Miracle-dz/UniFAR-FTUs huggingface dataset:
Internally Guided Lower Limb Movement Recruits Compensatory Cerebellar Activity in People With Parkinson's Disease

Background: Externally guided (EG) and internally guided (IG) movements are postulated to recruit two parallel neural circuits, in which motor cortical neurons interact with either the cerebellum or striatum via distinct thalamic nuclei. Research suggests EG movements rely more heavily on the cerebello-thalamo-cortical circuit, whereas IG movements rely more on the striato-pallido-thalamo-cortical circuit (1). Because Parkinson's (PD) involves striatal dysfunction, individuals with PD have difficulty generating IG movements (2). Objectives: Determine whether individuals with PD would employ a compensatory mechanism favoring the cerebellum over the striatum during IG lower limb movements. Methods: 22 older adults with mild-moderate PD, who had abstained at least 12 h from anti-PD medications, and 19 age-matched controls performed EG and IG rhythmic foot-tapping during functional magnetic resonance imaging. Participants with PD tapped with their right (more affected) foot. External guidance was paced by a researcher tapping participants' ipsilateral 3rd metacarpal in a pattern with 0.5 to 1 s intervals, while internal guidance was based on pre-scan training in the same pattern. BOLD activation was compared between tasks (EG vs. IG) and groups (PD vs. control). Results: Both groups recruited the putamen and cerebellar regions. The PD group demonstrated less activation in the striatum and motor cortex than controls. A task (EG vs. IG) by group (PD vs. control) interaction was observed in the cerebellum with increased activation for the IG condition in the PD group. Conclusions: These findings support the hypothesized compensatory shift in which the dysfunctional striatum is assisted by the less affected cerebellum to accomplish IG lower limb movement in individuals with mild-moderate PD. These findings are of relevance for temporal gait dysfunction and freezing of gait problems frequently noted in many people with PD and may have implications for future therapeutic application.
In vitro Evaluation of Photodynamic Effects Against Biofilms of Dermatophytes Involved in Onychomycosis

Dermatophytes are the most common cause of onychomycosis, counting for 90% fungal nail infection. Although dermatophyte pathogens are normally susceptible to antifungal agents, onychomycosis often results in refractory chronic disease, and the formation of biofilms frequently underlines the inadequate responses and resistance to standard antifungal treatment. Numerous in vitro and in vivo antimicrobial photodynamic therapy (aPDT) studies have shown biofilm eradication or substantial reduction, however, such investigation has not yet been expanded to the biofilms of dermatophytes involved in onychomycosis. To shed a light on the potential application of aPDT in the clinic management of onychomycosis, in particular with the manifestation of dermatophytoma, we investigated photodynamic effects on the viabilities and the drug susceptibilities of the biofilm of dermatophytes in vitro. Here, methylene blue at the concentration of 8, 16, and 32 μg/ml applied as photosensitizing agent and LED (635 ± 10 nm, 60 J/cm2) as light source were employed against six strains of Trichophyton rubrum, ten strains of Trichophyton mentagrophytes and three strains of Microsporum gypseum isolated from clinical specimens. Our results indicated highly efficient photodynamic inhibition, exhibiting CFU (colony forming unit) reduction up to 4.6 log10, 4.3 log10, and 4.7 log10 against the biofilms formed by T. rubrum, T. mentagrophytes, and M. gypseum, respectively. Subjected biofilms displayed considerable decreases in SMICs (sessile minimum inhibitory concentrations) to multiple antifungal agents when compared with untreated groups, indicating the biofilms of dermatophytes became more susceptible to conventional antifungal drugs after aPDT. Additionally, the obliteration of biofilm after aPDT could be observed as shattered and ruptured structures being evident in SEM (Scanning Electron Microscopy) images. These findings suggest that aPDT is an attractive alternative treatment holding great promise for combating recalcitrant onychomycosis associated with the biofilm formation.
Measuring Height Change Around the Periphery of the Greenland Ice Sheet With Radar Altimetry

