Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial Dysfunction Treatment

Abstract Endothelial dysfunction is characterised by the low bioavailability of nitric oxide with a relevant negative impact on the nitric oxide/cGMP pathway. The loss of nitric oxide/cGMP signaling may be caused by an increased arginase activity. Plant-derived substances, especially polyphenols, are compounds that have the potential to inhibit arginase activity and they may represent an attractive therapeutic option to combat clinical outcomes related to endothelial dysfunction. An extensive review was carried out using all available data published in English in the Pubmed database, and without restriction regarding the year of publication. Despite the increased number of new substances that have been tested as arginase inhibitors, it is rare to find a compound that satisfies all the toxicological criteria to be used in the development of a new drug. On the other hand, recent data have shown that substances from plants have great potential to be applied as arginase inhibitors, most of which are polyphenols. Of the relevant mechanisms in this process, the inhibition of arginase by natural products seems to act against endothelial dysfunction by reestablishing the vascular function and elevating nitric oxide levels (by increasing the amounts of substrate (L-arginine, and endothelial nitric oxide synthase activation and stabilisation) as well as decreasing the generation of reactive species (formed by uncoupledendothelial nitric oxide synthase). This review summarises several topics regarding arginase inhibition by natural substances as well as indicating this pathway as an emergent strategy to elevate nitric oxide levels in disorders involving endothelial dysfunction. In addition, some aspects regarding structural activity and future perspectives are discussed.
Physical activity and sedentary behavior in patients with Systemic Lupus Erythematosus

Introduction The aim of this study was to evaluate the proportion of patients with Systemic Lupus Erythematosus (SLE) who did not met the WHO recommendations for physical activity and to evaluate the amount of time spent in sedentary behavior. Methods SLE patients were consecutively enrolled in a cross sectional study. The type and the time spent in physical activity and sedentary behavior were evaluated using the IPAQ short form questionnaire. The adequate physical activity was defined according to the 2010 WHO recommendations for health and the sedentary behavior according to the 2017 SBRN consensus. We also assessed quality of life using SF-36, mood disorders using BDI and HAM-H, fatigue using Facit-Fatigue and sleep disorders using PSQI scores. Results Physical activity was not sufficient to meet WHO recommendations in 56 of 93 SLE patients (60%). SLE patients spent a median (95% range) of 180 (0–600) minutes everyday in sedentary activities. The length of daily sedentary time was more than 6 hours in 25% of SLE patients. In multivariable analysis, the factors associated to the probability of not meeting WHO criteria was only the time of exposure to antimalarials (OR 0.88, p 0.03) and the factors related to the probability of being in the upper tertile of sedentary time (more than 270 minutes) were age (OR 1.04, p 0.02), disease activity expressed by SELENA-SLEDAI score (OR 1.2, p 0.01) and Facit-fatigue score (OR 0.94, p 0.04). Conclusion A relevant proportion of SLE patients were inadequately physically active. It is essential to improve the awareness of the importance of increase physical activity and reduce sedentary time. A better control of disease activity and fatigue and a prolonged use of antimalarials could help to reach this notable goal.
Chronic Stress Effects on Hippocampal Structure and Synaptic Function: Relevance for Depression and Normalization by Anti-Glucocorticoid Treatment

Exposure of an organism to environmental challenges activates two hormonal systems that help the organism to adapt. As part of this adaptational process, brain processes are changed such that appropriate behavioral strategies are selected that allow optimal performance at the short term, while relevant information is stored for the future. Over the past years it has become evident that chronic uncontrollable and unpredictable stress also exerts profound effects on structure and function of limbic neurons, but the impact of chronic stress is not a mere accumulation of repeated episodes of acute stress exposure. Dendritic trees are reduced in some regions but expanded in others, and cells are generally exposed to a higher calcium load upon depolarization. Synaptic strengthening is largely impaired. Neurotransmitter responses are also changed, e.g., responses to serotonin. We here discuss: (a) the main cellular effects after chronic stress with emphasis on the hippocampus, (b) how such effects could contribute to the development of psychopathology in genetically vulnerable individuals, and (c) their normalization by brief treatment with anti-glucocorticoids.
Venous access and long-term pacemaker lead failure: comparing contrast-guided axillary vein puncture with subclavian puncture and cephalic cutdown

