Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor

Significance The inflammasomes are signaling platforms that promote the activation of inflammatory caspases such as caspases-1, -4, -5, and -11, which cleave gasdermin D (GSDMD) to induce pyroptotic cell death. The mechanisms of GSDMD recognition by inflammatory caspases remain poorly understood. Here, we demonstrate that the catalytic domains of inflammatory caspases can directly bind to GSDMD or its cleavage site peptide, FLTD. A GSDMD-derived inhibitor, N-acetyl-Phe-Leu-Thr-Asp-chloromethylketone (Ac-FLTD-CMK), inhibits GSDMD cleavage in vitro and suppresses pyroptosis downstream of both canonical and noncanonical inflammasomes. By contrast, the inhibitor does not target caspase-3 or apoptosis, suggesting that it is specific for inflammatory caspases. Structure of caspase-1 in complex with Ac-FLTD-CMK reveals extensive enzyme–inhibitor interactions that shed light on GSDMD recognition by inflammatory caspases. The inflammasomes are signaling platforms that promote the activation of inflammatory caspases such as caspases-1, -4, -5, and -11. Recent studies identified gasdermin D (GSDMD) as an effector for pyroptosis downstream of the inflammasome signaling pathways. Cleavage of GSDMD by inflammatory caspases allows its N-terminal domain to associate with membrane lipids and form pores that induce pyroptotic cell death. Despite the important role of GSDMD in pyroptosis, the molecular mechanisms of GSDMD recognition and cleavage by inflammatory caspases that trigger pyroptosis are poorly understood. Here, we demonstrate that the catalytic domains of inflammatory caspases can directly bind to both the full-length GSDMD and its cleavage site peptide, FLTD. A GSDMD-derived inhibitor, N-acetyl-Phe-Leu-Thr-Asp-chloromethylketone (Ac-FLTD-CMK), inhibits GSDMD cleavage by caspases-1, -4, -5, and -11 in vitro, suppresses pyroptosis downstream of both canonical and noncanonical inflammasomes, as well as reduces IL-1β release following activation of the NLRP3 inflammasome in macrophages. By contrast, the inhibitor does not target caspase-3 or apoptotic cell death, suggesting that Ac-FLTD-CMK is a specific inhibitor for inflammatory caspases. Crystal structure of caspase-1 in complex with Ac-FLTD-CMK reveals extensive enzyme–inhibitor interactions involving both hydrogen bonds and hydrophobic contacts. Comparison with other caspase-1 structures demonstrates drastic conformational changes at the four active-site loops that assemble the catalytic groove. The present study not only contributes to our understanding of GSDMD recognition by inflammatory caspases but also reports a specific inhibitor for these caspases that can serve as a tool for investigating inflammasome signaling.
An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis After Methotrexate or After 1 or 2 TNF Inhibitors from a U.S. Payer Perspective

BACKGROUND: Treatment cycling with biologic disease-modifying anti-rheumatic drugs, such as tumor necrosis factor inhibitors (TNFi), is common among patients with rheumatoid arthritis (RA) and can result in reduced clinical efficacy and increased economic burden. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. OBJECTIVE: To evaluate and compare the economic effect of tofacitinib 5 mg twice daily (BID) treatment directly after methotrexate (MTX) in the MTX-inadequate responder population, or after MTX and 1 TNFi (adalimumab [ADA] or etanercept [ETN]) or 2 TNFi (ADA and ETN) in TNF-inadequate responder patients with RA, from a U.S. payer perspective. METHODS: A decision-tree economic model was used to evaluate costs over 2 years. Treatment response was modeled as American College of Rheumatology (ACR) 20/50/70 response. ACR response rates at 6-month intervals were derived from U.S. prescribing information for monotherapy and combination therapy. Safety event rates were sourced from a meta-analysis. It was assumed that 75% of patients switched therapy after an adverse event or lack of response. Cost inputs included drugs, monitoring and administration (including physician visits), health care utilization, and treatment for adverse events. The population comprised all organization members (i.e., RA and non-RA members); RA patients receiving TNFi were estimated using epidemiologic data. Results were based on an organization size of 1 million. Economic endpoints were total 2-year costs, costs per member per month (PMPM), and costs per ACR20/50 responder. RESULTS: 1,321 patients were included for analysis. Based on ACR20 switch criteria and either 100% or 50% monotherapy rates for all treatments, total 2-year costs and costs PMPM were lower for patients receiving tofacitinib as second-line therapy after MTX and as third-line therapy after MTX and 1 TNFi; costs were highest for patients who cycled through 2 TNFi. Similar trends were observed for switch criteria based on ACR50 response and addition of 20% rebates for ADA and ETN and 0% for tofacitinib, although differences were mitigated slightly. CONCLUSIONS: A treatment strategy with tofacitinib as either second- or third-line therapy after MTX may be a lower cost treatment option, compared with fourth-line introduction of tofacitinib after cycling through 2 TNFi following MTX.
The 1‐year Renal Biopsy Index: a scoring system to drive biopsy indication at 1‐year post‐kidney transplantation

