Miracle-dz/UniFAR-FTUs huggingface dataset:
Excess variants in AFF 2 detected by massively parallel sequencing of males with autism spectrum disorder

Autism spectrum disorder (ASD) is a heterogeneous disorder with substantial heritability, most of which is unexplained. ASD has a population prevalence of one percent and affects four times as many males as females. Patients with fragile X E (FRAXE) intellectual disability, which is caused by a silencing of the X-linked gene AFF2, display a number of ASD-like phenotypes. Duplications and deletions at the AFF2 locus have also been reported in cases with moderate intellectual disability and ASD. We hypothesized that other rare X-linked sequence variants at the AFF2 locus might contribute to ASD. We sequenced the AFF2 genomic region in 202 male ASD probands and found that 2.5% of males sequenced had missense mutations at highly conserved evolutionary sites. When compared with the frequency of missense mutations in 5545 X chromosomes from unaffected controls, we saw a statistically significant enrichment in patients with ASD (OR: 4.9; P < 0.014). In addition, we identified rare AFF2 3′ UTR variants at conserved sites which alter gene expression in a luciferase assay. These data suggest that rare variation in AFF2 may be a previously unrecognized ASD susceptibility locus and may help explain some of the male excess of ASD.
Training Deep Face Recognition Systems with Synthetic Data

Recent advances in deep learning have significantly increased the performance of face recognition systems. The performance and reliability of these models depend heavily on the amount and quality of the training data. However, the collection of annotated large datasets does not scale well and the control over the quality of the data decreases with the size of the dataset. In this work, we explore how synthetically generated data can be used to decrease the number of real-world images needed for training deep face recognition systems. In particular, we make use of a 3D morphable face model for the generation of images with arbitrary amounts of facial identities and with full control over image variations, such as pose, illumination, and background. In our experiments with an off-the-shelf face recognition software we observe the following phenomena: 1) The amount of real training data needed to train competitive deep face recognition systems can be reduced significantly. 2) Combining large-scale real-world data with synthetic data leads to an increased performance. 3) Models trained only on synthetic data with strong variations in pose, illumination, and background perform very well across different datasets even without dataset adaptation. 4) The real-to-virtual performance gap can be closed when using synthetic data for pre-training, followed by fine-tuning with real-world images. 5) There are no observable negative effects of pre-training with synthetic data. Thus, any face recognition system in our experiments benefits from using synthetic face images. The synthetic data generator, as well as all experiments, are publicly available.
A Validated Model for Design and Evaluation of Control Architectures for a Continuous Tablet Compaction Process

The systematic design of an advanced and efficient control strategy for controlling critical quality attributes of the tablet compaction operation is necessary to increase the robustness of a continuous pharmaceutical manufacturing process and for real time release. A process model plays a very important role to design, evaluate and tune the control system. However, much less attention has been made to develop a validated control relevant model for tablet compaction process that can be systematically applied for design, evaluation, tuning and thereby implementation of the control system. In this work, a dynamic tablet compaction model capable of predicting linear and nonlinear process responses has been successfully developed and validated. The nonlinear model is based on a series of transfer functions and static polynomial models. The model has been applied for control system design, tuning and evaluation and thereby facilitate the control system implementation into the pilot-plant with less time and resources. The best performing control algorithm was used in the implementation and evaluation of different strategies for control of tablet weight and breaking force. A characterization of the evaluated control strategies has been presented and can serve as a guideline for the selection of the adequate control strategy for a given tablet compaction setup. A strategy based on a multiple input multiple output (MIMO) model predictive controller (MPC), developed using the simulation environment, has been implemented in a tablet press unit, verifying the relevance of the simulation tool.
A molecular basis of human T cell receptor autoreactivity toward self-phospholipids

