Miracle-dz/UniFAR-FTUs huggingface dataset:
PERK Activation by SB202190 Attenuates Amyloidogenesis via TFEB-induced Autophagy-Lysosomal Pathway

The protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK), a key ER stress sensor of the unfolded protein response (UPR), can confer beneficial effects by facilitating the removal of cytosolic aggregates through the autophagy-lysosome pathway (ALP). In neurodegenerative diseases, the ALP ameliorates the accumulation of intracellular protein aggregates in the brain. Transcription factor-EB (TFEB), a master regulator of the ALP, positively regulates key genes involved in the cellular degradative pathway. However, in neurons, the role of PERK activation in mitigating amyloidogenesis by ALP remains unclear. In this study, we found that SB202190 selectively activates PERK independently of its inhibition of p38 mitogen-activated protein kinase, but not inositol-requiring transmembrane kinase/endoribonuclease-1α (IRE1α) or activating transcription factor 6 (ATF6), in human neuroblastoma cells. PERK activation by SB202190 was dependent on mitochondrial ROS production and promoted Ca2+-calcineurin activation. The activation of the PERK-Ca2+-calcineurin axis by SB202190 positively affects TFEB activity to increase ALP in neuroblastoma cells. Collectively, our study reveals a novel physiological mechanism underlying ALP activation, dependent on PERK activation, for ameliorating amyloidogenesis in neurodegenerative diseases.
Linking the brain with behaviour: the neural dynamics of success and failure in goal-directed behaviour

The human brain is extremely flexible and capable of rapidly selecting relevant information in accordance with task goals. Regions of frontoparietal cortex flexibly represent relevant task information such as task rules and stimulus features when participants perform tasks successfully, but less is known about how information processing breaks down when participants make mistakes. This is important for understanding whether and when information coding recorded with neuroimaging is directly meaningful for behaviour. Here, we used magnetoencephalography (MEG) to assess the temporal dynamics of information processing, and linked neural responses with goal-directed behaviour by analysing how they changed on behavioural error. Participants performed a difficult stimulus-response task using two stimulus-response mapping rules. We used time-resolved multivariate pattern analysis to characterise the progression of information coding from perceptual information about the stimulus, cue and rule coding, and finally, motor response. Response-aligned analyses revealed a ramping up of perceptual information prior to a correct response, suggestive of internal evidence accumulation. Strikingly, when participants made a stimulus-related error, and not when they made other types of errors, patterns of activity initially reflected the stimulus presented, but later reversed, and accumulated towards a representation of the incorrect stimulus. This suggests that the patterns recorded at later timepoints reflect an internally generated stimulus representation that was used to make the (incorrect) decision. These results illustrate the orderly and overlapping temporal dynamics of information coding in perceptual decision-making and show a clear link between neural patterns in the late stages of processing and behaviour.
A Neuroscience-Inspired Spiking Neural Network for Auditory Spatial Attention Detection Using Single-Trial EEG

Recently, studies have shown that the alpha band (8-13 Hz) EEG signals enable the decoding of auditory spatial attention. However, deep learning methods typically requires a large amount of training data. Inspired by “sparse coding” in cortical neurons, we propose a spiking neural network model for auditory spatial attention detection. The model is composed of three neural layers, two of them are spiking neurons. We formulate a new learning rule that is based on firing rate of pre-synaptic and post-synaptic neurons in the first layer and the second layer of spiking neurons. The third layer consists of 10 spiking neurons that the pattern of their firing rate after training is used in test phase of the method. The proposed method extracts the patterns of recorded EEG of leftward and rightward attention, independently, and uses them to train network to detect the auditory spatial attention. In addition, a computational approach is presented to find the best single-trial EEG data as training samples of leftward and rightward attention EEG. In this model, the role of using low connectivity rate of the layers and specific range of learning parameters in sparse coding is studied. Importantly, unlike most prior model, our method requires 10% of EEG data as training data and has shown 90% accuracy in average. This study suggests new insights into the role of sparse coding in both biological networks and brain-inspired machine learning.
Identification of bipotent progenitors that give rise to myogenic and connective tissues in mouse

