Miracle-dz/UniFAR-FTUs huggingface dataset:
The FXII c.-4T>C Polymorphism as a Disease Modifier in Patients With Hereditary Angioedema Due to the FXII p.Thr328Lys Variant

Background Hereditary angioedema due to the Thr328Lys variant in the coagulation factor XII (HAE-FXII) affects mainly women in whom the symptomatology is dependent on high estrogen levels. Clinical variability and incomplete penetrance are challenging features that hinder the diagnosis and management of HAE-FXII. The c. -4T>C Kozak polymorphism is the only common variation accounting for FXII plasma levels and was previously shown to modify the course of HAE due to C1-Inhibitor deficiency. Objectives To assess the influence of the c. -4T>C polymorphism on disease expression in 39 Spanish HAE-FXII index patients. Methods The c. -4T>C polymorphism was sequenced by the standard Sanger method, and HAE severity was calculated according to the score by Cumming et al. (2003) The activation of the contact system was quantified by the kallikrein-like activity of plasma in chromogenic assays upon activation with high-molecular-weight dextran sulfate. Results The c. -4CC genotype was overrepresented in the studied cohort: 82% were CC-homozygous (expected frequency = 59%) and 18% were CT-heterozygous (expected frequency = 39%) (p = 0.001). Patients with a c. -4CC genotype exhibited higher kallikrein-like activity (0.9659 ± 0.1136) than those with a c. -4TC genotype (0.7645 ± 0.1235) (p = 0.024) or healthy donors. Moreover, the polymorphism influenced HAE-FXII severity score (c.-4CC = 4.43 ± 2.28 vs c.-4TC = 2.0 ± 1.15; p = 0.006) but not the degree of estrogen dependence or time until remission. Conclusion The c. -4T>C polymorphism is overrepresented in a Spanish HAE-FXII cohort and significantly influences the degree of contact system activation and the clinical severity of the disease.
Cellulose Nanocomposite Hydrogels: From Formulation to Material Properties

Poly(vinyl alcohol) (PVA) hydrogels produced using the freeze-thaw method have attracted attention for a long time since their first preparation in 1975. Due to the importance of polymer intrinsic features and the advantages associated with them, they are very suitable for biomedical applications such as tissue engineering and drug delivery systems. On the other hand, there is an increasing interest in the use of biobased additives such as cellulose nanocrystals, CNC. This study focused on composite hydrogels which were produced by using different concentrations of PVA (5 and 10%) and CNC (1 and 10 wt.%), also, pure PVA hydrogels were used as references. The main goal was to determine the impact of both components on mechanical, thermal, and water absorption properties of composite hydrogels as well as on morphology and initial water content. It was found that PVA had a dominating effect on all hydrogels. The effect of the CNC addition was both concentration-dependent and case-dependent. As a general trend, addition of CNC decreased the water content of the prepared hydrogels, decreased the crystallinity of the PVA, and increased the hydrogels compression modulus and strength to some extent. The performance of composite hydrogels in a cyclic compression test was studied; the hydrogel with low PVA (5) and high CNC (10) content showed totally reversible behavior after 10 cycles.
Mortality Rates in People With Convulsive Epilepsy in Rural Northeast China

Purpose: To examine the mortality rate and causes of death of phenobarbital (PB) monotherapy and sodium valproate (VPA) monotherapy in patients with convulsive epilepsy in rural northeast China and compare the differences in the results between the two antiepileptic drugs. Methods: Patients with convulsive epilepsy were recruited by trained public health workers in a project for epilepsy prevention and treatment. Patients were enrolled between January 2010 and December 2018 and were treated with PB or VPA. Mortality rate (MR), the proportional mortality ratio (PMR) for each cause, standardized mortality ratio, and years of potential life lost (YPLL) for sex, age, and cause were estimated based on the 2018 Chinese rural population. Results: A total of 3,916 patients with convulsive epilepsy enrolled in the study, of whom 3,418 received PB and 498 received VPA. There were 325 reported deaths (300 from the PB group) during the follow-up period. The MRs were 9.96 and 5.73% in the PB and VPA groups, respectively. The overall SMRs were 12.92 (95% confidence intervals [CI]: 11.50–13.93) and 7.39 (95% CI: 4.78–10.91), for the PB and VPA groups, respectively. Cerebrovascular disease and heart disease were the major causes of death in both treatment groups. The average YPLL for the PB group (21.9 years) was higher than that for the VPA group (13.4 years). Conclusion: This is the first epidemiological study to examine the MR of patients with epilepsy in rural northeast China. Our study is somewhat different from previous studies reported in China, and we provide new relevant data from northeast China.
Humanized Rodent Models for Cancer Research

