Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Insights on MRGPRX2-Mediated Hypersensitivity to Neuromuscular Blocking Agents And Fluoroquinolones

Neuromuscular blocking agents (NMBAs) like atracurium and rocuronium as well as fluoroquinolones (FQs) cause mast cell-mediated anaphylaxis by activating Mas-related G protein-coupled receptor X2 (MRGPRX2), but many questions remain unanswered. Here, we address three of them, namely whether primary human mast cells show similar activation by these drugs as murine mast cells and mast cell lines, how sugammadex protects from atracurium-induced MRGPRX2-mediated mast cell activation, and why some but not all patients treated with rocuronium develop anaphylaxis. We used peripheral blood-derived cultured mast cells from healthy donors and patients, assessed mast cell activation and degranulation by quantifying intracellular calcium and CD63 expression, respectively, and made use of MRGPRX2-silencing, via electroporation with Dicer-substrate small interfering RNAs, and single cell flow cytometric analyses. Atracurium, ciprofloxacin, and levofloxacin activated and degranulated primary human mast cells, but only MRGPRX2-positive and not MRGPRX2-negative or -silenced mast cells. Sugammadex attenuated the atracurium-induced and MRGPRX2-mediated activation and degranulation of human mast cells by reducing free atracurium levels. The mast cells of patients with IgE-independent anaphylaxis to rocuronium were similar, in their MRGPRX2 expression and function, to those of patients with IgE-mediated anaphylaxis. These findings further improve our understanding of the role and relevance of MRGPRX2-driven mast cell activation in anaphylactic reactions to NMBAs and FQs and may help to improve their prediction, prevention, and treatment.
The Effect of Orthographic Transparency on Auditory Word Recognition Across the Development of Reading Proficiency

A question under debate in psycholinguistics is the nature of the relationship between spoken and written languages. Although it has been extensively shown that orthographic transparency, which varies across writing systems, strongly affects reading performance, its role in speech processing is much less investigated. The present study addressed this issue in Persian, whose writing system provides a possibility to assess the impact of orthographic transparency on spoken word recognition in young children at different stages of reading acquisition. In Persian, the long vowels are systematically present in the script, whereas the spelling correspondence of short vowels is progressively omitted from the script in the course of reading acquisition, thus, turning transparent into opaque spelling. Based on this unique characteristic, we tested 144 monolingual Persian-speaking nonreaders (i.e., preschoolers) and readers (second graders to fifth graders and young adults) in an auditory lexical decision task using transparent and opaque words. Overall, the results showed that, in accordance with the fact that the diacritics of short vowels are progressively omitted during the second year of schooling, the stimuli containing short vowels (opaque words) were recognized more slowly than transparent ones in third graders. Interestingly, there is a hint that the emergence of the transparency effect in the third graders was associated with an overall slower recognition speed in this group compared to their younger peers. These findings indicate that learning opaque spelling-sound correspondence might not only generate interference between the two language codes but also induce a general processing cost in the entire spoken language system.
Follistatin Attenuates Myocardial Fibrosis in Diabetic Cardiomyopathy via the TGF-β–Smad3 Pathway

Follistatin (FST) is an endogenous protein that irreversibly inhibits TGF-β superfamily members and plays an anti-fibrotic role in other diseases. However, the role of FST in diabetic cardiomyopathy remains unclear. In this study, we investigated the effects of FST on diabetic cardiomyopathy. The expression of FST was downregulated in the hearts of db/db mice. Remarkably, overexpressing FST efficiently protected against cardiac dysfunction. In addition, overexpression of FST promoted cardiac hypertrophy with an unchanged expression of atrial natriuretic peptide (ANP) and the ratio of myosin heavy chain-β/myosin heavy chain-α (MYH7/MYH6). Furthermore, FST reduced cardiac fibrosis and the production of reactive oxygen species (ROS), and enhanced matrix metallopeptidase 9 (MMP9) activities in db/db mouse hearts. We also observed that overexpressing FST decreased the level of transforming growth factor beta (TGF-β) superfamily members and the phosphorylation of Smad3; consistently, in vitro experiments also verified the above results. Our findings revealed the cardioprotective role of FST in attenuating diabetic cardiomyopathy through its anti-fibrotic effects through the TGF-β–Smad3 pathway and provided a promising therapeutic strategy for diabetic cardiomyopathy.
Complete Elimination of Peripheral Auditory Input Before Onset of Hearing Causes Long-Lasting Impaired Social Memory in Mice

