Miracle-dz/UniFAR-FTUs huggingface dataset:
NATURAL RATE OF INTEREST ESTIMATES FOR BRAZIL AFTER ADOPTION OF THE INFLATION TARGETING REGIME

This paper estimates the natural rate of interest (NRI) for Brazil between the third quarter of 1999 and the second quarter of 2019. The seminal model proposed by Laubach and Williams (2003), re-specified by Holston, Laubach and Williams (2017), is used. Results indicate an NRI with a downward trend, with the lowest values during the 2015-2016 recession. In the last observation of the sample, the NRI was 1.8% for the ex-ante rate. Analyzing the difference between the real interest rate (RIR) and the NRI, we identify three distinct periods in the conduction of Brazilian monetary policy. The first one, from 1999 to 2007, is called adaptation phase and is characterized by a contractionary policy after the adoption of the inflation-targeting regime. The average RIR was 12.2% for the period compared to an average NRI of 6.9%. The second period, from 2007 to 2014, the policy stance went from a neutral to expansionary, with an average RIR of 5.0% compared to an NRI of 7.1%. The third period began in 2015 and was characterized by a contractionary impulse in a recessive economic environment. In that period, the average RIR was 5.6% against an NRI of 3.5%. For the sake of comparison and robustness, the NRI was estimated using an alternative method, based on Basdevant, Björksten and Karagedikli (2004). The estimation produced similar results to the ones mentioned above. Both models show a continuous reduction in the NRI over time, in line with the empirical literature for developing countries. It is important to notice that our estimates indicate a reduction in the NRI gap between Brazil and other countries. This result may imply that the period of abnormally high real interest rates in Brazil is over. They also show that Brazilian Central Bank extended the last contractionary cycle even after the inflation surge of 2015 had been purged.
Influences of sodium and glycosaminoglycans on skin oedema and the potential for ulceration: a finite-element approach

Venous ulcers are chronic transcutaneous wounds common in the lower legs. They are resistant to healing and have a 78% chance of recurrence within 2 years. It is commonly accepted that venous ulcers are caused by the insufficiency of the calf muscle pump, leading to blood pooling in the lower legs, resulting in inflammation, skin oedema, tissue necrosis and eventually skin ulceration. However, the detailed physiological events by which inflammation contributes to wound formation are poorly understood. We therefore sought to develop a model that simulated the inflammation, using it to determine the internal stresses and pressure on the skin that contribute to venous ulcer formation. A three-layer finite-element skin model (epidermis, dermis and hypodermis) was developed to explore the roles in wound formation of two inflammation identifiers: glycosaminoglycans (GAG) and sodium. A series of parametric studies showed that increased GAG and sodium content led to oedema and increased tissue stresses of 1.5 MPa, which was within the reported range of skin tissue ultimate tensile stress (0.1–40 MPa). These results suggested that both the oedema and increased fluid pressure could reach a threshold for tissue damage and eventual ulcer formation. The models presented here provide insights to the pathological events associated with venous insufficiency, including inflammation, oedema and skin ulceration.
Online Diagnostic Assessment in Support of Personalized Teaching and Learning: The eDia System

The aims of this paper are: to provide a comprehensive introduction to eDia, an online diagnostic assessment system; to show how the use of technology can contribute to solve certain crucial problems in education by supporting the personalization of learning; and to offer a general reference for further eDia-based studies. The primary function for which the system is designed is to provide regular diagnostic feedback in three main domains of education, reading, mathematics, and science, from the beginning of schooling to the end of the 6 years of primary education. The cognitive foundations of the system, the assessment frameworks, are based on a three-dimensional approach in each domain, distinguishing the psychological (reasoning), the application, and the disciplinary (curricular content) dimensions of learning. The frameworks have been carefully mapped into item banks containing over a 1,000 innovative (multimedia-supported) items in each dimension. The online assessments were piloted, and the system has been operating in experimental mode in over 1,000 schools for several years. This paper outlines the theoretical foundations of the eDia system and summarizes how results from research on the cognitive sciences, learning and instruction, and technology-based assessment have been integrated into a working system designed to assess a large population of students. The paper describes the main functions of eDia and discusses how it supports item writing, constructing tests, online test delivery, automated scoring, data processing, scaling and the provision of feedback both for students and teachers. It shows how diagnostic assessments can be implemented in school practice to facilitate differentiated instruction through regular measurements and to provide instruments for teachers to make formative assessments. Beyond its main function (supporting development toward personalizing education), the eDia platform has been used for assessments in a number of areas from pre-school to higher education both in Hungary and in a number of other countries as well. The paper also reviews results from eDia-based studies and highlights how technology-based assessment extends the possibilities of educational research by making more constructs measurable.
The Interplay Between Theory of Mind and Social Emotional Functioning in Adolescents With Communication and Language Problems

