Miracle-dz/UniFAR-FTUs huggingface dataset:
PNPLA3 overexpression results in reduction of proteins predisposing to fibrosis

Abstract Liver fibrosis is a pathological scarring response to chronic hepatocellular injury and hepatic stellate cells (HSCs) are key players in this process. PNPLA3 I148M is a common variant robustly associated with liver fibrosis but the mechanisms underlying this association are unknown. We aimed to examine a) the effect of fibrogenic and proliferative stimuli on PNPLA3 levels in HSCs and b) the role of wild type and mutant PNPLA3 overexpression on markers of HSC activation and fibrosis. Here, we show that PNPLA3 is upregulated by the fibrogenic cytokine transforming growth factor-beta (TGF-β), but not by platelet-derived growth factor (PDGF), and is involved in the TGF-β-induced reduction in lipid droplets in primary human HSCs. Furthermore, we show that retinol release from human HSCs ex vivo is lower in cells with the loss-of-function PNPLA3 148M compared with 148I wild type protein. Stable overexpression of PNPLA3 148I wild type, but not 148M mutant, in human HSCs (LX-2 cells) induces a reduction in the secretion of matrix metallopeptidase 2 (MMP2), tissue inhibitor of metalloproteinase 1 and 2 (TIMP1 and TIMP2), which is mediated by retinoid metabolism. In conclusion, we show a role for PNPLA3 in HSC activation in response to fibrogenic stimuli. Moreover, we provide evidence to indicate that PNPLA3-mediated retinol release may protect against liver fibrosis by inducing a specific signature of proteins involved in extracellular matrix remodelling.
We present a multi-instrument study of a hot flow anomaly ( HFA ) observed by the Venus Express spacecraft in the Venusian foreshock , on 22 March 2008 , incorporating both Venus Express Magnetometer and Analyzer of Space Plasmas

[1] We present a multi-instrument study of a hot flow anomaly (HFA) observed by the Venus Express spacecraft in the Venusian foreshock, on 22 March 2008, incorporating both Venus Express Magnetometer and Analyzer of Space Plasmas and Energetic Atoms (ASPERA) plasma observations. Centered on an interplanetary magnetic field discontinuity with inward convective motional electric fields on both sides, with a decreased core field strength, ion observations consistent with a flow deflection, and bounded by compressive heated edges, the properties of this event are consistent with those of HFAs observed at other planets within the solar system.
Efficacy and Safety of Second-Line 5-Day Dactinomycin in Case of Methotrexate Failure for Gestational Trophoblastic Neoplasia

Objective The objective of this study was to evaluate the characteristics and outcomes of patients treated for gestational trophoblastic neoplasia (GTN) with second-line 5-day dactinomycin after failed first-line 8-day methotrexate. Methods From 1999 to 2017, patients with methotrexate resistant GTN treated with second line dactinomycin were identified at the French Trophoblastic Disease Reference Center. Using univariate and multivariate analysis, we identified significant predictive factors of second line dactinomycin failure. Results A total of 877 GTN patients were treated with first-line 8-day methotrexate, of which 103 required second-line 5-day dactinomycin for methotrexate failure. Complete response was observed in 78 patients (75.7% [95% confidence interval, 66.3–83.6]; P < 0.0001), whereas 25 needed third-line treatment, 13 for dactinomycin resistance and 12 for post–dactinomycin relapse. Overall survival of patients treated with dactinomycin was 100%. An interval of greater than or equal to 7 months between antecedent pregnancy termination and methotrexate initiation was a predictive factor significantly associated with second-line dactinomycin failure in multivariate analysis (exact odds ratio, 9.17 [95% confidence interval, 1.98–50.70]; P = 0.0029). No grades 4 and 5 adverse effects were experienced and the most common toxicity being grade 1 nausea (14.6%). Conclusion Given a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies.
Large-scale replication study reveals a limit on probabilistic prediction in language comprehension

Do people routinely pre-activate the meaning and even the phonological form of upcoming words? The most acclaimed evidence for phonological prediction comes from a 2005 Nature Neuroscience publication by DeLong, Urbach and Kutas, who observed a graded modulation of electrical brain potentials (N400) to nouns and preceding articles by the probability that people use a word to continue the sentence fragment (‘cloze’). In our direct replication study spanning 9 laboratories (N=334), pre-registered replication-analyses and exploratory Bayes factor analyses successfully replicated the noun-results but, crucially, not the article-results. Pre-registered single-trial analyses also yielded a statistically significant effect for the nouns but not the articles. Exploratory Bayesian single-trial analyses showed that the article-effect may be non-zero but is likely far smaller than originally reported and too small to observe without very large sample sizes. Our results do not support the view that readers routinely pre-activate the phonological form of predictable words.
Stereotactic Radiotherapy and Particle Therapy for Pancreatic Cancer

