Miracle-dz/UniFAR-FTUs huggingface dataset:
Dipeptide of ψ-GSH Inhibits Oxidative Stress and Neuroinflammation in an Alzheimer’s Disease Mouse Model

Supplementation of glutathione (GSH) levels through varying formulations or precursors has thus far appeared to be a tenable strategy to ameliorate disease-associated oxidative stress. Metabolic liability of GSH and its precursors, i.e., hydrolysis by the ubiquitous γ-glutamyl transpeptidase (γ-GT), has limited successful clinical translation due to poor bioavailability. We addressed this problem through the design of γ-GT-resistant GSH analogue, ψ-GSH, which successfully substituted in GSH-dependent enzymatic systems and also offered promise as a therapeutic for Alzheimer’s disease (AD). With the aim to improve its bioavailability, we studied the utility of a ψ-GSH precursor, dipeptide 2, as a potential AD therapeutic. Compound 2 retains the γ-GT stable ureide linkage and the thiol group for antioxidant property. By engaging glutathione synthetase, compound 2 was able to generate ψ-GSH in vivo. It was found to be a modest cofactor of glutathione peroxidase and prevented cytotoxicity of Aβ1–42-aggregates in vitro. Studies of compound 2 in an acute AD model generated by intracerebroventricular injection of Aβ1–42 showed cognitive benefits, which were augmented by its combination with glycine along with mitigation of oxidative stress and inflammatory pathology. Collectively, these results support further optimization and evaluation of ψ-GSH dipeptide as a potential therapeutic in transgenic AD models.
Investigating the effects of a programming course using flipped learning

ABSTRACT In recent years, flipping classrooms has become a popular topic of discussion. However, few previous studies have focused on the effect of the flow experience on programming self-efficacy. To address this gap, the present researchers developed a model that included six research hypotheses. The study applied a flipped classroom model to a programming course in order to examine the relationship between self-efficacy, flow experience, and learning performance in a flipped programming course. The research model was empirically examined using a survey to collect data from 46 college students in Taiwan. Programming courses were conducted for 180 minutes once a week, with six weeks of total teaching time. The findings of this study indicate that there is a positive relationship between programming self-efficacy and enjoyment, engagement, and flow control. The study also revealed that certain important implications and factors to improve the design and delivery of such courses.
The effects of psychological interventions on menopausal hot flashes: A systematic review

Abstract Background Menopause is a normal physiological phenomenon, closely identified with a great deal of physical-psychological symptoms, including hot flashes (HFs) with a prevalence rate of 20-80%. Various pharmacological and non-pharmacological interventions have been thus far practiced to reduce this common symptom of the menopausal transition. Objective This systematic review was conducted to evaluate the effects of psychological interventions on menopausal HFs. Materials and Methods In this review, the databases of Google Scholar, Scopus, PubMed, Web of Science, Science Direct, the Cochrane Library, and Scientific Information Database were searched applying the Boolean searching operators as well as the keywords of `hot flashes', `menopause', `psychological intervention', and `vasomotor symptoms'. Accordingly, a total number of 20,847 articles published from January 2000 to June 2019 were retrieved. After excluding the duplicate and irrelevant ones, the risk of bias of 19 clinical or quasi-experimental clinical trials was assessed using the Cochrane collaboration tool. Results The interventions implemented in the studies on menopausal HFs included cognitive behavioral therapy, mindfulness-based stress reduction, hypnotherapy, and relaxation techniques. All of the articles reported improvements in HFs in postmenopausal women, except for 4 studies. Conclusion Based on the findings of this systematic review, psychological interventions, especially cognitive behavioral therapy and relaxation techniques, are potentially effective for vasomotor symptoms and HFs in healthy postmenopausal women, although the quality of published research on this topic is sometimes questionable.
CFTR Modulators in People with Cystic Fibrosis: Real-World Evidence in France