Structure of autoreactive CD1b-restricted T cell receptor (TCR) provides insights into lipid autoreactivity of TCRs. Avoiding lipid autoreactivity The importance of self-tolerance is appreciated in the context of presentation of peptide antigens to T cells. Much less is known about how lipid-reactive T cells avoid reacting to abundant self-lipids. Here, Shahine et al. studied an autoreactive T cell receptor (TCR) that recognizes a rare self-phospholipid, phosphatidylglycerol (PG). They solved the structure of this TCR bound to CD1b-PG complex and compared this with previously solved structures of CD1-lipid-TCR ternary complexes. The authors found that, in the context of CD1b, TCR binding to abundant self-phospholipids is usually sterically or electrostatically repelled, and propose that this facilitates avoidance of T cell autoreactivity to ubiquitous self-phospholipids. Human T cell autoreactivity toward lipid antigens presented by CD1 proteins can manifest in numerous diseases, including psoriasis, contact hypersensitivities, and allergies. However, the molecular mechanisms for regulating T cell autoreactivity toward lipid antigens remain unclear. We determined the basis for T cell receptor (TCR) autoreactivity toward CD1b bound to self-phospholipids. The spectrum of self-antigens captured by CD1b skews toward abundant membrane phospholipids such as phosphatidylcholine and phosphatidylethanolamine. However, TCRs can specifically recognize rare phospholipids, including phosphatidylglycerol (PG). The structure of an autoreactive TCR bound to CD1b-PG shows that discrimination occurs through a marked induced fit movement of PG so that its polar head group fits snugly into the cationic cup of the TCR. Conversely, TCR binding toward ubiquitous self-phospholipids was sterically or electrostatically repelled. Accordingly, we describe a mechanism of TCR autoreactivity toward rare phospholipids and avoidance of autoreactivity to the most abundant self-phospholipids.
Three-Dimensional Resistive Metamaterial Absorber Loaded with Metallic Resonators for the Enhancement of Lower-Frequency Absorption

Resistive patch array incorporating with metallic backplane provided an effective way to achieve broadband metamaterial absorbers (MAs) in microwave frequency, and the outstanding construction contributed more flexible and diversified broadband absorption. In this paper, we attempted to load metallic resonators (MRs) to three-dimensional resistive MA to further enhance the lower-frequency absorption performance. Simulation showed that the partial absorption peak was separated to the lower frequency, while the rest of broadband absorption was unaffected. Meanwhile, after combining multi-unit of the proposed MAs, the stair-stepping broadband absorption was also achieved. Finally, three samples were fabricated. The agreements between simulations and experimental results demonstrated that resistive MA loaded with MRs provided an effective way for further enhancement of lower-frequency absorption with almost no change of the absorbing structure and lightweight characteristic. Thus, it was worthy to expect a wide range of applications to emerge inspired from the proposed attempt.
Magnetoelastic modelling of composites containing randomly dispersed ferromagnetic particles

Coupled magnetoelastic behaviour is investigated for two-phase composites containing randomly dispersed ferromagnetic particles under both magnetic and mechanical loading. The pair-wise particle interactions for magnetic field and elastic field are first defined by the solution for two particles embedded in the infinite domain, which is explicitly solved by the Green's function technique. By integrating the interactions from all other particles in the representative volume element, the homogenized magnetic and elastic fields are then obtained. Effective magnetostriction due to the magnetic interaction force is further derived. Without consideration of magnetic loading, this micromechanical model provides an effective elasticity with the pair-wise particle interactions. By dropping the interaction term, this model is reduced into Mori–Tanaka's model. Finally, magnetoelasticity is numerically solved by considering the magnetomechanical coupling effect. It is predicted that the effective Young's modulus and shear modulus decrease along with the increase of magnetic loading for random composites.
Data Analysis of Multiplex Sequencing at SOLiD Platform: A Probabilistic Approach to Characterization and Reliability Increase