Adolescents with developmental language disorders (DLDs) and adolescents who are deaf or hard of hearing (D/HH) are at greater risk of social emotional problems. These problems may not only be attributed to communication and language problems but, at least in part, to Theory of Mind (ToM) deficits as well. In this mini review, an overview is provided of studies on social emotional functioning and ToM performance in adolescents with DLD and D/HH adolescents. A possible interplay between social emotional functioning and Theory of Mind is discussed. There is empirical evidence for social emotional problems and ToM problems in both adolescents with DLD and D/HH. We hypothesized that language deficits as seen in adolescents with DLD and impoverished exposure to language and communication, as seen in adolescents who are D/HH can explain differences in social emotional functioning and ToM performance. The present mini review provides a possible framework for the relation between ToM and social emotional functioning in adolescents with communication and language problems, which is mediated by their limited linguistic ability or restricted language exposure and gives suggestions for future research.
Protein O-Fucosyltransferase 2 Is Not Essential for Plasmodium berghei Development

Thrombospondin type I repeat (TSR) domains are commonly O-fucosylated by protein O-fucosyltransferase 2 (PoFUT2), and this modification is required for optimal folding and secretion of TSR-containing proteins. The human malaria parasite Plasmodium falciparum expresses proteins containing TSR domains, such as the thrombospondin-related anonymous protein (TRAP) and circumsporozoite surface protein (CSP), which are O-fucosylated. TRAP and CSP are present on the surface of sporozoites and play essential roles in mosquito and human host invasion processes during the transmission stages. Here, we have generated PoFUT2 null-mutant P. falciparum and Plasmodium berghei (rodent) malaria parasites and, by phenotyping them throughout their complete life cycle, we show that PoFUT2 disruption does not affect the growth through the mosquito stages for both species. However, contrary to what has been described previously by others, P. berghei PoFUT2 null mutant sporozoites showed no deleterious motility phenotypes and successfully established blood stage infection in mice. This unexpected result indicates that the importance of O-fucosylation of TSR domains may differ between human and RODENT malaria parasites; complicating our understanding of glycosylation modifications in malaria biology.
Machine Learning Approaches for the Estimation of Biological Aging: The Road Ahead for Population Studies

In recent years, different machine learning algorithms have been developed for the estimation of Biological Age (BA), defined as the hypothetical underlying age of an organism. BA can be computed based on different circulating and non-circulating biomarkers. In this perspective, identifying biomarkers with a prominent influence on BA and developing reliable models for its estimation is of fundamental importance for monitoring healthy aging, and could provide new tools to screen health status and the risk of clinical events in the general population. Here, we briefly review the different machine learning (ML) approaches used for BA estimation, focusing on those methods with potential application to the Moli-sani study, a prospective population-based cohort study of 24,325 subjects (35–99 years). In particular, we discuss the potential of BA estimation based on blood biomarkers, which likely represents the easiest and most immediate way to compute organismal BA. Similarly, we describe ML methods for the estimation of brain age based on structural neuroimaging features. For each method, we discuss the relation with epidemiological variables (e.g., mortality), genetic and environmental factors, and common age-related diseases (e.g., Alzheimer disease), to examine the potential as aging biomarker in the general population. Finally, we hypothesize new approaches for BA estimation, both at the single organ and at the whole organism level. Overall, here we trace the road ahead in the Big Data era for our and other prospective general population cohorts, presenting ways to exploit the notable amount of data available nowadays.
A Genetic System for Methanocaldococcus jannaschii: An Evolutionary Deeply Rooted Hyperthermophilic Methanarchaeon

Phylogenetically deeply rooted methanogens belonging to the genus of Methanocaldococcus living in deep-sea hydrothermal vents derive energy exclusively from hydrogenotrophic methanogenesis, one of the oldest respiratory metabolisms on Earth. These hyperthermophilic, autotrophic archaea synthesize their biomolecules from inorganic substrates and perform high temperature biocatalysis producing methane, a valuable fuel and potent greenhouse gas. The information processing and stress response systems of archaea are highly homologous to those of the eukaryotes. For this broad relevance, Methanocaldococcus jannaschii, the first hyperthermophilic chemolithotrophic organism that was isolated from a deep-sea hydrothermal vent, was also the first archaeon and third organism for which the whole genome sequence was determined. The research that followed uncovered numerous novel information in multiple fields, including those described above. M. jannaschii was found to carry ancient redox control systems, precursors of dissimilatory sulfate reduction enzymes, and a eukaryotic-like protein translocation system. It provided a platform for structural genomics and tools for incorporating unnatural amino acids into proteins. However, the assignments of in vivo relevance to these findings or interrogations of unknown aspects of M. jannaschii through genetic manipulations remained out of reach, as the organism was genetically intractable. This report presents tools and methods that remove this block. It is now possible to knockout or modify a gene in M. jannaschii and genetically fuse a gene with an affinity tag sequence, thereby allowing facile isolation of a protein with M. jannaschii-specific attributes. These tools have helped to genetically validate the role of a novel coenzyme F420-dependent sulfite reductase in conferring resistance to sulfite in M. jannaschii and to demonstrate that the organism possesses a deazaflavin-dependent system for neutralizing oxygen.
Individual Differences in Math Ability Determine Neurocognitive Processing of Arithmetic Complexity: A Combined fNIRS-EEG Study

