Miracle-dz/UniFAR-FTUs huggingface dataset:
Andrographolide restores glucose uptake in rat hippocampal neurons

Cerebral glucose hypometabolism is a common pathophysiological characteristic of many neurodegenerative diseases. This metabolic dysfunction includes alterations in glucose transport from the blood into the neurons by the facilitative glucose transporters (GLUTs). Several studies suggest that metabolic disturbances precede clinical symptoms and correlate with disease progression. Some groups have started to explore the use of therapeutic strategies that target decreased cerebral glucose metabolism to promote its availability. We selected Andrographolide (Andro), a natural product obtained from Andrographis paniculate that has both anti‐hyperglycemic and anti‐diabetic effects. Although it was shown to promote glucose uptake in vivo, the underlying mechanisms remain unclear. Here, we evaluated the acute effects of Andro on glucose transport and metabolism using primary rat hippocampal neuronal cultures. Our results showed that Andro enhances neuronal glucose uptake and stimulates glucose metabolism by inducing GLUT3 and 4 expression in neurons, as well as by promoting glycolysis. We also observed that Andro‐mediated effects depend on the activity of AMP‐activated protein kinase (AMPK), one of the central regulators of glucose metabolism. Our studies open the possibility to use Andro as a drug to restore glucose levels in neurodegenerative diseases.
Effects of mixture ratio and cutting time on forage yield and silage quality of intercropped berseem clover and italian ryegrass

The research was carried out to determine the effects of different mixture ratios and cutting times on dry-matter yield and silage quality of mixtures of bersem clover (Trifolium alexandrinum L.) with Italian ryegrass (Lolium multiflorum Lam.) in Adana province, Turkey. The experiment was laid out in split plot design with four replications during the years of 2011-2013. The mixture-ratios ( 80% BC + 20% IR, 60% BC + % 40 IR, 40% BC+ % 60 IR, 20% BC + 80 % IR, pure berseem clover (BC) and Italian ryegrass (IR) ) were main plots, and harvest times (beginning of the flowering, mid flowering and full flowering of BC) were sub-plots. From the result of the study, it was concluded that the mixture of 60 % BC +40 % IR harvested at full flowering of BC was superior in terms of dry matter yield and silage quality.
What Lies Behind Teaching and Learning Green Chemistry to Promote Sustainability Education? A Literature Review

In this qualitative study, we aim to identify suitable pedagogical approaches to teaching and learning green chemistry among college students and preservice teachers by examining the teaching methods that have been used to promote green chemistry education (GCE) and how these methods have supported green chemistry learning (GCL). We found 45 articles published in peer-reviewed scientific journals since 2000 that specifically described teaching methods for GCE. The content of the articles was analyzed based on the categories of the teaching methods used and the revised version of Bloom’s taxonomy. Among the selected articles, collaborative and interdisciplinary learning, and problem-based learning were utilized in 38 and 35 articles, respectively. These were the most frequently used teaching methods, alongside a general combination of multiple teaching methods and teacher presentations. Developing collaborative and interdisciplinary learning skills, techniques for increasing environmental awareness, problem-centered learning skills, and systems thinking skills featuring the teaching methods were seen to promote GCL in 44, 40, 34, and 29 articles, respectively. The results showed that the integration of green chemistry teaching (GCT), e.g., with sustainable education, promoted GCL by fostering environmental consciousness and behavioral change and cognitive processes in a sustainable direction.
Early Life Adversity and Pubertal Timing: Implications for Cardiometabolic Health.

