Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroprotection Against Parkinson’s Disease Through the Activation of Akt/GSK3β Signaling Pathway by Tovophyllin A

Parkinson’s disease (PD) is one of the most prevalent and life-threatening neurodegenerative disease and mainly characterized by lack of sufficient dopaminergic neurons in the substantia nigra pars compacta (SNc). Although current treatments help to alleviate clinical symptoms, effective therapies preventing neuronal loss remain scarce. Tovophyllin A (TA), one of the xanthones extracted from Garcinia mangostana L. (GM), has recently been reported to play a beneficial role in the therapy of neurodegenerative diseases. In our research, we explored whether TA has protective effects on dopaminergic neurons in PD models. We found that TA significantly reduced apoptotic cell death in primary cortical neurons treated with 1-methyl-4-phenyl pyridinium (MPP+) or paraquat (PQ) in the in vitro PD model. In an in vivo acute PD model induced by 1-methyl4-phenyl-1,2,3,5-tetrahydropyridine (MPTP) treatment, TA also attenuated the resulting behavioral dysfunctions and dopaminergic neuron loss. In the collected brain tissues, TA increased the phosphorylation of Akt and GSK-3β, which may be related to TA-mediated dopaminergic neuronal protective effects. In summary, our results illustrated that TA is a powerful cytoprotective agent for dopaminergic neurons in the MPTP-induced PD model, suggesting TA as a possible therapeutic candidate for PD.
Adaptive Foraging in Dynamic Environments Using Scale-Free Interaction Networks

Group interactions are widely observed in nature to optimize a set of critical collective behaviors, most notably sensing and decision making in uncertain environments. Nevertheless, these interactions are commonly modeled using local (proximity) networks, in which individuals interact within a certain spatial range. Recently, other interaction topologies have been revealed to support the emergence of higher levels of scalability and rapid information exchange. One prominent example is scale-free networks. In this study, we aim to examine the impact of scale-free communication when implemented for a swarm foraging task in dynamic environments. We model dynamic (uncertain) environments in terms of changes in food density and analyze the collective response of a simulated swarm with communication topology given by either proximity or scale-free networks. Our results suggest that scale-free networks accelerate the process of building up a rapid collective response to cope with the environment changes. However, this comes at the cost of lower coherence of the collective decision. Moreover, our findings suggest that the use of scale-free networks can improve swarm performance due to two side-effects introduced by using long-range interactions and frequent network regeneration. The former is a topological consequence, while the latter is a necessity due to robot motion. These two effects lead to reduced spatial correlations of a robot's behavior with its neighborhood and to an enhanced opinion mixing, i.e., more diversified information sampling. These insights were obtained by comparing the swarm performance in presence of scale-free networks to scenarios with alternative network topologies, and proximity networks with and without packet loss.
Neurovascular Inflammaging in Health and Disease

Aging is characterized by a chronic low-grade sterile inflammation dubbed as inflammaging, which in part originates from accumulating cellular debris. These, acting as danger signals with many intrinsic factors such as cytokines, are sensed by a network of pattern recognition receptors and other cognate receptors, leading to the activation of inflammasomes. Due to the inflammasome activity-dependent increase in the levels of pro-inflammatory interleukins (IL-1β, IL-18), inflammation is initiated, resulting in tissue injury in various organs, the brain and the spinal cord included. Similarly, in age-related diseases of the central nervous system (CNS), inflammasome activation is a prominent moment, in which cells of the neurovascular unit occupy a significant position. In this review, we discuss the inflammatory changes in normal aging and summarize the current knowledge on the role of inflammasomes and contributing mechanisms in common CNS diseases, namely Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and stroke, all of which occur more frequently with aging.
Design principles for matrix adaptation evolution strategies

Permission to make digital or hard copies of part or all of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for third-party components of this work must be honored. For all other uses, contact the Owner/Author(s). GECCO ’20 Companion, Cancun, Mexico c © 2020 Copyright is held by the owner/author(s). ACM ISBN 978-1-4503-7127-8/20/07. $15.00. doi:10.1145/3377929.3389870 Instructor
Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update

