Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytoprotective and Neurotrophic Effects of Octadecaneuropeptide (ODN) in in vitro and in vivo Models of Neurodegenerative Diseases

Octadecaneuropeptide (ODN) and its precursor diazepam-binding inhibitor (DBI) are peptides belonging to the family of endozepines. Endozepines are exclusively produced by astroglial cells in the central nervous system of mammals, and their release is regulated by stress signals and neuroactive compounds. There is now compelling evidence that the gliopeptide ODN protects cultured neurons and astrocytes from apoptotic cell death induced by various neurotoxic agents. In vivo, ODN causes a very strong neuroprotective action against neuronal degeneration in a mouse model of Parkinson's disease. The neuroprotective activity of ODN is based on its capacity to reduce inflammation, apoptosis, and oxidative stress. The protective effects of ODN are mediated through its metabotropic receptor. This receptor activates a transduction cascade of second messengers to stimulate protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) signaling pathways, which in turn inhibits the expression of proapoptotic factor Bax and the mitochondrial apoptotic pathway. In N2a cells, ODN also promotes survival and stimulates neurite outgrowth. During the ODN-induced neuronal differentiation process, numerous mitochondria and peroxisomes are identified in the neurites and an increase in the amount of cholesterol and fatty acids is observed. The antiapoptotic and neurotrophic properties of ODN, including its antioxidant, antiapoptotic, and pro-differentiating effects, suggest that this gliopeptide and some of its selective and stable derivatives may have therapeutic value for the treatment of some neurodegenerative diseases.
Soy Isoflavones Accelerate Glial Cell Migration via GPER-Mediated Signal Transduction Pathway

Soybean isoflavones, such as genistein, daidzein, and its metabolite, S-equol, are widely known as phytoestrogens. Their biological actions are thought to be exerted via the estrogen signal transduction pathway. Estrogens, such as 17β-estradiol (E2), play a crucial role in the development and functional maintenance of the central nervous system. E2 bind to the nuclear estrogen receptor (ER) and regulates morphogenesis, migration, functional maturation, and intracellular metabolism of neurons and glial cells. In addition to binding to nuclear ER, E2 also binds to the G-protein-coupled estrogen receptor (GPER) and activates the nongenomic estrogen signaling pathway. Soybean isoflavones also bind to the ER and GPER. However, the effect of soybean isoflavone on brain development, particularly glial cell function, remains unclear. We examined the effects of soybean isoflavones using an astrocyte-enriched culture and astrocyte-derived C6 clonal cells. Isoflavones increased glial cell migration. This augmentation was suppressed by co-exposure with G15, a selective GPER antagonist, or knockdown of GPER expression using RNA interference. Isoflavones also activated actin cytoskeleton arrangement via increased actin polymerization and cortical actin, resulting in an increased number and length of filopodia. Isoflavones exposure increased the phosphorylation levels of FAK (Tyr397 and Tyr576/577), ERK1/2 (Thr202/Tyr204), Akt (Ser473), and Rac1/cdc42 (Ser71), and the expression levels of cortactin, paxillin and ERα. These effects were suppressed by knockdown of the GPER. Co-exposure of isoflavones to the selective RhoA inhibitor, rhosin, selective Cdc42 inhibitor, casin, or Rac1/Cdc42 inhibitor, ML-141, decreased the effects of isoflavones on cell migration. These findings indicate that soybean isoflavones exert their action via the GPER to activate the PI3K/FAK/Akt/RhoA/Rac1/Cdc42 signaling pathway, resulting in increased glial cell migration. Furthermore, in silico molecular docking studies to examine the binding mode of isoflavones to the GPER revealed the possibility that isoflavones bind directly to the GPER at the same position as E2, further confirming that the effects of the isoflavones are at least in part exerted via the GPER signal transduction pathway. The findings of the present study indicate that isoflavones may be an effective supplement to promote astrocyte migration in developing and/or injured adult brains.
Ice Paddles, CO2 Invaders, and Exploding Planets: How Young Students Transform Climate Science Into Serious Games