Some individuals experience more difficulties with math than others, in particular when arithmetic problems get more complex. Math ability, on one hand, and arithmetic complexity, on the other hand, seem to partly share neural underpinnings. This study addresses the question of whether this leads to an interaction of math ability and arithmetic complexity for multiplication and division on behavioral and neural levels. Previously screened individuals with high and low math ability solved multiplication and division problems in a written production paradigm while brain activation was assessed by combined functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG). Arithmetic complexity was manipulated by using single-digit operands for simple multiplication problems and operands between 2 and 19 for complex multiplication problems and the corresponding division problems. On the behavioral level, individuals with low math ability needed more time for calculation, especially for complex arithmetic. On the neural level, fNIRS results revealed that these individuals showed less activation in the left supramarginal gyrus (SMG), superior temporal gyrus (STG) and inferior frontal gyrus (IFG) than individuals with high math ability when solving complex compared to simple arithmetic. This reflects the greater use of arithmetic fact retrieval and also the more efficient processing of arithmetic complexity by individuals with high math ability. Oscillatory EEG analysis generally revealed theta and alpha desynchronization with increasing arithmetic complexity but showed no interaction with math ability. Because of the discovered interaction for behavior and brain activation, we conclude that the consideration of individual differences is essential when investigating the neurocognitive processing of arithmetic.
Different or the Same? Determination of Discriminatory Power Threshold and Category Formation for Vague Linguistic Frequency Expressions

In psychological research, many questionnaires use verbal response scales with vague linguistic terms (e.g., frequency expressions). The words’ meanings can be formalized and evaluated using fuzzy membership functions (MFs), which allow constructing distinct and equidistant response scales. The discriminatory power value of MFs indicates how distinct the functions and, hence, the verbal expressions are. The present manuscript interrogates the threshold of discriminatory power necessary to indicate a sufficient difference in meaning. Using an empirical validation procedure, participants (N = 133) estimated (1) three correspondence values for verbal expressions to determine MFs, and (2) similarities of words by pairwise comparison ratings. Results show a non-linear relationship between discriminatory power and similarity, and fuzzy MFs, as well as the searched-for threshold value for discriminatory power. Implications for the selection of verbal expressions and the construction of verbal categories in questionnaire response scales are discussed.
How Do We Perceive “Aliens”? About the Implicit Processes Underlying the Perception of People With Alien Paraphernalia

People often draw trait assessments of unfamiliar persons on the basis of minimal visual information like facial features. Most studies focus on explicit person evaluations, even though automatic processes of perception are the underlying basis. Furthermore, previous experiments on automatic processes only address very general levels of association. We conducted two experiments employing the multidimensional IAT (md-IAT) to examine automatic processes of perception in a more differentiated way, testing essential variables that are often used to characterize aliens. Results show that personality trait associations of people perceived and categorized as aliens (acquired solely through usage of paraphernalia) are not consistently negative in comparison to more familiar-looking people but might point to the core variables of xenophobic stereotypes (e.g., being aggressive, threatening, and untrustworthy). Proceeding in revealing such variables and testing them might help to understand the main cognito-emotive pattern behind xenophobia and help challenging and tackling stereotypes against aliens.
Macrophages Down-Regulate Gene Expression of Intervertebral Disc Degenerative Markers Under a Pro-inflammatory Microenvironment

