Miracle-dz/UniFAR-FTUs huggingface dataset:
Modifiable pathways in Alzheimer’s disease: Mendelian randomisation analysis

Abstract Objective To determine which potentially modifiable risk factors, including socioeconomic, lifestyle/dietary, cardiometabolic, and inflammatory factors, are associated with Alzheimer’s disease. Design Mendelian randomisation study using genetic variants associated with the modifiable risk factors as instrumental variables. Setting International Genomics of Alzheimer’s Project. Participants 17 008 cases of Alzheimer’s disease and 37 154 controls. Main outcome measures Odds ratio of Alzheimer’s per genetically predicted increase in each modifiable risk factor estimated with Mendelian randomisation analysis. Results This study included analyses of 24 potentially modifiable risk factors. A Bonferroni corrected threshold of P=0.002 was considered to be significant, and P<0.05 was considered suggestive of evidence for a potential association. Genetically predicted educational attainment was significantly associated with Alzheimer’s. The odds ratios were 0.89 (95% confidence interval 0.84 to 0.93; P=2.4×10−6) per year of education completed and 0.74 (0.63 to 0.86; P=8.0×10−5) per unit increase in log odds of having completed college/university. The correlated trait intelligence had a suggestive association with Alzheimer’s (per genetically predicted 1 SD higher intelligence: 0.73, 0.57 to 0.93; P=0.01). There was suggestive evidence for potential associations between genetically predicted higher quantity of smoking (per 10 cigarettes a day: 0.69, 0.49 to 0.99; P=0.04) and 25-hydroxyvitamin D concentrations (per 20% higher levels: 0.92, 0.85 to 0.98; P=0.01) and lower odds of Alzheimer’s and between higher coffee consumption (per one cup a day: 1.26, 1.05 to 1.51; P=0.01) and higher odds of Alzheimer’s. Genetically predicted alcohol consumption, serum folate, serum vitamin B12, homocysteine, cardiometabolic factors, and C reactive protein were not associated with Alzheimer’s disease. Conclusion These results provide support that higher educational attainment is associated with a reduced risk of Alzheimer’s disease.
Implementing a cultural competence training as a psychopolitical empowerment process

ABSTRACT The cultural competence training (CCT) of health care professionals represents a useful resource to face the challenges involved in health care assistance for multicultural populations. However, the traditional perspective has shown limited results, as it does not consider professionals in their contexts and avoids continuous assessment processes. In response to these limitations, we describe a model of CCT implemented by two professors of the Faculty of Nursing at the University of Seville in Spain as a psychopolitical empowerment process, and exemplified by the experience of the emergency nurses at the Virgen Macarena Hospital. This process adds the notion of power to traditional CCT and uses dialogic learning to: (a) state a mission and develop critical thinking; (b) take stock of the actions for change and increase the capacity of nurses to respond; and (c) motivate nurses to plan the future and take action. As a result, professionals become a learning community, able to develop a new professional identity and role, and can also implement actions for the transformation of health care settings.
Tumor-Derived Suppressor of Fused Mutations Reveal Hedgehog Pathway Interactions

The Hedgehog pathway is a potent regulator of cellular growth and plays a central role in the development of many cancers including basal cell carcinoma (BCC). The majority of BCCs arise from mutations in the Patched receptor resulting in constitutive activation of the Hedgehog pathway. Secondary driver mutations promote BCC oncogenesis and occur frequently due to the high mutational burden resulting from sun exposure of the skin. Here, we uncover novel secondary mutations in Suppressor of Fused (SUFU), the major negative regulator of the Hedgehog pathway. SUFU normally binds to a Hedgehog transcriptional activator, GLI1, in order to prevent it from initiating transcription of Hedgehog target genes. We sequenced tumor-normal pairs from patients with early sporadic BCCs. This resulted in the discovery of nine mutations in SUFU, which were functionally investigated to determine whether they help drive BCC formation. Our results show that four of the SUFU mutations inappropriately activate the Hedgehog pathway, suggesting they may act as driver mutations for BCC development. Indeed, all four of the loss of function SUFU variants were found to disrupt its binding to GLI, leading to constitutive pathway activation. Our results from functional characterization of these mutations shed light on SUFU’s role in Hedgehog signaling, tumor progression, and highlight a way in which BCCs can arise.
Video Person Re-Identification by Temporal Residual Learning