In game-based curricula that leverage game design, students can learn creatively by transforming serious topics into video games (i.e., serious games). However, as these games remain mostly under-explored, we know little about how students design them and the extent to which they reflect content uptake. Here, we leverage a framework for serious games called Triadic Game Design (TGD) to analyze 391 games on climate science, which were designed by 8th-grade students with Scratch. Based on a large-scale TGD-based analysis, we provide an overview of design outcomes emerging from student games, and analyze how reality, meaning, and play are articulated in these games to reflect content uptake. Then, we ask two experts in game design and education to assess a subset of the 20 most representative games, to reflect on further design and pedagogical insights that may have not been captured by the large-scale analysis. Our results reveal a wide range of design outcomes, where Pong-like games teach players about the ice-albedo feedback loop, and CO2 molecules become targets to be shot in games like Space Invaders. Our work can serve as guidance and inspiration to help both researchers and educators evaluate student-designed games, as well as reason about how to use them as assessment tools in game-based constructionist curricula.
Tailoring Gamification for Adolescents: a Validation Study of Big Five and Hexad in Dutch

Gamification researchers deem adolescents a particularly interesting audience for tailored gamification. However, empirical validation of popular player typologies and personality trait models thus far has been limited to adults. As adolescents exhibit complex behaviours that differ from older adults, these models may need adaptation. To that end, we collected a unique data set of Big Five Inventory and Hexad questionnaire answers in Dutch from 402 adolescents. Confirmatory factor analysis showed that the Dutch forms of the BFI-10, BFI-44 and Hexad scales performed substandard when used with adolescents. Through exploratory factor analysis, we investigated underlying problems, and provide preliminary suggestions on how to improve measurements. In particular, we propose to simplify the Hexad model, and to reformulate specific items. With this study, we hope to contribute to the debate on how to improve the tailoring of interactive systems for adolescents.
Quantifying the potential of data-driven mobility support systems

When traveling it is often necessary to take a detour, for example to find an on-street parking opportunity or a charging station. Numerous systems intending to reduce time or other resources spent on such detours have been presented. An example are methods guiding drivers to free on-street parking opportunities. However, the question of how much can actually be saved by using such solutions when compared to the status quo remains largely unanswered. Often, the cost attached to these detours is unclear. In this work, we present a generalized approach to answer these questions: A methodology consisting of an evaluation environment powered by real-world data and implementations of different scenarios. We then illustrate our proposal by using it to quantify the potential of an optimal assistant for finding on-street parking opportunities. We further show how to generate synthetic but realistic parking data when real-world data is not available.
Predicting ambient traffic of a vehicle from road abrasion measurements using random forest

The development and application of Intelligent Transportation Systems (ITSs) leads to a growing demand of traffic data. Floating Car Observers (FCOs) contribute by providing information about ambient traffic of vehicles while driving. We present an approach to implement an FCO that uses particulate matter sensors for obtaining road abrasion from cars driving ahead of a test vehicle. Using Random Forest (RF), we predict presence and absence of ambient traffic in the vicinity of test vehicle with particulate matter readings (PM01, PM2.5, PM10) as predictor variables. Results show that RF reaches prediction accuracy ranging from 86 to 99 percent for different train/test split options when analysing individual trajectories as well as 88 to 91 percent accuracy when analysing all trajectories combined. We face limitations mainly when merging single trajectories, due to different initial ambient particulate matter values. We conclude that presence and absence of ambient traffic are predictable using Random Forest with road abrasion values as predictor variables. Further, rainfall events (that may cause wash-off effects on roads) do not significantly change the accuracy of our classification. Optimisation of the model and the need of testing more diverse weather and road conditions remain open tasks for future research.
Game Atmosphere: Effects of Audiovisual Thematic Cohesion on Player Experience and Psychophysiology