As one of the most popular laboratory animal models, rodents have been playing crucial roles in mechanistic investigations of oncogenesis as well as anticancer drug or regimen discoveries. However, rodent tumors show different or no responses to therapies against human cancers, and thus, in recent years, increased attention has been given to mouse models with xenografted or spontaneous human cancer cells. By combining with the human immune system (HIS) mice, these models have become more sophisticated and robust, enabling in vivo exploration of human cancer immunology and immunotherapy. In this review, we summarize the pros and cons of these humanized mouse models, with a focus on their potential as an in vivo platform for human cancer research. We also discuss the strategies for further improving these models.
Association of Low-Density Lipoprotein Receptor-Related Protein 1 and Its rs1799986 Polymorphism With Mild Cognitive Impairment in Chinese Patients With Type 2 Diabetes

Background Low-density lipoprotein receptor-related protein 1 (LRP1) is involved in cerebral glucose metabolism and amyloid-β clearance. This study aimed to investigate the pathogenetic roles of LRP1 and its rs1799986 polymorphism in mild cognitive impairment (MCI) among patients with type 2 diabetes mellitus (T2DM). Methods A total of 166 Chinese patients with T2DM were enrolled and divided into two groups according to Montreal Cognitive Assessment (MoCA) scores. Neuropsychological tests were performed. Soluble LRP1 (sLRP1) levels were assessed using enzyme-linked immunosorbent assay, and the genotype of LRP1 rs1799986 was detected using the Sequenom method. Results Diabetic patients with MCI (n = 60) exhibited significantly lower plasma sLRP1 levels (p = 0.033) and worse glucose control (p = 0.009) than the healthy cognition controls (n = 106). Multivariate regression analysis revealed plasma sLRP1 levels [odds ratio (OR) = 0.971, p = 0.005] and HbA1c (OR = 1.298, p = 0.003) as a risk factor for MCI in diabetic patients, in addition to insulin use and hypertension. However, there was no association between plasma sLRP1 levels and HbA1c. After adjusting for age, sex, and education level, plasma sLRP1 levels in the MCI group were negatively correlated with Stroop Color Word Test B number (r = −0.335, p = 0.011), which represents selective attention, cognitive flexibility, and processing speed. Additionally, patients with T2DM carrying the T allele of LRP1 rs1799986 showed higher Auditory Verbal Learning Test (AVLT) delayed recall scores (p = 0.025). Conclusion Decreased plasma sLRP1 levels are associated with MCI, particularly with attention dysfunction, in patients with T2DM. Moreover, the T allele of LRP1 rs1799986 may decrease susceptibility to MCI. Further studies with large cohorts should be designed to elucidate the roles of LRP1 in hyperglycemia-induced cognitive decline.
Assessing Multi-Temporal Snow-Volume Trends in High Mountain Asia From 1987 to 2016 Using High-Resolution Passive Microwave Data

