Miracle-dz/UniFAR-FTUs huggingface dataset:
Prolonged inhibition of hepatocellular carcinoma cell proliferation by combinatorial expression of defined transcription factors

Hepatocellular carcinoma (HCC) accounts for a large proportion of liver cancer cases and has an extremely poor prognosis. Therefore, novel innovative therapies for HCC are strongly desired. As gene therapy tools for HCC, 2 hepatic transcription factors (TF), HNF4A and HNF1A, have been used to suppress proliferation and to extinguish cancer‐specific characteristics of target cells. However, our present data demonstrated that single transduction of HNF4A or HNF1A had only a limited effect on suppression of HCC cell proliferation. Thus, in this study, we examined whether combinations of TF could show more effective antitumor activity, and found that combinatorial transduction of 3 hepatic TF, HNF4A, HNF1A and FOXA3, suppressed HCC cell proliferation more stably than single transduction of these TF. The combinatorial transduction also suppressed cancer‐specific phenotypes, such as anchorage‐independent growth in culture and tumorigenicity after transplantation into mice. HCC cell lines transduced with the 3 TF did not recover their proliferative property after withdrawal of anticancer drugs, indicating that combinatorial expression of the 3 TF suppressed the growth of all cell subtypes within the HCC cell lines, including cancer stem‐like cells. Transcriptome analyses revealed that the expression levels of a specific gene set involved in cell proliferation were only decreased in HCC cells overexpressing all 3 TF. Moreover, combined transduction of the 3 TF could facilitate hepatic differentiation of HCC cell lines. Our strategy for inducing stable inhibition and functional differentiation of tumor cells using a defined set of TF will become an effective therapeutic strategy for various types of cancers.
Double Bounded Rough Set, Tension Measure, and Social Link Prediction

This paper describes a new approach of viewing a social relation as a string with various forces acting on it. Accordingly, a tension measure for a relation is defined. Various component forces of the tension measure are identified based on the structural information of the network. A new variant of rough set, namely, double bounded rough set, is developed in order to define these forces mathematically. It is revealed experimentally with synthetic and real-world data that positive and negative tension characterizes, relatively, the presence and absence of a physical link between two nodes. An algorithm based on tension measure is proposed for link prediction. Superiority of the algorithm is demonstrated on nine real-world networks, which include four temporal networks. The source code for calculating tension measure and link prediction algorithm is publicly available at https://gitlab.com/suman5/social-tension-measure.
Increased developmental density decreases the magnitude of indirect genetic effects expressed during agonistic interactions in an insect

The expression of aggression depends not only on the direct genetic effects (DGEs) of an individual's genes on its own behavior, but also on indirect genetic effects (IGEs) caused by heritable phenotypes expressed by social partners. IGEs can affect the amount of heritable variance on which selection can act. Despite the important roles of IGEs in the evolutionary process, it remains largely unknown whether the strength of IGEs varies across life stages or competitive regimes. Based on manipulations of nymphal densities and > 3000 pair‐wise aggression tests across multiple life stages, we experimentally demonstrate that IGEs on aggression are stronger in field crickets (Gryllus bimaculatus) that develop at lower densities than in those that develop at higher densities, and that these effects persist with age. The existence of density‐dependent IGEs implies that social interactions strongly determine the plastic expression of aggression when competition for resources is relaxed. A more competitive (higher density) rearing environment may fail to provide crickets with sufficient resources to develop social cognition required for strong IGEs. The contribution of IGEs to evolutionary responses was greater at lower densities. Our study thereby demonstrates the importance of considering IGEs in density‐dependent ecological and evolutionary processes.
TED Talk Recommender Using Speech Transcripts

Nowadays, online video platforms mostly recommend related videos by analyzing user-driven data such as viewing patterns, rather than the content of the videos. However, content is more important than any other element when videos aim to deliver knowledge. Therefore, we have developed a web application which recommends related TED lecture videos to the users, considering the content of the videos from the transcripts. TED Talk Recommender constructs a network for recommending videos that are similar content-wise and providing a user interface. Our demo system is available at http://dmserver6.kaist. ac.kr:24673/.
Adenosine A2A receptors facilitate synaptic NMDA currents in CA1 pyramidal neurons

NMDA receptors play a key role in both synaptic plasticity and neurodegeneration. Adenosine is an endogenous neuromodulator and through membrane receptors of the A2A subtype can influence both synaptic plasticity and neuronal death. The present work was designed to evaluate the influence of adenosine A2A receptors upon NMDA receptor activity in CA1 hippocampal neurons. We discriminated between modulation of synaptic versus extrasynaptic receptors, since extrasynaptic NMDA receptors are mostly associated with neurodegeneration while synaptic NMDA receptors are linked to plasticity phenomena.
Schwann cell–derived periostin promotes autoimmune peripheral polyneuropathy via macrophage recruitment

Chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barre syndrome (GBS) are inflammatory neuropathies that affect humans and are characterized by peripheral nerve myelin destruction and macrophage-containing immune infiltrates. In contrast to the traditional view that the peripheral nerve is simply the target of autoimmunity, we report here that peripheral nerve Schwann cells exacerbate the autoimmune process through extracellular matrix (ECM) protein induction. In a spontaneous autoimmune peripheral polyneuropathy (SAPP) mouse model of inflammatory neuropathy and CIDP nerve biopsies, the ECM protein periostin (POSTN) was upregulated in affected sciatic nerves and was primarily expressed by Schwann cells. Postn deficiency delayed the onset and reduced the extent of neuropathy, as well as decreased the number of macrophages infiltrating the sciatic nerve. In an in vitro assay, POSTN promoted macrophage chemotaxis in an integrin-AM (ITGAM) and ITGAV-dependent manner. The PNS-infiltrating macrophages in SAPP-affected nerves were pathogenic, since depletion of macrophages protected against the development of neuropathy. Our findings show that Schwann cells promote macrophage infiltration by upregulating Postn and suggest that POSTN is a novel target for the treatment of macrophage-associated inflammatory neuropathies.
Isolated seizures during the first episode of relapsing myelin oligodendrocyte glycoprotein antibody‐associated demyelination in children

Myelin oligodendrocyte glycoprotein (MOG) antibodies have a strong association with acute disseminated encephalomyelitis (ADEM) in children, and bilateral and recurrent optic neuritis in children and adults. Recent reports suggest that seizures and encephalopathy may occur in children and adults with MOG antibody‐associated disease. We describe the clinical, laboratory, and radiological course of four MOG antibody‐positive children who first presented with isolated seizures without fulfilling clinical or radiological criteria for ADEM or other central nervous system demyelination syndromes, who months to years later developed more typical demyelination. This case series highlights a novel observation that isolated seizures in the absence of ADEM may be the index presentation for MOG antibody‐associated disease, which should therefore be considered a form of autoimmune epilepsy. It would be reasonable to test for MOG antibodies in children with seizures accompanied by subtle inflammatory changes on magnetic resonance imaging or cerebrospinal fluid analyses, particularly if followed by demyelination, given the clinical and therapeutic implications of an expedited diagnosis in minimizing long‐term disability.
Aspirin promotes apoptosis and inhibits proliferation by blocking G0/G1 into S phase in rheumatoid arthritis fibroblast-like synoviocytes via downregulation of JAK/STAT3 and NF-κB signaling pathway

Rheumatoid arthritis (RA) is a commonly occurring autoimmune disease. Its defining pathological characteristic is the excessive proliferation of fibroblast-like synoviocytes (FLS), which is similar to tumor cells and results in a range of clinical problems. As a commonly used antipyretic, analgesic and anti-inflammatory drug, aspirin is the first-line treatment for RA. However, its mechanism of action has not been well explained. The goal is to investigate the biological effects of aspirin on primary RA-FLS and its underlying mechanisms. In this experiment we treated cells with various concentrations of aspirin (0, DMSO, 1, 2, 5, 10 mM). Cell proliferation activity was detected with CCK-8 assays. Apoptosis and cell cycle distribution were detected via flow cytometry. Apoptosis and cell cycle-associated proteins (Bcl-2, Bax, PRAP1, Cyclin D1, P21), as well as the key proteins and their phosphorylation levels of the NF-κB and JAK/STAT3 signaling pathways, were detected via western blot analysis. Bioinformatics prediction revealed that aspirin was closely associated with cell proliferation and apoptosis, including the p53 and NF-κB signaling pathways. By stimulating with aspirin, cell viability decreased, while the proportion of apoptotic cells increased, and the number of cells arrested in the G0/G1 phase increased in a dose-dependent manner. The expression of Bax increased with aspirin stimulation, while the levels of Bcl-2, PRAP1, Cyclin D1 and P21 decreased; p-STAT3, p-P65 and p-50 levels also decreased while STAT3, P65, P50, p-P105 and P105 remained unchanged. From our data, it can be concluded that aspirin is able to promote apoptosis and inhibit the proliferation of RA-FLS through blocking the JAK/STAT3 and NF-κB signaling pathways.
Facility infrastructure of primary health services regarding tuberculosis control: a countrywide cross-sectional study

