Miracle-dz/UniFAR-FTUs huggingface dataset:
Antioxidant and developmental capacity of retinol on the in vitro culture of rabbit embryos

Summary Oxidative stress is a major cause of defective embryo development during in vitro culture. Retinoids are recognized as non-enzymatic antioxidants and may have an important role in the regulation of cell differentiation and vertebrate development. However, there are not enough reports discussing the antioxidant and developmental capacity of retinoids, including retinol (RT), on the in vitro development of embryos recovered from livestock animals, particularly in rabbit species. Therefore, morula embryos obtained from nulliparous Red Baladi rabbit does were cultured for 48 h in TCM199 medium in the absence of RT (control group) or in the presence of RT at concentrations of 10, 100 and 1000 nM. The developmental capacity to the hatched blastocyst stage, the antioxidant biomarker assay and the expression of several selected genes were analyzed in each RT group. The data show that RT significantly (P<0.001) promoted the embryo hatchability rate at the concentration of 1000 nM to 69.44% versus 29.71% for the control. The activity of malondialdehyde (MDA) level was significantly (P<0.05) lower in the RT groups than in the control group, while the total antioxidant capacity (TAC), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were significantly (P<0.05) higher following treatment with RT. Furthermore, RT treatment considerably upregulated the relative expression of gap junction protein alpha 1 (GJA1), POU class 5 homeobox 1 (POU5F1) and superoxide dismutase 1 (SOD1) genes compared with the control group. The current study highlights the potential effects of RT as antioxidant in the culture medium on the in vitro development of rabbit embryos.
Weisfeiler and Leman Go Neural: Higher-order Graph Neural Networks

In recent years, graph neural networks (GNNs) have emerged as a powerful neural architecture to learn vector representations of nodes and graphs in a supervised, end-to-end fashion. Up to now, GNNs have only been evaluated empirically—showing promising results. The following work investigates GNNs from a theoretical point of view and relates them to the 1-dimensional Weisfeiler-Leman graph isomorphism heuristic (1-WL). We show that GNNs have the same expressiveness as the 1-WL in terms of distinguishing non-isomorphic (sub-)graphs. Hence, both algorithms also have the same shortcomings. Based on this, we propose a generalization of GNNs, so-called k-dimensional GNNs (k-GNNs), which can take higher-order graph structures at multiple scales into account. These higher-order structures play an essential role in the characterization of social networks and molecule graphs. Our experimental evaluation confirms our theoretical findings as well as confirms that higher-order information is useful in the task of graph classification and regression.
Performance evaluation of the GastroPlusTM software tool for prediction of the toxicokinetic parameters of chemicals

ABSTRACT The accurate prediction of toxicokinetic parameters arising from oral, dermal and inhalation routes of chemical exposure is a key element in chemical safety assessments. In this research, the physiologically based pharmacokinetic (PBPK) GastroPlusTM software was evaluated against a series of chemicals for the prediction of toxicokinetic parameters. Overall, 67% of predicted intrinsic clearance (Clint) values were within 1- to 10-fold of empirical data for 463 compounds, and 87% of the predicted fraction unbounded in plasma (Fup) values were 1- to 3-fold of empirical data for 441 compounds. The r2 (coefficient of determination) of predicted Cmax (maximum plasma concentration) and AUC (Area Under Curve) values versus the corresponding empirical values from oral, inhalation and dermal exposures ranged from 0.04 to 0.92. Among the three exposures, the highest r2 values, ranging from 0.80 to 0.92, were observed for oral exposure predictions, where 88% of the compounds had 1- to 10-fold differences between predicted and empirical values for Cmax and AUC. The predicted plasma Css (steady-state plasma concentration) values were consistent with those Css values calculated by in vitro-to-in vivo extrapolation (IVIVE) approaches using experimental parameters. Based on the evaluation results, GastroPlus™ can be used as a QSAR/PBPK tool for toxicokinetic parameter predictions.
Memristor-based Deep Convolution Neural Network: A Case Study