Ice loss measurements around the periphery of the Greenland Ice Sheet can provide key information on the response to climate change. Here we use the excellent spatial and temporal coverage provided by the European Space Agency (ESA) CryoSat satellite, together with NASA airborne Operation IceBridge and automatic weather station data, to study the influence of changing conditions on the bias between the height estimated by the satellite radar altimeter and the ice sheet surface. Surface and near-surface conditions on the ice sheet periphery change with season and geographic position in a way that affects the returned altimeter waveform and can therefore affect the estimate of the surface height derived from the waveform. Notwithstanding the possibility of a varying bias between the derived and real surface, for the lower accumulation regions in the western and northern ice sheet periphery (< ~1 m snow accumulation yearly) we show that the CryoSat altimeter can measure height change throughout the year, including that associated with ice dynamics, summer melt and winter accumulation. Further, over the 9-year CryoSat lifetime it is also possible to relate height change to change in speed of large outlet glaciers, for example, there is significant height loss upstream of two branches of the Upernavik glacier in NW Greenland that increased in speed during this time, but much less height loss over a third branch that slowed in the same time period. In contrast to the west and north, winter snow accumulation in the south-east periphery can be 2 - 3 m and the average altimeter height for this area can decrease by up to 2 m during the fall and winter when the change in the surface elevation is much smaller. We show that vertical downward movement of the dense layer from the last summer melt coupled with overlying dry snow, are responsible for the anomalous altimeter height change. However, it is still possible to estimate year-to-year height change measurements in this area by using data from the late-summer to early-fall when surface returns dominate the altimeter signal.
Adolescents’ Mindfulness and Psychological Distress: The Mediating Role of Emotion Regulation

Mindfulness has been widely linked with psychological well-being in general population. There are emerging studies supporting the relationship between adolescents’ mindfulness and their mental health. However, the mechanisms through which mindfulness may influence adolescents’ psychological distress have only recently been explored, and more related research is still needed. This study investigated the relationship between adolescents’ dispositional mindfulness and psychological symptoms of depression, anxiety and stress. The mediating variables were also explored in perspective of two common emotion regulation theories, which were measured through Difficulties in Emotion Regulation Scale (DERS) and Emotion Regulation Questionnaire (ERQ). DERS has been used as a comprehensive assessment of emotion regulation difficulties. ERQ is also widely accepted to measure the emotion regulation process including dimensions of cognitive reappraisal and expressive suppression. Measures assessing mindfulness, emotion regulation, and psychological distress were administered to 1067 adolescents in mainland China. The results confirmed that adolescents’ dispositional mindfulness was negatively associated with depression, anxiety, and stress. DERS, especially the sub-dimensions of Acceptance and Strategies, significantly mediated the relationship between mindfulness and symptoms of depression, anxiety and stress. Whereas, ERQ including subscales of cognitive reappraisal and expressive suppression exerted limited mediating effect. These findings provided insights for the potential underlying mechanism between adolescents’ mindfulness and psychological distress, demonstrating that DERS might be more pervasive than ERQ. Further research was suggested to explore other mediating variables underlying mindfulness and psychological distress among adolescents and develop mindfulness-based programs to improve adolescents’ mindfulness and emotion regulation ability.
Causal Discovery with Reinforcement Learning

Discovering causal structure among a set of variables is a fundamental problem in many empirical sciences. Traditional score-based casual discovery methods rely on various local heuristics to search for a Directed Acyclic Graph (DAG) according to a predefined score function. While these methods, e.g., greedy equivalence search, may have attractive results with infinite samples and certain model assumptions, they are usually less satisfactory in practice due to finite data and possible violation of assumptions. Motivated by recent advances in neural combinatorial optimization, we propose to use Reinforcement Learning (RL) to search for the DAG with the best scoring. Our encoder-decoder model takes observable data as input and generates graph adjacency matrices that are used to compute rewards. The reward incorporates both the predefined score function and two penalty terms for enforcing acyclicity. In contrast with typical RL applications where the goal is to learn a policy, we use RL as a search strategy and our final output would be the graph, among all graphs generated during training, that achieves the best reward. We conduct experiments on both synthetic and real datasets, and show that the proposed approach not only has an improved search ability but also allows a flexible score function under the acyclicity constraint.
Competing (Semi-)Selfish Miners in Bitcoin