High Mountain Asia (HMA) is dependent upon both the amount and timing of snow and glacier meltwater. Previous model studies and coarse resolution (0.25° × 0.25°, ∼25 km × 25 km) passive microwave assessments of trends in the volume and timing of snowfall, snowmelt, and glacier melt in HMA have identified key spatial and seasonal heterogeneities in the response of snow to changes in regional climate. Here we use recently developed, continuous, internally consistent, and high-resolution passive microwave data (3.125 km × 3.125 km, 1987–2016) from the special sensor microwave imager instrument family to refine and extend previous estimates of changes in the snow regime of HMA. We find an overall decline in snow volume across HMA; however, there exist spatially contiguous regions of increasing snow volume—particularly during the winter season in the Pamir, Karakoram, Hindu Kush, and Kunlun Shan. Detailed analysis of changes in snow-volume trends through time reveal a large step change from negative trends during the period 1987–1997, to much more positive trends across large regions of HMA during the periods 1997–2007 and 2007–2016. We also find that changes in high percentile monthly snow-water volume exhibit steeper trends than changes in low percentile snow-water volume, which suggests a reduction in the frequency of high snow-water volumes in much of HMA. Regions with positive snow-water storage trends generally correspond to regions of positive glacier mass balances.
C2C12 Mouse Myoblasts Damage Induced by Oxidative Stress Is Alleviated by the Antioxidant Capacity of the Active Substance Phloretin

A new direction for the treatment of skeletal myopathies, which are mainly caused by abnormal mitochondrial metabolism, is the application of drugs and active substances to relieve oxidative stress in mitochondria. Phloretin, a dihydrochalcone active substance widely present in succulent fruits, has attracted attention for its strong antioxidant activity. This study aimed to investigate the potential antioxidant effects of phloretin and its potential mechanism of action in C2C12 mouse myoblasts. Under oxidative stress caused by 500 μmol/L H2O2, the addition of 10 μmol/L phloretin ameliorated the high level of reactive oxygen species, increased CuZn/Mn-dependent superoxide dismutase activities, and restored the loss of mitochondrial membrane potential. Additionally, apoptosis, necrocytosis, and the inhibition of cell proliferation caused by H2O2 stimulation were alleviated by phloretin. Moreover, phloretin significantly increased the expression of cyclin D1 and alleviated the stagnation trend of the G1 phase of cell proliferation caused by H2O2. Furthermore, the addition of phloretin simultaneously significantly increased the protein and mRNA expression of heme oxygenase-1 (HO-1) and alleviated the inhibitory phosphorylation of p-nuclear factor erythroid 2-related factor 2 (Nrf2), p-AMP-activated protein kinase (AMPK), and p-liver kinase B1 (LKB1) induced by H2O2. Moreover, the expression of nuclear Nrf2 was higher with phloretin treatment than without phloretin treatment. Overall, phloretin alleviated the proliferation inhibition and apoptosis induced by H2O2 and exerted antioxidant effects via the LKB1/AMPK/Nrf2/HO-1 pathway in C2C12 cells. These results provide insight for the application of phloretin to alleviate oxidative damage to muscle.
Administration of Extensive Hydrolysates From Caseins and Lactobacillus rhamnosus GG Probiotic Does Not Prevent Cow’s Milk Proteins Allergy in a Mouse Model