In this paper, we propose a novel feature learning framework for video person re-identification (re-ID). The proposed framework largely aims to exploit the adequate temporal information of video sequences and tackle the poor spatial alignment of moving pedestrians. More specifically, for exploiting the temporal information, we design a temporal residual learning (TRL) module to simultaneously extract the generic and specific features of consecutive frames. The TRL module is equipped with two bi-directional LSTM (BiLSTM), which are, respectively, responsible to describe a moving person in different aspects, providing complementary information for better feature representations. To deal with the poor spatial alignment in video re-ID data sets, we propose a spatial-temporal transformer network (ST2N) module. Transformation parameters in the ST2N module are learned by leveraging the high-level semantic information of the current frame as well as the temporal context knowledge from other frames. The proposed ST2N module with less learnable parameters allows effective person alignments under significant appearance changes. Extensive experimental results on the large-scale MARS, PRID2011, ILIDS-VID, and SDU-VID data sets demonstrate that the proposed method achieves consistently superior performance and outperforms most of the very recent state-of-the-art methods.
Smart Money, Noise Trading and Stock Price Behavior

This paper derives and estimates an equilibrium model of stock price behavior in which exogenous "noise traders" interact with risk-averse "smart money" investors. The model assumes that changes in exponentially detrended dividends and prices are normally distributed, and that smart money investors have constant absolute risk aversion. In equilibrium, the stock price is the present value of expected dividends, discounted at the riskless interest rate, less a constant risk premium, plus a term which is due to noise trading. The model expresses both stock prices and dividends as sums of unobserved components in continuous time. The model is able to explain the volatility and predictability of U.S. stock returns in the period 1871-1986 in either of two ways. Either the discount rate is 4% or below, and the constant risk premium is large; or the discount rate is 5% or above, and noise trading, correlated with fundamentals, increases the volatility of stock prices. The data are not well able to distinguish between these explanations.
Learning to See Physics via Visual De-animation

We introduce a paradigm for understanding physical scenes without human annotations. At the core of our system is a physical world representation that is first recovered by a perception module and then utilized by physics and graphics engines. During training, the perception module and the generative models learn by visual de-animation --- interpreting and reconstructing the visual information stream. During testing, the system first recovers the physical world state, and then uses the generative models for reasoning and future prediction. Even more so than forward simulation, inverting a physics or graphics engine is a computationally hard problem; we overcome this challenge by using a convolutional inversion network. Our system quickly recognizes the physical world state from appearance and motion cues, and has the flexibility to incorporate both differentiable and non-differentiable physics and graphics engines. We evaluate our system on both synthetic and real datasets involving multiple physical scenes, and demonstrate that our system performs well on both physical state estimation and reasoning problems. We further show that the knowledge learned on the synthetic dataset generalizes to constrained real images.
High levels of GSK-3&bgr; signalling reduce osteogenic differentiation of stem cells in osteonecrosis of femoral head

Osteonecrosis of the femoral head (ONFH) is a common but intractable disease. In this study, we investigated the mechanisms regulating alterations in mesenchymal stem cell (MSC) differentiation in ONFH. Five patients who were diagnosed with ONFH were enrolled in this study. Bone MSCs (BMSCs) were isolated from the osteonecrotic zone in the femoral head (FH-pMSCs) and from the normal zone in the pelvis (hMSCs) of the same patient. Morphology, cell proliferation and expression of mediators of the Wnt signalling pathway were evaluated. There were significant differences in cell proliferation and expression of surface markers between the two populations of cells. FH-pMSCs exhibited significantly lower osteogenic differentiation compared with hMSCs (P < 0.0001). Dissection of the Wnt pathway showed that FH-pMSCs had significantly higher GSK3β expression compared with hMSCs (P < 0.001). Addition of LiCl, a GSK3β inhibitor, significantly increased osteogenic differentiation in FH-pMSCs, suggesting a relationship between the microenvironment and regulation of stem cell behaviour in ONFH. FH-pMSCs also exhibited significant downregulation of other mediators of the Wnt signalling pathway, including runx2 and β-catenin. Our data suggested that mediators of the Wnt signalling pathway, such as GSK3β could be important therapeutic targets for early-stage ONFH.
Modification of Gene Expression and Virulence Traits in Streptococcus mutans in Response to Carbohydrate Availability