Hearing is one of the most important senses needed for survival, and its loss is an independent risk factor for dementia. Hearing loss (HL) can lead to communication difficulties, social isolation, and cognitive dysfunction. The hippocampus is a critical brain region being greatly involved in the formation of learning and memory and is critical not only for declarative memory but also for social memory. However, until today, whether HL can affect learning and memory is poorly understood. This study aimed to identify the relationship between HL and hippocampal-associated cognitive function. Mice with complete auditory input elimination before the onset of hearing were used as the animal model. They were first examined via auditory brainstem response (ABR) to confirm hearing elimination, and behavior estimations were applied to detect social memory capacity. We found significant impairment of social memory in mice with HL compared with the controls (p < 0.05); however, no significant differences were seen in the tests of novel object recognition, Morris water maze (MWM), and locomotion in the open field (p > 0.05). Therefore, our study firstly demonstrates that hearing input is required for the formation of social memory, and hearing stimuli play an important role in the development of normal cognitive ability.
Base Editing in Plants: Applications, Challenges, and Future Prospects

The ability to create targeted modifications in the genomes of plants using genome editing technologies has revolutionized research in crop improvement in the current dispensation of molecular biology. This technology has attracted global attention and has been employed in functional analysis studies in crop plants. Since many important agronomic traits are confirmed to be determined by single-nucleotide polymorphisms, improved crop varieties could be developed by the programmed and precise conversion of targeted single bases in the genomes of plants. One novel genome editing approach which serves for this purpose is base editing. Base editing directly makes targeted and irreversible base conversion without creating double-strand breaks (DSBs). This technology has recently gained quick acceptance and adaptation because of its precision, simplicity, and multiplex capabilities. This review focuses on generating different base-editing technologies and how efficient they are in editing nucleic acids. Emphasis is placed on the exploration and applications of these base-editing technologies to enhance crop production. The review also highlights the drawbacks and the prospects of this new technology.
The Role of Statistical Learning and Verbal Short-Term Memory in Impaired and Typical Lexical Development

Purpose: Studies on the interface between statistical learning and language are dominated by its role in word segmentation and association with grammar skills, while research on its role in lexical development is scarce. The current study is aimed at exploring whether and how statistical learning and verbal short-term memory are associated with lexical skills in typically developing German-speaker primary school children (Experiment 1) and Hungarian-speaking children with developmental language disorder (DLD, Experiment 2). Methods: We used the language-relevant Peabody Picture Vocabulary Tests to measure individual differences in vocabulary. Statistical learning skills were assessed with the Weather Prediction task, in which participants learn probabilistic cue-outcome associations based on item-based feedback. Verbal short-term memory span was assessed with the Forward digit span task. Results: Hierarchical linear regression modelling was used to test the contribution of different functions to vocabulary size. In TD children, statistical learning skills had an independent contribution to vocabulary size over and above age, receptive grammatical abilities and short-term memory, whereas working memory did not have an independent contribution. The pattern was reverse in SLI: Vocabulary size was predicted by short-term memory skills over and above age, receptive grammar and statistical learning, whereas statistical learning had no independent contribution. Conclusion: Our results suggest that lexical development rely on different underlying memory processes in typical development and in developmental language disorder to different degrees. This qualitative difference is discussed in the light of different stages of lexical development, as well as the contribution of the different human memory systems to vocabulary acquisition.
Coronavirus Disease-2019 Survival in Mexico: A Cohort Study on the Interaction of the Associated Factors

The pandemic caused by the new coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries. The most lethal clinical presentation is respiratory insufficiency, requiring attention in intensive care units (ICU). The most susceptible people are over 60 years old with comorbidities. The health systems organization may represent a transcendental role in survival. Objective: To analyze the correlation of sociodemographic factors, comorbidities and health system organization variables with survival in cases infected by SARS-CoV-2 during the first 7 months of the pandemic in Mexico. Methods: The cohort study was performed in a health system public basis from March 1st to September 30th, 2020. The included subjects were positive for the SARS-CoV-2 test, and the target variable was mortality in 60 days. The risk variables studied were: age, sex, geographic distribution, comorbidities, health system, hospitalization, and access to ICU. Bivariate statistics (X2-test), calculation of fatality rates, survival analyses and adjustment of confusing variables with Cox proportional-hazards were performed. Results: A total of 753,090 subjects were analyzed, of which the 52% were men. There were 78,492 deaths (10.3% of general fatality and 43% inpatient). The variables associated with a higher risk of hospital mortality were age (from 60 years onwards), care in public sectors, geographic areas with higher numbers of infection and endotracheal intubation without management in the ICU. Conclusions: The variables associated with a lower survival in cases affected by SARS-CoV-2 were age, comorbidities, and respiratory insufficiency (with endotracheal intubation without care in the ICU). Additionally, an interaction was observed between the geographic location and health sector where they were treated.
A Sound Prediction: EEG-Based Neural Synchrony Predicts Online Music Streams