Background Early nutrition may influence the development of food allergies later in life. In the absence of breastfeeding, hydrolysates from cow’s milk proteins (CMP) were indicated as a prevention strategy in at risk infants, but their proof of effectiveness in clinical and pre-clinical studies is still insufficient. Thanks to a validated mouse model, we then assessed specific and nonspecific preventive effects of administration of extensive hydrolysates from caseins (eHC) on the development of food allergy to CMP. The additional nonspecific effect of the probiotic Lactobacillus GG (LGG), commonly used in infant formula, was also assessed. Methods Groups of young BALB/cByJ female mice were pretreated by repeated gavage either with PBS (control mice), or with PBS solution containing non-hydrolyzed milk protein isolate (MPI), eHC or eHC+LGG (eq. of 10 mg of protein/gavage). All mice were then experimentally sensitized to CMP by gavage with whole CM mixed with the Th2 mucosal adjuvant Cholera toxin. All mice were further chronically exposed to cow’s milk. A group of mice was kept naïve. Sensitization to both caseins and to the non-related whey protein β-lactoglobulin (BLG) was evaluated by measuring specific antibodies in plasma and specific ex vivo Th2/Th1/Th17 cytokine secretion. Elicitation of the allergic reaction was assessed by measuring mMCP1 in plasma obtained after oral food challenge (OFC) with CMP. Th/Treg cell frequencies in gut-associated lymphoid tissue and spleen were analyzed by flow cytometry at the end of the protocol. Robust statistical procedure combining non-supervised and supervised multivariate analyses and univariate analyses, was conducted to reveal any effect of the pretreatments. Results PBS pretreated mice were efficiently sensitized and demonstrated elicitation of allergic reaction after OFC, whereas mice pretreated with MPI were durably protected from allergy to CMP. eHC+/-LGG pretreatments had no protective effect on sensitization to casein (specific) or BLG (non-specific), nor on CMP-induced allergic reactions. Surprisingly, eHC+LGG mice demonstrated significantly enhanced humoral and cellular immune responses after sensitization with CMP. Only some subtle changes were evidenced by flow cytometry. Conclusion Neither specific nor nonspecific preventive effects of administration of casein-derived peptides on the development of CMP food allergy were evidenced in our experimental setup. Further studies should be conducted to delineate the mechanisms involved in the immunostimulatory potential of LGG and to clarify its significance in clinical use.
Self-Views and Positive Psychology Constructs Among Second Language Learners in Japan, Taiwan, and the United States

The present study is the first to empirically test a hierarchical, positive-oriented model of the self and its relationship to second language (L2) achievement motivation, and compare it in three different cultural contexts of Japan, the United States, and Taiwan. Based on the L2 self-model (Lake, 2016), three levels of constructs were developed: Global Self (i.e., Flourishing, Curiosity, and Hope); Positive L2 domain self (i.e., interested-in-L2 self, harmonious passion for L2 learning, and mastery L2 goal orientation); and L2 Motivational Variables (i.e., reading, speaking and listening self-efficacy). A total of 667 students participated in this study, including 181 first-year college students in Japan, 159 high school students in Taiwan, and 327 community college students in the United States. All the participants were learning L2 in school. Results showed that the measures of positive global self, L2 domain self, and L2 motivational self all had a stronger relationship within their respective levels, and progressively weaker relationships as level of generality/specificity became more distal. Furthermore, the relationships among measures varied in the differing cultural contexts with the Japan-based student participants relatively lower on all measures. Implications for teacher educators in the L2 context have been discussed.
Young Adults’ Short-Term Trajectories of Moderate Physical Activity: Relations With Self-Evaluation Processes

Young adults face numerous barriers that can undermine their engagement in healthy behaviors. For example, young adults on average experience disproportionally large declines in physical activity (PA) participation compared to other demographic groups. Self-evaluation processes may help explain these declines. This study investigated young adults’ weekly trajectories of moderate physical activity, exploring self-evaluation processes, including self-efficacy and shame as time-varying covariates. A total of 71 young adults (Mage = 21.25, SD = 1.18; 55% male) reported moderate physical activity, exercise self-efficacy, and anticipated shame toward exercise once a week for 5 weeks. Latent growth curve models showed that a linear slope fit these data better than alternative models. Parameters of the linear model revealed that these young adults reported engaging in 40 min of moderate PA approximately 3 days per week. However, there were physical activity differences in initial levels and rates of change. Exercise self-efficacy consistently predicted physical activity in a positive direction and with a small-to-medium magnitude. Anticipated shame was an inconsistent predictor of physical activity, showing a negative direction and small magnitude at time one and on average across the 5 weeks. These findings highlight considerable variability in young adults’ short-term trajectories of physical activity and underscore both positive and negative processes of exercise related self-evaluations. Future physical activity interventions targeting young adults should incorporate strategies that enhance self-efficacy (e.g., mastery experiences) and reduce feelings of shame (e.g., attribution training).
Effects of Occupational Fatigue on Cognitive Performance of Staff From a Train Operating Company: A Field Study