New sequencing technologies such as Illumina/Solexa, SOLiD/ABI, and 454/Roche, revolutionized the biological researches. In this context, the SOLiD platform has a particular sequencing type, known as multiplex run, which enables the sequencing of several samples in a single run. It implies in cost reduction and simplifies the analysis of related samples. Meanwhile, this sequencing type requires an additional filtering step to ensure the reliability of the results. Thus, we propose in this paper a probabilistic model which considers the intrinsic characteristics of each sequencing to characterize multiplex runs and filter low-quality data, increasing the data analysis reliability of multiplex sequencing performed on SOLiD. The results show that the proposed model proves to be satisfactory due to: 1) identification of faults in the sequencing process; 2) adaptation and development of new protocols for sample preparation; 3) the assignment of a degree of confidence to the data generated; and 4) guiding a filtering process, without discarding useful sequences in an arbitrary manner.
Novel encoding and updating of positional, or directional, spatial cues are processed by distinct hippocampal subfields: Evidence for parallel information processing and the “what” stream

The specific roles of hippocampal subfields in spatial information processing and encoding are, as yet, unclear. The parallel map theory postulates that whereas the CA1 processes discrete environmental features (positional cues used to generate a “sketch map”), the dentate gyrus (DG) processes large navigation‐relevant landmarks (directional cues used to generate a “bearing map”). Additionally, the two‐streams hypothesis suggests that hippocampal subfields engage in differentiated processing of information from the “where” and the “what” streams. We investigated these hypotheses by analyzing the effect of exploration of discrete “positional” features and large “directional” spatial landmarks on hippocampal neuronal activity in rats. As an indicator of neuronal activity we measured the mRNA induction of the immediate early genes (IEGs), Arc and Homer1a. We observed an increase of this IEG mRNA in CA1 neurons of the distal neuronal compartment and in proximal CA3, after novel spatial exploration of discrete positional cues, whereas novel exploration of directional cues led to increases in IEG mRNA in the lower blade of the DG and in proximal CA3. Strikingly, the CA1 did not respond to directional cues and the DG did not respond to positional cues. Our data provide evidence for both the parallel map theory and the two‐streams hypothesis and suggest a precise compartmentalization of the encoding and processing of “what” and “where” information occurs within the hippocampal subfields.
Community-deliverable exercise and anxiety in adults with arthritis and other rheumatic diseases: a systematic review with meta-analysis of randomised controlled trials

Background/purpose Given conflicting findings, the purpose of this study was to use the meta-analytic approach to examine the effects of exercise (aerobic, strength training or both) on anxiety in adults with arthritis and other rheumatic diseases (AORD). Methods Randomised controlled exercise intervention trials ≥4weeks in adults ≥18 years of age with osteoarthritis, rheumatoid arthritis or fibromyalgia were included. Studies were located by searching eight electronic databases, cross-referencing and expert review. Dual selection and data abstraction of studies were performed. Hedge’s standardised effect size (ES) was calculated for each result and pooled using the recently developed inverse heterogeneity model. Two-tailed z-alpha values ≤0.05 and non-overlapping 95% CI were considered statistically significant. Heterogeneity was estimated using Q and I2 with alpha values ≤0.10 for Q considered statistically significant. Small-study effects were examined using funnel plots and Egger’s regression test. In addition, the number needed to treat (NNT), percentile improvement and meta-regression were conducted. Results Of the 639 citations screened, 14 studies representing 926 initially enrolled participants (539 exercise, 387 control) met the criteria for inclusion. Length of training (mean±SD) averaged 15.8±6.7 weeks, frequency 3.3±1.3 times per week and duration 28.8±14.3 min per session. Overall, statistically significant reductions in anxiety were found (exercise minus control changes ES=−0.40, 95% CI −0.65 to −0.15, tau2=0.14; Q=40.3, P=0.0004; I2 =62.8%). The NNT was 6 with a percentile improvement of 15.5% and an estimated 5.3 million inactive US adults with AORD improving their anxiety if they started exercising regularly. Statistically significant small-study effects were observed (P<0.0001). Conclusions Exercise is associated with reductions in anxiety among adults with selected types of AORD. However, a need exists for additional, well-designed, randomised controlled trials on this topic. PROSPERO registration number CRD42016048728.
The Efficacy of Internet-based Cognitive Behavioral Therapy on the Anxiety Disorders among Adolescent Girls