Surveillance biopsies after renal transplantation remain debatable. To drive the decision of such intervention, we propose a predictive score of abnormal histology at 1‐year post‐transplantation, named 1‐year Renal Biopsy Index (1‐RBI). We studied 466 kidney recipients from the DIVAT cohort alive with a functioning graft and a surveillance biopsy at 1‐year post‐transplantation. Patients displaying abnormal histology (49%) (borderline, acute rejection, interstitial fibrosis and tubular atrophy [IFTA] grade 2 or 3, glomerulonephritis) were compared to the normal or subnormal (IFTA grade 1) histology group. Obtained from a lasso penalized logistic regression, the 1‐RBI was composed of recipient gender, serum creatinine at 3, 6, and 12 month post‐transplantation and anticlass II immunization at transplantation (internal validation: AUC = 0.71, 95% CI [0.53–0.83]; external validation: AUC = 0.62, 95% CI [0.58–0.66]). While we could not determinate a threshold able to identify patients at high chance of normal or subnormal histology, we estimated and validated a discriminating threshold capable of identifying a subgroup of 15% of the patients with a risk of abnormal histology higher than 80%. The 1‐RBI is computable online at www.divat. fr. The 1‐RBI could be a useful tool to standardize 1‐year biopsy proposal and may for instance help to indicate one in case of high risk of abnormal histology.
Hysteresis and change of persistence in unemployment rates, international evidence

1 STRUCTURE OF THE WORK . 1 1. CONCEPT OF UNEMPLOYMENT IN A MACROECONOMICS WAY . 2 2. THE CONCEPT OF HYSTERESIS. WHY IS IT SO IMPORTANT IN THIS WORK? 3 2.1. THEORIES OF HYSTERESIS . 3 2.2. HYSTERESIS MECHANISMS IN THE LABOR MARKET . 4 2.3. PERSISTENCE VERSUS HYSTERESIS . 6 3. UNEMPLOYMENT RATE AND ECONOMETRICS . 7 3.2. HYSTERESIS IN ECONOMETRICS: . 9 3.3. DICKEY-FULLER GLS-DETRENDED TEST . 10 4. EMPIRICAL RESULTS . 10 4.
Convex mixture regression for quantitative risk assessment

There is wide interest in studying how the distribution of a continuous response changes with a predictor. We are motivated by environmental applications in which the predictor is the dose of an exposure and the response is a health outcome. A main focus in these studies is inference on dose levels associated with a given increase in risk relative to a baseline. In addressing this goal, popular methods either dichotomize the continuous response or focus on modeling changes with the dose in the expectation of the outcome. Such choices may lead to information loss and provide inaccurate inference on dose‐response relationships. We instead propose a Bayesian convex mixture regression model that allows the entire distribution of the health outcome to be unknown and changing with the dose. To balance flexibility and parsimony, we rely on a mixture model for the density at the extreme doses, and express the conditional density at each intermediate dose via a convex combination of these extremal densities. This representation generalizes classical dose‐response models for quantitative outcomes, and provides a more parsimonious, but still powerful, formulation compared to nonparametric methods, thereby improving interpretability and efficiency in inference on risk functions. A Markov chain Monte Carlo algorithm for posterior inference is developed, and the benefits of our methods are outlined in simulations, along with a study on the impact of dde exposure on gestational age.
Intense physical exercise potentiates glucose inhibitory effect over food intake of male Wistar rats