Aims Existing data on the relationship between venous access and long-term pacemaker lead failure (PLF) are scarce and inconsistent. We aim to study the hypothesis that contrast-guided axillary vein puncture (AP) is better than subclavian puncture (SP) and similar to cephalic vein cutdown (CV) in the incidence of PLF and the success rate of AP is higher than CV. Methods and results The case records of 409 patients with 681 implantable pacemaker leads were reviewed. Two hundred and fifty-two, 217, and 212 leads were implanted via AP, CV, and SP, respectively. With a mean follow-up of 73.6 ± 33.1 months, 20 (2.9%) PLF occurred. Three (1.2%), 5 (2.3%), and 12 (5.6%) PLF occurred in the AP, CV, and SP groups, respectively. On multivariate Cox regression analysis, the only independent predictor for PLF was the use of SP instead of AP (AP vs. SP; hazard ratio: 0.261; 95% confidence interval: 0.071-0.954, P = 0.042). The success rate of CV (78.2%) was significantly lower than those of AP (97.6%) and SP (96.8%) (P < 0.001). Conclusion Compared with SP, the use of AP but not CV independently predicted a lower risk of PLF. The success rates in achieving venous accesses were similar between AP and SP, but significantly lower for CV. Axillary vein puncture may thus be considered the venous access of choice for pacemaker lead implantation.
Origins and genetic legacies of the Caribbean Taino

Significance Ancient DNA has revolutionized the field of archaeology, but in the Caribbean and other tropical regions of the world, the work has been hampered by poor DNA preservation. We present an ancient human genome from the Caribbean and use it to shed light on the early peopling of the islands. We demonstrate that the ancestors of the so-called “Taino” who inhabited large parts of the Caribbean in pre-Columbian times originated in northern South America, and we find evidence that they had a comparatively large effective population size. We also show that the native components in some modern Caribbean genomes are closely related to the ancient Taino, suggesting that indigenous ancestry in the region has survived through the present day. The Caribbean was one of the last parts of the Americas to be settled by humans, but how and when the islands were first occupied remains a matter of debate. Ancient DNA can help answering these questions, but the work has been hampered by poor DNA preservation. We report the genome sequence of a 1,000-year-old Lucayan Taino individual recovered from the site of Preacher’s Cave in the Bahamas. We sequenced her genome to 12.4-fold coverage and show that she is genetically most closely related to present-day Arawakan speakers from northern South America, suggesting that the ancestors of the Lucayans originated there. Further, we find no evidence for recent inbreeding or isolation in the ancient genome, suggesting that the Lucayans had a relatively large effective population size. Finally, we show that the native American components in some present-day Caribbean genomes are closely related to the ancient Taino, demonstrating an element of continuity between precontact populations and present-day Latino populations in the Caribbean.
Modification of wheat gluten for improvement of binding capacity with keratin in hair

In this study, enzymatic hydrolysis and cationization with epoxypropyldodecyldimethylammonium chloride of wheat protein, an economic protein complex containing great amount of disulfide bonds, were conducted to improve properties such as solubility and disassociation behaviour for recovery of damaged hair when used in shampoo. The optimal conditions for enzymatic hydrolysis were pH 8.2, 55°C with Alcalase for 60 min. After the selected hydrolysis, the degree of hydrolysis, nitrogen solubility index, foaming capacity index, foam stability index, emulsifying activity index and emulsion stability index of hydrolysate with 58.71% of short-chain peptides (less than 1000 Da) were 8.81%, 39.07%, 225%, 56.67%, 9.62 m2 g−1 and 49.08, respectively. The cationization was followed to raise the isoelectric point of wheat protein hydrolysate from 7.0 to 10.0, which could facilitate the quaternized protein hydrolysate to adhere to the surface of hair at the range of pH 5–6 of hair care products to form more disulfide bonds. The results show that a shampoo with quaternized wheat proteins hydrolysate possesses excellent properties in recovering damaged hair, making the surface of hair smooth and compact.
Factors Affecting Physicians’ Intentions to Communicate Personalized Prognostic Information to Cancer Patients at the End of Life

Purpose. To explore the effects of personalized prognostic information on physicians’ intentions to communicate prognosis to cancer patients at the end of life, and to identify factors that moderate these effects. Methods. A factorial experiment was conducted in which 93 family medicine physicians were presented with a hypothetical vignette depicting an end-stage gastric cancer patient seeking prognostic information. Physicians’ intentions to communicate prognosis were assessed before and after provision of personalized prognostic information, while emotional distress of the patient and ambiguity (imprecision) of the prognostic estimate were varied between subjects. General linear models were used to test the effects of personalized prognostic information, patient distress, and ambiguity on prognostic communication intentions, and potential moderating effects of 1) perceived patient distress, 2) perceived credibility of prognostic models, 3) physician numeracy (objective and subjective), and 4) physician aversion to risk and ambiguity. Results. Provision of personalized prognostic information increased prognostic communication intentions (P < 0.001, η2 = 0.38), although experimentally manipulated patient distress and prognostic ambiguity had no effects. Greater change in communication intentions was positively associated with higher perceived credibility of prognostic models (P = 0.007, η2 = 0.10), higher objective numeracy (P = 0.01, η2 = 0.09), female sex (P = 0.01, η2 = 0.08), and lower perceived patient distress (P = 0.02, η2 = 0.07). Intentions to communicate available personalized prognostic information were positively associated with higher perceived credibility of prognostic models (P = 0.02, η2 = 0.09), higher subjective numeracy (P = 0.02, η2 = 0.08), and lower ambiguity aversion (P = 0.06, η2 = 0.04). Conclusions. Provision of personalized prognostic information increases physicians’ prognostic communication intentions to a hypothetical end-stage cancer patient, and situational and physician characteristics moderate this effect. More research is needed to confirm these findings and elucidate the determinants of prognostic communication at the end of life.
College students’ experiences of hedonia and eudaimonia in their everyday activities