Low back pain is a highly prevalent clinical problem and intervertebral disc (IVD) degeneration is now accepted as the major pathophysiological mechanism responsible for this condition. Accumulating evidence suggests that inflammation plays a crucial role in the progression of human IVD degeneration, with macrophages being pointed as the key immune cell players in this process since their infiltration in degenerated IVD samples has been extensively demonstrated. Since they are highly plastic, macrophages can play different roles depending on the microenvironmental cues. The study of inflammation associated with IVD degeneration has been somehow neglected and one of the reasons is related with lack of adequate models. To overcome this, we established and characterized a new model of IVD organ culture under pro-inflammatory conditions to further dissect the role of macrophages in IVD associated immune response. For that, human monocyte-derived macrophages were co-cultured either with bovine caudal IVD punches in the presence of the pro-inflammatory cytokine IL-1β, or IVD-conditioned medium (CM), to investigate how IVD-produced factors influence macrophage phenotype. After 72 h, metabolic activity, gene expression and cytokine profile of macrophages and IVD cells were measured. Our results show that macrophages and IVDs remain metabolically active in the presence of IL-1β, significantly upregulate CCR7 gene expression and increase production of IL-6 on macrophages. When treating macrophages with IL-1β-IVD-CM, CCR7 upregulation follows the same trend, while for IL-6 an opposite effect was observed. On the other hand, macrophages interfere with IVD ECM remodeling, decreasing MMP3 expression and downregulating aggrecan and collagen II gene expression in the presence of IL-1β. Overall, the co-culture model established in this study can be considered a suitable approach to address the cellular and molecular pathways that regulate macrophage-IVD crosstalk, suggesting that degenerated IVD tissue tends to polarize human macrophages toward a more pro-inflammatory profile, which seems to aggravate IVD degeneration. This model could be used to improve the knowledge of the mechanisms that link IVD degeneration and the immune response.
Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study

Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ9-tetrahydrocannabinol (THC): CBD up to 10–12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified. Results: All seven participants tolerated the CHE up to 10–12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS, Min levels of THC remained lower than what would be expected to cause intoxication. Conclusion: The preliminary data suggest an initial CBD target dose of 5–6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible non-linear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.
Rational Engineering of Chorismate-Related Pathways in Saccharomyces cerevisiae for Improving Tyrosol Production

Tyrosol is extensively used in the pharmaceutical industry as an important natural product from plants. In this study, an exogenous pathway involved in catalyzing tyrosine to tyrosol was introduced into Saccharomyces cerevisiae. Furthermore, The pyruvate decarboxylase gene pdc1 was deleted to redirect the flux distribution at the pyruvate node, and a bifunctional NAD+-dependent fused chorismate mutase/prephenate dehydrogenase from E. coli (EcTyrA) and its' tyrosine inhibition resistant mutant (EcTyrAM53I/A354V) were heterologously expression in S. cerevisiae to tuning up the chorismate metabolism effectively directed the metabolic flux toward tyrosol production. Finally, the tyrosol yield of the engineered strain GFT-4 was improved to 126.74 ± 6.70 mg/g DCW at 48 h, increased 440 times compared with that of the control strain GFT-0 (0.28 ± 0.01 mg/g DCW). The new synergetic engineering strategy developed in this study can be further applied to increase the production of high value-added aromatic compounds derived from aromatic amino acid or shikimate in S. cerevisiae.
Fluid Balance Variations During the Early Phase of Large Hemispheric Stroke Are Associated With Patients' Functional Outcome

Background: From the variety of factors underlying the ischemia-associated edema formation in large hemispheric stroke (LHS), an increased brain water content during the early phase seems to have a pivotal role for long-lasting tissue damage. However, the importance of the fluid management during the acute phase of LHS has so far not been adequately studied. Therefore, this study explored the association between the fluid balance and functional outcome in patients suffering from LHS. Methods: We analyzed hospital-based medical records of 39 consecutive patients with LHS and decompressive hemicraniectomy. Over the first 10 days after admission, the volumes of all administered fluids were assessed daily and corrected for daily urinary output and insensible loss. Functional outcome at 3 months was assessed with the modified Rankin Scale (mRS) and dichotomized into an acceptable (mRS ≤ 4) vs. a poor outcome (mRS ≥ 5). Results: Compared to patients with a poor functional outcome (n = 19), those with an acceptable outcome (n = 20) were characterized by a significantly lower cumulative net fluid balance at day 5 (1.6 ± 2.5 vs. 3.4 ± 4.4 l), day 7 (2.0 ± 2.9 vs. 4.6 ± 5.2 l), and day 10 (0 ± 2.5 vs. 5.6 ± 6.2 l). In addition to age, only the cumulative net fluid balance at day 10 served as an independent factor for poor functional outcome in multiple regression analyses. Conclusion: These data provide evidence for a critical role of the early phase net fluid balance with respect to the functional outcome after LHS. This observation leads to the hypothesis that patients with LHS might benefit from a more restrictive volume therapy. However, prospective studies are warranted to establish a causal relationship and recommendations for treatment strategies.