What is the central question of this study? How does an acute session of exercise affect food intake of male Wistar rats? What is the main finding and its importance? Food intake in male Wistar rats is decreased in the first hour after physical exercise independent of the intensity. Moreover, high‐intensity exercise potentiates the anorexic effect of peripheral glucose administration. This work raises new feeding‐related targets that would explain how exercise drives body weight loss.
Alcohol Use and Sexual and Physical Assault Victimization Among University Students: Three Years of Follow-Up

The aim of this study was to determine the incidence of sexual and physical assault among university students and its association with alcohol use. The research is part of a wider cohort study (Spit for ScienceTM) at a large public university in the United States. The follow-up data include the first two cohorts (2011, 2012; n = 5,170). The dependent variables were victim of sexual assault and victim of physical assault. The independent variables were alcohol dependence and abuse according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.), cannabis use, residence, ethnicity, sexual orientation, and previous experience of sexual assault and/or physical assault. We used multilevel logistic regression for repeated measures. All data were analyzed using generalized linear mixed models. Incidence rates of sexual and physical assault (per 100 students a year) were 15.1 and 27.6 among nonabusers/dependents versus 36.4 and 56.7 among alcohol-dependent females at the first year, and 2.8 and 4.7 versus 7.7 and 23.1 at the third year; while in males, incident rates were 6.0 and 3.1 versus 18.5 and 66.6, and 2.3 and 7.4 versus 18.9 and 15.1, respectively. Our results show that alcohol abuse and dependence constitute risk factors to be victim of sexual assault in males (odds ratio [OR] = 2.21 and OR = 2.73) and alcohol dependence in females (OR = 2.16). Similarly, alcohol abuse and dependence are risk factors to physical assault among both males (OR = 1.52 and OR = 2.03) and females (OR = 1.70 and OR = 2.88). Ethnicity, sexual orientation, and whether the individual had been victimized in the past were associated with sexual assault. Regarding physical assault, cannabis use and past victimization are also risk factors. Our study has shown that assault victimization is strongly related to alcohol abuse and dependence diagnoses in both genders. Ethnicity and sexual orientation are also associated to both assaults. Our results show that incidence rates of both types of assaults were clearly higher in the first 6 months of university, probably explained by the novel and potentially risky environment.
Myoelectric control with abstract decoders

Objective. The objective of this study was to compare the use of muscles appropriate for partial-hand prostheses with those typically used for complete hand devices and to determine whether differences in their underlying neural substrates translate to different levels of myoelectric control. Approach. We developed a novel abstract myoelectric decoder based on motor learning. Three muscle pairs, namely, an intrinsic and independent, an intrinsic and synergist and finally, an extrinsic and antagonist, were tested during abstract myoelectric control. Feedback conditions probed the roles of feed-forward and feedback mechanisms. Results. Both performance levels and rates of improvement were significantly higher for intrinsic hand muscles relative to muscles of the forearm. Intrinsic hand muscles showed considerable improvement generalising to decoder use without visual feedback. Results indicate that visual feedback from the decoder is used for transitioning between muscle activity levels, but not for maintaining state. Both individual and group performance were found to be strongly related to motor variability. Significance. Physiological differences inherent to the hand muscles can translate to improved prosthesis control. Our results support the use of motor learning based techniques for upper-limb myoelectric control and strongly argues for their utility in control of partial-hand prostheses. We provide evidence of myoelectric control skill acquisition and offer a formal definition for abstract decoding in the context of prosthetic control.
Changes in the Sociodemographic Factors of Tobacco and Alcohol Consumption in Chinese Adolescents from 2004 to 2011