Cystic fibrosis (CF) is a rare genetic multisystemic disease, the manifestations of which are due to mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein and can lead to respiratory insufficiency and premature death. CFTR modulators, which were developed in the past decade, partially restore CFTR protein function. Their clinical efficacy has been demonstrated in phase 3 clinical trials, particularly in terms of lung function and pulmonary exacerbations, nutritional status, and quality of life in people with gating mutations (ivacaftor), homozygous for the F508del mutation (lumacaftor/ivacaftor and tezacaftor/ivacaftor), and in those with at least one F508del mutation (elexacaftor/tezacaftor/ivacaftor). However, many questions remain regarding their long-term safety and effectiveness, particularly in patients with advanced lung disease, liver disease, renal insufficiency, or problematic bacterial colonization. The impact of CFTR modulators on other important outcomes such as concurrent treatments, lung transplantation, chest imaging, or pregnancies also warrants further investigation. The French CF Reference Network includes 47 CF centers that contribute patient data to the comprehensive French CF Registry and have conducted nationwide real-world studies on CFTR modulators. This review seeks to summarize the results of these real-world studies and examine their findings against those of randomized control trials.
Effect of Sonication on the Functional Properties of Different Citrus Fruit Juices

ABSTRACT The present study was conducted to evaluate the effect of ultrasound on the functional properties of citrus juices. Citrus fruits and juices were analyzed for physico-chemical properties. The ‘Pamelo’ excelled in terms of average fruit weight (451.83 ± 7.1 g), fruit volume (543.33 ± 9.1 cm3) and rag percentage (68.64 ± 1.1%). ‘Valencia late’ (48.67 ± 0.3%), ‘Flame’ (48.38 ± 1.3%) and ‘Kinnow’ (35.95 ± 4.9%) were good in juice %. The juice was subjected to sonication treatment at 15°C for 5 min keeping pulse duration 5 s on and 5 s off (70% amplitude level and 20 kHz frequency). Total phenol, flavonoids, free radical scavenging activity, antioxidant capacity, and reducing power increased in fruit juices as a result of sonication. The total phenolic contents in the juices of all citrus cultivars ranged from 223.49 ± 4.5 to 590.47 ± 5.5 µg gallic acid equivalent/g and increased from 315.18 ± 6.1 to 645.44 ± 7.1 µg GAE/g after ultrasonic processing. The DPPH values of juices of all citrus cultivars ranged from 791.54 to 1251.93 µmol equivalent of trolox/mL and increased from 1001.54 to 1336.77 µmol equivalent of trolox/mL after applying ultrasound. The sonication is highly feasible for practical use in the industry for the production of citrus fruit juices with improved quality in terms of nutrients.
Association between Intra-Arrest Blood Glucose Level and Outcomes of Resuscitation at the Emergency Department: A Retrospective Study

Since current cardiac arrest guidelines do not address the benefit of blood glucose measurement, the ideal ranges and target of blood glucose (BG) levels during cardiac arrest to achieve a better result are warranted. We intended to investigate the associations between intra-arrest BG levels and outcomes of cardiac arrest resuscitation at the emergency department (ED). We conducted a retrospective observational study at a single university hospital. Cardiac arrest patients at the ED between 2017 and 2020 were included. Multivariable logistic regression analysis was performed to examine the associations between intra-arrest BG levels and clinical outcomes. We categorized intra-arrest BG into five groups: <70 mg/dL, 70–99 mg/dL, 100–180 mg/dL, 181–250 mg/dL, and >250 mg/dL. Eight hundred and nineteen patients experienced ED cardiac arrest during the study period. Of all, 385 intra-arrest BG measurements were included in the data analysis. The mean age was 60.4 years. The mean intra-arrest BG level was 171.1 mg/dL, with 64 (16.6%) patients who had intra-arrest BG level below 70 mg/dL and 73 (19.0%) patients who had intra-arrest BG level more than 250 mg/dL. Markedly low (<70 mg/dL) and low (70–99 mg/dL) intra-arrest BG levels were significantly associated with a lower chance of return of spontaneous circulation (ROSC, OR 0.36, 95% CI 0.14–0.99, p = 0.05 and OR 0.33, 95% CI 0.12–0.93, p = 0.04, respectively). For patients who experienced cardiac arrest at the ED, an intra-arrest BG level of less than 100 was inversely correlated with sustained ROSC. Although we could not draw a causal relationship between variables concerning this study design, normalizing intra-arrest BG was shown to result in good clinical outcomes.
The predicted impact of resource provisioning on the epidemiological responses of different parasites

