Miracle-dz/UniFAR-FTUs huggingface dataset:
α-Synuclein Impacts on Intrinsic Neuronal Network Activity Through Reduced Levels of Cyclic AMP and Diminished Numbers of Active Presynaptic Terminals

α-synuclein (α-Syn) is intimately linked to synucleinopathies like Parkinson’s disease and dementia with Lewy bodies. However, the pathophysiological mechanisms that are triggered by this protein are still largely enigmatic. α-Syn overabundance may cause neurodegeneration through protein accumulation and mitochondrial deterioration but may also result in pathomechanisms independent from neuronal cell death. One such proposed pathological mechanism is the influence of α-Syn on non-stimulated, intrinsic brain activity. This activity is responsible for more than 90% of the brain’s energyconsumption, and is thus thought to play an eminent role in basic brain functionality. Here we report that α-Syn substantially disrupts intrinsic neuronal network burst activity in a long-term neuronal cell culture model. Mechanistically, the impairment of network activity originates from reduced levels of cyclic AMP and cyclic AMP-mediated signaling as well as from diminished numbers of active presynaptic terminals. The profound reduction of network activity due to α-Syn was mediated only by intracellularly expressed α-Syn, but not by α-Syn that is naturally released by neurons. Conversely, extracellular pre-formed fibrils of α-Syn mimicked the effect of intracellular α-Syn, suggesting that they trigger an off-target mechanism that is not activated by naturally released α-Syn. A simulation-based model of the network activity in our cultures demonstrated that even subtle effect sizes in reducing outbound connectivity, i.e., loss of active synapses, can cause substantial global reductions in non-stimulated network activity. These results suggest that even low-level loss of synaptic output capabilities caused by α-Syn may result in significant functional impairments in terms of intrinsic neuronal network activity. Provided that our model holds true for the human brain, then α-Syn may cause significant functional lesions independent from neurodegeneration.
Genetic Diversity in Nitrogen Fertiliser Responses and N Gas Emission in Modern Wheat

Crops assimilate nitrogen (N) as ammonium via the glutamine synthetase/glutamate synthase (GS/GOGAT) pathway which is of central importance for N uptake and potentially represents a bottle neck for N fertiliser-use efficiency. The aim of this study was to assess whether genetic diversity for N-assimilation capacity exists in wheat and could be exploited for breeding. Wheat plants rapidly, within 6 h, responded to N application with an increase in GS activity. This was not accompanied by an increase in GS gene transcript abundance and a comparison of GS1 and GS2 protein models revealed a high degree of sequence conservation. N responsiveness amongst ten wheat varieties was assessed by measuring GS enzyme activity, leaf tissue ammonium, and by a leaf-disc assay as a proxy for apoplastic ammonia. Based on these data, a high-GS group showing an overall positive response to N could be distinguished from an inefficient, low-GS group. Subsequent gas emission measurements confirmed plant ammonia emission in response to N application and also revealed emission of N2O when N was provided as nitrate, which is in agreement with our current understanding that N2O is a by-product of nitrate reduction. Taken together, the data suggest that there is scope for improving N assimilation capacity in wheat and that further investigations into the regulation and role of GS-GOGAT in NH3 emission is justified. Likewise, emission of the climate gas N2O needs to be reduced, and future research should focus on assessing the nitrate reductase pathway in wheat and explore fertiliser management options.
Exercise Capacity in Children and Adolescents With Congenital Heart Disease: A Systematic Review and Meta-Analysis