Pancreatic cancer is a devastating disease with poor survival outcomes. Recent studies have shown that the addition of radiotherapy to chemotherapy in the setting of locally advanced pancreatic cancer did not improve overall survival outcome. These studies commonly utilize conventional radiotherapy treatment fractionation and technique (typically 3-D conformal radiotherapy or intensity modulated radiotherapy). Although no clear benefit in overall survival was demonstrated in those studies, those who received radiotherapy did have a clear benefit in terms of local control. Therefore, there is increasing interest in exploring different techniques and/or modality of radiotherapy and dose/fractionation. Stereotactic radiotherapy, which employs a hypofractionated regimen, has the potential advantage of delivering a high dose of radiation to the tumor in a short period of time (typically over 5 days) with minimal dose to the surrounding normal structures. Particle therapy such as proton and carbon ion therapy are being explored as potential radiation modality that could cause greater biological damage to the tumor compared to photon treatment, with rapid dose falloff resulting in minimal to no dose to adjacent structures. This review will discuss the current literature and emerging roles of stereotactic radiotherapy and particle therapy in pancreatic cancer.
PP242 Counteracts Glioblastoma Cell Proliferation, Migration, Invasiveness and Stemness Properties by Inhibiting mTORC2/AKT

Glioblastoma multiforme (GBM) is the most malignant brain tumor and is associated with poor prognosis due to its thorny localization, lack of efficacious therapies and complex biology. Among the numerous pathways driving GBM biology studied so far, PTEN/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling plays a pivotal role, as it controls cell survival, proliferation and metabolism and is involved in stem cell maintenance. In front of recent and numerous evidences highlighting mTOR upregulation in GBM, all the strategies developed to inhibit this pathway have been substantially unsuccessful. Our study focused on mTOR complex 2 (mTORC2) to understand its involvement in GBM cell growth, proliferation, migration and invasiveness. We utilized an in vitro model, characterized by various genetic alterations (i.e., GL15, U257, U87MG and U118MG cell lines) in order to achieve the clonal heterogeneity observed in vivo. Additionally, being the U87MG cell line endowed with glioblastoma stem cells (GSCs), we also investigated the role of the PTEN/PI3K/AKT/mTOR pathway in this specific cell population, which is responsible for GBM relapse. We provide further insights that explain the reasons for the failure of numerous clinical trials conducted to date targeting PI3K or mTOR complex 1 (mTORC1) with rapamycin and its analogs. Additionally, we show that mTORC2 might represent a potential clinically valuable target for GBM treatment, as proliferation, migration and GSC maintenance appear to be mTORC2-dependent. In this context, we demonstrate that the novel ATP-competitive mTOR inhibitor PP242 effectively targets both mTORC1 and mTORC2 activation and counteracts cell proliferation via the induction of high autophagy levels, besides reducing cell migration, invasiveness and stemness properties.
Styrene‐Butadiene Rubber/Modified Ground Tire Rubber Blends Co‐Vulcanization: Effect of Accelerator Type

Summary Ground tire rubber was thermo-mechanically modified with using a co-rotating twin screw extruder. Modification of GTR was conducted in autothermal conditions. Styrene-butadiene rubber and modified ground tire rubber blends were prepared via two-roll milling. Obtained compounds were cured with conventional system (sulfur/vulcanization accelerator ratio was 2:1). During this research three commonly vulcanization accelerators (MBT, TBBS, TMTD) were used. Curing characteristics, static mechanical properties (tensile strength, elongation at break, hardness, resilience), dynamic mechanical properties, swelling degree and thermal properties of obtained SBR/mGTR blends were determined. SBR/modified GTR blends with higher amount of modified GTR shown improvement in tensile strength, on the other hand vulcanization accelerator type had strong influence on curing parameters, tensile strength, elongation at break, swelling degree and glass transition temperature. The best curing and mechanical properties were estimated for SBR/mGTR blend with 50 phr mGTR cured with TMTD accelerator.
Theoretical Analysis of Thermal Transport in Graphene Supported on Hexagonal Boron Nitride: The Importance of Strong Adhesion Due to π -Bond Polarization