Background. Experiences of hedonia (i.e., seeking pleasure) and eudaimonia (i.e., actualizing human potential in pursuit of meaningful goals) are central to the study of human well-being. Purpose. This study sought to examine levels of hedonia (pleasure) and eudaimonia (productivity) in a convenience sample of college (university) students’ (n = 264) daily activities, controlling for levels of perceived stress. Method. Data were gathered using a 24-hr time-use recall diary designed to assess objective and subjective information about everyday activities. Descriptions of self-reported everyday activities were coded into 20 activity types. Findings. Activities reported high in pleasure were eating, listening to music/watching movies, and exercise. Activities reported as high in productivity were studying and working. Activities reported as high in both pleasure and productivity were reported less frequently and often had a recognizable outcome or provided social connection. Implications. Developing a greater understanding of how college students experience their daily activities could strengthen programs designed to enable students to manage stress and sustain their well-being.
Multidisciplinary perspectives on banana (Musa spp.) domestication

Original multidisciplinary research hereby clarifies the complex geodomestication pathways that generated the vast range of banana cultivars (cvs). Genetic analyses identify the wild ancestors of modern-day cvs and elucidate several key stages of domestication for different cv groups. Archaeology and linguistics shed light on the historical roles of people in the movement and cultivation of bananas from New Guinea to West Africa during the Holocene. The historical reconstruction of domestication processes is essential for breeding programs seeking to diversify and improve banana cvs for the future.
The Use of Size Exclusion Chromatography to Monitor Protein Self-Assembly

High resolution size exclusion chromatography (SEC) coupled with static light scattering (SLS) analyses were conducted to study the effect of the mobile phase ionic strength and protein concentration on the output of SEC experiments. The results highlight the effect of small changes in the mobile phase composition on the estimation of molar masses estimated from retention time-based calibration curve compared with those obtained from SLS analysis. By comparing the SLS data with the SEC chromatograms, we show that SEC can provide helpful information on the protein aggregation state as macromolecules approach known precipitation points in their phase diagrams. This suggests the potential use of SEC as an easily accessible lab-based scanning methodology to monitor protein self-assembly prior to nucleation and crystallization. Implications for the use of SEC to study protein phase diagrams are discussed.
Treatment timing for functional jaw orthopaedics followed by fixed appliances: a controlled long-term study

Objective To evaluate the role of treatment timing on long-term dentoskeletal effects of Class II treatment with removable functional appliances followed by full-fixed appliance therapy. Materials and methods A group of 46 patients (23 females and 23 males) with Class II malocclusion treated consecutively with either Bionator or Activator, followed by fixed appliances was compared with a matched control group of 31 subjects (16 females and 15 males) with untreated Class II malocclusion. The treated sample was evaluated at T1, start of treatment (mean age: 9.9 ± 1.3 years); T2, end of functional treatment and prior to fixed appliances (mean age: 11.9 ± 1.3 years); and T3, long-term observation (mean age: 18.3 ± 2.1 years). The treated and the control samples were divided into pre-pubertal and pubertal groups according to skeletal maturity observed at the start of treatment. Statistical comparisons were performed with independent sample t-tests. Results When treatment was initiated before puberty, Class II correction was mostly confined to the dentoalveolar changes, with significant improvements of both overjet and molar relationships. On the other hand, treatment with the outset at puberty produced significant long-term improvement of sagittal skeletal relationships, which were mainly sustained by mandibular changes. Conclusions Treatment with removable functional appliances (Bionator or Activator) followed by full-fixed appliances produced significant skeletal long-term changes when it begins at puberty. Prepubertal Class II treatment results primarily in dentoalveolar changes.
Synthesizing Neural Network Controllers with Probabilistic Model-Based Reinforcement Learning

