Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors associated with variation in single-dose albendazole pharmacokinetics: A systematic review and modelling analysis

Background Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown the drug to be characterised by significant inter-individual pharmacokinetic variation. This variation is thought to have important consequences for treatment success, but current understanding of the factors associated with this variation remains incomplete. Methodology/Principal Findings We carried out a systematic review to identify references containing temporally disaggregated data on the blood concentration of albendazole and/or (its pharmacologically-active metabolite) albendazole sulfoxide following a single oral dose. These data were then integrated into a mathematical modelling framework to infer key pharmacokinetic parameters and relate them to characteristics of the populations being treated. These characteristics included age, weight, sex, dosage, infection status, and whether patients had received a fatty meal prior to treatment or other drugs alongside albendazole. Our results highlight a number of factors systematically associated with albendazole pharmacokinetic variation including age, existing parasitic infection and receipt of a fatty meal. These factors impact different aspects of the drugs pharmacokinetic profile. Whilst age is significantly associated with albendazole sulfoxide half-life, receipt of a fatty meal prior to treatment was associated with increased albendazole bioavailability (and by extension, peak blood concentration and total drug exposure following the dose). Parasitic infection (particularly echinococcosis and neurocysticercosis) was associated with altered pharmacokinetic parameters, with infected populations displaying distinct characteristics to uninfected ones. Conclusions/Significance These results highlight the extensive inter-individual variation that characterises albendazole pharmacokinetics and provides insight into some of the factors associated with this variation.
Risk of Plasmodium vivax recurrences follows a 30-70 rule and indicates relapse heterogeneity in the population

A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P vivax endemic regions and are thought to be influenced by factors such as febrile infections, immunity, and transmission intensity. Some of these factors may cause temporary changes in hypnozoite activation over time, leading to 'temporal heterogeneity' in reactivation risk. In addition, variation in exposure to infection may be a longer-term characteristic of individuals that leads to 'population heterogeneity' in hypnozoite activation. We analyze data on risk of P vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P vivax risk of recurrences.
Expression of Ectonucleoside Triphosphate Diphosphohydrolase 2 (NTPDase2) Is Negatively Regulated Under Neuroinflammatory Conditions In Vivo and In Vitro

Ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2) hydrolyzes extracellular ATP to ADP, which is the ligand for P2Y1,12,13 receptors. The present study describes the distribution of NTPDase2 in adult rat brains in physiological conditions, and in hippocampal neurodegeneration induced by trimethyltin (TMT). The study also describes the regulation of NTPDase2 by inflammatory mediators in primary astrocytes and oligodendroglial cell line OLN93. In physiological conditions, NTPDase2 protein was most abundant in the hippocampus, where it was found in fibrous astrocytes and synaptic endings in the synaptic-rich hippocampal layers. In TMT-induced neurodegeneration, NTPDase2-mRNA acutely decreased at 2-dpi and then gradually recovered to the control level at 7-dpi and 21-dpi. As determined by immunohistochemistry and double immunofluorescence, the decrease was most pronounced in the dentate gyrus (DG), where NTPDase2 withdrew from the synaptic boutons in the polymorphic layer of DG, whereas the recovery of the expression was most profound in the subgranular layer. Concerning the regulation of NTPDase2 gene expression, proinflammatory cytokines IL-6, IL-1β, TNFα, and IFNγ negatively regulated the expression of NTPDase2 in OLN93 cells, while did not altering the expression in primary astrocytes. Different cell-intrinsic stressors, such as depletion of intracellular energy store, oxidative stress, endoplasmic reticulum stress, and activation of protein kinase C, also massively disturbed the expression of the NTPDase2 gene. Together, our results suggest that the expression and the activity of NTPDase2 transiently cease in neurodegeneration and brain injury, most likely as a part of the acute adaptive response designed to promote cell defense, survival, and recovery.
HoBi-like pestivirus in 2 cases of fatal respiratory disease of feedlot cattle in Argentina

HoBi-like pestivirus (HoBiPeV) is an emerging virus that has been detected in cattle and other ruminants. We diagnosed 2 cases of fatal bovine respiratory disease complex (BRDC) associated with infection with HoBiPeV in a feedlot in Argentina. The main findings in 2 steers autopsied were interstitial bronchopneumonia (case 1) and fibrinous bronchopneumonia (case 2). HoBiPeV was detected by RT-PCR in lungs of both animals and by immunohistochemistry in case 2. Phylogenetic analysis showed that both strains clustered within the “Brazilian-Italian” clade. In case 2, Mannheimia haemolytica was isolated from the lung. There is scant information about the contribution of HoBiPeV to the pathogenesis of BRDC. To our knowledge, HoBiPeV has not been reported previously in association with M. haemolytica pneumonia. Our findings further support the involvement of HoBiPeV in cases of BRDC and contribute to understanding the synergy of this etiologic agent in the pathogenesis of BRD, which is critical for the development of appropriate preventive strategies.
Pharmacological effects of Artocarpus lakoocha methanol extract on inhibition of squalene synthase and other downstream enzymes of the cholesterol synthesis pathway