The successful maternal tolerance of the semi-allogeneic fetus provides an apparent immunologic paradox. Indeed, deep invasion of placental trophoblast cells into maternal uterine tissue and the following growth of the fetus have to be tolerated by a pregnant woman’s immune system. Among the various possible protective mechanisms that may be involved in human pregnancy, the expression of a non-classical pattern of human leukocyte antigen (HLA) class I molecules and the complete lack of expression of HLA class II molecules in placental tissues seem to be the most relevant mechanisms of fetal escape from maternal immune recognition. The importance of HLA molecules in fetal toleration by the maternal immune system is highlighted by pregnancy complications occurring in cases of abnormal HLA molecule expression at the maternal–fetal interface. In this review, we summarize evidences about the role of placental HLA molecules in normal and pathological pregnancies.
Improvement of Attention in Elementary School Students through Fixation Focus Training Activity

The attentional problems of school children are a crucial topic due to abundant information in this digital era. There are five attention dimensions for children: focused attention, sustained attention, selective attention, alternating attention, and divided attention. Focused training is a traditional method of improving attention ability. Subjects are required to focus on a fixed point for an extensive period without blinking and to perceive small objects as large. This study investigates which types of attention indicators are influenced by focus training. Eighty-two grade five and six elementary school students (45 experiment group, 37 control group) were involved. The experiment group underwent focus training for 12 weeks. The training was conducted once per week, and the Attention Scales for Elementary School Children were used before and after the training to examine the children’s attention. The percentile rank scores of five attention dimensions and the total attention scale were evaluated. The results gave difference data, defined as post-test results minus the pretest results, where significant differences occurred for the total scale (p < 0.05), focused attention (p < 0.05), and selective attention (p < 0.01). Participants also noted that the training helped them improve concentration during school lessons (54.15%), fall asleep (29.1%), and relax the body (8.4%).
Monodominance in an African Rain Forest: Is Reduced Herbivory Important? 1

Tropical monodominant forests in which one tree species dominates the canopy occur in all three major tropical regions, but few studies have focused on the mechanisms responsible for dominance. This study tests the hypothesis that relative to other species in the community, dominant species are well defended and escape herbivore and pathogen damage. We surveyed the rate of damage on young expanding leaves of seedlings and saplings belonging to eight species within both monodominant Gilbertiodendron dewevrei forests and adjacent mixed–species forests in eastern Congo. Results showed that escape from herbivore and pathogen damage is not a mechanism by which Gilbertiodendron achieves dominance, as it suffered the highest damage level of any species surveyed. Similarly, other sub–dominant common species also suffered high rates of damage. These results are discussed in relation to the phenolic, fiber, and nitrogen content of leaves, and in the context of current theories pertaining to plant–herbivore interactions.
Editorial

Language, culture and communication – these three elements constitute the virtuous trinity upon which these pages are founded: language – a palette of semiotic symbols from which we select (paradigmatically) and generate (syntagmatically) in order to both position ourselves and be positioned; culture – sets of commonality realised through symbols, artefacts, behaviours and attitudes; communication – the manifold ways in which humans convey meanings to each other developed over millennia from basic sounds and gestures in the primordial forest, via hieroglyphics etched on papyral sheets, to multi-modal texts beamed across the world. At the centre of this triangle – so the story goes (Kuhn, 1970) – lies the phenomenon of identity. And it seems to us that in different ways, different facets of identity again underlie the six papers featured in this final issue of volume 13. Identity has informed many memorable papers published in these pages over the past 13 years. However, the concept has also come to saturate the social sciences since the ‘cultural turn’ some 40 years ago, and has given rise to such a multiplicity of meanings that sometimes one can be sceptical about the work that the concept is still capable of doing. Recently, we have been introduced to an article by Brubaker and Cooper (2000) thus far overlooked by us, which we think is helpful to pin down the notion of identity a little more firmly. In it, the authors not only articulate their doubts about the value of the concept, but also suggest a number of ways in which the idea of identity can be developed. They address the problematic rather sternly:
Percutaneous microwave ablation of renal cell carcinoma: practice guidelines of the ultrasound committee of Chinese medical association, interventional oncology committee of Chinese research hospital association

