Miracle-dz/UniFAR-FTUs huggingface dataset:
Social cognition and quality of life in Huntington's disease

Individuals with Huntington's disease (HD) and their close others report difficulties with social interaction, and previous studies have shown that the areas of quality of life detrimentally impacted by HD include social and emotional domains. However, despite the finding that people with HD often exhibit difficulties on standard tests of social cognition, the relationship between such impairments and patients' everyday life has remained largely unexplored. We used a range of tasks assessing empathy, emotion recognition and Theory of Mind, to investigate whether patients' performance may predict quality of life within the social and emotional domains, while also accounting for broader cognitive function, behavioural changes, motor symptoms, disease stage and functional capacity. Poorer social functioning was predicted specifically by a reduced tendency to attribute intentionality while viewing social animations, in addition to emotional blunting and apathy, while role limitations due to emotional problems were predicted by personal distress, irritability and aspects of executive function. These findings highlight the potential impact of Theory of Mind impairment on quality of life in HD, and suggest that enhanced assessment of social cognition will offer unique insight into patients' social function and related wellbeing.
Feeding foliar nano-selenium biofortified panax notoginseng could reduce the occurrence of glycolipid metabolism disorder in mice caused by high-fat diets

Nano-selenium (nano-Se) has been extensively explored as a biostimulant for improving the quality of grain crops. However, there are few reports about the effect on the medicinal components of Chinese herbal medicine cultured with nano-Se. Here, we sprayed nano-Se during the cultivation of Panax notoginseng (SePN), and measured the changes of medicinal components compared with conventional Panax notoginseng (PN). Furthermore, we identified a more pronounced effect of SePN on reducing obesity in animals compared with PN. By measuring antioxidant capacity, histopathology, gene expression related to glycolipid metabolism, and gut microbiota composition, we propose a potential mechanism for SePN to improve animal health. Compared with the control groups, foliar spraying of nano-Se increased saponins contents (Rb2, Rb3, Rc, F2, Rb2, and Rf) in the roots of Panax notoginseng, the content of Rb2 increased by 3.9 times particularly. Interestingly, animal studies indicated that taking selenium-rich Panax notoginseng (SePN) can further ameliorate liver antioxidation (SOD, MDA, and GSH) and enzyme activities involved in glycolipid metabolism (ATGL and PFK). It also relieved inflammation and regulated the expression of genes (MCAD, PPAR-α, and PCSK9) related to fatty acid oxidation. The abundance ratio of Firmicutes/Bacteroides and beneficial bacteria abundance (Bifidobacterium, Butyricimonas, and Parasutterella) in gut microbiota were improved relative to the control. In summary, the application of nano-Se on PN may effectively raise the content of Panax notoginseng saponins (PNS) and immensely lower the risk of metabolic disorders of glycolipids.
Yuan-Zhi decoction in the treatment of Alzheimer’s disease: An integrated approach based on chemical profiling, network pharmacology, molecular docking and experimental evaluation

Yuan-Zhi Decoction (YZD) is a traditional Chinese medical formulation with demonstrated clinical benefits in Alzheimer’s disease (AD). We used liquid chromatography coupled with mass spectrometry to identify 27 unique chemical components of YZD. Analyzing these using network pharmacology and molecular docking models identified 34 potential interacting molecular targets involved in 26 biochemical pathways. When tested in an animal model of AD, the APP/PS1 transgenic mice showed measurable improvements in spatial orientation and memory after the administration of YZD. These improvements coincided with significantly reduced deposition of Aβ plaques and tau protein in the hippocampi in the treated animals. In addition, a decreased BACE1 and beta-amyloid levels, a downregulation of the p-GSK-3β/GSK-3β, and an upregulation of the PI3K and p-AKT/AKT pathway was seen in YZD treated animals. These in vivo changes validated the involvement of molecular targets and pathways predicted in silico analysis of the chemical components of YZD. This study provides scientific support for the clinical use of YZD and justifies further investigations into its effects in AD. Furthermore, it demonstrates the utility of network pharmacology in elucidating the biochemical mechanisms underlying the beneficial effects of traditional Chinese medicines (TCM).
ClC-3 regulates the excitability of nociceptive neurons and is involved in inflammatory processes within the spinal sensory pathway

