Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduction of the α-synuclein expression promotes slowing down early neuropathology development in the Drosophila model of Parkinson’s disease

Abstract Parkinson’s disease (PD) is a neurodegenerative disease characterised by the formation of Lewy bodies and progressive loss of dopaminergic (DA) neurons in the substantia nigra. Lewy bodies mainly consist of α-synuclein, which plays a critical role in the pathophysiology of PD. The α-synuclein is encoded by the SNCA gene and is the first identified gene associated with hereditary PD. Currently, there are at least six disease-associated mutations in α-synuclein that cause dominantly inherited familial forms of PD. Targeted expression of human SNCA.WT/SNCA.A30P/SNCA.A53T gene in Drosophila melanogaster over specific times employing a temperature-dependent UAS/GAL4 – GAL80 system allows for the evaluation of neurodegenerative processes. In this study, SNCA was expressed only in the adult stage of Drosophila development for 1 or 2 weeks, followed by repression of gene expression for the rest of the fly’s life. It was demonstrated that the level of pathology significantly depends on the duration of α-synuclein expression. SNCA gene expression over a longer period of time caused the death of DA neurons, decreased levels of dopamine and locomotor ability. In this case, the observed neurodegenerative processes correlated with the accumulation of α-synuclein in the Drosophila brain. Importantly, repression of α-synuclein expression led to elimination of the soluble protein fraction, in contrast to the insoluble fraction. No further significant development of characteristic signs of pathology was observed after the α-synuclein expression was blocked. Thus, we suggest that reduction of α-synuclein expression alone contributes to slowing down the development of PD-like symptoms.
CROP: a retromer‐PROPPIN complex mediating membrane fission in the endo‐lysosomal system

Endo‐lysosomal compartments exchange proteins by fusing, fissioning, and through endosomal transport carriers. Thereby, they sort many plasma membrane receptors and transporters and control cellular signaling and metabolism. How the membrane fission events are catalyzed is poorly understood. Here, we identify the novel CROP complex as a factor acting at this step. CROP joins members of two protein families: the peripheral subunits of retromer, a coat forming endosomal transport carriers, and membrane inserting PROPPINs. Integration into CROP potentiates the membrane fission activity of the PROPPIN Atg18 on synthetic liposomes and confers strong preference for binding PI(3,5)P2, a phosphoinositide required for membrane fission activity. Disrupting CROP blocks fragmentation of lysosome‐like yeast vacuoles in vivo. CROP‐deficient mammalian endosomes accumulate micrometer‐long tubules and fail to export cargo, suggesting that carriers attempt to form but cannot separate from these organelles. PROPPINs compete for retromer binding with the SNX‐BAR proteins, which recruit retromer to the membrane during the formation of endosomal carriers. Transition from retromer–SNX‐BAR complexes to retromer–PROPPIN complexes might hence switch retromer activities from cargo capture to membrane fission.
Linkage of Optimism With Depressive Symptoms Among the Stroke Survivor and Caregiver Dyads at 2 Years Post Stroke

Background Depressive symptoms are substantial among stroke survivors and their caregivers in poststroke management. Optimism and social support are known to protect against depressive symptoms. However, little is known about how optimism and social support contribute to depressive symptoms among stroke survivor–caregiver dyads. The study's purpose was to examine actor and partner effects of optimism on depressive symptoms through perceived social support among stroke survivors and caregiver dyads in the chronic stage of rehabilitation. Methods Stroke survivors and caregivers (N = 105 dyads) completed the survey at 2 years of follow-up after the first stroke. Depressive symptoms, optimism, and perceived social support were assessed using the Center for Epidemiologic Studies-Depression, the Life Orientation Test, and the Interpersonal Support Evaluation List. The Actor-Partner Interdependence Model Extended to Mediation analysis was used to test the indirect effect of optimism on depressive symptoms through perceived social support. Results Higher optimism was significantly associated with lower depressive symptoms for caregivers (direct actor effect, −0.6844; 95% confidence interval [CI], −0.9844 to −0.3844) and stroke survivors (direct partner effect, −0.4189; 95% CI, −0.0789 to −0.0889). Perceived social support availability significantly mediated the association between optimism and depressive symptoms for stroke survivors (indirect effect, −0.1957; 95% CI, −0.3923 to −0.0670). Caregiver perceived social support availability was also a significant mediator between caregivers' optimism and stroke survivors' depressive symptoms (indirect effect, 0.1658; 95% CI, 0.0559–0.3128). Conclusions Intervention improving dyad members' optimism and social support would be beneficial to improve depressive symptoms of the stroke survivors and caregivers in chronic stroke management.
Undeserved reward but not inevitable loss biases attention: Personal control moderates evaluative attentional biases in the additional-singleton paradigm

