Miracle-dz/UniFAR-FTUs huggingface dataset:
Disrupted reinforcement learning and maladaptive behavior in women with a history of childhood sexual abuse: a high-density event-related potential study.

IMPORTANCE Childhood sexual abuse (CSA) has been associated with psychopathology, particularly major depressive disorder (MDD), and high-risk behaviors. Despite the epidemiological data available, the mechanisms underlying these maladaptive outcomes remain poorly understood. OBJECTIVE We examined whether a history of CSA, particularly in conjunction with a past episode of MDD, is associated with behavioral and neural dysfunction in reinforcement learning, and whether such dysfunction is linked to maladaptive behavior. DESIGN Participants completed a clinical evaluation and a probabilistic reinforcement task while 128-channel event-related potentials were recorded. SETTING Academic setting; participants recruited from the community. PARTICIPANTS Fifteen women with a history of CSA and remitted MDD (CSA + rMDD), 16 women with remitted MDD with no history of CSA (rMDD), and 18 healthy women (controls). EXPOSURE Three or more episodes of coerced sexual contact (mean [SD] duration, 3.00 [2.20] years) between the ages of 7 and 12 years by at least 1 male perpetrator. MAIN OUTCOMES AND MEASURES Participants' preference for choosing the most rewarded stimulus and avoiding the most punished stimulus was evaluated. The feedback-related negativity and error-related negativity-hypothesized to reflect activation in the anterior cingulate cortex-were used as electrophysiological indices of reinforcement learning. RESULTS No group differences emerged in the acquisition of reinforcement contingencies. In trials requiring participants to rely partially or exclusively on previously rewarded information, the CSA + rMDD group showed (1) lower accuracy (relative to both controls and the rMDD group), (2) blunted electrophysiological differentiation between correct and incorrect responses (relative to controls), and (3) increased activation in the subgenual anterior cingulate cortex (relative to the rMDD group). A history of CSA was not associated with impairments in avoiding the most punished stimulus. Self-harm and suicidal behaviors correlated with poorer performance of previously rewarded, but not previously punished, trials. CONCLUSIONS AND RELEVANCE Irrespective of past MDD episodes, women with a history of CSA showed neural and behavioral deficits in utilizing previous reinforcement to optimize decision making in the absence of feedback (blunted "Go learning"). Although our study provides initial evidence for reward-specific deficits associated with CSA, future research is warranted to determine if disrupted positive reinforcement learning predicts high-risk behavior following CSA.
Correlated Component Regression: A Prediction/Classification Methodology for Possibly Many Features

A new ensemble dimension reduction regression technique, called Correlated Component Regression (CCR), is proposed that predicts the dependent variable based on K correlated components. For K = 1, CCR is equivalent to the corresponding Naive Bayes solution, and for K = P, CCR is equivalent to traditional regression with P predictors. An optional step-down variable selection procedure provides a sparse solution, with each component defined as a linear combination of only P* < P predictors. For high-dimensional data, simulation results suggest that good prediction is generally attainable for K = 3 or 4 regardless of the number of predictors, and estimation is fast. When predictors include one or more suppressor variables, common with gene expression data, simulations based on linear regression, logistic regression and discriminant analysis suggest that CCR predicts outside the sample better than comparable approaches based on stepwise regression, penalized regression and/or PLS regression. A major reason for the improvement is that the CCR/step-down algorithm is much better than other sparse techniques in capturing important suppressor variables among the final predictors.
Human CREB-binding Protein/p300-interacting Transactivator with ED-rich Tail (CITED) 4, a New Member of the CITED Family, Functions as a Co-activator for Transcription Factor AP-2*