Abstract Anthropogenic activities and natural events such as periodic tree masting can alter resource provisioning in the environment, directly affecting animals, and potentially impacting the spread of infectious diseases in wildlife. The impact of these additional resources on infectious diseases can manifest through different pathways, affecting host susceptibility, contact rate and host demography. To date however, empirical research has tended to examine these different pathways in isolation, for example by quantifying the effects of provisioning on host behaviour in the wild or changes in immune responses in controlled laboratory studies. Furthermore, while theory has investigated the interactions between these pathways, this work has focussed on a narrow subset of pathogen types, typically directly transmitted microparasites. Given the diverse ways that provisioning can affect host susceptibility, contact patterns or host demography, we may expect the epidemiological consequences of provisioning to vary among different parasite types, dependent on key aspects of parasite life history, such as the duration of infection and transmission mode. Focusing on an exemplar empirical system, the wood mouse Apodemus sylvaticus, and its diverse parasite community, we developed a suite of epidemiological models to compare how resource provisioning alters responses for a range of these parasites that vary in their biology (microparasite and macroparasite), transmission mode (direct, environmental and vector transmitted) and duration of infection (acute, latent and chronic) within the same host population. We show there are common epidemiological responses to host resource provisioning across all parasite types examined. In particular, the epidemiological impact of provisioning could be driven in opposite directions, depending on which host pathways (contact rate, susceptibility or host demography) are most altered by the addition of resources to the environment. Broadly, these responses were qualitatively consistent across all parasite types, emphasising the importance of identifying general trade‐offs between provisioning‐altered parameters. Despite the qualitative consistency in responses to provisioning across parasite types, we predicted notable quantitative differences between parasites, with directly transmitted parasites (those conforming to SIR and SIS frameworks) predicted to show the strongest responses to provisioning among those examined, whereas the vector‐borne parasites showed negligible responses to provisioning. As such, these analyses suggest that different parasites may show different scales of response to the same provisioning scenario, even within the same host population. This highlights the importance of knowing key aspects of host–parasite biology, to understand and predict epidemiological responses to provisioning for any specific host–parasite system.
Biopolymer-Based Films from Sodium Alginate and Citrus Pectin Reinforced with SiO2

Blend films based on sodium alginate (SA) and citrus pectin (P) reinforced with different concentrations of SiO2 (0–10% w/w) were developed in this study. From the morphological (SEM) and structural (FT-IR) evaluation, it was verified that the incorporation of the reinforcing agent did not drastically modify the microstructure of the films, nor did new chemical bonds form. However, the XRD results suggested a slight reduction in the crystallinities of the blends by the incorporation of SiO2. Among the formulations prepared, the addition of a 5% reinforcing agent was responsible for the simultaneous improvement of mechanical and barrier properties. Comparing the control sample (SA/P) with the SA/P/5.0%SiO2 film, the tensile strength increased from 27.7 ± 3.7 to 40.6 ± 4.5 MPa, and the water-vapor transmission rate decreased from 319.8 ± 38.7 to 288.9 ± 23.5 g m−2 day−1. Therefore, SiO2, as a reinforcing agent in SA/P blends, represents a simple and effective strategy for improving the properties of biopolymer-based films in applications, such as packaging.
Combination of C-Reactive Protein and Procalcitonin in Distinguishing Fungal from Bacterial Infections Early in Immunocompromised Children