It is important for organisms to notice signals of opportunities (i.e., chances for performance-dependent reward) and dangers (i.e., performance-dependent risks of loss). Attentional biases towards opportunity and danger signals should therefore be functionally valuable. By contrast, the functional value of attentional biases towards signals of performance-independent (i.e., uncontrollable) rewards or losses is not obvious. The present study compares attentional biases towards positive and negative stimuli, depending on whether the stimuli signal performance-dependent or performance-independent reward or loss. Specifically, we induced colour-valence associations before engaging participants in an additional-singleton task that measures attentional bias. In the valence-induction phase, one colour signalled a potential reward, and another colour signalled a potential loss; importantly, in one group, rewards and losses were performance-dependent, whereas in another group, they were performance-independent (i.e., seemingly random). In the subsequent additional-singleton task, we found increased additional-singleton effects for colours associated with performance-dependent rewards and losses (i.e., opportunities and dangers). If, however, rewards and losses were performance-independent, the singleton effect was enhanced only for reward but not loss stimuli.
Brain magnetic resonance imaging findings and brain volumetric differences in a large series of benign rolandic epilepsy

Background Several studies with a small sample size have investigated the relationship between structural and functional changes on MRI and the clinical and natural history of BRE. We aim to assess the frequency of incidental epileptogenic lesions on brain MRI in a large cohort of patients diagnosed with BRE and to assess the difference in volumetric brain measurements in BRE patients compared to healthy controls. Methods The case–control study includes 214 typical BRE cases and 197 control children with non-epileptic spells. Brain MRIs were evaluated for abnormalities which were classified into normal and abnormal with or without epileptogenic lesions with categorization of epileptogenic lesions. Brain segmentation was also performed for a smaller group of BRE patients and another healthy control group. Pearson’s chi-squared test and two-tailed independent samples t-test were used. Results In patients with BRE, 7% had an epileptogenic lesion on their MRI. The frequency of epileptogenic lesion in the control group was 10.2% and not significantly different from those with BRE (p= 0.2). Significantly higher intracranial and white matter volumes were found in BRE patients compared to the healthy group while lower gray matter volume was found in BRE patients. Cortical and subcortical regions showed either higher or lower volumes with BRE. Interestingly, altered subcallosal cortex development which has a known association with depression was also found in BRE. Conclusions Our findings confirm the absence of any association between specific brain MRI abnormalities and BRE. However, the altered cortical and subcortical development in BRE patients suggests a microstructural-functional correlation.
Cognitive effort-based decision-making in major depressive disorder

Abstract Background The association between major depressive disorder and motivation to invest cognitive effort for rewards is unclear. One reason might be that prior tasks of cognitive effort-based decision-making are limited by potential confounds such as physical effort and temporal delay discounting. Methods To address these interpretive challenges, we developed a new task – the Cognitive Effort Motivation Task – to assess one's willingness to exert cognitive effort for rewards. Cognitive effort was manipulated by varying the number of items (1, 2, 3, 4, 5) kept in spatial working memory. Twenty-six depressed patients and 44 healthy controls went through an extensive learning session where they experienced each possible effort level 10 times. They were then asked to make a series of choices between performing a fixed low-effort-low-reward or variable higher-effort-higher-reward option during the task. Results Both groups found the task more cognitively (but not physically) effortful when effort level increased, but they still achieved ⩾80% accuracy on each effort level during training and >95% overall accuracy during the actual task. Computational modelling revealed that a parabolic model best accounted for subjects' data, indicating that higher-effort levels had a greater impact on devaluing rewards than lower levels. These procedures also revealed that MDD patients discounted rewards more steeply by effort and were less willing to exert cognitive effort for rewards compared to healthy participants. Conclusions These findings provide empirical evidence to show, without confounds of other variables, that depressed patients have impaired cognitive effort motivation compared to the general population.
Cost per responder of Adalimumab biosimilars MSB11022 and ABP 501 versus the originator and methotrexate in chronic plaque psoriasis