How distinct cell fates are manifested by direct lineage ancestry from bipotent progenitors, or by specification of individual cell types within a field of cells is a key question for understanding the emergence of tissues. The interplay between skeletal muscle progenitors and associated connective tissues cells provides a model for examining how muscle functional units are established. Most craniofacial structures originate from the vertebrate-specific neural crest cells except in the dorsal portion of the head, where they arise from cranial mesoderm. Here, using multiple lineage-traced single cell RNAseq, advanced computational methods and in situ analyses, we identify Myf5+ bipotent progenitors that give rise to both muscle and juxtaposed connective tissue. Following this bifurcation, muscle and connective tissue cells retain complementary signalling features and maintain spatial proximity. Interruption of upstream myogenic identity shifts muscle progenitors to a connective tissue fate. Interestingly, Myf5-derived connective tissue cells, which adopt a novel regulatory signature, were not observed in ventral craniofacial structures that are colonised by neural crest cells. Therefore, we propose that an ancestral program gives rise to bifated muscle and connective tissue cells in skeletal muscles that are deprived of neural crest.
Age and Infectious Dose Significantly Affect Disease Progression after RHDV2 Infection in Naïve Domestic Rabbits

Rabbit haemorrhagic disease virus 2 (RHDV2 or GI.2, referring to any virus with lagovirus GI.2 structural genes) is a recently emerged calicivirus that causes generalised hepatic necrosis and disseminated intravascular coagulation leading to death in susceptible lagomorphs (rabbits and hares). Previous studies investigating the virulence of RHDV2 have reported conflicting results, with case fatality rates ranging from 0% to 100% even within a single study. Lagoviruses are of particular importance in Australia and New Zealand where they are used as biocontrol agents to manage wild rabbit populations; wild rabbits threaten over 300 native species and result in economic impacts in excess of $200 million AUD to Australian agricultural industries. It is critically important that any pest control method is both highly effective (i.e., virulent, in the context of viral biocontrols) and has minimal animal welfare impacts. To determine whether RHDV2 might be a suitable candidate biocontrol agent, we investigated the virulence and disease progression of a naturally occurring Australian recombinant RHDV2 in both 5-week-old and 11-week-old New Zealand White laboratory rabbits after either high or low dose oral infection. Objective measures of disease progression were recorded through continuous body temperature monitoring collars, continuous activity monitors, and twice daily observations. We observed a 100% case fatality rate in both infected kittens and adult rabbits after either high dose or low dose infection. Clinical signs of disease, such as pyrexia, weight loss, and reduced activity, were evident in the late stages of infection. Clinical disease, i.e., welfare impacts, were limited to the period after the onset of pyrexia, lasting on average 12 hours and increasing in severity as disease progressed. These findings confirm the high virulence of this RHDV2 variant in naïve rabbits. While age and infectious dose significantly affected disease progression, the case fatality rate was consistently 100% under all conditions tested.
Regional Differences in Brain Plasticity and Behaviour as a Function of Sex and Enrichment Type: Oxytocin Matters

The early environment is critical to brain development, but the relative contribution of physical vs. social stimulation is unclear. Here, we investigated in male and female rats the response to early physical and social environmental enrichment in relation to oxytocin (OT) and brain-derived neurotrophic factor (BDNF) expression. The findings show that males and females respond differently to prolonged sensorimotor stimulation from postnatal day 21-110 in terms of functional, structural and molecular changes in the hippocampus vs. medial prefrontal cortex (mPFC). Physical enrichment promoted motor and cognitive functions and hippocampal BDNF mRNA and protein expression in both sexes. Combined physical and social enrichment, however, promoted functional and structural gain predominantly in females. These changes were accompanied by elevated plasma oxytocin (OT) levels and BDNF mRNA expression in the mPFC while the hippocampus was not affected. Administration of an OT antagonist in females blocked the beneficial effects of enrichment and led to reduced cortical BDNF signaling. These findings suggest that an OT-based mechanism selectively stimulates a region-specific BDNF response which is dependent on the type of experience.
New Viscoelastic Hydrogel Hymovis MO.RE. Single Intra-articular Injection for the Treatment of Knee Osteoarthritis in Sportsmen: Safety and Efficacy Study Results