Members of the CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) family bind CREB-binding protein and p300 with high affinity and regulate gene transcription. Gene knockout studies indicate that CITED2 is required for neural crest and neural tube development and that it functions as a co-activator for transcription factor AP-2 (TFAP2). Here we describe human CITED4, a new member of this family, which is encoded by a single exon mapping to chromosome 1p34–1p35. CITED4 and p300/CREB-binding protein are present in endogenous naturally occurring complexes, indicating that they interact physiologically. The interaction occurs between the cysteine-histidine-rich domain 1 of p300 and the carboxyl terminus of CITED4. In keeping with this, CITED4 functions as a transactivator when artificially targeted to a promoter element. CITED4 physically interacts with all TFAP2 isoforms in vitro and strongly co-activates all TFAP2 isoforms in Hep3B cells. Co-activation of TFAP2 requires amino-terminal and carboxyl-terminal residues of CITED4. In HepG2 cells, CITED4 is significantly weaker than CITED2 for TFAP2C co-activation. These results suggest that CITED4 may function as a co-activator for TFAP2. They also suggest the existence of cell type- and TFAP2 isoform-specific co-activation by CITED2 and CITED4, which may result in differential modulation of TFAP2 function.
Measure of Landmark Semantic Salience through Geosocial Data Streams

Research in the area of spatial cognition demonstrated that references to landmarks are essential in the communication and the interpretation of wayfinding instructions for human being. In order to detect landmarks, a model for the assessment of their salience has been previously developed by Raubal and Winter. According to their model, landmark salience is divided into three categories: visual, structural, and semantic. Several solutions have been proposed to automatically detect landmarks on the basis of these categories. Due to a lack of relevant data, semantic salience has been frequently reduced to objects’ historical and cultural significance. Social dimension (i.e., the way an object is practiced and recognized by a person or a group of people) is systematically excluded from the measure of landmark semantic salience even though it represents an important component. Since the advent of mobile Internet and smartphones, the production of geolocated content from social web platforms—also described as geosocial data—became commonplace. Actually, these data allow us to have a better understanding of the local geographic knowledge. Therefore, we argue that geosocial data, especially Social Location Sharing datasets, represent a reliable source of information to precisely measure landmark semantic salience in urban area.
PHENICX: Performances as Highly Enriched aN d Interactive Concert Experiences

Mo dern digital multimedia and internet technology have radically changed the ways people find entertainment and discovernew interests online, seeminglywithout anyphysical or social barriers. Such new access paradigms are in sharp contrast with the traditional means of entertainment. An illustrative example of this is live music concert performances that are largely being attended by dedicated audiences only. ThispapersintroducesthePHENICX project,whichaims at enriching traditional concert experiences by using stateof-the-artmultimediaandinternettechnologies. Theproject focuses on classical music and its main goal is twofold: (a) to make live concerts appealing to potential new audience and (b) to maximize the quality of concert experience for everyone. Concerts will then become multimodal, multi-perspective and multilayer digital artifacts that can be easily explored, customized, personalized, (re)enjoyed and shared among the users. The paper presents the main scientific objectives on the project, provides a state of the art review on related research and presents the main challenges to be addressed.
A Cellular Automata Model for Use with Real Freeway Data

The exponential rate of increase in freeway traffic is expanding the need for accurate and realistic methods to model and predict traffic flow. Traffic modeling and simulation facilitate an examination of both microscopic and macroscopic views of traffic flows and are therefore considered one of the most important analytical tools in traffic engineering. This report presents a cellular automata model for traffic flow simulation and prediction (CATS). Cellular automata models quantize complex behavior into simple individual components. In this model, the freeway being simulated is discretized into homogeneous cells of equal length, and time is discretized into timesteps of equal duration. The CATS model allows users to define locations within the road topology where volume and density data will be calculated so that the model results can be compared to observed highway data.
The Conceptual Model on Smart Phone Addiction among Early Childhood