Background: The prevalence of anxiety disorders among children and adolescents are found to be approximately between 8–12 and 5–10, respectively, and the long-lasting effects of such disorders can expose the sufferers to impairment and dysfunction in several areas of life the examples of which are poor educational performance, low self-esteem, and depression. The present study aims to evaluate the efficacy of internet-based, cognitive-behavioral therapy (ICBT) in treating the anxiety disorders among adolescent females. Materials and Methods: The sample included thirty girls aged between 10 and 18 years suffering from a variety of anxiety disorders, under pharmaceutical therapy and referred to clinics of child and adolescent psychiatry specialists in Isfahan. The sample was selected through diagnostic interviews by psychiatrists based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision; afterward, they were randomly assigned to either the experimental or the control groups. To evaluate the efficacy of an ICBT in reducing anxiety disorder symptoms, Screen for Child Anxiety Related Emotional Disorders questionnaire was administered among the patients both before and 4 weeks after the treatment. Results: The covariance analysis results aimed to compare the anxiety disorder score variations between the two groups which demonstrate the fact that anxiety disorder scores in these two groups differ from one another (P < 0.001). Conclusions: This study is comprised of two Conclusions.the significant reduction in the mean of anxiety disorders scores in the experimental group compared to those in control group can be indicative of the efficacy of ICBT. In addition the significant reduction in the average of anxiety disorders symptoms' scores according to the type of anxiety disorders in the experimental group, compared to those in control group, can be indicative of the efficacy of ICBT.
Study of the selective laser sintering of polycarbonate and postprocess for parts reinforcement

Polycarbonate (PC) powder, a common and low-cost amorphous polymer, can be moulded easily by the process of selective laser sintering (SLS). However, the sintered parts cannot be used as functional parts because of their poor mechanical properties. In this article, epoxy resin was applied to improve the mechanical properties of PC SLS parts. Specimens for testing dimensional accuracy, tensibility, flexibility, and impact strength were made by SLS with 75-100 μ PC powder. Some of the specimens were posttreated with two types of epoxy resins. Dimensional accuracy and mechanical properties of the specimens were measured. Microstructures of tensile fracture were observed by scanning electron microscopy. The result shows that the mechanical properties of the specimens are reinforced greatly after the epoxy resin has been infiltrated. Extent of the reinforcement depends on curing agents of epoxy resins. For example, with curing agent W, it is increased to 13.82, 8.00, and 3.69 times, respectively, in tensile, flexural, and impact strength and with curing agent Y, it is increased to 19.87, 7.43, and 1.55 times, respectively, in the same properties. The reinforcement in mechanical properties of PC SLS parts can be improved a step further by means of optimizing the epoxy resin system. Therefore, the PC SLS parts reinforced by epoxy resin can be used as functional parts, if the requirement on mechanical properties is not very high.
Downregulated IL-21 Response and T Follicular Helper Cell Exhaustion Correlate with Compromised CD8 T Cell Immunity during Chronic Toxoplasmosis