Ahstract- We present an algorithm for rapidly learning neural network policies for robotics systems. The algorithm follows the model-based reinforcement learning paradigm and improves upon existing algorithms: PILeO and a sample-based version of PILeo with neural network dynamics (Deep-PILeO). To improve convergence, we propose a model-based algorithm that uses fixed random numbers and clips gradients during optimization. We propose training a neural network dynamics model using variational dropout with truncated Log-Normal noise. These improvements enable data-efficient synthesis of complex neural network policies. We test our approach on a variety of benchmark tasks, demonstrating data-efficiency that is competitive with that of PILeO, while being able to optimize complex neural network controllers. Finally, we assess the performance of the algorithm for learning motor controllers for a six legged autonomous underwater vehicle. This demonstrates the potential of the algorithm for scaling up the dimensionality and dataset sizes, in more complex tasks.
Digitizing Medicines for Remote Capture of Oral Medication Adherence Using Co‐encapsulation

High‐resolution measurement of medication adherence is essential to personalized drug therapy. A US Food and Drug Administration (FDA)‐cleared device, using an edible ingestion sensor (IS), external wearable patch, and paired mobile device can detect and record ingestion events. Oral medications must be combined with an IS to generate precise “digitized‐medication” ingestion records. We developed a Good Manufacturing Practice protocol to repackage oral medications with the IS within certified Capsugel capsules, termed co‐encapsulation (CoE). A randomized bioequivalence study of CoE‐IS‐Rifamate (Isoniazid/Rifampin 150/300 mg) vs. native‐Rifamate was conducted in 12 patients with active Mycobacterium tuberculosis and demonstrated bioequivalence using the population method ratio test (95% confidence interval). Subsequently, CoE‐IS‐medications across all biopharmaceutical classes underwent in vitro dissolution testing utilizing USP and FDA guidelines. CoE‐IS medications tested met USP dissolution specifications and were equivalent to their native formulations. CoE combines oral medications with the IS without altering the quality of the native formulation, generating “digitized” medications for remote capture of dosing histories.
Characterization of human fetal brain endothelial cells reveals barrier properties suitable for in vitro modeling of the BBB with syngenic co-cultures

Endothelial cells (ECs) form the basis of the blood–brain barrier (BBB), a physical barrier that selectively restricts transport into the brain. In vitro models can provide significant insight into BBB physiology, mechanisms of human disease pathology, toxicology, and drug delivery. Given the limited availability of primary human adult brain microvascular ECs (aBMVECs), human fetal tissue offers a plausible alternative source for multiple donors and the opportunity to build syngenic tri-cultures from the same host. Previous efforts to culture fetal brain microvascular ECs (fBMVECs) have not been successful in establishing mature barrier properties. Using optimal gestational age for isolation and flow cytometry cell sorting, we show for the first time that fBMVECs demonstrate mature barrier properties. fBMVECs exhibited similar functional phenotypes when compared to aBMVECs for barrier integrity, endothelial activation, and gene/protein expression of tight junction proteins and transporters. Importantly, we show that tissue used to culture fBMVECs can also be used to generate a syngenic co-culture, creating a microfluidic BBB on a chip. The findings presented provide a means to overcome previous challenges that limited successful barrier formation by fBMVECs. Furthermore, the source is advantageous for autologous reconstitution of the neurovascular unit for next generation in vitro BBB modeling.
Deficiency in T follicular regulatory cells promotes autoimmunity

T follicular regulatory (Tfr) cells are a new subset of regulatory T (T reg) cells localized in the germinal center to limit the humoral response. Until now, the physiological function of Tfr cells has been largely unknown. In this study, we developed a Bcl6fl/flFoxp3Cre mouse to analyze the function of Tfr cells in immune and autoimmune responses. These mice exhibited enhanced immunity to influenza virus; moreover, Bcl6fl/flFoxp3Cre/Cre mice developed late-onset spontaneous autoimmune diseases, affecting the salivary glands with lymphocyte infiltration and antibody deposition. In a mouse experimental Sjögren’s syndrome model, ablation of Bcl6 in T reg cells greatly enhanced disease development. Conversely, Bcl6fl/flCd4Cre mice were protected in the model. Thus, our study indicates that Tfr cells control autoimmune diseases and can be targeted in infectious and autoimmune disease.
Assessing the effects of gami fi cation in the classroom : A longitudinal study on intrinsic motivation , social comparison , satisfaction , effort , and academic performance

Gamification, the application of game elements to non-game settings, continues to grow in popularity as a method to increase student engagement in the classroom. We tested students across two courses, measuring their motivation, social comparison, effort, satisfaction, learner empowerment, and academic performance at four points during a 16-week semester. One course received a gamified curriculum, featuring a leaderboard and badges, whereas the other course received the same curriculum without the gamified elements. Our results found that students in the gamified course showed less motivation, satisfaction, and empowerment over time than those in the non-gamified class. The effect of course type on students' final exam scores was mediated by students' levels of intrinsic motivation, with students in the gamified course showing less motivation and lower final exam scores than the non-gamified class. This suggests that some care should be taken when applying certain gamification mechanics to educational settings. © 2014 Elsevier Ltd. All rights reserved.