Background Congenital heart disease (CHD) entails structural defects in the morphogenesis of the heart or its main vessels. Analyzing exercise capacity of children and adolescents with CHD is important to improve their functional condition and quality of life, since it can allow timely intervention on poor prognostic factors associated with higher risk of morbidity and mortality. Objective To describe exercise capacity in children and adolescents with CHD compared with healthy controls. Methods A systematic review was carried out. Randomized clinical trials and observational studies were included assessing exercise capacity through direct and indirect methods in children and adolescents between 5 and 17 years-old. A sensitive analysis was performed including studies with CHD repaired participants. Additionally, it was sub-analyzed by age range (< and ≥ 12 years old). Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of the evidence. Results 5619 articles were found and 21 were considered for the review. Eighteen articles used the direct exercise capacity measurement method by cardiopulmonary exercise test (CPET). The CHD group showed significant differences in peak oxygen consumption (VO2peak) with a value of −7.9 ml/Kg/min (95% CI: −9.9, −5.9, p = 0.00001), maximum workload (Wmax) −41.5 (95% CI: −57.9, −25.1 watts, p = 0.00001), ventilatory equivalent (VE/VCO2) slope 2.6 (95% CI: 0.3, 4.8), oxygen pulse (O2 pulse)−2.4 ml/beat (95% CI: −3.7, −1.1, p = 0.0003), and maximum heart rate (HRmax) −15 bpm (95% CI: −18, −12 bpm, p = 0.00001), compared with healthy controls. Adolescents (≥ 12 yrs) with CHD had a greater reduction in VO2peak (−10.0 ml/Kg/min (95% CI: −12.0, −5.3), p < 0.00001), Wmax (−45.5 watts (95% CI: −54.4, −36.7), p < 0.00001) and HRmax (−21 bpm (95% CI: −28, −14), p<0.00001). Conclusion Suffering CHD in childhood and adolescence is associated with lower exercise capacity as shown by worse VO2peak, Wmax, VE/VCO2 slope, O2 pulse, and HRmax compared with matched healthy controls. The reduction in exercise capacity was greater in adolescents. Systematic Review Registration www.crd. york.ac. uk/prospero/display_record. php? RecordID=208963, identifier: CRD42020208963.
Is Undernutrition Associated With Deterioration of Outcomes in the Pediatric Intensive Care Unit (PICU): Systematic and Meta-Analysis Review

Background and aim Undernutrition (UN) may negatively impact clinical outcomes for hospitalized patients. The relationship between UN status at pediatric intensive care unit (PICU) admission and clinical outcomes is still not well-reported. This systematic meta-analysis review evaluated the impact of UN at admission to PICU on clinical outcomes, including mortality incidence, length of stay (LOS), and the need for and length of time on mechanical ventilation (MV). Methods A search was conducted using relevant and multi-medical databases from inception until January 2022. We considered studies that examined the link between UN at PICU admission and clinical outcomes in patients aged 18 years or younger. Pooled risk difference estimates for the PICU outcomes were calculated using a random-effects model. Result There were a total of 10,638 patients included in 17 observational studies; 8,044 (75.61%) and 2,594 (24.38%) patients, respectively, were normal-nourished (NN) and undernourished (UN). In comparison to NN patients, UN patients had a slightly higher risk of mortality (RD = 0.02, P = 0.05), MV usage (RD = 0.05, P = 0.02), and PICU LOS (RD = 0.07, P = 0.007). While the duration of MV was significantly longer in UN than in NN (RD = 0.13, P < 0.0001). Sensitivity analysis of UN classification cohorts with a z-score < -2 or in the 5%, patetints age up to 18 years, and mixed diagnose for PICU admission demonstrated a 6-fold increase in the probability of PICU LOS in UN patients compared to NN patients (RD = 0.06, 95% CI = 0.01, 0.12). UN patients have a higher risk of MV usage RD = 0.07, 95% CI = 0.00, 0.14) in studies involving cohorts with a mixed primary diagnosis for PICU admission. Conclusion In PICU, UN is linked to mortality incidence, longer PICU stay, MV usage, and duration on MV. The primary diagnosis for PICU admission may also influence clinical outcomes. Determining the prevalence of UN in hospitalized patients, as well as the subgroups of patients diagnosed at the time of admission, requires more research. This may help explain the relationship between nutritional status and clinical outcomes in PICU patients.
Pre-processing of Sub-millimeter GE-BOLD fMRI Data for Laminar Applications