Finding ways to reduce tobacco and alcohol consumption among adolescents has been a major public health challenge in China. In relation to this issue, the current study evaluated the changes in the sociodemographic factors of tobacco and alcohol consumption among Chinese adolescents who are 12–18 years old. Trends in sociodemographic factors associated with tobacco and alcohol consumption were investigated based on the 2004–2011 China Health and Nutrition Survey data. Questionnaires that extracted data on tobacco and alcohol consumption (i.e., prior experience of smoking cigarettes and drinking alcoholic beverages) were distributed. Additional variables (e.g., age, residence, gender, etc.) were used in the analyses. Firth penalized logistic regression was conducted with drinking and smoking status variables as the dependent variables. Male adolescents were more inclined to smoke in 2004, 2006, 2009, and 2011 (p < 0.05 for all). Adolescents aged 15–16 years were more inclined to smoke compared with those aged 12–14 years in 2004, 2006, and 2011 (p < 0.05 for all). Among adolescents aged 15–18 years, older ones were more inclined to not smoke in 2004 (odds ratio (OR) = 0.531, 95% confidence interval (CI) 0.343–0.821). Adolescents who did not attend school were more inclined to smoke in 2004, 2006, 2009, and 2011 (p < 0.05 for all). Adolescents who were drinkers were more inclined to smoke in 2004, 2006, 2009, and 2011 (p < 0.05 for all). Male adolescents were more likely to drink in 2004, 2006, and 2009 (p < 0.05 for all). In 2006 and 2009, adolescents aged 15–16 years were more inclined to drink compared with those aged 12–14 years (p < 0.05 for all). Among adolescents aged 15–18 years, older ones were less inclined to drink in 2004 (OR = 0.719, 95% CI 0.527–0.980) and 2006 (OR = 0.716, 95% CI 0.527–0.972). Adolescents who smoked were more likely to drink in 2004, 2006, 2009, and 2011 (p < 0.05 for all). The prevalence of tobacco and alcohol consumption among adolescents has not changed significantly. The current study identified adolescent high-risk groups for tobacco and alcohol consumption.
9p24 triplication in syndromic hydrocephalus with diffuse villous hyperplasia of the choroid plexus

Hydrocephalus, a disorder of impaired cerebrospinal fluid (CSF) homeostasis, often results from an imbalance between CSF production and reabsorption. Rarely, hydrocephalus is the consequence of CSF hypersecretion in the context of diffuse villous hyperplasia of the choroid plexus (DVHCP). The limited genetic information in previously reported cases suggests a high prevalence of gains of Chromosome 9p in this disease, although the critical genes involved in DVHCP pathogenesis have not been identified. Here, we report a patient with syndromic hydrocephalus with DVHCP associated with a novel 9p24.3-11.2 triplication and 15q13.2-q13.3 microdeletion. We review the clinical, radiological, and pathological features of DVHCP, as well as its surgical management. A better understanding of the genetic basis of DVHCP could spur the development of rational, targeted nonsurgical hydrocephalus treatments.
Long-term visual outcome and its predictors in macular oedema secondary to retinal vein occlusion treated with dexamethasone implant

Background To evaluate the functional long-term outcome in patients with macular oedema (MO) secondary to central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) treated with dexamethasone implant (DEX implant) and to identify its clinical predictors. Methods A 24-month, retrospective, multinational, real-world study. Chart review of patients with either naïve or recurrent MO secondary to CRVO/BRVO treated with DEX implant, including best-corrected visual acuity (BCVA), central subfield thickness (CST), demographic baseline characteristics and details of any additional treatment during follow-up. Results A total of 155 eyes (65 CRVO, 90 BRVO) from 155 patients were included. At 24 months, mean BCVA did not change significantly in CRVO (−2.1±24.5 letters, p=0.96) and BRVO patients (1.3±27.0 letters, p=0.07). A worse baseline BCVA (p<0.001), visual acuity (VA) gain ≥5 letters at 2 months (p=0.006) and no need for adjunctive intravitreal therapy after first DEX implant (p=0.001) were associated with a better final BCVA gain. Treatment-naïve patients (p=0.006, OR: 0.25, 95% CI 0.11 to 0.57) and those with a baseline CST≤400 µm (p=0.02, OR: 0.25, 95% CI 0.10 to 0.63) were identified as being less likely to need additional intravitreal therapy. Conclusion Clinical baseline characteristics and the early treatment response were identified as possible predictors for long-term outcome and the need of adjunctive intravitreal therapy in MO secondary to BRVO/CRVO treated by DEX implant.
FraudDroid: automated ad fraud detection for Android apps