The Bitcoin protocol prescribes certain behavior by the miners who are responsible for maintaining and extending the underlying blockchain; in particular, miners who successfully solve a puzzle, and hence can extend the chain by a block, are supposed to release that block immediately. Eyal and Sirer showed, however, that a selfish miner is incentivized to deviate from the protocol and withhold its blocks under certain conditions. The analysis by Eyal and Sirer, as well as in followup work, considers a single selfish miner (who may control a large fraction of the hashing power in the network) interacting with a remaining pool of honest miners. Here, we extend this analysis to the case where there are multiple (non-colluding) selfish miners. We find that in this setting there are cases in which it may be profitable for those miners to deviate even when they would not be incentivized to deviate individually.
Gal-3 Deficiency Suppresses Novosphyngobium aromaticivorans Inflammasome Activation and IL-17 Driven Autoimmune Cholangitis in Mice

Gal-3 has the role in multiple inflammatory pathways. Multiple-hit etiology of primary biliary cholangitis (PBC) and evolving immune response at various stages of the disease includes involvement of Gal-3 in PBC pathogenesis. In this study we aimed to clarify the role of Gal-3 in Novosphingobium aromaticivorans (N. aromaticivorans) induced biliary disease. Autoimmune cholangitis was induced in mice by two intra-peritoneal injections of N. aromaticivorans within 2 weeks. The role of Gal-3 was evaluated by using Lgals3−/− mice and mice treated with Gal-3 inhibitor. The histological and serological parameters of disease, phenotype of dendritic, NK, NKT, and T cells and inflammasome expression were evaluated. Marked attenuation of the disease in Lgals3−/− and Gal-3 inhibitor, DAVANAT®, treated mice is manifested by the absence of bile duct damage, granulomas and fibrosis. Liver infiltrates of N. aromaticivorans infected wild type mice had higher incidence of pro-inflammatory macrophages, dendritic cells, NK, NKT, and T cells. Lgals3 deletion and treatment with Gal-3 inhibitor reduced inflammatory mononuclear cell infiltrate, expression of NLRP3 inflammasome in the liver infiltrates and interleukin-1β (IL-1β) production in the livers of N. aromaticivorans infected mice. In vitro stimulation of wild type peritoneal macrophages with N. aromaticivorans caused increased NLRP3 expression, caspase-1 activity and IL-1β production compared with Lgals3−/− cells. Our data highlight the importance of Gal-3 in promotion of inflammation in N. aromaticivorans induced PBC by enhancing the activation of NLRP3 inflammasome and production of IL-1β and indicate Gal-3 as possible therapeutical target in autoimmune cholangitis. Galectin-3 appears involved in inflammatory response to gut commensal leading to PBC.
The Inhibition of RasGRF2, But Not RasGRF1, Alters Cocaine Reward in Mice