Over the past 30 years, brain function has primarily been evaluated non-invasively using functional magnetic resonance imaging (fMRI) with gradient-echo (GE) sequences to measure blood-oxygen-level-dependent (BOLD) signals. Despite the multiple advantages of GE sequences, e.g., higher signal-to-noise ratio, faster acquisitions, etc., their relatively inferior spatial localization compromises the routine use of GE-BOLD in laminar applications. Here, in an attempt to rescue the benefits of GE sequences, we evaluated the effect of existing pre-processing methods on the spatial localization of signals obtained with EPIK, a GE sequence that affords voxel volumes of 0.25 mm3 with near whole-brain coverage. The methods assessed here apply to both task and resting-state fMRI data assuming the availability of reconstructed magnitude and phase images.
Associations Between Online Learning, Smartphone Addiction Problems, and Psychological Symptoms in Chinese College Students After the COVID-19 Pandemic

Background Smartphone-based online education gained popularity during and after the COVID-19 pandemic. Although recent studies have highlighted the association between problematic smartphone use (PSU) and mental health symptoms, the potential role of online learning in this relationship remains unclear. This study aimed to analyze the relationships between higher education modes, PSU, and related psychological symptoms in university students. Methods A total of 1,629 Chinese university students from five provinces completed a web-based questionnaire survey between March 2020 and October 2021. Demographic characteristics and learning conditions were recorded. All participants completed the Smartphone Addiction Scale-Short Version, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, and Athens Insomnia Scale. Multiple regressions models and stratified analyses were used to examine the association between online education mode, PSU, and symptoms of depression, anxiety, and insomnia. Results The prevalence of PSU was 58.5%. Students who relied primarily on online learning had a higher prevalence of depressive symptoms (29.95% vs. 22.24%), anxiety symptoms (25.13% vs. 18.91%), and insomnia symptoms (75.89% vs. 70.27%) than those who relied on traditional face-to-face learning (Ps < 0.05). After adjusting for covariates, subjects with PSU were more likely to report depressive symptoms (AdjOR = 3.14, 95% CI = 2.26–4.37), anxiety symptoms (AdjOR = 3.73, 95% CI = 2.13–4.59), and insomnia symptoms (AdjOR = 2.96, 95% CI = 2.23–3.92) than those without PSU. Furthermore, the associations of PSU with depressive symptoms (OR = 4.66 vs. 2.33, P for interaction = 0.015) and anxiety symptoms (OR = 6.05 vs. 2.94, P for interaction = 0.021) were more pronounced in the online learning group. Conclusion Our study provides preliminary evidence that Chinese university students have serious smartphone addiction problems, which are associated with depressive, anxiety, and insomnia symptoms. Online learning is found to exacerbate PSU and mental health problems. Our findings provide valuable information for targeted psychological interventions in the post-COVID-19 era.
Contribution of Intermediate and High Trophic Level Species to Benthic-Pelagic Coupling: Insights From Modelling Analysis

Benthic-pelagic coupling (BPC) is a combination of downward (from pelagic to benthic) and upward (from benthic to pelagic) flows of organic matter and nutrients mediated by trophic interactions in the food web. Hydrological changes in marine ecosystems affect BPC patterns at several temporal and spatial scales. Thus, a food-web perspective help to to quantify and disentangle the role of ecosystem components and high trophic levels species in the BPC. This study investigated the spatio-temporal variability of energy and matter flows between the benthic and pelagic domains in two areas (Salento and Calabria) of the Northern Ionian Sea (Central Mediterranean Sea) during two different periods. The region is subject to large-scale oceanographic changes, e.g., the Adriatic-Ionian Bimodal Oscillating Systems (BiOS), that might result in relevant spatial and temporal BPC changes. Four food-web models describe the trophic structure, the role of ecosystem components and energy flows in the Salento and Calabrian areas, during two BiOS periods, the anticyclonic (1995-1997) and the cyclonic phases (2003-2005). The food webs are described by 58 functional groups obtained by aggregating species into ecological domains, depth gradients and biological traits. The role of species in the BPC has been quantified using a new Benthic-Pelagic Coupling Index calculated on the basis of food web flows estimated by models. The results highlight the pivotal role of deep faunal communities, in which demersal and benthopelagic species sustain upward energy flows towards the pelagic domain and shelf faunal communities. Temporal changes driven by BiOS affect the trophic state of the deep communities resulting in considerable variations in their amount of consumption flows. In addition, the presence of submarine canyons seems to better support the stability of the Calabrian food web in both investigated periods, whereas geomorphological traits of the Salento area seem to support greater pelagic production during the cyclonic period than the anticyclonic one. Benthopelagic species show an important role as couplers. In particular, Aristaemorpha foliacea, Hoplostetus mediterraneus, Macrourids and Plesionika martia are important couplers of bathyal communities in both areas.
Comparison of Potato Viromes Between Introduced and Indigenous Varieties