This study examined the antecedents and consequences of children's smart phone addiction. Antecedents of smart phone addiction among children were divided into parental variables and child variables. When parents' education/income/age is higher, dual-income family, the longer parents themselves use smart phones, permissive parenting style, and positive attitudes towards smart phone, children tend to have higher possibility to be addicted to smart phones. Related to child variables, younger children, boys, less siblings, and not attending education institution, predict smart phone addiction. Children with smart phone addiction show problems in mental and physical development. The implications and further study are suggested based on the conceptual model.
Epithelial Sodium Channel Inhibition by AMP-activated Protein Kinase in Oocytes and Polarized Renal Epithelial Cells*

The epithelial Na+ channel (ENaC) regulates epithelial salt and water reabsorption, processes that require significant expenditure of cellular energy. To test whether the ubiquitous metabolic sensor AMP-activated kinase (AMPK) regulates ENaC, we examined the effects of AMPK activation on amiloride-sensitive currents in Xenopus oocytes and polarized mouse collecting duct mpkCCDc14 cells. Microinjection of oocytes expressing mouse ENaC (mENaC) with either active AMPK protein or an AMPK activator inhibited mENaC currents relative to controls as measured by two-electrode voltage-clamp studies. Similarly, pharmacological AMPK activation or overexpression of an activating AMPK mutant in mpkCCDc14 cells inhibited amiloride-sensitive short circuit currents. Expression of a degenerin mutant β-mENaC subunit (S518K) along with wild type α and γ increased the channel open probability (Po) to ∼1. However, AMPK activation inhibited currents similarly with expression of either degenerin mutant or wild type mENaC. Single channel recordings under these conditions demonstrated that neither Po nor channel conductance was affected by AMPK activation. Moreover, expression of a Liddle's syndrome-type β-mENaC mutant (Y618A) greatly enhanced ENaC whole cell currents relative to wild type ENaC controls and prevented AMPK-dependent inhibition. These findings indicate that AMPK-dependent ENaC inhibition is mediated through a decrease in the number of active channels at the plasma membrane (N), presumably through enhanced Nedd4-2-dependent ENaC endocytosis. The AMPK-ENaC interaction appears to be indirect; AMPK did not bind ENaC in cells, as assessed by in vivo pull-down assays, nor did it phosphorylate ENaC in vitro. In summary, these results suggest a novel mechanism for coupling ENaC activity and renal Na+ handling to cellular metabolic status through AMPK, which may help prevent cellular Na+ loading under hypoxic or ischemic conditions.
Shear-induced force transmission in a multicomponent, multicell model of the endothelium

Haemodynamic forces applied at the apical surface of vascular endothelial cells (ECs) provide the mechanical signals at intracellular organelles and through the inter-connected cellular network. The objective of this study is to quantify the intracellular and intercellular stresses in a confluent vascular EC monolayer. A novel three-dimensional, multiscale and multicomponent model of focally adhered ECs is developed to account for the role of potential mechanosensors (glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs) and adherens junctions (ADJs)) in mechanotransmission and EC deformation. The overriding issue addressed is the stress amplification in these regions, which may play a role in subcellular localization of mechanotransmission. The model predicts that the stresses are amplified 250–600-fold over apical values at ADJs and 175–200-fold at FAs for ECs exposed to a mean shear stress of 10 dyne cm−2. Estimates of forces per molecule in the cell attachment points to the external cellular matrix and cell–cell adhesion points are of the order of 8 pN at FAs and as high as 3 pN at ADJs, suggesting that direct force-induced mechanotransmission by single molecules is possible in both. The maximum deformation of an EC in the monolayer is calculated as 400 nm in response to a mean shear stress of 1 Pa applied over the EC surface which is in accord with measurements. The model also predicts that the magnitude of the cell–cell junction inclination angle is independent of the cytoskeleton and glycocalyx. The inclination angle of the cell–cell junction is calculated to be 6.6° in an EC monolayer, which is somewhat below the measured value (9.9°) reported previously for ECs subjected to 1.6 Pa shear stress for 30 min. The present model is able, for the first time, to cross the boundaries between different length scales in order to provide a global view of potential locations of mechanotransmission.
Continuity and cascade in offspring of bipolar parents: A longitudinal study of externalizing, internalizing, and thought problems