OBJECTIVE To identify early life adversity (ELA) risk factors for earlier pubertal timing, itself a risk factor for poor cardiometabolic health, and to determine whether such ELA-related risk may be mediated by pre-pubertal body mass index (BMI). METHODS Subjects included 426 female participants in a prospective birth cohort study, the NICHD Study of Early Child Care and Youth Development. Survival analysis models were fit to examine ELA exposures, representing childhood socioeconomic status (SES), maternal sensitivity, mother-child attachment, and negative life events, along with child health indicators and covariates, in relation to pubertal timing outcomes, including age at menarche and ages at Tanner stage II for breast and pubic hair development. RESULTS Higher childhood SES emerged as an independent predictor of older age at menarche, showing each one standard deviation increase in childhood SES corresponded to a 1.3% increase in age at menarche (factor change = 1.013; 1.003-1.022; p < .01), but did not predict breast or pubic hair development (ps > .05). In mediation analyses, indirect (mediated) effects of mother-child attachment on the pubertal timing outcomes, via pre-pubertal BMI, were all statistically significant (ps < .05). CONCLUSIONS Higher childhood SES predicted directly, and secure (vs. insecure) mother-child attachment predicted indirectly (via pre-pubertal BMI), later pubertal timing, suggesting these factors may protect girls from earlier pubertal development. By extension, clinical implications are that intervention strategies designed to lessen ELA- and pre-pubertal obesity-related risk may be effective in remediating life course pathways linking ELA, accelerated pubertal development, and cardiometabolic risk.
Effects of various levels of organic acids and of virginiamycin on performance, blood parameters, immunoglobulins and microbial population of broiler chicks

This experiment was conducted to investigate the effects of various levels of organic acids and virginiamycin on performance, blood parameters, immunoglobulin and microbial population of broiler chickens. This trial was conducted in a completely randomized design using five treatments and four replicates. The dietary treatments included a control diet without additives, diets containing 0.05%, 0.10% and 0.15% mixtures of organic acids, and a diet containing virginiamycin as an antibiotic. Based on the results, there was no significant effect of the experimental diets on feed intake of the broilers during the starter period. However, at the end of the grower period and throughout the rearing period, feed intake was significantly improved by experimental dietary treatments. Moreover, diets including organic acids enhanced the microbial population of broiler gut. Thus, the current findings support the conclusion that organic acids improve productive traits and health status in broiler chickens. Keywords: Broiler, growth, haematology, gut
Beyond Conventional: The New Horizon of Anti-Angiogenic microRNAs in Non-Small Cell Lung Cancer Therapy

GLOBOCAN 2018 identified lung cancer as the leading oncological pathology in terms of incidence and mortality rates. Angiogenesis is a key adaptive mechanism of numerous malignancies that promotes metastatic spread in view of the dependency of cancer cells on nutrients and oxygen, favoring invasion. Limitation of the angiogenic process could significantly hamper the disease advancement through starvation of the primary tumor and impairment of metastatic spread. This review explores the basic molecular mechanisms of non-small cell lung cancer (NSCLC) angiogenesis, and discusses the influences of the key proangiogenic factors—the vascular endothelial growth factor-A (VEGF-A), basic fibroblast growth factor (FGF2), several matrix metalloproteinases (MMPs—MMP-2, MMP-7, MMP-9) and hypoxia—and the therapeutic implications of microRNAs (miRNAs, miRs) throughout the entire process, while also providing critical reviews of a number of microRNAs, with a focus on miR-126, miR-182, miR-155, miR-21 and let-7b. Finally, current conventional NSCLC anti-angiogenics—bevacizumab, ramucirumab and nintedanib—are briefly summarized through the lens of evidence-based medicine.
The gut microbiome in differential diagnosis of diabetic kidney disease and membranous nephropathy

Abstract Background Diabetic kidney disease (DKD) and membranous nephropathy (MN) are the two major causes of end-stage renal disease (ESRD). Increasing evidence has shown that intestinal dysbiosis is associated with many diseases. The aim of this study was to explore the composition of the gut microbiome in DKD and MN patients. Methods 16S rRNA gene sequencing was performed on 271 fecal samples (DKD = 129 and MN = 142), and taxonomic annotation of microbial composition and function was completed. Results We observed distinct microbial communities between the two groups, with MN samples exhibiting more severe dysbiosis than DKD samples. Relative increases in genera producing short-chain fatty acids (SCFAs) in DKD and a higher proportion of potential pathogens in MN were the main contributors to the microbiome alterations in the two groups. Five-fold cross-validation was performed on a random forest model, and four operational taxonomic unit (OTU)-based microbial markers were selected to distinguish DKD from MN. The results showed 92.42% accuracy in the training set and 94.52% accuracy in the testing set, indicating high potential for these microbiome-based markers in separating MN from DKD. Overexpression of several amino acid metabolic pathways, carbohydrate metabolism and lipid metabolism was found in DKD, while interconversion of pentose/glucoronate and membrane transport in relation to ABC transporters and the phosphotransferase system were increased in MN. Conclusion The composition of the gut microbiome appears to differ considerably between patients with DKD and those with MN. Thus, microbiome-based markers could be used as an alternative tool to distinguish DKD and MN.
Mycobacterium chimaera infection after cardiac surgery: Catastrophic effects of delayed diagnosis