Game atmosphere and game audio are critical factors linked to the commercial success of video games. However, game atmosphere has been neither operationalized nor clearly defined in games user research literature, making it difficult to study. We define game atmosphere as the emerging subjective experience of a player caused by the strong audiovisual thematic cohesion (i.e., the harmonic fit of sounds and graphics to a shared theme) of video game elements. We studied players' experience of thematic cohesion in two between-subjects, independent-measures experiments (N=109) across four conditions differing in their level of audiovisual thematic fit. Participants' experiences were assessed with physiological and psychometric measurements to understand the effect of game atmosphere on player experience. Results indicate that a lack of thematic fit between audio and visuals lowers the degree of perceived atmosphere, but that while audiovisual thematic dissonance may lead to higher-intensity negative-valence facial events, it does not impact self-reported player experience or immersion.
Rapid Response Subunit Vaccine Design in the Absence of Structural Information

Prior to 2020, the threat of a novel viral pandemic was omnipresent but largely ignored. Just 12 months prior to the Coronavirus disease 2019 (COVID-19) pandemic our team received funding from the Coalition for Epidemic Preparedness Innovations (CEPI) to establish and validate a rapid response pipeline for subunit vaccine development based on our proprietary Molecular Clamp platform. Throughout the course of 2019 we conducted two mock tests of our system for rapid antigen production against two potential, emerging viral pathogens, Achimota paramyxovirus and Wenzhou mammarenavirus. For each virus we expressed a small panel of recombinant variants of the membrane fusion protein and screened for expression level, product homogeneity, and the presence of the expected trimeric pre-fusion conformation. Lessons learned from this exercise paved the way for our response to COVID-19, for which our candidate antigen is currently in phase I clinical trial.
More Sensitive Identification for Bradykinesia Compared to Tremors in Parkinson’s Disease Based on Parkinson’s KinetiGraph (PKG)

The effective management and therapies for Parkinson’s disease (PD) require appropriate clinical evaluation. The Parkinson’s KinetiGraph (PKG) is a wearable sensor system that can monitor the motion characteristics of PD objectively and continuously. This study was aimed to assess the correlations between PKG data and clinical scores of bradykinesia, rigidity, tremor, and fluctuation. It also aims to explore the application value of identifying early motor symptoms. An observational study of 100 PD patients wearing the PKG for ≥ 6 days was performed. It provides a series of data, such as the bradykinesia score (BKS), percent time tremor (PTT), dyskinesia score (DKS), and fluctuation and dyskinesia score (FDS). PKG data and UPDRS scores were analyzed, including UPDRS III total scores, UPDRS III-bradykinesia scores (UPDRS III-B: items 23–26, 31), UPDRS III-rigidity scores (UPDRS III-R: item 22), and scores from the Wearing-off Questionnaire (WOQ-9). This study shows that there was significant correlation between BKS and UPDRS III scores, including UPDRS III total scores, UPDRS III-B, and UPDRS III-R scores (r = 0.479–0.588, p ≤ 0.001), especially in the early-stage group (r = 0.682, p < 0.001). Furthermore, we found that BKS in patients with left-sided onset (33.57 ± 5.14, n = 37) is more serious than in patients with right-sided onset (29.87 ± 6.86, n = 26). Our findings support the feasibility of using the PKG to detect abnormal movements, especially bradykinesia in PD. It is suitable for the early detection, remote monitoring, and timely treatment of PD symptoms.
Biotechnology and Biomaterial-Based Therapeutic Strategies for Age-Related Macular Degeneration. Part I: Biomaterials-Based Drug Delivery Devices