Abstract Context Artocarpus lakoocha Roxb. (Moraceae) is reported to possess antioxidant, anti-inflammatory, and anti-skin ageing agents. Objective This study evaluates the pharmacological effects of A. lakoocha leaves methanol extract on enzymes involved in the cholesterol synthesis pathway in high-fat diet-induced hyperlipidemic rats. Materials and methods Twenty-four male Wistar rats, weighing approximately 180–220 g, were divided into four groups: control, diseased (hyperlipidemic), A. lakoocha leaves extract treated, and simvastatin treated. The rats were fed with high-fat diet for 2 months to induce hyperlipidaemia, afterward, experimental groups received A. lakoocha leaves methanol extract (250 mg/kg) and simvastatin (10 mg/kg) orally until the 89th day of the experiment, while the diseased group continued to receive high-fat diet along with normal saline. Results It was found that A. lakoocha extract significantly lowered the serum total cholesterol, triglycerides, and low-density lipoprotein (LDL) levels, while effectively increasing serum high-density lipoprotein (HDL) levels as compared to the diseased group (p ≤ 0.05). The mRNA expression levels of squalene synthase and HMG-CoA reductase were found to be effectively down-regulated after the treatment with A. lakoocha leaves extract (17.45 ± 2.48 vs. 31.91 ± 5.292 and 5.85 ± 3.164 vs. 37.37 ± 6.492) and simvastatin (7.148 ± 0.76 vs. 31.91 ± 5.292, and 3.098 ± 2.09 vs. 37.37 ± 6.492) as compared to the diseased group. Discussion and Conclusions The results suggested that A. lakoocha leaves extract have observable beneficial effects on inhibition of enzymes involved in cholesterol synthesis pathway and improve lipid profile analogous to simvastatin.
Study on Integration & Network Sharing of Big Data in Supply Chain Management Field

A great challenge for big-data-driven SCM is its integration in current systems. This paper discuses the necessity to integrate big data in SCM field, then analyzes the main sources and contents of the data in SCM, and probes preliminarily into the methods of its integration so as to provide reference to the application of big data in SCM.
Once a reservoir, always a reservoir? Seasonality affects the pathogen maintenance potential of amphibian hosts.

Host species that can independently maintain a pathogen in a host community and contribute to infection in other species are important targets for disease management. However, the potential of host species to maintain a pathogen is not fixed over time, and an important challenge is understanding how within- and across-season variability in host maintenance potential affects pathogen persistence over longer time scales relevant for disease management (e.g., years). Here, we sought to understand the causes and consequences of seasonal infection dynamics in leopard frogs (Rana sphenocephala and R. pipiens) infected with the fungal pathogen Batrachochytrium dendrobatidis (Bd). We addressed three questions broadly applicable to seasonal host-parasite systems. First, to what degree are observed seasonal patterns in infection driven by temperature-dependent infection processes compared to seasonal host demographic processes? Second, how does seasonal variation in maintenance potential affect long-term pathogen persistence in multihost communities? Third, does high deterministic maintenance potential relate to the long-term stochastic persistence of pathogens in host populations with seasonal infection dynamics? To answer these questions, we used field data collected over three years on >1400 amphibians across four geographic locations, laboratory and mesocosm experiments, and a novel mathematical model. We found that the mechanisms that drive seasonal prevalence were different than those driving seasonal infection intensity. Seasonal variation in Bd prevalence was driven primarily by changes in host contact rates associated with breeding migrations to and from aquatic habitat. In contrast, seasonal changes in infection intensity were driven by temperature-induced changes in Bd growth rate. Using our model, we found that the maintenance potential of leopard frogs varied significantly throughout the year and that seasonal troughs in infection prevalence made it unlikely that leopard frogs were responsible for long-term Bd persistence in these seasonal amphibian communities, highlighting the importance of alternative pathogen reservoirs for Bd persistence. Our results have broad implications for management in seasonal host-pathogen systems, showing that seasonal changes in host and pathogen vital rates, rather than the depletion of susceptible hosts, can lead to troughs in pathogen prevalence and stochastic pathogen extirpation.
Clinical application and feasibility of utilizing the PEDI-CAT to assess activity and participation among children receiving physical therapy incorporating hippotherapy