To the Editor: The interesting and timely paper by Cain et al.1, in press in the Journal of Cardiac Surgery , provides important details concerning the devastating consequences of Mycobacterium chimaera (MC ) infection. In their patient extreme fragility of the mediastinal tissues was observed after repair of an acute aortic dissection; during follow-up multiple reoperations were required to treat recurrent dehiscence of the aortic grafts. Despite repeat explantation of foreign materials infection persisted with mediastinitis and eventual systemic diffusion with fatal outcome.MC infection after open cardiac surgery using cardiopulmonary bypass has been recently reported as a clinical outbreak worldwide and identified as originating by contaminated water in heater-cooler units2. Current experience shows that MC causes a slow-growing and extremely difficult to treat infection with an incubation period which has been recently demonstrated to be as long as >12 years3.We have recently treated a patient, quite similar to that reported by Cain et al.1, who presented with a pseudoaneurysm of the distal suture line twelve years after repair of type A aortic dissection4. At first operation replacement of the ascending aorta and hemiarch using of a Djumbodis®dissection system (Saint Come-Chirurgie, Marseille, France) was performed. At reoperation extremely fragile tissues were noted and, after removing the metallic stent, the aortic arch was replaced with a frozen elephant trunk technique. Cultures of the excised material grewMC . In this case we hypothesized that the stent played an important role in the onset of infection for at least 2 reasons: presence of foreign material in the blood stream and injury to the aortic wall by the edges of the stent. The case described by Cain et al.1 also supports our belief that extreme fragility of the aortic tissues caused by MB was a further important factor in the occurrence of this complication.Interestingly, a delayed diagnosis occurred in both cases; this most likely played a critical role in favouring development of extra‐cardiac manifestations of the disease, in reducing the effectiveness of antibiotic therapy due to immunologic impairment and causing a negative outcome in both patients.MB infection may have different locations ranging from single-organ to systemic manifestations5. When it involves the mediastinum and particularly the major vascular structures often results in life-threatening complications despite proper antimycobacterial treatment. An early diagnosis, even with significantly extended surveillance, appears extremely difficult due to slow-growing and long incubation period of MB . Although no specific guidelines are so far available, intra-operative prevention with improvement of setting and development of heater-cooler units is mandatory and should be based on specific recommendations5.
Recent Advances in the Pharmacology of Tardive Dyskinesia

Tardive dyskinesia (TD) is a syndrome of abnormal involuntary movements that follows treatment with dopamine D2-receptor antagonists. Recent approval of vesicular monoamine transporter-2 (VMAT2) inhibitors offers hope for reducing the impact of TD. Although these drugs represent a significant advance in patient care and a practical step forward in providing relief for patients with TD, understanding of the pharmacology of TD that could inform future research to prevent and reverse TD remains incomplete. This review surveys evidence for the effectiveness of VMAT2 inhibitors and other agents in the context of theories of pathogenesis of TD. In patients for whom VMAT2 inhibitors are ineffective or intolerable, as well as for extending therapeutic options and insights regarding underlying mechanisms, a review of clinical trial results examined as experimental tests of etiologic hypotheses is worthwhile. There are still compelling reasons for further investigations of the pharmacology of TD, which could generate alternative preventive and potentially curative treatments. Finally, benefits from novel drugs are best realized within an overall treatment strategy addressing the condition and needs of individual patients.
Nutritional Neuroscience as Mainstream of Psychiatry: The Evidence-Based Treatment Guidelines for Using Omega-3 Fatty Acids as a New Treatment for Psychiatric Disorders in Children and Adolescents