Neuroforecasting predicts population-wide choices based on neural data of individuals and can be used, for example, in neuromarketing to estimate campaign successes. To deliver true value, the brain activity metrics should deliver predictive value above and beyond traditional stated preferences. Evidence from movie trailer research has proposed neural synchrony, which compares the similarity of brain responses across participants and has shown to be a promising tool in neuroforecasting for movie popularity. The music industry might also benefit from these increasingly accurate success predictors, but only one study has been forecasting music popularity, using functional magnetic resonance imaging measures. Current research validates the strength of neural synchrony as a predictive measure for popularity of music, making use of electroencephalogram to capture moment-to-moment neural similarity between respondents while they listen to music. Neural synchrony is demonstrated to be a significant predictor for public appreciation on Spotify 3 weeks and 10 months after the release of the albums, especially when combined with the release of a single. On an individual level, other brain measures were shown to relate to individual subjective likeability ratings, including Frontal Alpha Asymmetry and engagement when combined with the factors artist and single release. Our results show the predictive value of brain activity measures outperforms stated preferences. Especially, neural synchrony carries high predictive value for the popularity on Spotify, providing the music industry with an essential asset for efficient decision making and investments, in addition to other practical implications that include neuromarketing and advertising industries.
The Contribution of Decreased Muscle Size to Muscle Weakness in Children With Spastic Cerebral Palsy

Muscle weakness is a common clinical symptom in children with spastic cerebral palsy (SCP). It is caused by impaired neural ability and altered intrinsic capacity of the muscles. To define the contribution of decreased muscle size to muscle weakness, two cohorts were recruited in this cross-sectional investigation: 53 children with SCP [median age, 8.2 (IQR, 4.1) years, 19/34 uni/bilateral] and 31 children with a typical development (TD) [median age, 9.7 (IQR, 2.9) years]. Muscle volume (MV) and muscle belly length for m. rectus femoris, semitendinosus, gastrocnemius medialis, and tibialis anterior were defined from three-dimensional freehand ultrasound acquisitions. A fixed dynamometer was used to assess maximal voluntary isometric contractions for knee extension, knee flexion, plantar flexion, and dorsiflexion from which maximal joint torque (MJT) was calculated. Selective motor control (SMC) was assessed on a 5-point scale for the children with SCP. First, the anthropometrics, strength, and muscle size parameters were compared between the cohorts. Significant differences for all muscle size and strength parameters were found (p ≤ 0.003), except for joint torque per MV for the plantar flexors. Secondly, the associations of anthropometrics, muscle size, gross motor function classification system (GMFCS) level, and SMC with MJT were investigated using univariate and stepwise multiple linear regressions. The associations of MJT with growth-related parameters like age, weight, and height appeared strongest in the TD cohort, whereas for the SCP cohort, these associations were accompanied by associations with SMC and GMFCS. The stepwise regression models resulted in ranges of explained variance in MJT from 29.3 to 66.3% in the TD cohort and from 16.8 to 60.1% in the SCP cohort. Finally, the MJT deficit observed in the SCP cohort was further investigated using the TD regression equations to estimate norm MJT based on height and potential MJT based on MV. From the total MJT deficit, 22.6–57.3% could be explained by deficits in MV. This investigation confirmed the disproportional decrease in muscle size and muscle strength around the knee and ankle joint in children with SCP, but also highlighted the large variability in the contribution of muscle size to muscle weakness.
Do Woody Tree Thinning and Season Have Effect on Grass Species’ Composition and Biomass in a Semi-Arid Savanna? The Case of a Semi-Arid Savanna, Southern Ethiopia

Encroachment of woody plants has negative effects on grass species and seriously challenging livestock production and pastoral livelihood in semi-arid savanna. The effect of thinning and season on grass species composition and biomass was investigated in lowland grazing area for three seasons. The study consisted of 15 plots (each 50 m × 50 m), thinned to differing intensities. The plots were located next to each other on a homogeneous area of 3.8 ha. Five thinning intensities (0, 25, 50, 75, and 100%) were allocated randomly to the plots and replicated three times. The 0% plot was left unthinned referred to as the control plot. The remaining plots were thinned to the equivalents of 25, 50, 75, and 100% of the tree density of that of the control plot. A two-way analysis of variance and Tukey Honest Significant Differences tests were used to compare responses of grass species. Ordination of variables was carried out by multivariate technique using correspondence analysis to explore the similarity relationship of plots, seasons and species. The differences in species composition and biomass in the control and the thinned plots were significant (p < 0.05). Higher grass species composition and biomass were documented in thinned plots than in the control plot. Species abundance in thinned plots ranged from 11 to 12, while that of the 0% plot was six species. Grass biomass (Kg ha-1) varied from 2,688.4 ± 736.8 to 5,035.8 ± 743.9 across thinned plots, whereas in the control plot the yield was 885.8 ± 369.1. The result showed that grass species composition and biomass increased with the increasing intensity of thinning. Grass values appeared to be optimum at the heavy intensity of thinning woody plants. Seasons were also significant with the highest values recorded in the rainy season. Rainfall played an important role by interacting with thinning and influenced total grass values. Overall, thinning that combined improved soil moisture negatively influenced woody cover and enhanced grass species composition and biomass production. Thinning of bushes to the 75% of tree density would sustain the original savanna and maximize forage production for grazers.
Elabela Protects Spontaneously Hypertensive Rats From Hypertension and Cardiorenal Dysfunctions Exacerbated by Dietary High-Salt Intake