ABSTRACT Background Pharmacoeconomic studies comparing the cost of adalimumab biosimilars versus the originator and conventional drugs in psoriasis are lacking. Research design and methods To assess the cost per responder of adalimumab biosimilars versus the originator and methotrexate for psoriasis treatment. A cost per responder analysis comparing adalimumab biosimilars MSB11022 (Idacio®) and ABP 501 (Amgevita®), and methotrexate to the originator (Humira®) was performed. The incremental cost per responder was calculated by multiplying the cost of treatment based on the perspective of the National Healthcare System and number needed to treat for each therapy. Results Considering the PASI75 response rate at 16 weeks, the cost per responder for MSB11022 and ABP 501 compared to the originator was € 500 versus 1,831 and € 968 versus 1,949, respectively. For the same endpoint, the cost per responder for subcutaneous or oral methotrexate was € 543 or 34 compared to 2,117 for adalimumab originator. At an indirect comparison among methotrexate, MSB11022 and ABP 501, the costs per PASI75 responder at week 16 were 2%, 26%, 27% and 50% of that of the originator, respectively. Conclusions The use of biosimilars was confirmed as a valuable pharmacoeconomic strategy to lower healthcare cost in patients with psoriasis.
Tribbles homolog 3 contributes to high glucose-induced injury in retinal pigment epithelial cells via binding to growth factor receptor-bound 2

ABSTRACT Diabetic retinopathy (DR) is the most typical complication of diabetes, which severely threatens sight. Tribbles homolog 3 (TRB3), a kind of pseudokinase, is discovered to be highly expressed in diabetes and retinas after retinal detachment. TRB3 expression in human retinal pigment epithelial (hRPE) cells exposed to different concentrations of glucose was tested by RT-qPCR and western blot. Then, cells were induced with 30 mM high glucose (HG) to establish a DR cell model. Following TRB3 knockdown, cell viability estimation employed CCK-8 assay. The mRNA levels of inflammatory factors were detected by RT-qPCR. Reactive oxygen species (ROS) level was measured by DCFH-DA assay, and levels of oxidative stress markers were evaluated applying corresponding kits. Cell apoptosis was assayed by TUNEL assay and western blot. Following, the growth factor receptor-bound 2 (GRB2) expression was also examined by RT-qPCR and western blot. The interaction between TRB3 and GRB2 was verified by Co-IP assay. After GRB2 was overexpressed in HG-induced hRPE cells transfected with shRNA-TRB3, functional experiments were conducted again. The results manifested that TRB3 expression was elevated under HG conditions. Deficiency of TRB3 enhanced the viability while alleviated inflammation, oxidative stress, and apoptosis in HG-induced hRPE cells. GRB2 was also increased in HG-exposed hRPE cells. Moreover, GRB2 had a strong affinity with TRB3 and positively regulated by TRB3. After GRB2 overexpression, the effects of TRB3 knockdown on HG-stimulated hRPE cells were all reversed. Briefly, this study confirmed the promoting role of TRB3/GRB2 axis in the progression of DR.
Durability of treatment effects following internet‐delivered cognitive behavioural therapy for depression and anxiety delivered within a routine care setting