ABSTRACT Background Hippotherapy (HPOT) is a physical therapy (PT) treatment tool using equine movement to improve mobility for children with movement impairments. Although research suggests HPOT improves body structure and function, there is limited evidence regarding its impact on activity and participation outcomes in a clinical setting. The Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) may be useful in HPOT settings to highlight changes in activity and participation. Purpose 1) Evaluate the PEDI-CAT’s sensitivity to changes in activity and participation among children receiving PT using HPOT; 2) determine feasibility of administering the PEDI-CAT in a HPOT setting; and 3) examine how PEDI-CAT scores influence clinical decision-making. Methods Participants (N = 34) were children who attended weekly PT using HPOT for 6 months. The PEDI-CAT was completed for all participants by a parent or caregiver at initial treatment (T1) and 6 months later (T2). A linear mixed effects model was used to evaluate changes in scores over time. Team meetings occurred monthly to discuss how PEDI-CAT scores impacted treatment. Results There were significant improvements across 3 PEDI-CAT domains between T1 and T2 for all children with small effect sizes and nonsignificant changes noted within two diagnostic subgroups with small-to-medium effect sizes. The PEDI-CAT was completed by all participants without interrupting treatment flow. PEDI-CAT score reports enriched therapist-client conversations increasing shared decision-making. Conclusion PTs who treat children using HPOT may feasibly use the PEDI-CAT to assess changes in activity level outcomes and to assist clinical decision-making.
Can Maine facilitate local growth of the cellulosic ethanol industry by sustainably using her extensive forest resources as a feedstock? A literature review and GIS based analysis on the how and where

Rising oil prices and increased scientific and political discussions of finding alternative energy sources have resulted in growth of support for developing ethanol as replacement or substitute fuel. Second generation (cellulosic) ethanol can be developed using biomass as its feedstock, but is produced commercially yet. The use of forest waste as a feedstock for generating ethanol is considered in the state of Maine. Background research examines current research in the field, the role of forests and an overview of the situation in Maine. The role of fire management is highlighted as fire prevention methods such as thinning could provide further inputs for ethanol generation. A spatial analysis is conducted finding paper mills located in Maine which are in close proximity to necessary resources. These mills can be converted to produce ethanol as well as paper. Such a conversion would be the recommended first step in Maine to produce significant amounts of ethanol using local resources. A discussion of the limitations of the data and process, as well as suggestions for further research, follows.
Glabellar Botulinum Toxin Injection Improves Depression Scores: A Systematic Review and Meta-Analysis

Background: Depression is a leading cause of disability worldwide. Preliminary evidence suggests that glabellar onabotulinumtoxinA injections improve depression scores with few side effects compared to current first-line antidepressant medications. The authors’ review reports on these studies, hypothesizing that glabellar onabotulinumtoxinA injections can be an alternative safe and effective treatment for depression. Methods: A systematic review and meta-analysis of the relevant literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Cochrane Library, Embase, and Scopus databases were searched in August of 2020 using the keywords [“botox” OR “botulinum”] AND [“mood” OR “depression”] for articles published between 1980 and 2020. Prospective studies and randomized controlled trials on the use of glabellar onabotulinumtoxinA injections for the primary purpose of treating depression were considered. The primary endpoint for the meta-analysis was the mean difference in primary depression scores after treatment, along with a second endpoint of the standardized mean difference in depression scores among treated patients including all nine studies. Results: Of the 499 reviewed articles, nine studies were included that reported improvement in mean depression scores from baseline. All five randomized controlled trials reported an improvement in mean depression scores at 6 weeks after treatment, with a weighted average change of −8.39 points (p < 0.0001). The aggregate standardized mean difference from baseline to the primary endpoint across all nine prospective studies was −1.61 SD (p < 0.0001). Conclusion: Meta-analysis and systematic review of the included studies provide support for an antidepressant effect of glabellar onabotulinumtoxinA injections.
Procurement from local producers for food service in primary and secondary school settings: a scoping review.

ISSUE ADDRESSED Australian school canteen guidelines do not broadly incentivise procuring food from local producers, despite evidence of this occurring abroad. This scoping review aims to investigate what is known about local food procurement for school foodservice. METHODS A scoping review of peer-reviewed articles published since 2000 was undertaken using MEDLINE, CINAHL and Scopus. RESULTS Twenty-one studies met the inclusion criteria. Local food was generally perceived as fresher and more nutritious. Small, positive impacts on fruit and vegetable intake have been demonstrated when food is procured locally. Challenges identified included concerns around food safety, varied availability, time spent coordinating food supply, lack of incentive from regional or national guidelines, inadequate kitchen facilities and budget constraints. CONCLUSIONS There is no universal definition or standard for procuring 'local food'. The main motivation for local food procurement was a sense of social responsibility, however there are barriers, including cost, facilities and food safety. Purchasing food locally holds potential to benefit the local economy but government funding and policy supporting local and small-scale producers is an important enabler. So what? Government support to build stakeholder capacity is important in establishing and maintaining these programs and would be crucial in achieving change in Australian schools. Investigating feasibility of a national school lunch service would be beneficial, as these programs may have merit not just in feeding children but also in supporting the local economy. Further research is warranted in this area.
The use of anticoagulants for rodent control in a mixed-use urban environmefent in Singapore: A controlled interrupted time series analysis