Abstract Background Tuberculosis (TB) is still a major public health problem in many countries, including Brazil. Primary health care (PHC) services are a set of important services with infrastructure and resources to diagnose, treat, and cure several diseases, including the TB. Aim The aim of this study is to analyse aspects of the facility infrastructure of Brazilian PHC, regarding the control and treatment of TB from a countrywide perspective. Methods This is a cross-sectional study based on PHC services. Data were collected from 38,812 health centres and were assessed by means of the National Program for Improving Access and Quality Primary Care. The outcome was obtained by the presence and availability of the following infrastructure items: air circulation in the consultation room, refrigerator, individual protective equipment, plastic jar for sputum examination, and TB notification form of the primary care information system. Poisson regression was used to calculate the prevalence ratio. Findings Of the 38,812 evaluated centres, only 1628 (4.2%) presented a positive result regarding the outcome. Primary health centres, among all types of centres, presented the highest quality of facility infrastructure for TB control. Centres with large workloads, as well as those that presented a list of offered services and a welcoming consulting room, also presented the highest quality infrastructure. The present study shows that major improvements should be made to the infrastructure to reach a satisfactory TB control in Brazil.
Evolution of melanoma cross-resistance to CD8+ T cells and MAPK inhibition in the course of BRAFi treatment

ABSTRACT The profound but frequently transient clinical responses to BRAFV600 inhibitor (BRAFi) treatment in melanoma emphasize the need for combinatorial therapies. Multiple clinical trials combining BRAFi and immunotherapy are under way to further enhance therapeutic responses. However, to which extent BRAFV600 inhibition may affect melanoma immunogenicity over time remains largely unknown. To support the development of an optimal treatment protocol, we studied the impact of prolonged BRAFi exposure on the recognition of melanoma cells by T cells in different patient models. We demonstrate that autologous CD8+ tumor-infiltrating lymphocytes (TILs) efficiently recognized short-term (3, 7 days) BRAFi-treated melanoma cells but were less responsive towards long-term (14, 21 days) exposed tumor cells. Those long-term BRAFi-treated melanoma cells showed a non-proliferative dedifferentiated phenotype and were less sensitive to four out of five CD8+ T cell clones, present in the preexisting TIL repertoire, of which three recognized shared antigens (Tyrosinase, Melan-A and CSPG4) and one being neoantigen-specific. Only a second neoantigen was steadily recognized independent of treatment duration. Notably, in all cases the impaired T cell activation was due to a time-dependent downregulation of their respective target antigens. Moreover, combinatorial treatment of melanoma cells with BRAFi and an inhibitor of its downstream kinase MEK had similar effects on T cell recognition. In summary, MAP kinase inhibitors (MAPKi) strongly alter the tumor antigen expression profile over time, favoring evolution of melanoma variants cross-resistant to both T cells and MAPKi. Our data suggest that simultaneous treatment with MAPKi and immunotherapy could be most effective for tumor elimination.
Implications of parents’ work travel on youth adjustment

ABSTRACT Guided by ecological, work–family spillover and crossover frameworks, this study examined mechanisms linking parental work travel (i.e. nights per year) to youth adjustment (i.e. externalizing and internalizing behaviours) through youth’s perceptions of parenting (i.e. knowledge, solicitation) with traveller and youth gender as moderators in a sample of 78 children in 44 two-parent families residing in the United States. The findings from multilevel analyses suggested that mothers’ travel nights predicted lower levels of maternal knowledge, with variation by traveller and youth gender. Mothers’ and fathers’ work travel and perceived parenting were predictors of youth’s externalizing behaviours, whereas only fathers’ work travel and perceived parenting were predictors of youth’s internalizing behaviours. Tests of indirect effects indicated that maternal work travel linked to youth’s externalizing behaviours through youth’s perceptions of maternal knowledge. These findings add to our limited understanding of work–family issues for parents who have the unique work demand of frequently travelling.
Early change in reward and punishment sensitivity as a predictor of response to antidepressant treatment for major depressive disorder: a CAN-BIND-1 report

Abstract Background In an effort to optimize patient outcomes, considerable attention is being devoted to identifying patient characteristics associated with major depressive disorder (MDD) and its responsiveness to treatment. In the current study, we extend this work by evaluating whether early change in these sensitivities is associated with response to antidepressant treatment for MDD. Methods Participants included 210 patients with MDD who were treated with 8 weeks of escitalopram and 112 healthy comparison participants. Of the original 210 patients, 90 non-responders received adjunctive aripiprazole for an additional 8 weeks. Symptoms of depression and anhedonia were assessed at the beginning of treatment and 8 weeks later in both samples. Reward and punishment sensitivity were assessed using the BIS/BAS scales measured at the initiation of treatment and 2 weeks later. Results Individuals with MDD exhibited higher punishment sensitivity and lower reward sensitivity compared with healthy comparison participants. Change in reward sensitivity during the first 2 weeks of treatment was associated with improved depressive symptoms and anhedonia following 8 weeks of treatment with escitalopram. Similarly, improvement in reward responsiveness during the first 2 weeks of adjunctive therapy with aripiprazole was associated with fewer symptoms of depression at post-treatment. Conclusions Findings highlight the predictive utility of early change in reward sensitivity during antidepressant treatment for major depression. In a clinical setting, a lack of change in early reward processing may signal a need to modify a patient's treatment plan with alternative or augmented treatment approaches.
Defending Elections Against Malicious Spread of Misinformation