Abstract Imaging-guided percutaneous microwave ablation (MWA) with high thermal efficiency comprises rapid, successful management of small renal cell carcinomas (RCCs) in selected patients. Ultrasound Committee of Chinese Medical Association, Interventional Oncology Committee of Chinese Research Hospital Association developed evidence-based guidelines for MWA of RCCs after systematically reviewing the 1969–2019 literature. Systematic reviews, meta-analyses, randomized controlled trials, cohort, and case–control studies reporting MWA of RCCs were included and levels of evidence assessed. Altogether, 146 articles were identified, of which 35 reported percutaneous MWA for T1a RCCs and 5 articles for T1b RCCs. Guidelines were established based on indications, techniques, safety, and effectiveness of MWA for RCCs, with the goal of standardizing imaging-guided percutaneous MWA treatment of RCCs. Key points Microwave ablation is recommended for managing small renal cell carcinoma in selected patients. Imaging protocols are tailored based on the procedural plan, guidance, and evaluation. Patient’s selection evaluation, updated technique information, clinical efficacy, and complications are recommended to standardize management. A joint task force (multidisciplinary team) summarized the key elements of the standardized report.
Monopolar Spindle 1 Kinase (MPS1/TTK) mRNA Expression is Associated with Earlier Development of Clinical Symptoms, Tumor Aggressiveness and Survival of Glioma Patients

Inhibition of the protein kinase MPS1, a mitotic spindle-checkpoint regulator, reinforces the effects of multiple therapies against glioblastoma multiforme (GBM) in experimental settings. We analyzed MPS1 mRNA-expression in gliomas WHO grade II, III and in clinical subgroups of GBM. Data were obtained by qPCR analysis of tumor and healthy brain specimens and correlated with the patients’ clinical data. MPS1 was overexpressed in all gliomas on an mRNA level (ANOVA, p < 0.01) and correlated with tumor aggressiveness. We explain previously published conflicting results on survival: high MPS1 was associated with poorer long term survival when all gliomas were analyzed combined in one group (Cox regression: t < 24 months, p = 0.009, Hazard ratio: 8.0, 95% CI: 1.7–38.4), with poorer survival solely in low-grade gliomas (LogRank: p = 0.02, Cox regression: p = 0.06, Hazard-Ratio: 8.0, 95% CI: 0.9–66.7), but not in GBM (LogRank: p > 0.05). This might be due to their lower tumor volume at the therapy start. GBM patients with high MPS1 mRNA-expression developed clinical symptoms at an earlier stage. This, however, did not benefit their overall survival, most likely due to the more aggressive tumor growth. Since MPS1 mRNA-expression in gliomas was enhanced with increasing tumor aggressiveness, patients with the worst outcome might benefit best from a treatment directed against MPS1.
Efficacy of a Novel Ophthalmic Antimicrobial Drug Combination Toward a Large Panel of Staphylococcus aureus Clinical Ocular Isolates From Around the World.

PURPOSE Staphylococcus aureus is a leading cause of keratitis requiring urgent antimicrobial treatment. However, rising antibiotic resistance has rendered current ophthalmic antibiotics increasingly ineffective. First, a diverse, ocular S. aureus strain set was evaluated for resistance to 6 commonly used ophthalmic antibiotics. Next, a recently discovered antimicrobial drug combination containing polymyxin B/trimethoprim (PT) + rifampin that displayed impressive efficacy toward S. aureus in both in vitro and in vivo studies was evaluated as a potential novel keratitis therapeutic through testing this combination's efficacy against the clinical strain set. METHODS A total of 163 S. aureus isolates were collected either commercially or from the Flaum Eye Institute, University of Rochester. The minimum inhibitory concentrations of moxifloxacin, levofloxacin, vancomycin, erythromycin, tobramycin, rifampin, and PT were determined for the entire strain set to establish the incidence of resistance to current treatment options among a contemporary clinical isolate set and compared with the performance of PT + rifampin. RESULTS Among all 163 isolates tested, high rates of antibiotic resistance were found toward erythromycin (69% resistance), moxifloxacin (33%), levofloxacin (40%), and tobramycin (17%). Conversely, the entire strain set, including multidrug resistant isolates, was sensitive to PT + rifampin, demonstrating the potency of this combination. CONCLUSIONS We established that antibiotic resistance is pervasive among clinical S. aureus isolates, underscoring the concern for the effectiveness of current ophthalmic antibiotics. The drug combination of PT + rifampin, however, eradicated 100% of isolates tested, demonstrating the ability to overcome existing circulating resistance factors, and as such, might represent a promising therapeutic for S. aureus keratitis.
Training the anxious brain: using fMRI‐based neurofeedback to change brain activity in adolescence