Viscosupplementation by hyaluronic acid (HA) is recommended for non-surgical management of knee osteoarthritis (OA). This study investigated the efficacy and safety of a single i.a. (32 mg/4 ml) Hymovis MO.RE. injection, a new HA derivative hydrogel, for the treatment of adult regular sports players affected by knee OA arising from overuse injuries. Patients were prospectively enrolled if regularly practicing sports and diagnosed with Kellgren-Lawrence grade I-III OA. They received a single Hymovis MO.RE. intra-articular (i.a.) injection and were evaluated 30, 90, 180, and 360 days thereafter. The assessment involved measuring changes in knee function, pain, the activity of daily living (ADL), and quality of life (QOL) by using the Knee injury and Osteoarthritis Outcome Score (KOOS), GAIT analysis, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for knee pain (WOMAC A) and function (WOMAC C), and a visual analogue scale (VAS) pain score. The study involved thirty-one patients, 23 women and eight men, whose median age was 49. KOOS function subscore, as well as GAIT cadence and velocity, showed a statistically significant increase at each time-point after injection (p < 0.0001). WOMAC, KOOS pain, symptoms, ADL, and QOL scores also significantly improved at all control visits. No severe adverse events or treatment-related events were detected. A single Hymovis MO.RE. (32 mg/4 ml) intra-articular injection provides a rapid, lasting, and safe response in regular sports players affected by knee OA, possibly representing a viable therapeutic option for this demanding patient subgroup. Further investigations are necessary to confirm these findings.
Bioinformatics Profiling of Five Immune-Related lncRNAs for a Prognostic Model of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), one of the most common tumors worldwide, has the fifth highest mortality rate, which is increasing every year. At present, many studies have revealed that immunotherapy has an important effect on many malignant tumors. The main purpose of our research was to verify and establish a new immune-related lncRNA model and to explore the potential immune mechanisms. We analysed the pathways and mechanisms of immune-related lncRNAs by bioinformatics analysis, screened key lncRNAs based on Cox regression analysis, and determined the characteristics of the immune-related lncRNAs. On this basis, a predictive model was established. Through a comparison of specificity and sensitivity, we found that the constructed model was superior to the known markers of HCC. Then, the cell types were identified by the relative subgroup (CIBERSORT) algorithm for RNA transcripts. A signature model was eventually constructed, and we proved that it was a survival factor for HCC. Moreover, five kinds of immune cells were significantly positively correlated with the signature. The results indicated that these five kinds of lncRNAs may be related to the immune infiltration of hepatocellular carcinoma. To verify these findings, we selected the top coexpressed lncRNA, AC099850.3, for further study. We found that AC099850.3 could promote the migration and proliferation of hepatocellular carcinoma cells in vitro. RT-PCR experiments found that AC099850.3 could promote the expression of the cell cycle molecules BUB1, CDK1, PLK1, and TTK, and western blotting to prove that the expression of the molecules CD155 and PD-L1 was inhibited in the interference group. In conclusion, we used five kinds of immune-related lncRNAs to construct prognostic signatures to explore the mechanism, which provides a new way to study therapies for HCC.
Pooled Analysis on the Effectiveness and Safety of Lipegfilgrastim in Patients With Urological Malignancies in the Real-World Setting