Viral disease in potatoes has been a major problem in potato production worldwide. In addition to the potential risk of introducing new diseases in new areas, viral-disease epidemics/pandemics can be initiated by “spillover” of indigenous viruses from infected alternative hosts into introduced cultivars. To investigate the tendency of potential viral infection/resistance, we analyzed the viromes of introduced and indigenous varieties of potatoes among different tissues using RNA-seq libraries. Bioinformatics analyses revealed that potato viruses PVM, PVY, and PVS were dominant and the most frequently identified viruses infecting potato virus-free plants in the field, and showed an infection bias between introduced and indigenous cultivars. PVY and PVS were the major viruses in introduced varieties, whereas PVM showed an extraordinarily high percentage in the indigenous variety. Other three common viruses, PVH, potato mop-top virus, and potato leafroll virus were identified specifically in the indigenous variety. There was a tendency for tissue-specific infection and sequence variation in viruses: underground parts (tubers, roots) harbored more unusual viruses, and tubers harbored relatively more variation with a high frequency of single nucleotide polymorphisms than other tissues. Taken together, our study provides a comprehensive overview of the composition, distribution, and sequence variation of viruses between introduced and indigenous varieties of potatoes.
Progress of Transposon Vector System for Production of Recombinant Therapeutic Proteins in Mammalian Cells

In recent years, mammalian cells have become the primary host cells for the production of recombinant therapeutic proteins (RTPs). Despite that the expression of RTPs in mammalian cells can be improved by directly optimizing or engineering the expression vectors, it is still influenced by the low stability and efficiency of gene integration. Transposons are mobile genetic elements that can be inserted and cleaved within the genome and can change their inserting position. The transposon vector system can be applied to establish a stable pool of cells with high efficiency in RTPs production through facilitating the integration of gene of interest into transcriptionally active sites under screening pressure. Here, the structure and optimization of transposon vector system and its application in expressing RTPs at high level in mammalian cells are reviewed.
Predicting the Stone-Free Status of Percutaneous Nephrolithotomy With the Machine Learning System: Comparative Analysis With Guy’s Stone Score and the S.T.O.N.E Score System

Purpose: The aim of the study was to use machine learning methods (MLMs) to predict the stone-free status after percutaneous nephrolithotomy (PCNL). We compared the performance of this system with Guy’s stone score and the S.T. O.N. E score system. Materials and Methods: Data from 222 patients (90 females, 41%) who underwent PCNL at our center were used. Twenty-six parameters, including individual variables, renal and stone factors, and surgical factors were used as input data for MLMs. We evaluated the efficacy of four different techniques: Lasso-logistic (LL), random forest (RF), support vector machine (SVM), and Naive Bayes. The model performance was evaluated using the area under the curve (AUC) and compared with that of Guy’s stone score and the S.T. O.N. E score system. Results: The overall stone-free rate was 50% (111/222). To predict the stone-free status, all receiver operating characteristic curves of the four MLMs were above the curve for Guy’s stone score. The AUCs of LL, RF, SVM, and Naive Bayes were 0.879, 0.803, 0.818, and 0.803, respectively. These values were higher than the AUC of Guy’s score system, 0.800. The accuracies of the MLMs (0.803% to 0.818%) were also superior to the S.T. O.N. E score system (0.788%). Among the MLMs, Lasso-logistic showed the most favorable AUC. Conclusion: Machine learning methods can predict the stone-free rate with AUCs not inferior to those of Guy’s stone score and the S.T. O.N. E score system.
Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models