Abstract There is growing evidence that many offspring of bipolar parents will develop moderate to severe forms of psychopathology during childhood and adolescence. The purpose of this study was to apply growth curve models to evaluate developmental progression with regard to continuity and cascades representative within the context of a family risk study of bipolar disorder (BD). Repeated assessments of externalizing, internalizing, and thought problems, spanning more than a decade, were examined in a total of 94 offspring of parents with BD (O-BD), major depressive disorder (O-UNI), or no significant psychiatric or medical problems (O-WELL). Continuity was defined by the growth curve of the O-WELL group who exhibited low levels of problems from early childhood through late adolescence. Discontinuity, as evidenced by greater complexity of growth curves relative to the O-WELL group, was exhibited in the at- risk offspring groups for internalizing problems. Different patterns of developmental cascades were supported for the at-risk group with O-UNI showing a robust cascade from self-regulatory deficits (externalizing problems) to internalizing problems. There was also support for a cascade from self-regulatory deficits to thought problems across the entire group (with some support that this pattern was accounted for primarily by O-BD). This study not only serves to advance our understanding of the risks associated with a family history of BD, but also provides a novel approach to examining developmental cascades.
High-Dose Atorvastatin Enhances the Decline in Inflammatory Markers in Patients With Acute Coronary Syndromes in the MIRACL Study

Background—Inflammation promotes acute coronary syndromes and ensuing clinical complications. Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina, the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown. Methods and Results—We measured C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects with unstable angina or non–Q-wave myocardial infarction were randomized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks. The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome, country, and initial level of marker. All 3 markers were markedly elevated at randomization and declined over the 16 weeks in both treatment groups. Compared with placebo, atorvastatin significantly reduced CRP, −83% (95% CI, −84%, −81%) versus −74% (95% CI, −75%, −71%) (P <0.0001) and SAA, −80% (95% CI, −82%, −78%) versus −77% (−79%, −75%) (P =0.0006) but not IL-6, −55% (95% CI, −57%, −53%) versus −53% (95% CI, −55%, −51%) (P =0.3). Reductions in CRP and SAA were observed in patients with unstable angina and non–Q-wave myocardial infarction, with initial LDL cholesterol <3.2 or ≥3.2 mmol/L (125 mg/dL), age ≥65 or <65 years, and in men and women. By 16 weeks, CRP was 34% lower with atorvastatin than with placebo. Conclusions—High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes. This supports the value of early statin therapy in these patients.
Aflatoxin, Fumonisin and Shiga Toxin-Producing Escherichia coli Infections in Calves and the Effectiveness of Celmanax®/Dairyman’s Choice™ Applications to Eliminate Morbidity and Mortality Losses

Mycotoxin mixtures are associated with Shiga toxin-producing Escherichia coli (STEC) infections in mature cattle. STEC are considered commensal bacteria in mature cattle suggesting that mycotoxins provide a mechanism that converts this bacterium to an opportunistic pathogen. In this study, we assessed the mycotoxin content of hemorrhaged mucosa in dairy calves during natural disease outbreaks, compared the virulence genes of the STECs, evaluated the effect of the mucosal mycotoxins on STEC toxin expression and evaluated a Celmanax®/Dairyman’s Choice™ application to alleviate disease. As for human infections, the OI-122 encoded nleB gene was common to STEC genotypes eliciting serious disease. Low levels of aflatoxin (1–3 ppb) and fumonisin (50–350 ppb) were detected in the hemorrhaged mucosa. Growth of the STECs with the mycotoxins altered the secreted protein concentration with a corresponding increase in cytotoxicity. Changes in intracellular calcium indicated that the mycotoxins increased enterotoxin and pore-forming toxin activity. A prebiotic/probiotic application eliminated the morbidity and mortality losses associated with the STEC infections. Our study demonstrates: the same STEC disease complex exists for immature and mature cattle; the significance of the OI-122 pathogenicity island to virulence; the significance of mycotoxins to STEC toxin activity; and, finally, provides further evidence that prebiotic/probiotic applications alleviate STEC shedding and mycotoxin/STEC interactions that lead to disease.
Differences in Metabolic Network Modulation Between Capsulotomy and Deep-Brain Stimulation for Refractory Obsessive-Compulsive Disorder