Lipegfilgrastim is a long-acting glycopegylated granulocyte-colony stimulating factor (G-CSF) approved for the management of chemotherapy-induced neutropenia. In general, there is little information on the use of any G-CSFs specifically in patients with urological malignancies receiving chemotherapy. This report combines information from two prospective non-interventional studies on the prophylactic use of lipegfilgrastim in urological cancer patients receiving chemotherapy in the real-world setting. Data were derived from two phase IV studies (NADIR and LEOS) with similar protocols conducted in nine European countries. Analysis included 228 patients (142 prostate, 50 testicular, 27 bladder, and 9 other urological cancers). Chemotherapy-induced febrile neutropenia risk was classified as high (43.0%), intermediate (49.1%), or low (7.5%). Lipegfilgrastim was administered as primary (n=180, 78.9%) or secondary (n=29, 12.7%) prophylaxis. The incidence of febrile neutropenia over all chemotherapy cycles (n=998) and first cycles (n=228) for which lipegfilgrastim was administered for prophylaxis was 2.6% and 1.3%, respectively. Corresponding results for Grade 3/4 neutropenia were 2.2% and 0.9%, respectively. Adverse drug reactions occurred in 24 patients (10.5%): those in more than one patient were bone pain (n=6, 2.6%) and pyrexia (n=3, 1.3%). The use of lipegfilgrastim for the prophylaxis of chemotherapy-induced neutropenia was effective and well tolerated in patients with urological malignancies in the real-world setting.
Sex-Specific Differences of the Inflammatory State in Experimental Autoimmune Myocarditis

Increasing evidence suggests male sex as a potential risk factor for a higher incidence of cardiac fibrosis, stronger cardiac inflammation, and dilated cardiomyopathy (DCM) in human myocarditis. Chronic activation of the immune response in myocarditis may trigger autoimmunity. The experimental autoimmune myocarditis (EAM) model has been well established for the study of autoimmune myocarditis, however the role of sex in this pathology has not been fully explored. In this study, we investigated sex differences in the inflammatory response in the EAM model. We analyzed the cardiac function, as well as the inflammatory stage and fibrosis formation in the heart of EAM male and female rats. 21 days after induction of EAM, male EAM rats showed a decreased ejection fraction, stroke volume and cardiac output, while females did not. A significantly elevated number of infiltrates was detected in myocardium in both sexes, indicating the activation of macrophages following EAM induction. The level of anti-inflammatory macrophages (CD68+ ArgI+) was only significantly increased in female hearts. The expression of Col3A1 and fibrosis formation were more prominent in males. Furthermore, prominent pro-inflammatory factors were increased only in male rats. These findings indicate sex-specific alterations in the inflammatory stage of EAM, with a pro-inflammatory phenotype appearing in males and an anti-inflammatory phenotype in females, which both significantly affect cardiac function in autoimmune myocarditis.
The Association Between Generalized and Specific Problematic Internet Use and Its Gender Differences Across Different Educational Levels

This study had two aims: to test the effect and the effect size of specific problematic Internet use (SPIU) [online shopping, online pornography, social network site (SNS) usage, and Internet gaming] on generalized problematic Internet use (GPIU) and to reveal the gender differences in GPIU and SPIU for students from the elementary school level to the university level. In total, 5,215 Chinese students (2,303 males, mean age = 16.20 years, range = 10–23 years) from four types of schools (elementary school, junior high school, senior high school, and university) provided self-report data on demographic variables (gender and educational levels), online shopping, online pornography, SNS usage, Internet gaming, and GPIU. After calculations had been controlled for demographic variables, the results indicated that (i) online shopping, online pornography, SNS usage, and Internet gaming positively predicted GPIU—and Internet gaming was the most critical predictor of GPIU—and that (ii) gender differences were revealed in Internet gaming and GPIU in all educational levels, except at senior high school where the gender differences in GPIU were not significant. Significant gender differences were found for online shopping and online pornography for all educational levels above elementary school. These results provided further understanding of the association between GPIU and SPIU and gender differences in PIU, which suggested that gender differences across different educational levels should be considered in interventions of PIU.
Attachment and Autism Spectrum Disorder (Without Intellectual Disability) During Middle Childhood: In Search of the Missing Piece