ClC-3 Cl–/H+ exchangers are expressed in multiple endosomal compartments and likely modify intra-endosomal pH and [Cl–] via the stoichiometrically coupled exchange of two Cl– ions and one H+. We studied pain perception in Clcn3–/– mice and found that ClC-3 not only modifies the electrical activity of peripheral nociceptors but is also involved in inflammatory processes in the spinal cord. We demonstrate that ClC-3 regulates the number of Nav and Kv ion channels in the plasma membrane of dorsal root ganglion (DRG) neurons and that these changes impair the age-dependent decline in excitability of sensory neurons. To distinguish the role of ClC-3 in Cl–/H+ exchange from its other functions in pain perception, we used mice homozygous for the E281Q ClC-3 point mutation (Clcn3E281Q/E281Q), which completely eliminates transport activity. Since ClC-3 forms heterodimers with ClC-4, we crossed these animals with Clcn4–/– to obtain mice completely lacking in ClC-3-associated endosomal chloride–proton transport. The electrical properties of Clcn3E281Q/E281Q/Clcn4–/– DRG neurons were similar to those of wild-type cells, indicating that the age-dependent adjustment of neuronal excitability is independent of ClC-3 transport activity. Both Clcn3–/– and Clcn3E281Q/E281Q/Clcn4–/– animals exhibited microglial activation in the spinal cord, demonstrating that competent ClC-3 transport is needed to maintain glial cell homeostasis. Our findings illustrate how reduced Cl–/H+ exchange contributes to inflammatory responses and demonstrate a role for ClC-3 in the homeostatic regulation of neuronal excitability beyond its function in endosomal ion balance.
Transcription factor VvibHLH93 negatively regulates proanthocyanidin biosynthesis in grapevine

Proanthocyanidins (PAs) derived from grape berries determine the astringency and bitterness of red wines. The two leucoanthocyanidin reductases (VviLAR1 and VviLAR2) are crucial for PA accumulation in grapevine. Our previous studies show that the promoter of VviLAR1 contains multiple proposed bHLH transcription factor binding sites, but the corresponding bHLH family regulators remain unknown. Here we identified and functionally characterized VvibHLH93 as a new bHLH transcription factor in PA pathway. Yeast one-hybrid and electrophoretic mobility shift assays showed that VvibHLH93 bound the E/G-box in VviLAR1 promoter. And VvibHLH93 gene was mainly expressed in grape flowers, tendrils, stems and berries at PA active stages. Overexpression of VvibHLH93 suppressed PA accumulation in grape callus, which was linked to the repression of the transcript levels of two VviLARs. The gene expression analysis in transgenic grape callus and the dual-luciferase assay in tobacco leaves together revealed that VvibHLH93 targeted a broad set of structural genes and transcription factors in flavonoid pathway. This research enriches the regulatory mechanism of the two VviLAR genes, and provides new insights into regulating PA content in grape berries.
Busyness, mental engagement, and stress: Relationships to neurocognitive aging and behavior

Considerable research identifies benefits of sustaining mental engagement in older adulthood. Frequent social, mental, and physical activities (e.g., exercise) and lifestyle factors that bolster cognitive reserve (i.e., education, occupation complexity) have been associated with cognitive benefits and delayed onset of dementia. Nevertheless, the relationship between general daily levels of busyness and cognition has been relatively understudied. Open questions remain about whether a causal link exists between a busy lifestyle and mental prowess, the relationship between busyness and stress, and methodological approaches to measure and track busyness levels. Here, the existing evidence is considered, along with future directions for research aimed at characterizing the effects of a busy lifestyle on neurocognitive aging and behavior.
A new antioxidant made from a pterostilbene functionalized graphene nanocomposite as an efficient treatment for dry eye disease

Dry eye disease is a common condition that affects the eyes. It is caused by problems with the tear film and the tear dynamics. Dry eye can be caused by an increase in the amount of reactive oxygen species (ROS) in the corneal epithelium. The treatment for dry eye typically focuses on relieving the uncomfortable symptoms by using eye drops such as artificial tears, antibiotics, and by using anti-inflammatory/immunosuppressive agents such as cyclosporine, and lifitegrast. However, the recovery of patients with dry eye can take several years particularly if the symptoms are severe. This is because the present treatment approaches for dry eye are not based on its cause, e.g., the oxidative stress arising from the rapid increase in ROS. This work describes a new type of antioxidant made from pterostilbene (PS) and carboxyl-chitosan modified graphene (CG). The use of a hydrophilic two-dimensional CG nanosheet to improve the properties of PS is reported. Superior enhanced properties including better cellular permeability, long sustained release period (over 30 h), and antioxidant properties, were realized by using PS-CG. A hyperosmotic (HS) damaged human corneal epithelial cell (HCEC) model was used for antioxidant tests. This model has an intracellular ROS level 4 times more than that of a control group. The ROS content was declined efficiently to the same amount as normal cells in the PS-CG treated HS group. There was a significant decline in the content of lactate dehydrogenase (LDH) and the apoptosis rate of HCEC in the PS-CG treated HS group when compared to that seen in the HS model. Real-time polymerase chain reaction (PCR) and western blots (WB) were used to understand the antioxidant mechanism of PS-CG. The results showed that the antioxidant was working by activating the Keap1-Nrf2-ARE signalling pathway. In vivo testing testing using a dry eye mouse model suggested that the PS-CG acted as an efficient antioxidant. More tear production and healthier corneal and conjunctival epithelial cells were achieved when PC-CG was applied to this model. The use of PS-CG could be a new strategy for treating dry eye and other ocular diseases caused by ROS.
Mothers with hypertensive disorders of pregnancy increased risk of periventricular leukomalacia in extremely preterm or extremely low birth weight infants: A propensity score analysis