Ras/Raf/MEK/ERK (Ras-ERK) signaling has been implicated in the effects of drugs of abuse. Inhibitors of MEK1/2, the kinases upstream of ERK1/2, have been critical in defining the role of the Ras-ERK cascade in drug-dependent alterations in behavioral plasticity, but the Ras family of small GTPases has not been extensively examined in drug-related behaviors. We examined the role of Ras Guanine Nucleotide Releasing Factor 1 (RasGRF1) and 2 (RasGRF2), upstream regulators of the Ras-ERK signaling cascade, on cocaine self-administration (SA) in male mice. We first established a role for Ras-ERK signaling in cocaine SA, demonstrating that pERK1/2 is upregulated following SA in C57BL/6N mice in striatum. We then compared RasGRF1 and RasGRF2 KO mouse lines, demonstrating that cocaine SA in RasGRF2 KO mice was increased relative to WT controls, whereas RasGRF1 KO and WT mice did not differ. This effect in RasGRF2 mice is likely mediated by the Ras-ERK signaling pathway, as pERK1/2 upregulation following cocaine SA was absent in RasGRF2 KO mice. Interestingly, the lentiviral knockdown of RasGRF2 in the NAc had the opposite effect to that in RasGRF2 KO mice, reducing cocaine SA. We subsequently demonstrated that the MEK inhibitor PD325901 administered peripherally prior to cocaine SA increased cocaine intake, replicating the increase seen in RasGRF2 KO mice, whereas PD325901 administered into the NAc decreased cocaine intake, similar to the effect seen following lentiviral knockdown of RasGRF2. These data indicate a role for RasGRF2 in cocaine SA in mice that is ERK-dependent, and suggest a differential effect of global versus site-specific RasGRF2 inhibition. SIGNIFICANCE STATEMENT Exposure to drugs of abuse activates a variety of intracellular pathways, and following repeated exposure, persistent changes in these pathways contribute to drug dependence. Downstream components of the Ras-ERK signaling cascade are involved in the acute and chronic effects of drugs of abuse, but their upstream mediators have not been extensively characterized. Here we show, using a combination of molecular, pharmacological, and lentiviral techniques, that the guanine nucleotide exchange factor RasGRF2 mediates cocaine self-administration via an ERK-dependent mechanism, whereas RasGRF1 has no effect on responding for cocaine. These data indicate dissociative effects of mediators of Ras activity on cocaine reward and expand the understanding of the contribution of Ras-ERK signaling to drug-taking behavior.
A refined primal-dual analysis of the implicit bias

Recent work shows that gradient descent on linearly separable data is implicitly biased towards the maximum margin solution. However, no convergence rate which is tight in both n (the dataset size) and t (the training time) is given. This work proves that the normalized gradient descent iterates converge to the maximum margin solution at a rate of O(ln(n)/ ln(t)), which is tight in both n and t. The proof is via a dual convergence result: gradient descent induces a multiplicative weights update on the (normalized) SVM dual objective, whose convergence rate leads to the tight implicit bias rate.
Fumonisins: Impact on Agriculture, Food, and Human Health and their Management Strategies

The fumonisins producing fungi, Fusarium spp. , are ubiquitous in nature and contaminate several food matrices that pose detrimental health hazards on humans as well as on animals. This has necessitated profound research for the control and management of the toxins to guarantee better health of consumers. This review highlights the chemistry and biosynthesis process of the fumonisins, their occurrence, effect on agriculture and food, along with their associated health issues. In addition, the focus has been put on the detection and management of fumonisins to ensure safe and healthy food. The main focus of the review is to provide insights to the readers regarding their health-associated food consumption and possible outbreaks. Furthermore, the consumers’ knowledge and an attempt will ensure food safety and security and the farmers’ knowledge for healthy agricultural practices, processing, and management, important to reduce the mycotoxin outbreaks due to fumonisins.
Lactate, bicarbonate and anion gap for evaluation of patients presenting with sepsis to the emergency department: A prospective cohort study

A serum lactate level >2 mmol/L has been chosen as the preferred cut‐off value for screening of patients with suspected sepsis. In patients with suspected sepsis presenting to the ED, we aimed to determine the outcomes of patients with initial lactate levels ≤2 mmoL/L, but abnormal bicarbonate or anion gaps (AGs).
The Validity and Reliability of Live Football Match Statistics From Champdas Master Match Analysis System