Invasive fungal infection (IFI) is life-threatening in children with cancer and hematology disorders, especially when diagnosis and treatment are delayed. Conventional β-D-glucan and galactomannan tests have poor positive predictive values in the diagnosis of IFI in children with cancer. This study aims to access the diagnostic performance of C-reactive protein (CRP) and procalcitonin (PCT) in differentiating IFI from bacterial bloodstream infections in children with malignant and hematology disorders. CRP and PCT levels were measured in samples taken from patients between 12 and 24 h after fever onset, of which 24 and 102 were in the IFI and bacterial groups, respectively. We found that the CRP levels were much higher in the IFI group than the bacterial group (100.57 versus 40.04 mg/L, median, p < 0.001), while the PCT levels remained significantly lower (0.45 versus 1.29 μg/L, median, p = 0.007). Both CRP and PCT showed significant diagnostic utilities with an area under the curve (AUC) of 0.780 (95% CI, 0.664–0.896, p < 0.001) and 0.731 (95% CI, 0.634–0.828, p < 0.001) when using the cut-off values of 94.93 mg/L and 2.00 μg/L, respectively. However, the combined biomarker of CRP and PCT yielded a better diagnostic performance with an AUC of 0.934 (95% confidential interval (CI), 0.881–0.987, p < 0.001), which was significantly higher than that of CRP or PCT (both p < 0.001), with a sensitivity of 87.5% and a specificity of 87.3%. Our study demonstrates high levels of CRP combined with low PCT could differentiate IFI from bacterial bloodstream infections in immunocompromised children.
Potential Composite Digenic Contribution of NPC1 and NOD2 Leading to Atypical Lethal Niemann-Pick Type C with Initial Crohn’s Disease-like Presentation: Genotype-Phenotype Correlation Study

Niemann–Pick disease type C (NPC) is an autosomal recessive neurovisceral disease characterized by progressive neurodegeneration with variable involvement of multisystemic abnormalities. Crohn’s disease (CD) is an inflammatory bowel disease (IBD) with a multifactorial etiology influenced by variants in NOD2. Here, we investigated a patient with plausible multisystemic overlapping manifestations of both NPC and CD. Her initial hospitalization was due to a prolonged fever and non-bloody diarrhea. A few months later, she presented with recurrent skin tags and anal fissures. Later, her neurological and pulmonary systems progressively deteriorated, leading to her death at the age of three and a half years. Differential diagnosis of her disease encompassed a battery of clinical testing and genetic investigations. The patient’s clinical diagnosis was inconclusive. Specifically, the histopathological findings were directed towards an IBD disease. Nevertheless, the diagnosis of IBD was not consistent with the patient’s subsequent neurological and pulmonary deterioration. Consequently, we utilized a genetic analysis approach to guide the diagnosis of this vague condition. Our phenotype–genotype association attempts led to the identification of candidate disease-causing variants in both NOD2 and NPC1. In this study, we propose a potential composite digenic impact of these two genes as the underlying molecular etiology. This work lays the foundation for future functional and mechanistic studies to unravel the digenic role of NOD2 and NPC1.
Prebiotics as a Tool for the Prevention and Treatment of Obesity and Diabetes: Classification and Ability to Modulate the Gut Microbiota

Diabetes and obesity are metabolic diseases that have become alarming conditions in recent decades. Their rate of increase is becoming a growing concern worldwide. Recent studies have established that the composition and dysfunction of the gut microbiota are associated with the development of diabetes. For this reason, strategies such as the use of prebiotics to improve intestinal microbial structure and function have become popular. Consumption of prebiotics for modulating the gut microbiota results in the production of microbial metabolites such as short-chain fatty acids that play essential roles in reducing blood glucose levels, mitigating insulin resistance, reducing inflammation, and promoting the secretion of glucagon-like peptide 1 in the host, and this accounts for the observed remission of metabolic diseases. Prebiotics can be either naturally extracted from non-digestible carbohydrate materials or synthetically produced. In this review, we discussed current findings on how the gut microbiota and microbial metabolites may influence host metabolism to promote health. We provided evidence from various studies that show the ability of prebiotic consumption to alter gut microbial profile, improve gut microbial metabolism and functions, and improve host physiology to alleviate diabetes and obesity. We conclude among other things that the application of systems biology coupled with bioinformatics could be essential in ascertaining the exact mechanisms behind the prebiotic–gut microbe–host interactions required for diabetes and obesity improvement.
Family‐reported barriers and predictors of short‐term attendance in a multidisciplinary intervention for managing childhood obesity: A psycho‐family‐system based randomised controlled trial (ENTREN‐F)