Astrocytes respond to injury, infection, and inflammation in the central nervous system by acquiring reactive states in which they may become dysfunctional and contribute to disease pathology. A sub-state of reactive astrocytes induced by proinflammatory factors TNF, IL-1α, and C1q (“TIC”) has been implicated in many neurodegenerative diseases as a source of neurotoxicity. Here, we used an established human induced pluripotent stem cell (hiPSC) model to investigate the surface marker profile and proteome of TIC-induced reactive astrocytes. We propose VCAM1, BST2, ICOSL, HLA-E, PD-L1, and PDPN as putative, novel markers of this reactive sub-state. We found that several of these markers colocalize with GFAP+ cells in post-mortem samples from people with Alzheimer’s disease. Moreover, our whole-cells proteomic analysis of TIC-induced reactive astrocytes identified proteins and related pathways primarily linked to potential engagement with peripheral immune cells. Taken together, our findings will serve as new tools to purify reactive astrocyte subtypes and to further explore their involvement in immune responses associated with injury and disease.
Improved Functionality of Poly(3,4-Ethylenedioxythiophene):Poly(Styrenesulfonate)/HeptaCoordinated Organotin Complex Films via Graphene Applied to Organic Solar Cell Fabrications

Enhanced transparency, conductivity, and stability are some of the most important factors to consider in order to prepare transparent electrodes (TEs) and hole transport layer (HTL) for organic solar cells. In this study, the transparency, optical, and electrical behavior of hybrid films formed by poly(3,4-ethylenedioxythiophene):poly (styrenesulfonate) (PEDOT:PSS) and heptacoordinated organotin (IV) complexes was improved by introducing graphene. The films were deposited by spin-coating and subsequently characterized by infrared and Raman spectroscopy, and by scanning electron microscopy (SEM) and atomic force microscopy (AFM). All the hybrid films transmitted more than 70% of light in the 600–1,000 nm wavelength region, and the optical band gap obtained is in the range of 2.64 and 3.09 eV. In addition, bathophenanthroline (BPhen) was introduced as an electron transport layer (ETL) in order to study the solar cell with complete architecture, conformed by glass/ITO/PEDOT:PSS-graphene-complex/BPhen/Ag. By incorporating the BPhen, the J–V curve current density values were increased, showing a conductivity change of as much as 2.1 × 10−4 S/cm, and under illuminated conditions a more pronounced J–V curve variation (as much as 2.5 × 101 A/cm2) was observed. In closing, the devices were subjected to accelerated lighting conditions to determine the stability and operating capacity of the solar cells. The electrical behavior of the devices changed. Within the first 2 h, the electrical behavior improved, where the organotin complex without a substituent (complex-a) device presents higher stability than the complex with the chloride substituent (complex-b) device due to the chloride radical interacting with the BPhen. However, the electrical behavior degraded after 4 h almost eight orders of magnitude in current density due to device films and interface degradation.
Neutral Processes Provide an Insight Into the Structure and Function of Gut Microbiota in the Cotton Bollworm

Gut-associated microbes can influence insect health and fitness. Understanding the structure of bacterial communities provides valuable insights on how different species may be selected and their functional characteristics in their hosts. The neutral model is powerful in predicting the structure of microbial communities, but its application in insects remains rare. Here, we examined the contribution of neutral processes to the gut-associated bacterial communities in Helicoverpa armigera caterpillars collected from different maize varieties at four locations. The gut-associated bacteria can be assigned to 37 Phyla, 119 orders, and 515 genera, with each individual gut containing 17–75% of the OTUs and 19–79% of the genera in the pooled samples of each population. The distribution patterns of most (75.59–83.74%) bacterial taxa were in good agreement with the neutral expectations. Of the remaining OTUs, some were detected in more individual hosts than would be predicted by the neutral model (i.e., above-partition), and others were detected in fewer individual hosts than predicted by the neutral model (i.e., below-partition). The bacterial taxa in the above-partitions were potentially selected by the caterpillar hosts, while the bacteria in the below-partitions may be preferentially eliminated by the hosts. Moreover, the gut-associated microbiota seemed to vary between maize varieties and locations, so ecological parameters outside hosts can affect the bacterial communities. Therefore, the structure of gut microbiota in the H. armigera caterpillar was mainly determined by stochastic processes, and the bacteria in the above-partition warrant further investigation for their potential roles in the caterpillar host.