Omega-3 polyunsaturated fatty acids (or omega-3 PUFAs, n-3 PUFAs) are essential nutrients throughout the life span. Recent studies have shown the importance of n-3 PUFAs supplementation during prenatal and perinatal period as a potential protective factor of neurodevelopmental disorders. N-3 PUFAs have been reported to be lower in youth with attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD). N-3 PUFAs supplementation has shown potential effects in the improvement of clinical symptoms in youth with ADHD, ASD, and MDD, especially those with high inflammation or a low baseline n-3 index. Moreover, it has been suggested that n-3 PUFAs had positive effects on lethargy and hyperactivity symptoms in ASD. For clinical application, the following dosage and duration are recommended in youth according to available randomized controlled trials and systemic literature review: (1) ADHD: a combination of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) ≥ 750 mg/d, and a higher dose of EPA (1,200 mg/d) for those with inflammation or allergic diseases for duration of 16−24 weeks; (2) MDD: a combination of a EPA + DHA of 1,000−2,000 mg/d, with EPA:DHA ratio of 2 to 1, for 12−16 weeks; (3) ASD: a combination of EPA + DHA of 1,300−1,500 mg/d for 16−24 weeks as add-on therapy to target lethargy and hyperactivity symptoms. The current review also suggested that n-3 index and inflammation may be potential treatment response markers for youth, especially in ADHD and MDD, receiving n-3 PUFA.
Development of a Curcumin-Loaded Polymeric Microparticulate Oral Drug Delivery System for Colon Targeting by Quality-by-Design Approach

The purpose of this study was to apply the quality-by-design (QbD) approach for the development of colon-targeted curcumin-loaded polymeric microparticles (Col-CUR-MPs). The proportion of the enterosoluble polymer (Eudragit® FS) in the polymeric matrix, curcumin concentration, and the concentration of the polymer mixture (Eudragit® FS-polycaprolactone) were identified as potential risk factors for the quality of the final product following risk assessment. The influence of these variables on the critical quality attributes (CQAs) of Col-CUR-MPs was investigated. Therefore, a central composite face experimental design was used in order to determine the functional relationships between variables and product CQAs. The obtained regression model and contour plots were used to establish the design space. Finally, the model was validated by preparing two microparticulate formulations, one corresponding to the robust setpoint from within the design space and one outside the established design space, and calculating the percentage bias between the experimental and predicted values. The in vivo study, which was conducted on a fluorescein-loaded formulation that corresponded to the robust setpoint determined by QbD and that contained a mixture of polycaprolactone and Eudragit® FS (60:40, w/w), confirmed the colon-targeting qualities of this formulation.
Improving the spatial‐temporal analysis of Amazonian fires

Amazonian fires have been of great scientific and political concern in recent years, as they indicate changes in environmental governance, altered environmental conditions, and lie at the interface of climate and land-use changes - two of the dominant stressors in tropical environments (Barlow et al., 2018). Research on complex socio-environmental systems, such as the Amazon, is crucial to inform more effective decision making. With this in mind, we were concerned that recent papers - including that of Xu et al. 2020 in this journal - have failed to contemplate critical nuances that underpin Amazonian fires, leading to flawed results. In the interest of supporting science that is more informative, we outline five key features of the Amazon that need to be considered when analyzing spatial-temporal patterns of fires.
Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors

The sex-specific effect of skeletal muscle mass (SMM) index (SMI) on 4-year first fatal/non-fatal cardiovascular disease (CVD) event in free-of-disease individuals was examined. In 2009, n = 1411 inhabitants (mean age = 64(12)) from Ikaria were selected. Follow-up was performed in 2013. SMI was created to reflect SMM through appendicular skeletal muscle mass (indirectly calculated through formulas) divided by body mass index (BMI). Fifteen and six tenths percent of participants exhibited CVD (19.8% in men/12% in women, p = 0.002). Significant U-shape trends were observed in participants >65 years old and women irrespective to age confirmed through multi-adjusted Cox regression analysis; in age >65 years, Hazard Ratio (HR)(2nd vs. 1st SMI tertile) = 0.80, 95% Confidence Interval (95%CI) (0.45, 0.96) and in women HR(2nd vs. 1st SMI tertile) = 0.71, 95% CI (0.33, 0.95), while, as for the 3rd SMI tertile, no significant trends were observed. Mediation analysis revealed that mediators of the aforementioned associations in men were the arterial distensibility and total testosterone, while, in women, inflammation, insulin resistance, and arterial distensibility. High SMM accompanied by obesity may not guarantee lower CVD risk. Specific cardiometabolic factors seem to explain this need for balance between lean and fat mass.
Synergistic Effect of Propolis and Antibiotics on Uropathogenic Escherichia coli