Abstract Objective This study was aimed to examine patient enrolment in the pre‐intervention stage, family‐reported barriers, attendance rates and underlying predictors of short‐term attendance in a family‐system‐based randomised controlled trial for managing childhood obesity in children aged 8–12‐years‐old (ENTREN‐F). Method Psychosocial and anthropometric measures were collected through primary health referral. The data were used for descriptive analyses of sample characteristics and linear regression analyses. Results Low enrolment rates and several family‐reported barriers were observed in the pre‐intervention stage. Logistical barriers were the most frequent family‐reported reason for attrition in the different stages of the study. Having a first face‐to‐face orientation session with the families and the use of motivational interviewing helped to improve adherence in the initial phases of the study. After 6 months of intervention, family based treatments (FBTs) under consideration achieve greater adherence compared with the standard intervention. Moreover, family involvement was a predictor of success for better treatment adherence rates. By contrast, participants who attended a brief standard intervention, mothers with primary education, greater body mass index, higher levels of depressive symptomatology and more critical comments towards their children, children with higher weight status and lower levels of self‐reported depressive symptoms at baseline attended interventions less frequently. Conclusions In future programmes a comprehensive screening of modifiable factors related to family and their setting characteristics is paramount prior to intervention, identifying key barriers related to drop‐out, especially in the case of less‐advantaged families.
Correction of LiDAR measurement error in complex terrain by CFD: Case study of the Yangyang pumped storage plant

In complex terrain, the inhomogeneity of wind speed in a horizontal plane at light detection and ranging (LiDAR) measurement heights is generally high due to the curvature of the flow. Consequently, it is impossible to avoid measurement errors when using LiDAR, a ground-based remote-sensing device in such terrain. To correct this measurement error, the vertical wind speed gradient along the horizontal direction is calculated by computational fluid dynamics (CFD) software such as WindSim. This article validated the effectiveness of the WindSim remote-sensing correction module by applying it to the Yangyang pumped storage plant site, which is surrounded by very complex mountainous terrain with a maximum difference in elevation of 765 m and an average terrain slope of 26.7°, and performed an 84-h short-term field campaign using a WindCube LiDAR. It is shown that the WindSim remote-sensing correction module slightly but systematically improved the accuracy of predicting wind speed and wind power output with respect to the supervisory control and data acquisition (SCADA) dataset of two adjacent wind turbines at the Yangyang pumped storage plant.
The role of VWF/FVIII in thrombosis and cancer progression in multiple myeloma and other hematological malignancies

Cancer associated thrombosis (CAT) is associated with significant morbidity and mortality, highlighting an unmet clinical need to improve understanding of the pathophysiology of CAT. Multiple myeloma (MM) is associated with one of the highest rates of thrombosis despite widespread use of thromboprophylactic agents. The pathophysiology of thrombosis in MM is multifactorial and patients with MM appear to display a hypercoagulable phenotype with potential contributory factors including raised von Willebrand factor (VWF) levels, activated protein C resistance, impaired fibrinolysis, and abnormal thrombin generation. In addition, the toxic effect of anti‐myeloma therapies on the endothelium and contribution to thrombosis has been widely described. Elevated VWF/factor VIII (FVIII) plasma levels have been reported in heterogeneous cohorts of patients with MM and other hematological malignancies. In specific studies, high plasma VWF levels have been shown to associate with VTE risk and reduced overall survival. While the mechanisms underpinning this remain unclear, dysregulation of the VWF and A Disintegrin And Metalloprotease Thrombospondin type 1, motif 13 (ADAMTS‐13) axis is evident in certain solid organ malignancies and correlates with advanced disease and thrombosis. Furthermore, thrombotic microangiopathic conditions arising from deficiencies in ADAMTS‐13 and thus an accumulation of prothrombotic VWF multimers have been reported in patients with MM, particularly in association with specific myeloma therapies. This review will discuss current evidence on the pathophysiological mechanisms underpinning thrombosis in MM and in particular summarize the role of VWF/FVIII in hematological malignancies with a focus on thrombotic risk and emerging evidence for contribution to disease progression.