Vector control remains an important strategy in preventing rodent-borne diseases. Studies quantifying the impact of anticoagulant bait use on rodent populations are scarce in tropical settings. This study examined the impact of anticoagulant bait use on three measures of rodent activity in Singapore to inform rodent-borne disease control strategies. Using a controlled interrupted time-series analytical design with negative binomial and linear regression models, the average rodent activity levels were compared in the pre- and post-intervention periods. There was a 62.7% (Incidence Rate Ratio (IRR): 0.373, 95% CI: [0.224, 0.620]) reduction in the number of rodents caught, a 25.8-unit (coefficient = -25.829, 95% CI: [-29.855, -21.804]) reduction in the number of 30 g/unit baits consumed and a 61.9% (IRR: 0.381, 95% CI: [0.218, 0.665]) reduction in the number of marred bait stations relative to the pre-intervention period. There was a rise in all three outcome measures within four months after the post-intervention period. This study provided strong evidence that anticoagulant baits substantially reduces rodent activity. The population resurgence after the post-intervention period reinforces the importance of timing the resumption of control measures aimed at reducing rodent-borne disease transmission.
Recent advances on discovery of enzyme inhibitors from natural products using bioactivity screening.

The essence of enzymes is to keep the homeostasis and balance of human by catalyzing metabolic responses and modulating cell. Suppression of enzyme slows the progress of some diseases, making it a therapeutic target. Therefore, it is important to develop enzyme inhibitors by proper bioactivity screening strategies for the future treatment of some major diseases. In this review, we summarized the recent (2015-2020) applications of several screening strategies (electrophoretically mediated microanalysis, enzyme immobilization, affinity chromatography, and affinity ultrafiltration) in finding enzyme inhibitors from certain species of bioactive natural compounds of plant origin (flavonoids, alkaloids, phenolic acids, saponins, anthraquinones, coumarins). At the same time, the advantages and disadvantages of each strategy were also discussed, and the future possible development direction in enzyme inhibitor screening has prospected. To sum up, it is expected to help readers select suitable screening strategies for enzyme inhibitors and provide useful information for the study of the biological of specific kinds of natural products. This article is protected by copyright. All rights reserved.
Gene, virulence and related regulatory mechanisms in Cryptococcus gattii

Cryptococcus gattii is a kind of basidiomycetous yeast, which grows in human and animal hosts. C. gattii has four distinct genomes, VGI/AFLP4, VGII/AFLP6, VGIII/AFLP5, and VGIV/AFLP7. The virulence of C. gattii is closely associated with genotype and related stress-signaling pathways, but the pathogenic mechanism of C. gattii has not been fully identified. With the development of genomics and transcriptomics, the relationship among genes, regulatory mechanisms, virulence, and treatment is gradually being recognized. In this review, to better understand how C. gattii causes disease and to characterize hypervirulent C. gattii strains, we summarize the current understanding of C. gattii genotypes, phenotypes, virulence, and the regulatory mechanisms.
Spoof Trace Disentanglement for Generic Face Anti-Spoofing

Prior studies show that the key to face anti-spoofing lies in the subtle image patterns, termed “spoof trace,” e.g., color distortion, 3D mask edge, and Moiré pattern. Spoof detection rooted on those spoof traces can improve not only the model's generalization but also the interpretability. Yet, it is a challenging task due to the diversity of spoof attacks and the lack of ground truth for spoof traces. In this work, we propose a novel adversarial learning framework to explicitly estimate the spoof related patterns for face anti-spoofing. Inspired by the physical process, spoof faces are disentangled into spoof traces and the live counterparts in two steps: additive step and inpainting step. This two-step modeling can effectively narrow down the searching space for adversarial learning of spoof trace. Based on the trace modeling, the disentangled spoof traces can be utilized to reversely construct new spoof faces, which is used as data augmentation to effectively tackle long-tail spoof types. In addition, we apply frequency-based image decomposition in both the input and disentangled traces to better reflect the low-level vision cues. Our approach demonstrates superior spoof detection performance on 3 testing scenarios: known attacks, unknown attacks, and open-set attacks. Meanwhile, it provides a visually-convincing estimation of the spoof traces. Source code and pre-trained models will be publicly available upon publication.