One important attribute of graphene that makes it attractive for high-performance electronics is its inherently large thermal conductivity (κ) for the purposes of thermal management. Using a combined density-functional theory and classical molecular-dynamics approach, we predict that the κ of graphene supported on hexagonal boron nitride (h-BN) can be as large as 90% of the κ of suspended graphene, in contrast to the significant suppression of κ (more than 70% reduction) on amorphous silica. Interestingly, we find that this enhanced thermal transport is largely attributed to increased lifetimes of the in-plane acoustic phonon modes, which is a notable contrast from the dominant contribution of out-of-plane acoustic modes in suspended graphene. This behavior is possible due to the charge polarization throughout graphene that induces strong interlayer adhesion between graphene and h-BN. These findings highlight the potential benefit of layered dielectric substrates such as h-BN for graphene-based thermal management, in addition to their electronic advantages. Furthermore, our study brings attention to the importance of understanding the interlayer interactions of graphene with layered dielectric materials which may offer an alternative technological platform for substrates in electronics.
The psychosocial impact of acne, vitiligo, and psoriasis: a review

Introduction Chronic skin conditions have been well reported to affect a patient’s quality of life on multiple dimensions, including the psychosocial domain. Psychosocial is defined as the interrelation of social factors with an individual’s thoughts and behavior. The assessment of the psychosocial impact of skin disease on a patient can help direct the dermatologists’ treatment goals. To evaluate the psychosocial impact of skin disease, we conducted a review of the literature on three skin conditions with onsets at various stages of life: acne, vitiligo, and psoriasis. Methods A PubMed search was conducted in March 2015 using the terms “psychosocial” AND “acne”, “psychosocial” AND “vitiligo”, and “psychosocial” AND “psoriasis”. The results were limited to articles published in English in the past 5 years studying patients of all ages. Results and their references were evaluated for relevance according to their discussion of psychosocial qualities in their patients and the validity of psychosocial assessments. The search for acne yielded 51 results, and eleven were found to be relevant; vitiligo yielded 30 results with ten found to be relevant; and psoriasis yielded 70 results with seven found to be relevant. Results According to the articles evaluated, 19.2% of adolescent patients with acne were affected in their personal and social lives. Social phobia was present in 45% of patients with acne compared to 18% of control subjects. Race and sex played a role in self-consciousness and social perceptions of the disease. Vitiligo negatively affected marriage potential and caused relationship problems in >50% of patients. Psoriasis negatively affected multiple domains of life, including work, relationships, and social activities. Anxiety and depression affected not only psoriasis patients but also their cohabitants; up to 88% of cohabitants had an impaired quality of life. Conclusion Though all three skin conditions resulted in an increase in anxiety and depression among their patient populations, the psychosocial focus varied slightly for each disease. Overall, acne, vitiligo, and psoriasis can have negative psychosocial impact in different stages of life development.
Data-driven model for the assessment of Mycobacterium tuberculosis transmission in evolving demographic structures

Significance Even though tuberculosis (TB) is acknowledged as a strongly age-dependent disease, it remains unclear how TB epidemics would react, in the following decades, to the generalized aging that human populations are experiencing worldwide. This situation is partly caused by the limitations of current transmission models at describing the relationship between demography and TB transmission. Here, we present a data-driven epidemiological model that, unlike previous approaches, explicitly contemplates relevant aspects of the coupling between age structure and TB dynamics, such as demographic evolution and contact heterogeneities. Using our model, we identify substantial biases in epidemiological forecasts rooted in an inadequate description of these aspects, at the level of both aggregated incidence and mortality rates and their distribution across age strata. In the case of tuberculosis (TB), the capabilities of epidemic models to produce quantitatively robust forecasts are limited by multiple hindrances. Among these, understanding the complex relationship between disease epidemiology and populations’ age structure has been highlighted as one of the most relevant. TB dynamics depends on age in multiple ways, some of which are traditionally simplified in the literature. That is the case of the heterogeneities in contact intensity among different age strata that are common to all airborne diseases, but still typically neglected in the TB case. Furthermore, while demographic structures of many countries are rapidly aging, demographic dynamics are pervasively ignored when modeling TB spreading. In this work, we present a TB transmission model that incorporates country-specific demographic prospects and empirical contact data around a data-driven description of TB dynamics. Using our model, we find that the inclusion of demographic dynamics is followed by an increase in the burden levels predicted for the next decades in the areas of the world that are most hit by the disease today. Similarly, we show that considering realistic patterns of contacts among individuals in different age strata reshapes the transmission patterns reproduced by the models, a result with potential implications for the design of age-focused epidemiological interventions.
Acculturation, Adaptation and Loneliness among Brazilian Migrants Living in Portugal