CD8 T cells are important for maintaining the chronicity of Toxoplasma gondii infection. In a T. gondii encephalitis susceptible model, we recently demonstrated that CD4 T cells play an essential helper role in the maintenance of the effector response and CD8 T cell dysfunctionality was linked to CD4 T cell exhaustion. However, CD4 T cells are constituted of different subsets with various functions and the population(s) providing help to the CD8 T cells has not yet been determined. In the present study, T follicular helper cells (Tfh), which are known to be essential for B cell maturation and are one of the main sources of IL-21, were significantly increased during chronic toxoplasmosis. However, at week 7 p.i. , when CD8 T cells are exhausted, the Tfh population exhibited increased expression of several inhibitory receptors and levels of IL-21 in the serum were decreased. The importance of IL-21 in the maintenance of CD8 T cells function after T. gondii infection was further demonstrated in IL-21R KO mouse model. Interestingly, while CD8 T cells from both knockout (KO) and wild-type mice expressed similar levels of PD-1, animals with defective IL-21 signaling exhibited lower polyfunctionality than wild-type controls. This reduced polyfunctional ability observed in CD8 T cells from KO mice was associated with a significant increase in other inhibitory receptors like Tim-3, LAG-3, and 2B4. Furthermore, the animals exhibited greater signs of Toxoplasma reactivation manifested by the reduced number of cysts and increased expression of tachyzoite (replicative form of the parasite) specific genes (SAG1 and ENO2) in the brain. Also, IL-21R KO mice displayed a higher frequency of tachyzoite-infected monocytes in the blood and spleen. Our findings suggest the importance of Tfh and IL-21 during chronic toxoplasmosis and establish a critical role for this cytokine in regulating CD8 T cell dysfunction by preventing the co-expression of multiple inhibitory receptors during chronic parasitic infection.
Can the SUVmax-liver-based interpretation improve prognostic accuracy of interim and posttreatment 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma?

Abstract In order to investigate whether the SUVmax-liver-based interpretation could improve prognostic accuracy of interim (PET-4) and posttreatment PET/CT (PET-end), 115 patients with newly diagnosed DLBCL were recruited in the study. ROC analysis revealed the optimal threshold is 1.6-fold of SUVmax-liver for PET-4 and 1.4-fold of SUVmax-liver for PET-end. The SUVmax-liver-based interpretation had a perfect interobserver agreement, higher prognostic accuracy and positive predictive value than 5-point scale and %ΔSUVmax criteria in both PET-4 and PET-end. Dramatic differences in the outcome between patients with positive and negative PET-4/PET-end were demonstrated using Kaplan–Meier survival curves (p < .05). Univariate and multifactor analysis found PET-4 and PET-end were independent prognostic factors for the outcome of DLBCL. In conclusion, the SUVmax-liver-based interpretation were superior to 5-point scale and %ΔSUVmax criteria in analyzing the PET-4 and PET-end for the prognosis of DLBCL patients.
Portuguese Medical Students' Knowledge and Attitudes Towards Homosexuality.

INTRODUCTION Lesbian, gay, bisexual and transgender people still face discrimination in healthcare environments and physicians often report lack of knowledge on this population's specific healthcare needs. In fact, recommendations have been put forward to include lesbian, gay, bisexual and transgender health in medical curricula. This study aimed to explore factors associated with medical students' knowledge and attitudes towards homosexuality in different years of the medical course. MATERIAL AND METHODS An anonymous online-based questionnaire was sent to all medical students enrolled at the Faculty of Medicine - University of Porto, Portugal, in December 2015. The questionnaire included socio-demographic questions, the Multidimensional Scale of Attitudes Toward Lesbians and Gay Men (27 items) and a Homosexuality Knowledge Questionnaire (17 items). Descriptive statistics, ANOVAs, Chi-square tests and Pearson's correlations were used in the analysis. RESULTS A total of 489 completed responses was analyzed. Male gender, religiosity and absence of lesbian, gay or bisexual friends were associated with more negative attitudes towards homosexuality. Attitudinal scores did not correlate with advanced years in medical course or contact with lesbian, gay or bisexual patients. Students aiming to pursue technique-oriented specialties presented higher scores in the 'Modern Heterosexism' subscale than students seeking patient-oriented specialties. Although advanced years in medical course correlated significantly with higher knowledge scores, items related with lesbian, gay or bisexual health showed the lowest percentage of correct answers. CONCLUSION There seems to be a lack of exploration of medical students' personal attitudes towards lesbians and gay men, and also a lack of knowledge on lesbian, gay or bisexual specific healthcare needs. This study highlights the importance of inclusive undergraduate curriculum development in order to foster quality healthcare.