In this paper, we firstly introduce a method to efficiently implement large-scale high-dimensional convolution with realistic memristor-based circuit components. An experiment verified simulator is adapted for accurate prediction of analog crossbar behavior. An improved conversion algorithm is developed to convert convolution kernels to memristor-based circuits, which minimizes the error with consideration of the data and kernel patterns in CNNs. With circuit simulation for all convolution layers in ResNet-20, we found that 8-bit ADC/DAC is necessary to preserve software level classification accuracy.
Combination immune checkpoint blockade as an effective therapy for mesothelioma

ABSTRACT Mesothelioma is an aggressive asbestos induced cancer with extremely poor prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has demonstrated effective therapy in melanoma and is now being applied to other cancers, including mesothelioma. However, the efficacy of ICPB and which immune checkpoint combinations constitute the best therapeutic option for mesothelioma have yet to be fully elucidated. Here, we used our well characterised mesothelioma tumour model to investigate the efficacy of different ICBP treatments to generate effective therapy for mesothelioma. We show that tumour resident regulatory T cell co-express high levels of CTLA-4, OX40 and GITR relative to T effector subsets and that these receptors are co-expressed on a large proportion of cells. Targeting any of CTLA-4, OX40 or GITR individually generated effective responses against mesothelioma. Furthermore, the combination of αCTLA-4 and αOX40 was synergistic, with an increase in complete tumour regressions from 20% to 80%. Other combinations did not synergise to enhance treatment outcomes. Finally, an early pattern in T cell response was predictive of response, with activation status and ICP receptor expression profile of T effector cells harvested from tumour and dLN correlating with response to immunotherapy. Taken together, these data demonstrate that combination ICPB can work synergistically to induce strong, durable immunity against mesothelioma in an animal model.
Health Technology Optimization Analysis: Conceptual Approach and Illustrative Application

We present a conceptual approach to determine the optimal solution to delivering a health technology, consistent with the objective of maximizing patient outcomes subject to resources available to a publicly funded health system. The article addresses two key policy questions: 1) adding system values through appropriate planning of health services delivery and 2) considering the tradeoff between patient outcomes and costs to the health system through appropriate use of health technologies for conditions with time-dependent treatment outcomes. We develop a health technology optimization framework that considers geographical variation and searches for the best delivery method through a pairwise comparison of all possible strategies, factoring in controlled variables including disease epidemiology, time or distance to hospitals, available medical services, treatment eligibility, treatment efficacy, and costs. Taking variations of these factors into account would help support a more efficient allocation of health resources. Drawing identified strategies together then creates a map of optimal strategies. We apply the proposed method to a policy-relevant health technology assessment of endovascular therapy (EVT) for treating acute ischemic stroke. The best strategy for providing EVT relies on the geographical location of stroke onset and the decision maker’s preference for either patient outcomes or economic efficiency. The proposed method produced an optimization map showing the optimal strategy for EVT delivery, which maximizes patient outcomes while minimizing health system costs. In the illustrative case study, there were no tradeoffs between health outcomes and costs, meaning that the delivery strategies that were clinically optimal for patients were also the most cost-effective. In conclusion, the health technology optimization approach is a useful tool for informing implementation decisions and coordinating the delivery of complex health services such as EVT.
Essais précliniques sur un vaccin contre la fièvre de Lassa

Le virus Lassa constitue une menace persistante pour la santé à l’échelle mondiale et est responsable d’environ un demi-million de cas de fièvre de Lassa chaque année en Afrique occidentale. Bien que la plupart des cas soient légers, la maladie entraîne une morbidité importante et jusqu’à 5 000 décès par année. Depuis 2015, le Nigéria est aux prises avec une éclosion grave et étendue de fièvre de Lassa, ce qui laisse craindre un débordement dans d’autres pays atteignant l’ampleur de l’éclosion du virus Ébola en Afrique occidentale de 2013 à 2016. Malgré le fardeau qu’impose la fièvre de Lassa en matière de santé publique, tant en Afrique qu’ailleurs dans le monde, il n’existe toujours pas de traitement ni de vaccin approuvés sur le plan clinique pour traiter ou prévenir la maladie. Néanmoins, des candidats-vaccins prometteurs ont été mis au point au cours des dernières années, et des efforts politiques et sociaux grandissants sont déployés pour favoriser l’homologation d’au moins un de ces candidats.
Efficient multi-task chemogenomics for drug specificity prediction