The study of Autism Spectrum Disorder (ASD) represents one of the most challenging areas for attachment research in view of the complex interrelation between socio-communication impairments and attachment processes (McKenzie and Dallos, 2017; Vivanti and Nuske, 2017). The fascinating debate, which focuses on whether ASD hampers the development of secure attachment, has not received sufficient attention so far. Prior studies often focused on attachment behaviors in preschoolers with ASD, whereas the study of attachment representations in older children remains mainly unexplored. The most recent systematic review (Teague et al., 2017) highlighted crucial unresolved questions in the study of attachment and ASD with reference to the paucity of data about predictors, correlates and outcomes of attachment in children with ASD. For instance, there is mixed evidence on the association between parental sensitivity and child attachment security, which has been widely documented in typically developing children (Van IJzendoorn et al., 2007). Importantly, the need to adopt a longitudinal perspective to examine the association between attachment and emotional or behavioral difficulties has been also highlighted. To this aim, the study of attachment requires a developmental lens based on age-appropriate methods. In this regard, research has not yet addressed the importance of investigating attachment representations in middle childhood and adolescence. In the last decade, only a limited number of studies on attachment and ASD has been published on children without intellectual disabilities during middle childhood (Bauminger et al., 2010; Chandler and Dissanayake, 2014; Keenan et al., 2016; Sivaratnam et al., 2018). The assessment of attachment in each study is based on questionnaires such as the Inventory of Parent and Peer Attachment (IPPA, Armsden and Greenberg, 1987) and/or the Security Scale (Kerns et al., 1996). Age range and number of the participants vary across studies, including only children from 6 to 14 years with High-functioning ASD. ASD sample size across studies was fairly small, ranging from 21 children with ASD in the Chandler and Dissanayake’s study to 44 children of Bauminger et al. (2010), which, however, includes participants from two countries (24 from Israel and 20 from the United States). These studies revealed no group differences on security of attachment to their caregivers between children with ASD and children typical development (TD), confirming previous findings on early childhood (Teague et al., 2017). Nonetheless, some relevant issues concerning the quality of attachment in school-aged children with ASD are still underinvestigated. Firstly, in contrast to the subsequent studies, Bauminger et al. (2010) found significant differences between groups (ASD
The Perception Modification Concept to Free the Path of An Automated Vehicle Remotely

Inner-city, automated vehicles will face situations in which they leave their operational design domain. That event may lead to an undesired vehicle standstill. Consequently, the vehicle’s independent continuation to its desired destination is not feasible. The undesired vehicle standstill can be caused by uncertainties in object detection, by environmental circumstances like weather, by infrastructural changes or by complex scenarios in general. Teleoperation is one approach to support the vehicle in such situations. However, it may not be clear which teleoperation concept is appropriate. In this paper, a teleoperation concept and its implementation to free the path of an automated vehicle is presented. The situation to be resolved is that a detection hinders the automated vehicle to proceed. However, the detection is either a false positive or it is an indeterminate object which can be ignored. The teleoperator corrects the object list and the occupancy grid map. Thereby, the teleoperator enables the automated vehicle to continue its path. The preliminary tests show that the teleoperation concept enables teleoperators to resolve the respective scenarios appropriately.
Spaced Learning Solution in the e-Learning Environment

The objective of the transdisciplinary research is to find the most effective solutions for spaced learning in the e-learning environment and to create an information system for the implementation of spaced e-learning in the learning management system (LMS). The method is based on short breaks (spaces) between repetitions acquiring the learning content in the e-environment. During breaks, students disconnect from the learning by watching engaging alternative content. During the research, the first prototype of spaced e-learning solution was implemented in the LMS OpenEdX and brought into action with bachelor level students. Experience from the first prototype showed the effectiveness of the method and advantages of personalization of the content of spaces. Research showed the need to take personal interests into account for spaces’ content personalization to motivate students to use the method in the learning process. In the light of the data obtained, an information system (IS) for the personalization of the method was developed for use in several kinds of