Around 7%–10% of patients with obsessive-compulsive disorder (OCD) are refractory to first-line treatment. Neurosurgical approaches are available such as capsulotomy or deep-brain stimulation (DBS). There is strong evidence for central involvement of the corticostriatopallidothalamocortical (CSPTC) circuit in OCD, but the exact mechanism through which these interventions lead to clinical improvement and potential differences in network modulation are not fully understood. Methods: In total, 13 capsulotomy patients (aged 29–59 y, 10 men and 3 women) and 16 DBS patients (aged 25–56 y, 6 men and 10 women) were prospectively included. 18F-FDG PET was performed before and after capsulotomy and before and after DBS in both stimulation-on and stimulation-off conditions. Presurgical scans were compared with scans of healthy volunteers using SPM8 and global scaling, and metabolic changes after DBS were compared with changes after capsulotomy. Correlations with clinical improvements were investigated using the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamilton Depression Rating Scale (HAM-D). Results: Both groups had similar pretreatment clinical morbidity as assessed by Y-BOCS and the Hamilton Depression Rating Scale. Preoperative superior frontal and supplementary motor cortex hypometabolism was common to both patient groups, and the subgenual anterior cingulate, occipital cortex (cuneus), and posterior cerebellum were relatively hypermetabolic. Postoperative metabolic decreases were common to both interventions in the anterior cingulate and the prefrontal and orbitofrontal cortices. Compared with DBS, capsulotomy resulted in more intense metabolic changes, with additional significant decreases in the mediodorsal thalamus, caudate nucleus, and cerebellum as well as increases in the precuneus and the fusiform and lingual gyrus. The stimulation-off condition of DBS patients showed no significant differences from the preoperative state. Improvement in Y-BOCS scores correlated with metabolic changes in the occipital cortex. Baseline metabolism in the subgenual anterior cingulate and superior temporal cortices were related to postoperative improvement of depressive symptoms. Conclusion: Capsulotomy and DBS lead to similar clinical improvement and similar metabolic network changes in the CSPTC circuit, with a prominent role for the subgenual anterior cingulate and other core structures of the CSPTC. However, metabolic changes are more pronounced and extended in capsulotomy than in DBS. Furthermore, cortical regions outside the CSPTC may also play an important role in OCD symptomatology.
Aromatic Amines in Experimental Cancer Research: Tissue-Specific Effects, an Old Problem and New Solutions

Carcinogenic aromatic amines usually produce tumors in specific target tissue, such as 2-acetylaminofluorene (AAF) producing liver tumors in rats, in contrast to some other structurally related arylamines. A hypothesis is presented that explains the mode of action in this rat liver model. Genotoxic and nongenotoxic effects work together and make AAF a complete rat liver carcinogen. The cytotoxic, promoting effects are particularly important. N-Hydroxy-2-aminofluorene and 2-nitrosofluorene, two metabolites of AAF, are able to uncouple the mitochondrial respiratory chain. They entertain a redox cycle that removes electrons from the respiratory chain and impairs ATP production. The dose-dependent opening of the mitochondrial permeability transition pore signals the viability of the cell. If the pore is opened to a certain extent, the cell is eliminated by apoptosis. As a consequence, oval cells proliferate, and as this process is overloaded, the liver transforms into a cirrhosis-like situation and thus provides the conditions under which initiated liver cells develop tumors. Such an interpretation is based on assumptions that have been debated for a long time. Some of these often forgotten developments are reviewed in support of the hypothesis, which allows a more comprehensive view of the complex in vivo situation at a time when in vitro models prevail.