Background Occupational fatigue is a key issue in the rail industry that can endanger staff, passenger, and train safety. There is a need to demonstrate the relationship between workload, fatigue, and performance among rail staff. Objective The present study, conducted in the workplace in realistic situations, integrating both subjective and objective measurements, aimed at demonstrating the relationship between workload, fatigue, and cognitive performance with a rail staff sample. Methods The “After-Effect” technique was applied in the current study. Online diaries and cognitive performance tasks were used to assess the fatigue, work experiences, and performance of rail staff before and after work on the first and last days of one working week. Results Reported fatigue was greater after work on both the first and last day of the working week. There were large individual differences in the change in fatigue and workload ratings. Analysis of covariance with age and the pre-work performance score as covariates and the post-work performance score as the dependent variable showed that high levels of fatigue were associated with impaired performance on both the visual search and logical reasoning tasks. Workload had fewer effects on performance than fatigue. Conclusion This field study provided evidence for the relationship between work-related fatigue and performance impairment. The findings show the need for future work on predicting fatigue-related performance decrements, and the necessity of providing interventions and support so that the risk to safety can be reduced.
Shape Evolutions in Fission Dynamics Within Time-Dependent Hartree-Fock Approach

We studied the nuclear shape evolutions in fission process of 240Pu by the time-dependent Hartree-Fock approach with various Skyrme forces. Calculations are performed for the later phase of the fission with large initial deformations toward the scission. We show that calculations with Skyrme forces with large surface energies and large symmetry energies can have extremely long fission evolution time. The symmetry energy plays a role in the evolution of neutron-rich necks. In addition, we also demonstrated the shape oscillations of fission fragments after the fission. We see that particularly the heavy near-spherical fragments have remarkable octupole oscillations.
Revisiting the Effects of Xenon on Urate Oxidase and Tissue Plasminogen Activator: No Evidence for Inhibition by Noble Gases

Although chemically inert, Xe and other noble gases have been shown to have functional effects on biological systems. For example, Xe is a powerful anesthetic with neuroprotective properties. Recent reports have claimed that Xe inhibits the activity of tissue plasminogen activator (tPA) and urate oxidase (UOX), indicating that the use of Xe as an anesthetic may have undesirable side effects. Here, we revisited the methods used to demonstrate Xe inhibition of UOX and tPA, testing both indirect and direct gas delivery methods with variable bubble sizes and gas flowrates. Our results indicate that Xe or Kr do not affect the activity of UOX or tPA and that the previously reported inhibition is due to protein damage attendant to directly bubbling gases into protein solutions. The lack of evidence to support Xe inhibition of UOX or tPA alleviates concerns regarding possible side effects for the clinical application of Xe as an anesthetic. Furthermore, this study illustrates the importance of using indirect methods of gas dissolution for studying gas-protein interactions in aqueous solution.
The Relationship Between Contextual and Dispositional Variables, Well-Being and Hopelessness in School Context

The literature’s interest has been focused on the study of well-being or depression. However, there has been little research that investigates the relationship between well-being and hopelessness (HPL) and the underlying contextual and dispositional variables. Therefore, the aim of the present study was to examine the relationship between some contextual (need-supportive interpersonal behavior and need-thwarting interpersonal behavior) and dispositional variables (dispositional optimism, positive/negative affectivity, explanatory style), academic achievement, general well-being, and school HPL in adolescent students. The results showed that general well-being was positively predicted by need-supportive interpersonal behavior, dispositional optimism, positive affectivity, and adaptive explanatory style (attribution to commitment in the school context), while it was negatively predicted by negative affectivity. Meanwhile, school HPL was positively predicted by need-thwarting interpersonal behavior, negative affectivity, dysfunctional explanatory style (attribution to luck in the school context), while it was negatively predicted by attribution to commitment in the school context and academic achievement. These results provide useful data for the implementation of well-being promotion and school HPL prevention. The implications are discussed as follows.