Anxiety disorders are a leading cause of morbidity and entail a lot of costs. Adolescence is characterized by social fears and poor emotion regulation abilities which together increase the likelihood of the emergence of anxiety disorders. This emotion dysregulation is potentially caused by the emotion regulating brain areas, such as the prefrontal cortex and temporal cortex, that are still undergoing developmental changes throughout late adolescence. Recently, new approaches have used functional magnetic resonance imaging‐based neurofeedback to help participants gain control over emotion regulation brain networks by receiving real‐time feedback on their brain activity and to use effective emotion regulation abilities. In this review, we provide an overview of the developmental changes in the brain and the corresponding behavioural changes, and explore how these can be influenced during adolescence using neurofeedback. We conclude that recent studies show promising results that children and adolescents can self‐regulate emotion regulation brain networks thereby supporting the development of effective emotion regulation abilities.
Effectiveness of prothrombin complex concentrate for the treatment of bleeding: A systematic review and meta‐analysis

Prothrombin complex concentrate (PCC) is increasingly being used as a treatment for major bleeding in patients who are not taking anticoagulants. The aim of this systematic review and meta‐analysis is to evaluate the effectiveness of PCC administration for the treatment of bleeding in patients not taking anticoagulants. Studies investigating the effectivity of PCC to treat bleeding in adult patients and providing data on either mortality or blood loss were eligible. Data were pooled using Mantel‐Haenszel random effects meta‐analysis or inverse variance random effects meta‐analysis. From 4668 identified studies, 17 observational studies were included. In all patient groups combined, PCC administration was not associated with mortality (odds ratio = 0.83; 95% confidence interval [CI], 0.66‐1.06; P = .13; I2 = 0%). However, in trauma patients, PCC administration, in addition to fresh frozen plasma, was associated with reduced mortality (odds ratio = 0.64; CI, 0.46‐0.88; P = .007; I2 = 0%). PCC administration was associated with a reduction in blood loss in cardiac surgery patients (mean difference: −384; CI, −640 to −128, P = .003, I2 = 81%) and a decreased need for red blood cell transfusions when compared with standard care across a wide range of bleeding patients not taking anticoagulants (mean difference: −1.80; CI, −3.22 to −0.38; P = .01; I2 = 92%). In conclusion, PCC administration was not associated with reduced mortality in the whole cohort but did reduce mortality in trauma patients. In bleeding patients, PCC reduced the need for red blood cell transfusions when compared with treatment strategies not involving PCC. In bleeding cardiac surgery patients, PCC administration reduced blood loss.
Pathways to gender affirmation in trans youth: A qualitative and participative study with youth and their parents

How trans youth realize about their gender identity and come out to their significant others is under-researched and very few studies include both youth and parental perspectives. This study was developed in Switzerland, a country where families with trans youth are just beginning to break invisibility. The research protocol draws on grounded theory methodology, is participative and developed in collaboration with a local trans NGO and a pan Canadian project. We conducted 20 semi-structured interviews with 10 trans youth and their caregivers/parents (10 interview). At least three developmental pathways seem to emerge: a) the affirmed children who affirm themselves very early, (b) the silent children who spend their childhood in a state of internal tension without being able to position themselves and (c) the neutral children who become aware of their gender difference at puberty following a childhood in which gender was not problematic. In all cases puberty is a crossroads, lived painfully with significant manifestations of both social and body dysphoria. A better understanding of the process of gender development in trans children and youth will help improve our interventions to better serve young people and their families, and help them overcome the different levels of oppressions they face.
Direct Oral to Parenteral Anticoagulants: Strategies for Inpatient Transition