ABSTRACT The genetic and phenotypic responses of Streptococcus mutans, an organism that is strongly associated with the development of dental caries, to changes in carbohydrate availability were investigated. S. mutans UA159 or a derivative of UA159 lacking ManL, which is the EIIAB component (EIIABMan) of a glucose/mannose permease of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) and a dominant effector of catabolite repression, was grown in continuous culture to steady state under conditions of excess (100 mM) or limiting (10 mM) glucose. Microarrays using RNA from S. mutans UA159 revealed that 174 genes were differentially expressed in response to changes in carbohydrate availability (P < 0.001). Glucose-limited cells possessed higher PTS activity, could acidify the environment more rapidly and to a greater extent, and produced more ManL protein than cultures grown with excess glucose. Loss of ManL adversely affected carbohydrate transport and acid tolerance. Comparison of the histidine protein (HPr) in S. mutans UA159 and the manL deletion strain indicated that the differences in the behaviors of the strains were not due to major differences in HPr pools or HPr phosphorylation status. Therefore, carbohydrate availability alone can dramatically influence the expression of physiologic and biochemical pathways that contribute directly to the virulence of S. mutans, and ManL has a profound influence on this behavior.
Effects of theory of mind performance training on reducing bullying involvement in children and adolescents with high-functioning autism spectrum disorder

Bullying involvement is prevalent among children and adolescents with autism spectrum disorder (ASD). This study examined the effects of theory of mind performance training (ToMPT) on reducing bullying involvement in children and adolescents with high-functioning ASD. Children and adolescents with high-functioning ASD completed ToMPT (n = 26) and social skills training (SST; n = 23) programs. Participants in both groups and their mothers rated the pretraining and posttraining bullying involvement of participants on the Chinese version of the School Bullying Experience Questionnaire. The paired t test was used to evaluate changes in bullying victimization and perpetration between the pretraining and posttraining assessments. Furthermore, the linear mixed-effect model was used to examine the difference in the training effect between the ToMPT and SST groups. The paired t test indicated that in the ToMPT group, the severities of both self-reported (p = .039) and mother-reported (p = .003) bullying victimization significantly decreased from the pretraining to posttraining assessments, whereas in the SST group, only self-reported bullying victimization significantly decreased (p = .027). The linear mixed-effect model indicated that compared with the SST program, the ToMPT program significantly reduced the severity of mother-reported bullying victimization (p = .041). The present study supports the effects of ToMPT on reducing mother-reported bullying victimization in children and adolescents with high-functioning ASD.
Single-Cell Stimulation in Barrel Cortex Influences Psychophysical Detection Performance

A single whisker stimulus elicits action potentials in a sparse subset of neurons in somatosensory cortex. The precise contribution of these neurons to the animal's perception of a whisker stimulus is unknown. Here we show that single-cell stimulation in rat barrel cortex of both sexes influences the psychophysical detection of a near-threshold whisker stimulus in a cell type–dependent manner, without affecting false alarm rate. Counterintuitively, stimulation of single fast-spiking putative inhibitory neurons increased detection performance. Single-cell stimulation of putative excitatory neurons failed to change detection performance, except for a small subset of deep-layer neurons that were highly sensitive to whisker stimulation and that had an unexpectedly strong impact on detection performance. These findings indicate that the perceptual impact of excitatory barrel cortical neurons relates to their firing response to whisker stimulation and that strong activity in a single highly sensitive neuron in barrel cortex can already enhance sensory detection. Our data suggest that sensory detection is based on a decoding mechanism that lends a disproportionally large weight to interneurons and to deep-layer neurons showing a strong response to sensory stimulation. SIGNIFICANCE STATEMENT Rat whisker somatosensory cortex contains a variety of neuronal cell types with distinct anatomical and physiological characteristics. How each of these different cell types contribute to the animal's perception of whisker stimuli is unknown. We explored this question by using a powerful electrophysiological stimulation technique that allowed us to target and stimulate single neurons with different sensory response types in whisker cortex. In awake, behaving animals, trained to detect whisker stimulation, only costimulation of single fast-spiking inhibitory neurons or single deep-layer excitatory neurons with strong responses to whisker stimulation enhanced detection performance. Our data demonstrate that single cortical neurons can have measurable impact on the detection of sensory stimuli and suggest a decoding mechanism based on select cell types.
Coarsely calibrated visual servoing of a mobile robot using a catadioptric vision system