Adverse drug reactions (also called side effects) often interrupt the long and costly process of drug development. Side effects occur when drugs bind to proteins other than their intended target. As experimentally testing drug specificity against the entire proteome is out of reach, we investigate in this paper the application of chemogenomics approaches. We formulate the study of drug specificity as a proteome-wide drug-protein interaction prediction problem, and build appropriate data sets on which we evaluate multi-task support vector machines. Our observations lead us to propose NNMT, an efficient Multi-Task SVM for chemogenomics that is trained on a limited number of data points. Finally, we demonstrate the suitability of NNMT to study the specificity of drug-like molecules in real-life situations by suggesting secondary targets for 36 recently withdrawn drugs. In 9 cases, we identified secondary targets responsible for the withdrawal of the drug.
First-line treatment strategies for newly diagnosed chronic myeloid leukemia: a network meta-analysis

Objectives With bosutinib proven to be available for frontline treatment, there are currently four frontline treatments as well as an additional strategy with high-dose imatinib for newly diagnosed chronic myeloid leukemia (CML). Due to the lack of direct comparison of high-dose imatinib, dasatinib, nilotinib, and bosutinib, we summarized the evidence to indirectly compare the efficacy among these treatment options. Methods In total, 14 randomized clinical trials including 5,630 patients were analyzed by direct and mixed-treatment comparisons. Outcomes assessed were the following: complete cytogenetic response at 12 months; major molecular response at 12, 24, and 36 months; deep molecular response at 12, 24, 36, and 60 months; early molecular response at 3 months; progression-free survival (PFS); overall survival (OS); and Grade 3 or 4 adverse events (AEs). Results The Bayesian network meta-analysis demonstrated that high-dose imatinib was less effective than all new-generation tyrosine kinase inhibitors and had a higher probability of Grade 3 or 4 AEs. For molecular response, 300 mg of nilotinib was likely to be the preferred frontline treatment, as demonstrated by higher response rates and faster, deeper, and longer molecular response. For PFS and OS, there were high likelihoods (79% and 74%, respectively) that 400 mg of nilotinib was the preferred option. For AEs, standard-dose imatinib has the highest probability (65%) of being the most favorable toxicity profile. Conclusion Considering the efficacy and toxicity profile, it is not recommended to use high-dose imatinib for treatment. This analysis also showed that nilotinib has the highest probability to become the preferred frontline agents for treating CML.
Climate change via CO2 drawdown from astrophysically initiated atmospheric ionization?

Abstract Motivated by the occurrence of a moderately nearby supernova near the beginning of the Pleistocene, possibly as part of a long-term series beginning in the Miocene, we investigated whether nitrate rainout resulting from the atmospheric ionization of enhanced cosmic ray flux could have, through its fertilizer effect, initiated carbon dioxide drawdown. Such a drawdown could possibly reduce the greenhouse effect and induce the climate change that led to the Pleistocene glaciations. We estimate that the nitrogen flux enhancement onto the surface from an event at 50 pc would be of order 10%, probably too small for dramatic changes. We estimate deposition of iron (another potential fertilizer) and find it is also too small to be significant. There are also competing effects of opposite sign, including muon irradiation and reduction in photosynthetic yield caused by UV increase from stratospheric ozone layer depletion, leading to an ambiguous result. However, if the atmospheric ionization induces a large increase in the frequency of lightning, as argued elsewhere, the amount of nitrate synthesis should be much larger, dominate over the other effects and induce the climate change. More work needs to be done to clarify the effects on lightning frequency.
Preemptive Analgesia by Paracetamol, Ibuprofen or Placebo in Pediatric Dental Care: A Randomized Controlled Study.