The primary objective of this study was to describe the impact on bleeding rates of 2 different strategies for transitioning from a direct oral anticoagulant (DOAC) to a parenteral anticoagulant: a delayed, clinically driven strategy versus the standard per‐package‐insert strategy. This was a single‐center descriptive cohort study conducted at a large academic medical center. Included patients were 18 years or older, admitted as an inpatient, and had received at least 1 dose of a DOAC prior to initiation of therapeutic parenteral anticoagulation. The primary end point was the incidence of major bleeds on the transition from a DOAC to a parenteral anticoagulant via a standard versus an intentionally delayed strategy. The secondary outcomes evaluated renal function, reason for delay, DOAC anti–factor Xa concentration, international normalized ratio values, blood product administration, and thrombotic complications. A total of 300 patients were included. The primary end point of bleeding was higher in the delayed group than the standard group, 25% and 12%, respectively (odds ratio, 0.39; P < .05). In both groups, patients who bled had a higher severity of illness, a greater incidence of acute kidney injury, and, when available, higher median DOAC anti–factor Xa concentrations. Despite a more conservative approach, patients in the delayed group experienced more bleeding, most likely attributable to a higher severity of illness, which highlights emerging challenges of inpatient anticoagulation management. Further prospective studies analyzing DOAC pharmacodynamics and pharmacokinetics in acutely ill patients are warranted.
Examining Uncertainty in in Vitro-in Vivo Extrapolation Applied in Fish Bioconcentration Models.

In vitro biotransformation rates were determined for 30 chemicals, mostly fragrance ingredients, using trout liver S9 fractions (RT-S9) and incorporated into in vitro-in vivo extrapolation (IVIVE) models to predict bioconcentration factors (BCFs). Predicted BCFs were compared against empirical BCFs to explore potential major uncertainties involved in the in vitro methods and IVIVE models: (i) in vitro chemical test concentrations; (ii) different gill uptake rate constant calculations (k1); (iii) protein binding (different calculations and measurement of the fraction of unbound chemical, fU); (iv) species differences, and (v) extrahepatic biotransformation. Predicted BCFs were within 0.5 log units for 44 % of the chemicals compared to empirical BCFs, whereas 56 % were overpredicted by >0.5 log units. This trend of overprediction was reduced by alternative k1 calculations to 32 % of chemicals being overpredicted. Moreover, hepatic in vitro rates scaled to whole body biotransformation rates (kB) were compared against in vivo kB estimates. In vivo kB was underestimated for 79 % of the chemicals. Neither lowering the test concentration, nor incorporation of new measured fU values, nor species matching avoided the tendency to overpredict BCFs indicating that further improvements to the IVIVE models are needed or extrahepatic biotransformation plays an underestimated role.
Reply: Exosomes are Comparable to Source Adipose Stem Cells in Fat Graft Retention with Up-regulating Early Inflammation and Angiogenesis.

injected under the mouse skin. Why did they use 40 μg of exosomes? Were 40 μg of adipose-derived stem cell–derived exosomes comparable to 1 × 104 adiposederived stem cells? If the doses are not comparable, should the conclusion be different? Besides, at the second and third injections, the exosome groups were injected with adipose-derived stem cell–derived exosomes, whereas cell-assisted lipotransfer groups were injected with phosphate-buffered saline. Why were cellassisted lipotransfer groups not injected with adiposederived stem cells? In conclusion, the authors presented an excellent study regarding the effects of exosomes, which may have great therapeutic potential in tissue repair and regenerative medicine. We expect further studies to provide more information. DOI: 10.1097/PRS.0000000000007201