Objectives: Arterial hypertension, when exacerbated by excessive dietary salt intake, worsens the morbidity and mortality rates associated with cardiovascular and renal diseases. Stimulation of the apelinergic system appears to protect against several circulatory system diseases, but it remains unknown if such beneficial effects are conserved in severe hypertension. Therefore, we aimed at determining whether continuous infusion of apelinergic ligands (i.e., Apelin-13 and Elabela) exerted cardiorenal protective effects in spontaneously hypertensive (SHR) rats receiving high-salt diet. Methods: A combination of echocardiography, binding assay, histology, and biochemical approaches were used to investigate the cardiovascular and renal effects of Apelin-13 or Elabela infusion over 6 weeks in SHR fed with normal-salt or high-salt chow. Results: High-salt intake upregulated the cardiac and renal expression of APJ receptor in SHR. Importantly, Elabela was more effective than Apelin-13 in reducing high blood pressure, cardiovascular and renal dysfunctions, fibrosis and hypertrophy in high-salt fed SHR. Unlike Apelin-13, the beneficial effects of Elabela were associated with a counter-regulatory role of the ACE/ACE2/neprilysin axis of the renin-angiotensin-aldosterone system (RAAS) in heart and kidneys of salt-loaded SHR. Interestingly, Elabela also displayed higher affinity for APJ in the presence of high salt concentration and better resistance to RAAS enzymes known to cleave Apelin-13. Conclusion: These findings highlight the protective action of the apelinergic system against salt-induced severe hypertension and cardiorenal failure. As compared with Apelin-13, Elabela displays superior pharmacodynamic and pharmacokinetic properties that warrant further investigation of its therapeutic use in cardiovascular and kidney diseases.
An R2R3-MYB Transcription Factor RmMYB108 Responds to Chilling Stress of Rosa multiflora and Conferred Cold Tolerance of Arabidopsis

A sudden cooling in the early spring or late autumn negatively impacts the plant growth and development. Although a number of studies have characterized the role of the transcription factors (TFs) of plant R2R3-myeloblastosis (R2R3-MYB) in response to biotic and abiotic stress, plant growth, and primary and specific metabolisms, much less is known about their role in Rosa multiflora under chilling stress. In the present study, RmMYB108, which encodes a nuclear-localized R2R3-MYB TF with a self-activation activity, was identified based on the earlier published RNA-seq data of R. multiflora plants exposed to short-term low-temperature stress and also on the results of prediction of the gene function referring Arabidopsis. The RmMYB108 gene was induced by stress due to chilling, salt, and drought and was expressed in higher levels in the roots than in the leaves. The heterologous expression of RmMYB108 in Arabidopsis thaliana significantly enhanced the tolerance of transgenic plants to freezing, water deficit, and high salinity, enabling higher survival and growth rates, earlier flowering and silique formation, and better seed quantity and quality compared with the wild-type (WT) plants. When exposed to a continuous low-temperature stress at 4°C, transgenic Arabidopsis lines–overexpressing RmMYB108 showed higher activities of superoxide dismutase and peroxidase, lower relative conductivity, and lower malondialdehyde content than the WT. Moreover, the initial fluorescence (Fo) and maximum photosynthetic efficiency of photosystem II (Fv/Fm) changed more dramatically in the WT than in transgenic plants. Furthermore, the expression levels of cold-related genes involved in the ICE1 (Inducer of CBF expression 1)-CBFs (C-repeat binding factors)-CORs (Cold regulated genes) cascade were higher in the overexpression lines than in the WT. These results suggest that RmMYB108 was positively involved in the tolerance responses when R. multiflora was exposed to challenges against cold, freeze, salt, or drought and improved the cold tolerance of transgenic Arabidopsis by reducing plant damage and promoting plant growth.