OBJECTIVE To compare postoperative pain among children who received an oral dose of paracetamol, ibuprofen or a placebo, prior to tooth extractions. STUDY DESIGN Thirty minutes prior to dental treatment, children received a liquid dosage, fruit flavored and orange colored, of paracetamol, ibuprofen, or a placebo. Data accessed included children's dental history, their behavior, and their feeling of pain or anxiety according to Wong-Baker FACES: before treatment, following local anesthesia, and following treatment. Parents were interviewed by telephone regarding their children's need for a postoperative analgesia (paracetamol or ibuprofen), and their feeling of pain at four and 24 hours posttreatment. RESULTS Parents reported administering paracetamol or nurofen following the dental procedure to 9/43 (21%), 2/33 (6%) and 12/29 (41%) of the children in the preemptive paracetamol, ibuprofen, and placebo groups, respectively. For the 3 groups, mean pain assessment were similar: around the middle of the Wong-Baker FACES scale at baseline, slightly higher following local anesthesia, and low (pain-free) at four and 24 hours postoperative. CONCLUSION Children who received paracetamol or ibuprofen prior to tooth extractions were less likely to need an analgesic following treatment, compared to children who received a placebo.
An application of the theory of normative social behavior to bystander intervention for sexual assault

Abstract Objective: Given the high prevalence of sexual assault on U.S. college campuses, the current study examines predictors of college students’ intentions to intervene to prevent sexual assault through the lens of the theory of normative social behavior (TNSB). Participants: One hundred eighty-six undergraduate students age 18–25 were recruited from an introductory course at a large Midwestern university. Methods: Data were collected through an online survey during the 2015–2016 academic year. Results: Results indicated that descriptive norms, injunctive norms, and outcome expectations had direct positive effects on behavioral intention. However, no direct effect of group identity on intention was found. In addition to these main effects, an interaction between descriptive and injunctive norms was also observed. Conclusions: The results of the current study speak to theoretical questions surrounding the nature of TNSB variables, as well as several practical implications for coordinated efforts to promote bystander intervention on college campuses.
Real Differences between OT and CRDT for Co-Editors

OT (Operational Transformation) was invented for supporting real-time co-editors in the late 1980s and has evolved to become a core technique used in today's working co-editors and adopted in major industrial products. CRDT (Commutative Replicated Data Type) for co-editors was first proposed around 2006, under the name of WOOT (WithOut Operational Transformation). Follow-up CRDT variations are commonly labeled as "post-OT" techniques capable of making concurrent operations natively commutative, and have made broad claims of superiority over OT solutions, in terms of correctness, time and space complexity, simplicity, etc. Over one decade later, however, CRDT solutions are rarely found in working co-editors, while OT solutions remain the choice for building the vast majority of co-editors. Contradictions between this reality and CRDT's purported advantages have been the source of much debate and confusion in co-editing research and developer communities. What is CRDT really to co-editing? What are the real differences between OT and CRDT for co-editors? What are the key factors that may have affected the adoption of and choice between OT and CRDT for co-editors in the real world? In this paper, we report our discoveries, in relation to these questions and beyond, from a comprehensive review and comparison study on representative OT and CRDT solutions and working co-editors based on them. Moreover, this work reveals facts and presents evidences that refute CRDT claimed advantages over OT. We hope the results reported in this paper will help clear up common myths, misconceptions, and confusions surrounding alternative co-editing techniques, and accelerate progress in co-editing technology for real world applications.
Prevalence and risk indicators of peri‐implant diseases in Spain