Age-related Macular Degeneration (AMD) is an up-to-date untreatable chronic neurodegenerative eye disease of multifactorial origin, and the main causes of blindness in over 65 years old people. It is characterized by a slow progression and the presence of a multitude of factors, highlighting those related to diet, genetic heritage and environmental conditions, present throughout each of the stages of the illness. Current therapeutic approaches, mainly consisting of intraocular drug delivery, are only used for symptoms relief and/or to decelerate the progression of the disease. Furthermore, they are overly simplistic and ignore the complexity of the disease and the enormous differences in the symptomatology between patients. Due to the wide impact of the AMD and the up-to-date absence of clinical solutions, the development of biomaterials-based approaches for a personalized and controlled delivery of therapeutic drugs and biomolecules represents the main challenge for the defeat of this neurodegenerative disease. Here we present a critical review of the available and under development AMD therapeutic approaches, from a biomaterials and biotechnological point of view. We highlight benefits and limitations and we forecast forthcoming alternatives based on novel biomaterials and biotechnology methods. In the first part we expose the physiological and clinical aspects of the disease, focusing on the multiple factors that give origin to the disorder and highlighting the contribution of these factors to the triggering of each step of the disease. Then we analyze available and under development biomaterials-based drug-delivery devices (DDD), taking into account the anatomical and functional characteristics of the healthy and ill retinal tissue.
Marine Ecosystem Assessment for the Southern Ocean: Birds and Marine Mammals in a Changing Climate

The massive number of seabirds (penguins and procellariiformes) and marine mammals (cetaceans and pinnipeds) – referred to here as top predators – is one of the most iconic components of the Antarctic and Southern Ocean. They play an important role as highly mobile consumers, structuring and connecting pelagic marine food webs and are widely studied relative to other taxa. Many birds and mammals establish dense breeding colonies or use haul-out sites, making them relatively easy to study. Cetaceans, however, spend their lives at sea and thus aspects of their life cycle are more complicated to monitor and study. Nevertheless, they all feed at sea and their reproductive success depends on the food availability in the marine environment, hence they are considered useful indicators of the state of the marine resources. In general, top predators have large body sizes that allow for instrumentation with miniature data-recording or transmitting devices to monitor their activities at sea. Development of scientific techniques to study reproduction and foraging of top predators has led to substantial scientific literature on their population trends, key biological parameters, migratory patterns, foraging and feeding ecology, and linkages with atmospheric or oceanographic dynamics, for a number of species and regions. We briefly summarize the vast literature on Southern Ocean top predators, focusing on the most recent syntheses. We also provide an overview on the key current and emerging pressures faced by these animals as a result of both natural and human causes. We recognize the overarching impact that environmental changes driven by climate change have on the ecology of these species. We also evaluate direct and indirect interactions between marine predators and other factors such as disease, pollution, land disturbance and the increasing pressure from global fisheries in the Southern Ocean. Where possible we consider the data availability for assessing the status and trends for each of these components, their capacity for resilience or recovery, effectiveness of management responses, risk likelihood of key impacts and future outlook.
Low H3K9me3 Expression Is Associated With Poor Prognosis in Patients With Distal Common Bile Duct Cancer

Background/Aim: Histone modification is associated with tumorigenesis and cancer progression. Recent studies have revealed the prognostic value of histone modification; however, its prognostic role in distal bile duct cancer remains unclear. Patients and Methods: We analyzed the expression of H3K9me3, H4K20me3, and H3K36me3 and its correlation with survival outcomes in resected samples from 88 patients with distal bile duct cancer. Results: Low expression rates of H3K9me3, H4K20me3, and H3K36me3 were significantly associated with poor overall survival (p=0.003, 0.008, and 0.047, respectively) and event-free survival (p=0.03 for H3K9m3). Additionally, low-expression of H3K9me3 was an independent poor prognostic indicator (p<0.001; HR=7.85; 95% CI=2.693-22.883). Conclusion: H3K9me3 was an independent poor prognostic factor in distal common bile duct cancer. Our results suggest that histone markers are potential prognostic markers and provide better management for patients at risk for an aggressive course of disease.
The Test-Retest Reliability of Heart Rate Variability and Its Association With Personality Functioning