A catadioptric vision system combines a camera and a mirror to achieve a wide field of view imaging system. This type of vision system has many potential applications in mobile robotics. This paper is concerned with the design of a robust image-based control scheme using a catadioptric vision system mounted on a mobile robot. We exploit the fact that the decoupling property contributes to the robustness of a control method. More precisely, from the image of a point, we propose a minimal and decoupled set of features measurable on any catadioptric vision system. Using the minimal set, a classical control method is proved to be robust in the presence of point range errors. Finally, experimental results with a coarsely calibrated mobile robot validate the robustness of the new decoupled scheme.
Regulation of activity and localization of the WNK1 protein kinase by hyperosmotic stress

Mutations within the WNK1 (with-no-K[Lys] kinase-1) gene cause Gordon's hypertension syndrome. Little is known about how WNK1 is regulated. We demonstrate that WNK1 is rapidly activated and phosphorylated at multiple residues after exposure of cells to hyperosmotic conditions and that activation is mediated by the phosphorylation of its T-loop Ser382 residue, possibly triggered by a transautophosphorylation reaction. Activation of WNK1 coincides with the phosphorylation and activation of two WNK1 substrates, namely, the protein kinases STE20/SPS1-related proline alanine–rich kinase (SPAK) and oxidative stress response kinase-1 (OSR1). Small interfering RNA depletion of WNK1 impairs SPAK/OSR1 activity and phosphorylation of residues targeted by WNK1. Hyperosmotic stress induces rapid redistribution of WNK1 from the cytosol to vesicular structures that may comprise trans-Golgi network (TGN)/recycling endosomes, as they display rapid movement, colocalize with clathrin, adaptor protein complex 1 (AP-1), and TGN46, but not the AP-2 plasma membrane–coated pit marker nor the endosomal markers EEA1, Hrs, and LAMP1. Mutational analysis suggests that the WNK1 C-terminal noncatalytic domain mediates vesicle localization. Our observations shed light on the mechanism by which WNK1 is regulated by hyperosmotic stress.
Comparing CT colonography and flexible sigmoidoscopy: a randomised trial within a population-based screening programme

Importance and aims The role of CT colonography (CTC) as a colorectal cancer (CRC) screening test is uncertain. The aim of our trial was to compare participation and detection rate (DR) with sigmoidoscopy (flexible sigmoidoscopy (FS)) and CTC in a screening setting. Design setting and participants We conducted two randomised clinical trials (RCTs). (1) Participation RCT: individuals, aged 58 years, living in Turin (Italy), were randomly assigned to be invited to FS or CTC screening; (2) detection RCT: residents in northern Italy, aged 58–60, giving their consent to recruitment, were randomly allocated to CTC or FS. Polyps ≥6 mm at CTC, or ‘high-risk’ distal lesions at FS, were referred for colonoscopy (TC). Main outcome measures Participation rate (proportion of invitees examined); DR of advanced adenomas or CRC (advanced neoplasia (AN)). Results Participation was 30.4% (298/980) for CTC and 27.4% (267/976) for FS (relative risk (RR) 1.1; 95% CI 0.98 to 1.29). Among men, participation was higher with CTC than with FS (34.1% vs 26.5%, p=0.011). In the detection RCT, 2673 subjects had FS and 2595 had CTC: the AN DR was 4.8% (127/2673, including 9 CRCs) with FS and 5.1% (133/2595, including 10 CRCs) with CTC (RR 1.08; 95% CI 0.85 to 1.37). Distal AN DR was 3.9% (109/2673) with FS and 2.9% (76/2595) with CTC (RR 0.72; 95% CI 0.54 to 0.96); proximal AN DR was 1.2% (34/2595) for FS vs 2.7% (69/2595) for CTC (RR 2.06; 95% CI 1.37 to 3.10). Conclusions and relevance Participation and DR for FS and CTC were comparable. AN DR was twice as high in the proximal colon and lower in the distal colon with CTC than with FS. Men were more likely to participate in CTC screening. Trial registration number NCT01739608; Pre-results.
Sensitivity to Shared Information in Social Learning

