helices in junctions using molecular dynamics simulations and in explicit consideration of non-canonical base pairing and base stacking interactions as well as long-range loop–loop interactions, the model can provide significantly improved predictions for multibranched junction structures than existing methods. Moreover, integrated with additional restraints from experiments, such as junction topology and long-range interactions, the model may serve as a useful structure generator for various applications.
Neutron Scattering Study of Magnetic Excitations in the Spin S = 1 One-Dimensional Heisenberg Antiferromagnet Y2BaNiO5

Magnetic excitations of the ideal one-dimensional, spin S =1, antiferromagnet Y 2 BaNiO 5 are studied by means of inelastic neutron scattering on single crystal sample. Our experimental results at low temperature indicate that Y 2 BaNiO 5 can be regarded as the best isotropic Haldane-system sofar studied with the intrachain exchange energy J / k B =-24.1 meV and the averaged gap Δ( T =7 K)=8.5 meV. Y 2 BaNiO 5 exhibits a good magnetic one-dimensionality with the inter-/intrachain exchange ratio of | J ′ / J |≤10 -4 and has only very small easy-axis and in-plane single ion anisotropy of | D / J |=0.03 and | E / J |∼0.01. In addition the temperature dependence of the Haldane gap Δ( T ) and its damping rate was determined.