Background At present, the conclusions about the impact of hypertensive disorders of pregnancy (HDP) on the clinical outcomes of preterm infants are inconsistent. This study used the propensity score matching (PSM) analysis to evaluate the effect of HDP on clinical outcomes of extremely preterm or extremely low birth weight (EP/ELBW) infants. Methods Retrospective analysis was performed on the EP/ELBW infants discharged from 26 tertiary neonatal intensive care units or died during hospitalization from 2008 to 2017, who were divided into HDP group and non-HDP group. The six covariates including sex, gestational age, birth weight, twin or multiple pregnancy, antenatal steroids administration, and conception method were matched through the PSM method at a ratio of 1:1. The survival rate at discharge and the major clinical complications were compared between the two groups. Results After matching the six covariates, compared with the non-HDP group, there was no significant difference in the survival rate at discharge (64 vs. 63.2%, p > 0.05), the incidence of bronchopulmonary dysplasia (BPD) or moderate to severe BPD in the HDP group (58.3 vs. 54.9%, p > 0.05; 5.2 vs. 6.2%, p > 0.05). The incidence of periventricular leukomalacia (PVL) in the HDP group was significantly increased (5.7 vs. 1.9%, p < 0.05). Conclusions HDP increased the risk of PVL in EP/ELBW infants, but had no significant effect on the survival rate at discharge, or the occurrence of other complications.
Factors affecting two-point discrimination in Argus II patients

Two of the main obstacles to the development of epiretinal prosthesis technology are electrodes that require current amplitudes above safety limits to reliably elicit percepts, and a failure to consistently elicit pattern vision. Here, we explored the causes of high current amplitude thresholds and poor spatial resolution within the Argus II epiretinal implant. We measured current amplitude thresholds and two-point discrimination (the ability to determine whether one or two electrodes had been stimulated) in 3 blind participants implanted with Argus II devices. Our data and simulations show that axonal stimulation, lift and retinal damage all play a role in reducing performance in the Argus 2, by either limiting sensitivity and/or reducing spatial resolution. Understanding the relative role of these various factors will be critical for developing and surgically implanting devices that can successfully subserve pattern vision.
Model Predictive Control–Based Load-Frequency Regulation of Grid-Forming Inverter–Based Power Systems

The high-penetrated renewables enable flexible and versatile dispatchable resources in power systems. As the digitalization process improves with the help of information and communication technology (ICT), a real-time online control framework is essential to regulate such a low-inertia power system dominated by renewables. To enable control practices, a control-oriented model is developed linking load increments to frequency dynamics. Based on such a control-oriented model, a model predictive control (MPC)–based online feedback algorithm is well designed by the virtue of rapid data transmission enabled by digitalization. The MPC optimization is a convex quadratic programming, where an objective function that balances frequency deviations and load increments is formulated and operational constraints are integrated into a matrix-type inequality. In the end, the proposed MPC-based load-frequency control framework is illustrated by several case studies, where validations and analyses of constraints inside the model are also included.
Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy

Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN. Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. Correlations between gut microbiota and clinical indicators were assessed by Spearman’s analysis. Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. Results: Bacteroides plebeius and Bacteroides vulgatus levels were higher, while Prevotella copri and Alistipes putredinis levels were lower in the IgAN group compared to HCs group. Enterotype I characterized by Bacteroides was closely related to the IgAN patients. Moreover, Bacteroides fragilis, Flavonifractor plautii and Ruminococcus gnavus were characteristic bacteria enriched in IgAN patients. Spearman’s correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients. Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN.
Intimate partner violence experienced by women living with—and without—disability in the European Union. A quantitative intersectional analysis