Social learning has been shown to be an evolutionarily adaptive strategy, but it can be implemented via many different cognitive mechanisms. The adaptive advantage of social learning depends crucially on the ability of each learner to obtain relevant and accurate information from informants. The source of informants' knowledge is a particularly important cue for evaluating advice from multiple informants; if the informants share the source of their information or have obtained their information from each other, then their testimony is statistically dependent and may be less reliable than testimony from informants who do not share information. In this study, we use a Bayesian model to determine how rational learners should incorporate the effects of shared information when learning from other people, conducting three experiments that examine whether human learners behave similarly. We find that people are sensitive to a number of different patterns of dependency, supporting the use of a sophisticated strategy for social learning that goes beyond copying the majority, and broadening the situations in which social learning is likely to be an adaptive strategy.
Thyroid functional parameters and correlative autoantibodies as prognostic factors for differentiated thyroid cancers

To evaluate the effect of preoperative thyroid functional parameters and thyroid autoantibodies on aggressive clinicopathologic features and lymph node metastasis (LNM) of differentiated thyroid cancer patients. Four hundred twenty consecutive patients with initial surgery were enrolled from July 2010 to July 2015. The associations between aggressive clinicopathologic and LNM factors and thyroid functional & autoantibodies parameters were analyzed. Higher levels of TSH, TGAb or TMAb were found in patients with tumor size≥1 cm (all P<0.05), especially when TSH≥2.5 ulU/ml (P=0.03) and TGAb≥1 (P=0.01). Higher levels of TSH and TGAb and lower levels of T3 and T4 were found in patients with capsular invasion (all P<0.05), particularly when TSH≥2.5ulU/ml (P=0.03) and TGAb≥1 (P=0.005). The patients with multifocality had higher TAbs level (TAbs>1). Higher level of TSH was also found in patients with central LNM (P=0.001) and lateral LNM (P=0.002), especially with TSH≥2.5ulU/ml (P=0.003 and P=0.03). TGAb level was also found higher in patients with central LNM (P=0.02) and lateral LNM (P=0.01), especially with TGAb≥1 (P<0.05 and P=0.01). Higher level of TMAb was found in patients with lateral LNM (P<0.05). Moreover, multivariable analysis revealed that only TGAb was an independently predictive factor for primary tumor size≥1cm (P=0.01); and TSH level (P=0.01) and TGAb≥1 (P<0.05) were associated independently with central LNM. Thus, TSH level and TGAb≥1 were significantly independent predictors for central LNM, and might help make the decision of central neck dissection.
Access to Lexical Information in Language Comprehension: Semantics before Syntax

The recognition of a word makes available its semantic and syntactic properties. Using electrophysiological recordings, we investigated whether one set of these properties is available earlier than the other set. Dutch participants saw nouns on a computer screen and performed push-button responses: In one task, grammatical gender determined response hand (left/right) and semantic category determined response execution (go/no-go). In the other task, response hand depended on semantic category, whereas response execution depended on gender. During the latter task, response preparation occurred on no-go trials, as measured by the lateralized readiness potential: Semantic information was used for response preparation before gender information inhibited this process. Furthermore, an inhibition-related N2 effect occurred earlier for inhibition by semantics than for inhibition by gender. In summary, electrophysiological measures of both response preparation and inhibition indicated that the semantic word property was available earlier than the syntactic word property when participants read single words.