Acculturation refers to the changes that individuals undergo following intercultural contact. Adaptation is the long‐term outcome of the process of acculturation, and lone‐ liness represents one indicator of negative psychological adaptation. This study, using acculturation strategies, looks to answer to four questions: (1) what is the relationship between intercultural strategies and loneliness? (2) What influence does cultural identity have on the loneliness of migrants? (3) What influence does perceived discrimination have on the loneliness of migrants? and (4) what influences do self‐worth and percep ‐ tions of others have on the loneliness? Answering these questions is important for reduc‐ ing migrants’ loneliness. This study, carried out in 2012, is constituted by 258 Brazilian migrants in Portugal (53% females and 47% males) with a mean age of 36 years. The mean length of residence in Portugal was 14 years. In order to measure loneliness, we used the ULS‐6 scale. Other scales were used to measure intercultural strategies, cul‐ tural identity, perceived discrimination, self‐esteem and attitudes towards ethnocultural groups. As predicted, in what concerns intercultural strategies, loneliness was negatively associated with the strategy of integration, and positively associated with assimilation, separation and marginalization. Ethnic identity was negatively associated with loneli‐ ness, but, contrary to expectations, national identity was positively associated with lone‐ liness. Perceived discrimination predicted positively loneliness. Finally, as expected, self‐esteem and perceptions of the in‐group predicted negatively loneliness. Implications of the study are discussed.
The Association between Maternal Stress and Childhood Eczema: A Systematic Review

Eczema is a chronic atopic disease that is highly prevalent among children worldwide. Identification of factors that may contribute to childhood eczema is needed in order to develop strategies in its prevention. Over the past decade, accumulating evidence has suggested a potential correlation between the experience of stress by mothers and the risk of eczema development in their child. The present review attempts to provide an overview of the studies that contribute data on this correlation. The literature search was conducted using five databases, resulting in the inclusion of eleven studies in the review. The findings of these studies were summarized narratively. Further, an appraisal of the reporting quality of the included studies was conducted using a twelve-item checklist adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Overall, the included studies showed that a positive correlation exists between the experience of stress among mothers and eczema risk of their child. The findings highlight the importance of the implementation of stress reduction programs for pregnant women and those in their postpartum period within communities in order to enable these individuals to relieve stress effectively.
Clustrophile 2: Guided Visual Clustering Analysis

Data clustering is a common unsupervised learning method frequently used in exploratory data analysis. However, identifying relevant structures in unlabeled, high-dimensional data is nontrivial, requiring iterative experimentation with clustering parameters as well as data features and instances. The number of possible clusterings for a typical dataset is vast, and navigating in this vast space is also challenging. The absence of ground-truth labels makes it impossible to define an optimal solution, thus requiring user judgment to establish what can be considered a satisfiable clustering result. Data scientists need adequate interactive tools to effectively explore and navigate the large clustering space so as to improve the effectiveness of exploratory clustering analysis. We introduce Clustrophile 2, a new interactive tool for guided clustering analysis. Clustrophile 2 guides users in clustering-based exploratory analysis, adapts user feedback to improve user guidance, facilitates the interpretation of clusters, and helps quickly reason about differences between clusterings. To this end, Clustrophile 2 contributes a novel feature, the Clustering Tour, to help users choose clustering parameters and assess the quality of different clustering results in relation to current analysis goals and user expectations. We evaluate Clustrophile 2 through a user study with 12 data scientists, who used our tool to explore and interpret sub-cohorts in a dataset of Parkinson's disease patients. Results suggest that Clustrophile 2 improves the speed and effectiveness of exploratory clustering analysis for both experts and non-experts.
Age-related changes on serum ggt activity and the assessment of ethanol intake.

AIMS Gamma-glutamyl transferase (GGT) is a commonly used marker of ethanol abuse. However, although increasing age has also been suggested to elevate serum GGT activities, the magnitude of such effects on GGT in the assessment of ethanol intake have remained poorly defined. METHODS GGT activities from 208 heavy drinkers were compared with those from a reference population including 1330 moderate drinkers and 1160 abstainers, who were further classified to following age intervals: 18-30, 30-50, 50-70, and >70 years. RESULTS GGT activities increased with increasing age until after 70 years decreasing values were noted in male abstainers. The heavy drinkers belonging to age groups 18-30, 30-50, and 50-70 years showed 2.7-, 8.0-, and 6.9-fold higher mean GGT activities than those in the corresponding groups of abstainers, respectively. The values in the group of moderate drinkers also exceeded those of abstainers in all age groups of men, whereas in women the difference was significant only among those aged 18-30 years. CONCLUSIONS The data indicate that GGT activities respond to ethanol intake in an age-dependent manner, which should be considered in the clinical use of GGT measurements for detecting alcohol use disorders.