This article aims to explore the specific combination and interactions of inequalities associated with experiencing Intimate Partner Violence that affects European women living with—or without—a disability. The analysis is based on the survey carried out by the European Union Agency for Fundamental Rights (FRA) between 2010 and 2012. In that survey, 42,002 women were interviewed, with a representative sample of women from each of the 28 countries of the European Union. We try to elucidate through a multiple logistic regression analysis if the experience of IPV is something that can simply be added to—or overlap with—social categories (feeling of household income, educational level, and marital status), the aggressor (partner abusing alcohol, partner violent against others), the relationship (duration, equal say in economic decisions), and the previous experience of IPV. The result of the analysis shows that living with a disability intersects with low income, which comes hand in hand with experiencing more violence. Other interactions like living with a disability when the woman is under 15 years and living with a disability and the partner abusing alcohol are also relevant. In terms of social policies, our result should induce investment in IPV prevention policies among poor women who live with a disability, who have a history of physical violence, and whose partners abuse alcohol.
Off-label use of cinacalcet in pediatric primary hyperparathyroidism: A French multicenter experience

Background Cinacalcet is a calcimimetic approved in adults with primary hyperparathyroidism (PHPT). Few cases reports described its use in pediatric HPT, with challenges related to the risk of hypocalcemia, increased QT interval and drug interactions. In this study, we report the French experience in this setting. Methods We retrospectively analyzed data from 18 pediatric patients from 7 tertiary centers who received cinacalcet for PHPT. The results are presented as median (interquartile range). Results At a median age of 10.8 (2.0–14.4) years, 18 patients received cinacalcet for primary HPT (N = 13 inactive CASR mutation, N = 1 CDC73 mutation, N = 1 multiple endocrine neoplasia type 1, N=3 unknown etiology). Cinacalcet was introduced at an estimated glomerular filtration rate (eGFR) of 120 (111–130) mL/min/1.73 m2, plasma calcium of 3.04 (2.96–3.14) mmol/L, plasma phosphate of 1.1 (1.0–1.3) mmol/L, age-standardized (z score) phosphate of −3.0 (−3.5;−1.9), total ALP of 212 (164–245) UI/L, 25-OHD of 37 (20–46) ng/L, age-standardized (z score) ALP of −2.4 (−3.7;−1.4), PTH of 75 (59–123) ng/L corresponding to 1.2 (1.0–2.3)-time the upper limit for normal (ULN). The starting daily dose of cinacalcet was 0.7 (0.6–1.0) mg/kg, with a maximum dose of 1.0 (0.9–1.4) mg/kg per day. With a follow-up of 2.2 (1.3–4.3) years on cinacalcet therapy, PTH and calcium significantly decreased to 37 (34–54) ng/L, corresponding to 0.8 (0.5–0.8) ULN (p = 0.01), and 2.66 (2.55–2.90) mmol/L (p = 0.002), respectively. In contrast, eGFR, 25-OHD, ALP and phosphate and urinary calcium levels remained stable. Nephrocalcinosis was not reported but one patient displayed nephrolithiasis. Cinacalcet was progressively withdrawn in three patients; no side effects were reported. Conclusions Cinacalcet in pediatric HPT can control hypercalcemia and PTH without significant side effects.
Training peripheral vision to read: Using stimulus exposure and identity priming

Reading in the periphery can be improved with perceptual learning. A conventional training paradigm involves repeated practice on a character-based task (e.g., recognizing random letters/words). While the training is effective, the hours of strenuous effort required from the trainees makes it difficult to implement the training in low-vision patients. Here, we developed a training paradigm utilizing stimulus exposure and identity priming to minimize training effort and improve training accessibility while maintaining the active engagement of observers through a stimulus visibility task. Twenty-one normally sighted young adults were randomly assigned to three groups: a control group, a with-repetition training group, and a without-repetition training group. All observers received a pre-test and a post-test scheduled 1 week apart. Each test consisted of measurements of reading speed, visual-span profile, the spatial extent of crowding, and isolated-letter profiles at 10° eccentricity in the lower visual field. Training consists of five daily sessions (a total of 7,150 trials) of viewing trigram stimuli (strings of three letters) with identity priming (prior knowledge of target letter identity). The with-repetition group was given the option to replay each stimulus (averaged 0.4 times). In comparison to the control group, both training groups showed significant improvements in all four performance measures. Stimulus replay did not yield a measurable benefit on learning. Learning transferred to various untrained tasks and conditions, such as the reading task and untrained letter size. Reduction in crowding was the main basis of the training-related improvement in reading. We also found that the learning can be partially retained for a minimum of 3 months and that complete retention is attainable with additional monthly training. Our findings suggest that conventional training task that requires recognizing random letters or words is dispensable for improving peripheral reading. Utilizing stimulus exposure and identity priming accompanied by a stimulus visibility task, our novel training procedure offers effective intervention, simple implementation, capability for remote and self-administration, and an easy translation into low-vision reading rehabilitation.