Although mobile ad frauds have been widespread, state-of-the-art approaches in the literature have mainly focused on detecting the so-called static placement frauds, where only a single UI state is involved and can be identified based on static information such as the size or location of ad views. Other types of fraud exist that involve multiple UI states and are performed dynamically while users interact with the app. Such dynamic interaction frauds, although now widely spread in apps, have not yet been explored nor addressed in the literature. In this work, we investigate a wide range of mobile ad frauds to provide a comprehensive taxonomy to the research community. We then propose, FraudDroid, a novel hybrid approach to detect ad frauds in mobile Android apps. FraudDroid analyses apps dynamically to build UI state transition graphs and collects their associated runtime network traffics, which are then leveraged to check against a set of heuristic-based rules for identifying ad fraudulent behaviours. We show empirically that FraudDroid detects ad frauds with a high precision (∼ 93%) and recall (∼ 92%). Experimental results further show that FraudDroid is capable of detecting ad frauds across the spectrum of fraud types. By analysing 12,000 ad-supported Android apps, FraudDroid identified 335 cases of fraud associated with 20 ad networks that are further confirmed to be true positive results and are shared with our fellow researchers to promote advanced ad fraud detection.
My partner’s stories: relationships between personal and vicarious life stories within romantic couples

ABSTRACT In this paper, we examined relationships and differences between personal and vicarious life stories, i.e., the life stories one knows of others. Personal and vicarious life stories of both members of 51 young couples (102 participants), based on McAdams’ Life Story Interview (2008), were collected. We found significant positive relationships between participants’ personal and vicarious life stories on agency and communion themes and redemption sequences. We also found significant positive relationships between participants’ vicarious life stories about their partners and those partners’ personal life stories on agency and communion, but not redemption. Furthermore, these relationships were not explained by similarity between couples’ two personal life stories, as no associations were found between couples’ personal stories on agency, communion and redemption. These results suggest that the way we construct the vicarious life stories of close others may reflect how we construct our personal life stories.
Adversarial Attacks on Variational Autoencoders

Adversarial attacks are malicious inputs that derail machine-learning models. We propose a scheme to attack autoencoders, as well as a quantitative evaluation framework that correlates well with the qualitative assessment of the attacks. We assess — with statistically validated experiments — the resistance to attacks of three variational autoencoders (simple, convolutional, and DRAW) in three datasets (MNIST, SVHN, CelebA), showing that both DRAW’s recurrence and attention mechanism lead to better resistance. As autoencoders are proposed for compressing data — a scenario in which their safety is paramount — we expect more attention will be given to adversarial attacks on them.
Subjectively perceived control drives affective, neural, and motivational markers of self-related outcome valuation

Experiencing one’s own life as controllable is essential for human well-being. Based on the theory that subjectively perceived control (SPC) hinges on the attribution of events to the self, we test the effects of SPC on the affective evaluation of task outcomes, neural dynamics, and ensuing behavioral preferences. In three independent studies we show that SPC increases dynamics in self-evaluative affect and engages brain networks processing self-referential information in the cortical midline. Specifically, the ventromedial prefrontal cortex tracks both outcome value and SPC and covaries with self-evaluative affect. Furthermore, high SPC and greater affective dynamics relate to greater functional coupling between the ventral striatum and cortical midline structures during outcome consumption. Finally, we show that these affective reactions promote motivation and the subjective value of controllable tasks. Our investigations emphasize the importance of subjective models of how behavior leads to desired outcomes for positive affect and intrinsic motivation.