Abstract Objective To investigate post‐treatment relapse and remission rates 3, 6 and 9 months after completion of an acute phase of a clinician‐supported internet‐delivered cognitive‐behavioural therapy (iCBT) for anxiety and depressive symptoms, within a routine care setting. Method Secondary analysis from a 12‐month pragmatic randomized‐controlled trial delivered within the Improving Access to Psychological Therapies (IAPT) programme in England. Participants in the intervention arm were included if they met criteria for reliable recovery from depression (PHQ‐9) and anxiety (GAD‐7) at post‐treatment assessment. Survival analysis was used to assess durability of treatment effects and determine predictors to relapse at 3‐, 6‐ and 9‐month follow‐up. Hazard ratios predicting time‐to‐relapse were estimated with semi‐parametric Cox proportional hazards model. Results Of the 241 participants in the intervention arm, 89 participants met the criteria for reliable recovery from depression and anxiety at the post‐treatment assessment. Of these 89 eligible cases, 29.2% relapsed within the 9‐month period, with 70.8% remaining in remission at 9 months post‐treatment. Of those who relapsed, 53.8% experienced a relapse of depression and anxiety; 7.7% experienced a relapse of depression only; and 38.4% experienced a relapse of anxiety only. Younger age, having a long‐term condition, and residual symptoms of anxiety at end‐of‐treatment were all significant predictors of relapse. Conclusions This study is the first to explore the remission and relapse rates after an acute phase of iCBT treatment, within a routine, stepped‐care setting. The results add to the scarce literature on the durability of the effects of iCBT treatment in routine care settings, where patients are not typically followed up after receiving a completed course of treatment.
Acetylation of SCFD1 regulates SNARE complex formation and autophagosome-lysosome fusion

ABSTRACT SCFD1 (sec1 family domain containing 1) was recently shown to function in autophagosome-lysosome fusion, and multiple studies have demonstrated the regulatory impacts of acetylation (a post-translational modification) on macroautophagy/autophagy. Here, we demonstrate that both acetylation- and phosphorylation-dependent mechanisms control SCFD1ʹs function in autophagosome-lysosome fusion. After detecting a decrease in the extent of SCFD1 acetylation under autophagy-stimulated conditions, we found that KAT2B/PCAF catalyzes the acetylation of residues K126 and K515 of SCFD1; we also showed that these two residues are deacetylated by SIRT4. Importantly, we showed that AMPK-controlled SCFD1 phosphorylation strongly disrupts the capacity of SCFD1 to interact with KAT2B, thus ensuring that the SCFD1 acetylation level remains low. Finally, we demonstrated that SCFD1 acetylation inhibits autophagic flux, specifically by blocking STX17-SNAP29-VAMP8 SNARE complex formation. Thus, our study reveals a mechanism through which phosphorylation and acetylation modifications of SCFD1 mediate SNARE complex formation to regulate autophagosome maturation.ACLY: ATP citrate lyase; CREB: cAMP responsive element binding protein; EBSS: nutrient-deprivation medium; EP300: E1A binding protein p300; KAT5/TIP60: lysine acetyltransferase 5; HOPS: homotypic fusion and protein sorting; MS: mass spectroscopy; SCFD1: sec1 family domain containing 1; SM: Sec1/Munc18; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; UVRAG: UV radiation resistance associated
Effect of multiple micronutrient supplements v. iron and folic acid supplements on neonatal mortality: a reanalysis by iron dose

Abstract Objective: Antenatal multiple micronutrient supplements (MMS) are a cost-effective intervention to reduce adverse pregnancy and birth outcomes. However, the current WHO recommendation on the use of antenatal MMS is conditional, partly due to concerns about the effect on neonatal mortality in a subgroup of studies comparing MMS with iron and folic acid (IFA) supplements containing 60 mg of Fe. We aimed to assess the effect of MMS v. IFA on neonatal mortality stratified by Fe dose in each supplement. Methods: We updated the neonatal mortality analysis of the 2020 WHO guidelines using the generic inverse variance method and applied the random effects model to calculate the effect estimates of MMS v. IFA on neonatal mortality in subgroups of trials (n 13) providing the same or different amounts of Fe, that is, MMS with 60 mg of Fe v. IFA with 60 mg of Fe; MMS with 30 mg of Fe v. IFA with 30 mg of Fe; MMS with 30 mg of Fe v. IFA with 60 mg of Fe; and MMS with 20 mg of Fe v. IFA with 60 mg of Fe. Results: There were no statistically significant differences in neonatal mortality between MMS and IFA within any of the subgroups of trials. Analysis of MMS with 30 mg v. IFA with 60 mg of Fe (7 trials, 14 114 participants), yielded a non-significant risk ratio of 1·12 (95 % CI 0·83 to 1·50). Conclusion: Neonatal mortality did not differ between MMS and IFA regardless of Fe dose in either supplement.
Use of MEMs and optical sensors for closed loop heliostat control