AIM To evaluate the prevalence of peri-implant diseases in Spain, as well as the associated risk indicators. MATERIAL AND METHODS This is a cross-sectional study using a network of sentinel dentists, who randomly selected 10 patients with implants (placed, at least, 5 years before), which were clinically and radiographically evaluated. Case definitions were established for peri-implant mucositis [bleeding on probing (BOP) and no bone level ≥2 mm] and peri-implantitis (BOP plus bone level ≥2 mm). Potential predictor variables, at univariate and multivariate levels, were explored by means of binary logistic regression. RESULTS A total of 49 sentinel dentists provided complete data from 474 implants in 275 patients. At implant level, prevalences for peri-implant mucositis and peri-implantitis were 27% (95% confidence interval [CI] 22-32) and 20% (95% CI: 15-24), respectively, with 17% of implants (14-21) with bone level ≥2 mm without BOP. At patient level, prevalences were 27% (22-32), 24% (19-29) and 18% (13-22), respectively. In the multiple regression analysis, statistically significant associations for peri-implantitis (p < 0.10) were found for gender, peri-implant supportive therapy, implant location, diameter and surface, type of prosthesis and access to interproximal hygiene. CONCLUSIONS In this representative subject sample across Spain, the prevalence of peri-implant diseases was high (51%).
XY oocytes of sex-reversed females with a Sry mutation deviate from the normal developmental process beyond the mitotic stage†

Abstract The fertility of sex‐reversed XY female mice is severely impaired by a massive loss of oocytes and failure of meiotic progression. This phenomenon remains an outstanding mystery. We sought to determine the molecular etiology of XY oocyte dysfunction by generating sex‐reversed females that bear genetic ablation of Sry, a vital sex determination gene, on an inbred C57BL/6 background. These mutant mice, termed XYsry− mutants, showed severe attrition of germ cells during fetal development, resulting in the depletion of ovarian germ cells prior to sexual maturation. Comprehensive transcriptome analyses of primordial germ cells (PGCs) and postnatal oocytes demonstrated that XYsry− females had deviated significantly from normal developmental processes during the stages of mitotic proliferation. The impaired proliferation of XYsry− PGCs was associated with aberrant &bgr;‐catenin signaling and the excessive expression of transposable elements. Upon entry to the meiotic stage, XYsry− oocytes demonstrated extensive defects, including the impairment of crossover formation, the failure of primordial follicle maintenance, and no capacity for embryo development. Together, these results suggest potential molecular causes for germ cell disruption in sex‐reversed female mice, thereby providing insights into disorders of sex differentiation in humans, such as “Swyer syndrome,” in which patients with an XY karyotype present as typical females and are infertile.
Helicobacter pylori induces intracellular galectin-8 aggregation around damaged lysosomes within gastric epithelial cells in a host O-glycan-dependent manner

Galectin-8, a beta-galactoside-binding lectin, is upregulated in the gastric tissues of rhesus macaques infected with Helicobacter pylori. In this study, we found that H. pylori infection triggers intracellular galectin-8 aggregation in human-derived AGS gastric epithelial cells, and that these aggregates colocalize with lysosomes. Notably, this aggregation is markedly reduced following the attenuation of host O-glycan processing. This indicates that H. pylori infection induces lysosomal damage, which in turn results in the accumulation of cytosolic galectin-8 around damaged lysosomes through the recognition of exposed vacuolar host O-glycans. H. pylori-induced galectin-8 aggregates also colocalize with autophagosomes, and galectin-8 ablation reduces the activation of autophagy by H. pylori. This suggests that galectin-8 aggregates may enhance autophagy activity in infected cells. We also observed that both autophagy and NDP52, an autophagy adapter, contribute to the augmentation of galectin-8 aggregation by H. pylori. Additionally, vacuolating cytotoxin A, a secreted H. pylori cytotoxin, may contribute to the increased galectin-8 aggregation and elevated autophagy response in infected cells. Collectively, these results suggest that H. pylori promotes intracellular galectin-8 aggregation, and that galectin-8 aggregation and autophagy may reciprocally regulate each other during infection.