Urinary tract infections (UTIs) are the most common bacterial infections around the world. Uropathogenic Escherichia coli (UPEC) is among the main pathogens isolated in UTIs. The rate of UPEC with high resistance towards antibiotics and multidrug-resistant bacteria have increased dramatically and conduct to the difficulty to treat UTIs. Due to the rarefaction of new antibiotics molecules, new alternative strategies must be evaluated. Since many years, propolis has demonstrated an interesting antibacterial activity against E. coli. Here, we evaluated its activity added to antibiotics on a panel of UPEC with different resistance mechanisms. Minimal inhibitory concentrations (MICs) and time–kill curves of fosfomycin, ceftriaxone, ertapenem and ofloxacin, with and without propolis, were determined. Significant diminution of the MICs was observed using ceftriaxone or ofloxacin + propolis. Propolis alone had a bacteriostatic activity with time-dependent effect against UPEC. The addition of this nutraceutical improved the effect of all the antibiotics evaluated (except fosfomycin) and showed a synergistic bactericidal effect (fractional inhibitory concentrations index ≤ 0.5 and a decrease ≥ 2 log CFU/mL for the combination of propolis plus antibiotics compared with the antibiotic alone). Propolis is able to restore in vitro antibiotic susceptibility when added to antibiotics against UPEC. This study showed that propolis could enhance the efficiency of antibiotics used in UTIs and could represent an alternative solution.
Differences in Gradient Emotion Perception: Human vs. Alexa Voices

The present study compares how individuals perceive gradient acoustic realizations of emotion produced by a human voice versus an Amazon Alexa text-to-speech (TTS) voice. We manipulated semantically neutral sentences spoken by both talk-ers with identical emotional synthesis methods, using three levels of increasing ‘happiness’ (0%, 33%, 66% ‘happier’). On each trial, listeners (native speakers of American English, n=99) rated a given sentence on two scales to assess dimensions of emotion: valence (negative-positive) and arousal (calm-excited). Participants also rated the Alexa voice on several parameters to assess anthropomorphism (e.g., naturalness, human-likeness, etc.). Results showed that the emotion manipulations led to increases in perceived positive valence and excitement. Yet, the effect differed by interlocutor: increasing ‘happiness’ manipulations led to larger changes for the human voice than the Alexa voice. Additionally, we observed individual differences in perceived valence/arousal based on participants’ anthropomorphism scores. Overall, this line of research can speak to theories of computer personiﬁcation and elucidate our chang-ing relationship with voice-AI technology.
Supervised Domain Adaptation for Text-Independent Speaker Verification Using Limited Data

To adapt the speaker veriﬁcation (SV) system to a target domain with limited data, this paper investigates the transfer learning of the model pre-trained on the source domain data. To that end, layer-by-layer adaptation with transfer learning from the initial and ﬁnal layers of the pre-trained model is investigated. We show that the model adapted from the initial layers outperforms the model adapted from the ﬁnal layers. Based on this evidence, and inspired by the works in image recognition ﬁeld, we hypothesize that low-level convolutional neural network (CNN) layers characterize domain-speciﬁc component while high-level CNN layers are domain-independent and have more discriminative power. For adapting these domain-speciﬁc components, angular margin softmax (AMSoftmax) applied on the CNN-based implementation of the x-vector architecture. In addition, to reduce the problem of over-ﬁtting on the limited target data, transfer learning on the batch norm layers is investigated. Mean shift and covariance estimation of batch norm allows to map the represented components of the target domain to the source domain. Using TDNN and E-TDNN versions of the x-vectors as baseline models, the adapted models on the development set of NIST SRE 2018 outperformed the baselines with relative improvements of 11.0 and 13.8 %, respectively.