The Helio 100 project at STERG (Stellenbosch Solar Thermal Research Group) aims to help reduce the cost of Concentrated Solar Thermal plants by deploying large numbers of small (1x2 m) low cost heliostats. One of the methods employed to reduce the cost of the heliostat field is to have a field that requires no site preparation (grading, leveling, vegetation clearance) and no expensive foundations or concrete pouring for each individual heliostat base. This implies that the heliostat pod frames and vertical mounts might be slightly out of vertical, and the normal method of dead reckoning using accurately surveyed and aligned heliostat bases cannot be used. This paper describes a combination of MEMs and optical sensors on the back of the heliostat, that together with a simple machine learning approach, give accurate and reproducible azimuth and elevation information for the heliostat plane. Initial experiments were done with an android phone mounted on the back of a heliostat as it was a readily available p.
Stereo slant discrimination of planar 3D surfaces: Frontoparallel versus planar matching

Binocular stereo cues are important for discriminating 3D surface orientation, especially at near distances. We devised a single-interval task where observers discriminated the slant of a densely textured planar test surface relative to a textured planar surround reference surface. Although surfaces were rendered with correct perspective, the stimuli were designed so that the binocular cues dominated performance. Slant discrimination performance was measured as a function of the reference slant and the level of uncorrelated white noise added to the test-plane images in the left and right eyes. We compared human performance with an approximate ideal observer (planar matching [PM]) and two subideal observers. The PM observer uses the image in one eye and back projection to predict a test image in the other eye for all possible slants, tilts, and distances. The estimated slant, tilt, and distance are determined by the prediction that most closely matches the measured image in the other eye. The first subideal observer (local planar matching [LPM]) applies PM over local neighborhoods and then pools estimates across the test plane. The second suboptimal observer (local frontoparallel matching [LFM]) uses only location disparity. We find that the ideal observer (PM) and the first subideal observer (LPM) outperforms the second subideal observer (LFM), demonstrating the additional benefit of pattern disparities. We also find that all three model observers can account for human performance, if two free parameters are included: a fixed small level of internal estimation noise, and a fixed overall efficiency scalar on slant discriminability.
A Survey on Secure Network: Intrusion Detection & Prevention Approaches

With the growth of the Internet and its potential, more and more people are getting connected to the Internet every day to take advantage of the e-Commerce. On one side, the Internet brings in tremendous potential to business in terms of reaching the end users. At the same time it also brings in lot of security risk to the business over the network. With the growth of cyber-attacks, information safety has become an important issue all over the world. Intrusion detection systems (IDSs) are an essential element for network security infrastructure and play a very important role in detecting large number of attacks. This survey paper introduces a detailed analysis of the network security problems and also represents a review of the current research. The main aim of the paper is to finds out the problem associated with network security for that various existing approaches related to intrusion detection and preventions are discussed. This survey focuses on presenting the different issues that must be addressed to build fully functional and practically usable intrusion detection systems (IDSs). It points out the state of the art in each area and suggests important open research issues.
High School Students’ Social Jetlag, Lifelong Competency, and Academic Stress During the COVID-19 Pandemic: A Cross-Sectional Study

With the prolongation of non-ordinary situations such as school closures due to the coronavirus disease 2019 (COVID-19) pandemic, high school students have experienced irregular sleep-wake cycles and elevated academic stress resulting from reduced academic achievement and widened gaps in academic performance. This cross-sectional study aimed to investigate the associations among chronotype, social jetlag, lifelong learning competency, and academic stress in high school students during the COVID-19 pandemic. Data were collected through an online survey from May–June 2021. The mean social jetlag was found to be 2 h and 9 min, and multiple regression analysis revealed that social jetlag and lifelong competency affected academic stress. Thus, measures to minimize social jetlag and improve lifelong learning competencies should be implemented to reduce academic stress among high school students. School nurses should identify students with severe social jetlag and provide guidance and interventions to promote sleep hygiene and regular lifestyles.