The aim of the present study was to investigate the validity of match variables and the reliability of Champdas Master System used by trained operators in live association football match. Twenty professional football coaches voluntarily participated in the validation of match variables used in the System. Four well-trained operators divided into two groups that independently analyzed a match of Spanish La Liga. The Aiken’s V averaged at 0.84 ± 0.03 and 0.85 ± 0.03 for the validation of indicators. The high Kappa values (Operator 1: 0.92, 0.90; Operator 2: 0.91, 0.88), high intra-class correlation coefficients (varied from 0.93 to 1.00), and low typical errors (varied from 0.01 to 0.34) between the first and second data collection represented a high level of intra-operator reliability. The Kappa values for the inter-operator reliability of were 0.97 and 0.89. The intra-class correlation coefficients and typical errors ranged from 0.90 to 1.00 and ranged from 0.01 to 0.24 for two independent operators within two data collections. The results suggest that the Champdas Master system can be used validly and reliably to gather live football match statistics by well-trained operators. Therefore, the data obtained by the company can be used by coaches, managers, researchers and performance analysts as valid match statistics from players and teams during their professional tasks and investigations.
Regulation of Innate Immune Responses by Platelets

The role of platelets has been extensively studied in the context of coagulation and vascular integrity. Their hemostatic imbalance can lead to known conditions as atherosclerotic plaques, thrombosis, and ischemia. Nevertheless, the knowledge regarding the regulation of different cell types by platelets has been growing exponentially in the past years. Among these biological systems, the innate immune response is remarkably affected by the crosstalk with platelets. This interaction can come from the formation of platelet-leukocyte aggregates, signaling by direct contact between membrane surface molecules or by the stimulation of immune cells by soluble factors and active microparticles secreted by platelets. These ubiquitous blood components are able to sense and react to danger signals, guiding leukocytes to an injury site and providing a scaffold for the formation of extracellular traps for efficient microbial killing and clearance. Using several different mechanisms, platelets have an important task as they regulate the release of different cytokines and chemokines upon sterile or infectious damage, the expression of cell markers and regulation of cell death and survival. Therefore, platelets are more than clotting agents, but critical players within the fine inflammatory equilibrium for the host. In this review, we present pointers to a better understanding about how platelets control and modulate innate immune cells, as well as a summary of the outcome of this interaction, providing an important step for therapeutic opportunities and guidance for future research on infectious and autoimmune diseases.
Microservices Migration in Industry: Intentions, Strategies, and Challenges

To remain competitive in a fast changing environment, many companies started to migrate their legacy applications towards a Microservices architecture. Such extensive migration processes require careful planning and consideration of implications and challenges likewise. In this regard, hands-on experiences from industry practice are still rare. To fill this gap in scientific literature, we contribute a qualitative study on intentions, strategies, and challenges in the context of migrations to Microservices. We investigated the migration process of 14 systems across different domains and sizes by conducting 16 in-depth interviews with software professionals from 10 companies. Along with a summary of the most important findings, we present a separate discussion of each case. As primary migration drivers, maintainability and scalability were identified. Due to the high complexity of their legacy systems, most companies preferred a rewrite using current technologies over splitting up existing code bases. This was often caused by the absence of a suitable decomposition approach. As such, finding the right service cut was a major technical challenge, next to building the necessary expertise with new technologies. Organizational challenges were especially related to large, traditional companies that simultaneously established agile processes. Initiating a mindset change and ensuring smooth collaboration between teams were crucial for them. Future research on the evolution of software systems can in particular profit from the individual cases presented.
First Error-Based Supervised Learning Algorithm for Spiking Neural Networks

Neural circuits respond to multiple sensory stimuli by firing precisely timed spikes. Inspired by this phenomenon, the spike timing-based spiking neural networks (SNNs) are proposed to process and memorize the spatiotemporal spike patterns. However, the response speed and accuracy of the existing learning algorithms of SNNs are still lacking compared to the human brain. To further improve the performance of learning precisely timed spikes, we propose a new weight updating mechanism which always adjusts the synaptic weights at the first wrong output spike time. The proposed learning algorithm can accurately adjust the synaptic weights that contribute to the membrane potential of desired and non-desired firing time. Experimental results demonstrate that the proposed algorithm shows higher accuracy, better robustness, and less computational resources compared with the remote supervised method (ReSuMe) and the spike pattern association neuron (SPAN), which are classic sequence learning algorithms. In addition, the SNN-based computational model equipped with the proposed learning method achieves better recognition results in speech recognition task compared with other bio-inspired baseline systems.