Background: Heart rate variability (HRV) is a widely used non-invasive index of emotion regulation ability. The main aim of our study was to investigate the relationship between HRV and level of personality functioning in a clinical sample, most of whom had a personality disorder. Our secondary aim was to examine the test-retest reliability of HRV in our sample as there is a lack of knowledge regarding the test-retest reliability in psychiatric populations. We hypothesized that trait HRV would be negatively associated with impairments of personality functioning. Method: Thirty-two adults (23 females, mean age = 27) with threshold or subthreshold personality disorders were recruited from two psychiatric outpatient clinics in Norway. Impairment of personality functioning was assessed by the first module of the Structured Clinical Interview for the DSM-5 Alternative Model for Personality Disorders (SCID-5-AMPD-I); Level of Personality Functioning Scale (LPFS). HRV was assessed during resting conditions with spontaneous breathing over three separate days. Trait HRV was calculated by averaging all three HRV assessments. The test-retest reliability of HRV was assessed using intraclass correlations. Results: Contrary to expected, a positive association between trait HRV and the LPFS Self-direction domain emerged. This was driven by positive associations between the LPFS and HRV at time point 2. Overall, the test-retest reliability of HRV was comparable to previous studies on healthy subjects. However, the reliability coefficients for the first two time points were considerably lower relative to the second and third time points. Conclusions: We propose that impairment of personality functioning may have increased the proportion of variance in HRV attributed to state relative to trait. This could explain the lower test-retest reliability for the first two time points. The increased test-retest reliability for the last two time points could reflect a habituation to the testing situation and hence, less pronounced influences of state in the second and third time points.
Microbial Resistance Movements: An Overview of Global Public Health Threats Posed by Antimicrobial Resistance, and How Best to Counter

Antibiotics changed medical practice by significantly decreasing the morbidity and mortality associated with bacterial infection. However, infectious diseases remain the leading cause of death in the world. There is global concern about the rise in antimicrobial resistance (AMR), which affects both developed and developing countries. AMR is a public health challenge with extensive health, economic, and societal implications. This paper sets AMR in context, starting with the history of antibiotics, including the discovery of penicillin and the golden era of antibiotics, before exploring the problems and challenges we now face due to AMR. Among the factors discussed is the low level of development of new antimicrobials and the irrational prescribing of antibiotics in developed and developing countries. A fundamental problem is the knowledge, attitude, and practice (KAP) regarding antibiotics among medical practitioners, and we explore this aspect in some depth, including a discussion on the KAP among medical students. We conclude with suggestions on how to address this public health threat, including recommendations on training medical students about antibiotics, and strategies to overcome the problems of irrational antibiotic prescribing and AMR.
Multi-language dynamic taint analysis in a polyglot virtual machine

Dynamic taint analysis is a popular program analysis technique in which sensitive data is marked as tainted and the propagation of tainted data is tracked in order to determine whether that data reaches critical program locations. This analysis technique has been successfully applied to software vulnerability detection, malware analysis, testing and debugging, and many other fields. However, existing approaches of dynamic taint analysis are either language-specific or they target native code. Neither is suitable for analyzing applications in which high-level dynamic languages such as JavaScript and low-level languages such as C interact.In these approaches, the language boundary forms an opaque barrier that prevents a sound analysis of data flow in the other language and can thus lead to the analysis being evaded. In this paper we introduce TruffleTaint, a platform for multi-language dynamic taint analysis that uses language-independent techniques for propagating taint labels to overcome the language boundary but still allows for language-specific taint propagation rules. Based on the Truffle framework for implementing runtimes for programming languages, TruffleTaint supports propagating taint in and between a selection of dynamic and low-level programming languages and can be easily extended to support additional languages. We demonstrate TruffleTaint’s propagation capabilities and evaluate its performance using several benchmarks from the Computer Language Benchmarks Game, which we implemented as combinations of C, JavaScript and Python code and which we adapted to propagate taint in various scenarios of language interaction. Our evaluation shows that TruffleTaint causes low to zero slowdown when no taint is introduced, rivaling state-of-the-art dynamic taint analysis platforms, and only up to ∼40x slowdown when taint is introduced.