The integrity of democratic elections depends on voters’ access to accurate information. However, modern media environments, which are dominated by social media, provide malicious actors with unprecedented ability to manipulate elections via misinformation, such as fake news. We study a zerosum game between an attacker, who attempts to subvert an election by propagating a fake new story or other misinformation over a set of advertising channels, and a defender who attempts to limit the attacker’s impact. Computing an equilibrium in this game is challenging as even the pure strategy sets of players are exponential. Nevertheless, we give provable polynomial-time approximation algorithms for computing the defender’s minimax optimal strategy across a range of settings, encompassing different population structures as well as models of the information available to each player. Experimental results confirm that our algorithms provide nearoptimal defender strategies and showcase variations in the difficulty of defending elections depending on the resources and knowledge available to the defender.
Tunable Magnetization Chains Induced With Annular Parabolic Mirrors

Based on the inverse Faraday effect, tunable light-induced magnetization chains are investigated by focusing narrow annular azimuthally polarized vortex beams with a 4<inline-formula><tex-math notation="LaTeX">$\pi$</tex-math> </inline-formula> focusing system composed of double annular parabolic mirrors. Using Richards–Wolf vector diffraction theory, approximate analytical expressions of all parameters of the magnetization chains are theoretically calculated, realizing that all parameters are tunable. The calculated results show that the parameters are independent of the amplitude distribution function of the incident beam and the apodization factor of the focusing system. Hence, different kinds of long (about <inline-formula><tex-math notation="LaTeX">$100\lambda$</tex-math></inline-formula>) chains with sub-wavelength lateral size can be achieved by adjusting the central angular position, the angular width, and the phase difference of two counter-propagating incident beams. Compared with lenses, parabolic mirrors can generate multi-needle fields that lenses cannot.
VoxelMorph: A Learning Framework for Deformable Medical Image Registration

We present VoxelMorph, a fast learning-based framework for deformable, pairwise medical image registration. Traditional registration methods optimize an objective function for each pair of images, which can be time-consuming for large datasets or rich deformation models. In contrast to this approach and building on recent learning-based methods, we formulate registration as a function that maps an input image pair to a deformation field that aligns these images. We parameterize the function via a convolutional neural network and optimize the parameters of the neural network on a set of images. Given a new pair of scans, VoxelMorph rapidly computes a deformation field by directly evaluating the function. In this paper, we explore two different training strategies. In the first (unsupervised) setting, we train the model to maximize standard image matching objective functions that are based on the image intensities. In the second setting, we leverage auxiliary segmentations available in the training data. We demonstrate that the unsupervised model’s accuracy is comparable to the state-of-the-art methods while operating orders of magnitude faster. We also show that VoxelMorph trained with auxiliary data improves registration accuracy at test time and evaluate the effect of training set size on registration. Our method promises to speed up medical image analysis and processing pipelines while facilitating novel directions in learning-based registration and its applications. Our code is freely available at https://github.com/voxelmorph/voxelmorph.
Relationship Between Postoperative Neutrophil–Lymphocyte Ratio and 6-Month Primary Patency of Percutaneous Transluminal Angioplasty in Femoropopliteal disease With Drug-Coated and Uncoated Balloons

We investigated the relationship of postoperative neutrophil–lymphocyte ratio (NLR) with 6-month primary patency of percutaneous transluminal angioplasty (PTA) in femoropopliteal disease using drug-coated balloon (DCB) or uncoated balloon (UCB). This retrospective study included 106 patients who received DCB (n = 44) or UCB (n = 62). The postoperative NLR was lower in the DCB group than that in the UCB group (2.60 vs 3.23; P = .004), and 6-month primary patency rate was significantly higher in DCB group than that in the UCB group (77.3% vs 53.2%; P = .011). Multivariate logistic analysis showed that the postoperative NLR was an independent predictor of 6-month primary patency after PTA in patients with femoropopliteal disease (odds ratio: 1.589, 95% confidence interval: 1.078-2.343; P = .019). The cutoff value of postoperative NLR was 3.05 for prediction of 6-month primary patency, with a sensitivity of 64.1% and specificity of 65.7%. The 6-month primary patency rate in the NLR ≤3.05 group was higher than that in the NLR >3.05 group (75.9% vs 47.9%; P = .003). In conclusion, DCB may improve early primary patency by inhibiting inflammation. A higher postoperative NLR was associated with early restenosis.