Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative cytotoxic effects of five commonly used triazole alcohol fungicides on human cells of different tissue types

Abstract The widespread application of triazole fungicides makes people attach great concern over its adverse effects in mammalian. In this paper, cytotoxic effects of triazole alcohol fungicides (TAFs) were assessed on human HeLa, A549, HCT116 and K562 cells, and the potential mechanism of TAFs cytotoxicity was studied preliminarily. Results showed that TAFs had cytotoxicity on human cells with different level and cytotoxic selectivity. TAFs cytotoxicity was resonated with a typical hormetic biphasic dose action that produced a complex pattern of stimulatory or inhibitory effects on cell viability. Among the five TAFs, diniconazole revealed a widest range of cytotoxicity to inhibit the viability of the adherent and the suspension cells, causing HeLa cells shrinkage, A549 cells shrunken, and K562 cells collapse, and showed stronger cytotoxicity than hexaconazole. Moreover, the involvement of ROS generation in the cytotoxicity of TAFs on human cells was observed, and the apoptosis of HeLa cells and the formation of apoptotic body in K562 cells induced by diniconazole were characterized. The results indicated the cytotoxicity of TAFs with different structures on human cells was depended on their own property and cell specificity, K562 cells were the most susceptible to TAFs and diniconazole was the strongest toxic.
Who is to blame for crashes involving autonomous vehicles? Exploring blame attribution across the road transport system

Abstract The introduction of fully autonomous vehicles is approaching. This warrants a re-consideration of road crash liability, given drivers will have diminished control. This study, underpinned by attribution theory, investigated blame attribution to different road transport system actors following crashes involving manually driven, semi-autonomous and fully autonomous vehicles. It also examined whether outcome severity alters blame ratings. 396 participants attributed blame to five actors (vehicle driver/user, pedestrian, vehicle, manufacturer, government) in vehicle–pedestrian crash scenarios. Different and unique patterns of blame were found across actors, according to the three vehicle types. In crashes involving fully autonomous vehicles, vehicle users received low blame, while vehicle manufacturers and government were highly blamed. There was no difference in the level of blame attributed between high and low severity crashes regarding vehicle type. However, the government received more blame in high severity crashes. The findings have implications for policy and legislation surrounding crash liability. Practitioner summary: Public views relating to blame and liability in transport accidents is a vital consideration for the introduction of new technologies such as autonomous vehicles. This study demonstrates how a systems ergonomics framework can assist to identify the implications of changing public opinion on blame for future road transport systems. Abbreviation: ANOVA: analysis of variance; DAT: defensive attribution theory; IV: independent variable
An Exploratory Analysis of Predictors of Concordance between Canadian Common Drug Review Reimbursement Recommendations and the Subsequent Decisions by Ontario, British Columbia and Alberta

Background: Concordance between Common Drug Review (CDR) recommendations and provincial plans has been studied previously. However, no study has, to the best of the authors' knowledge, examined the characteristics of CDR recommendations that may be associated with concordance. Methods: Recommendation–decision pairs were collected from the CDR and the provincial plans of Ontario, British Columbia and Alberta. Concordance was evaluated by province. Characteristics of each CDR recommendation were collected, and associations with concordance were evaluated by logistic regression. Results: Recommendation–listing concordance was high. Positive references to cost and clinical outcomes compared to placebo were statistically associated with concordance. Negative references to cost and to the consistency and certainty of economic evidence were statistically associated with discordance. However, these findings were inconsistent across the jurisdictions studied. Conclusions: Although concordance was high, the ability of recommendation characteristics to explain the relationship between province and CDR listing decisions was limited. This exploratory study highlights the complexity of the reimbursement process and possible reasons for drug listing differences across jurisdictions.
The Mosaic of Primary Care Nurses in Rural and Remote Canada: Results from a National Survey

Background and objective: Nurses provide essential primary care (PC) in rural and remote Canada. We examined the practice context and responsibilities of this little-known understudied workforce. Method: Data from Nursing Practice in Rural and Remote Canada II, a 2014 to 2015 pan-Canadian survey, were analyzed. Results: Of 3,822 respondents, 192 identified that PC was their only practice focus (PC-Only), and for 111, it was one focus among others (PC-Plus). Proportionally more PC-Only than PC-Plus nurses had graduate education, were employed in larger communities and had experienced higher job resources and lower job demands. Proportionally fewer PC-Only than PC-Plus nurses followed protocols/decision support tools, dispensed medications and provided emergency services. Proportionally more PC-Only than PC-Plus nurses ordered advanced diagnostic tests/imaging, and fewer PC-Only than PC-Plus nurses performed and interpreted laboratory tests and diagnostic imaging on site. Conclusion: Contributions of the rural and remote nursing workforce to PC are rendered invisible by contemporary characterizations of the PC workplace, limiting evaluation and improvement efforts.
Navigating the midwifery undergraduate programme: Is resilience the key?

Background: Student midwives face a number of challenges during their pre-registration programme, both academically and in clinical practice. Aims: This pilot study aimed to examine the role that resilience might play in supporting student midwives to continue on the midwifery undergraduate programme. Method: Five second-year student midwives volunteered to take part in the pilot. All five students completed Wagnild's updated True Resilience Scale (TRS), and partipated in a focus group and a one-to-one interview. Findings: One participant scored ‘moderate’ on the TRS, three ‘moderately high’ and one ‘high’. Six main themes emerged from the focus group and interviews: defining and recognising resilience; building and developing resilience through reflection; developing resilience through positive and negative encounters on the midwifery programme; the relevance of significant others; transferable resilience; and different styles of resilience. Conclusions: The pilot offered insights into the significance o.
Research on Scientific Thinking Training Mode of Medical Undergraduate

In recent years, undergraduate medical education faced with great challenges, with the gradual increase future capacity requirements of medical personnel, five-year duck injection of undergraduate medical education already can not meet the stringent requirements of the new era of community health workers, now stage clinical skills and research only thinking of both clinical medical personnel to come to the fore. Medical undergraduate education students how to develop scientific thinking is a key factor in the future to better integrate into society, so this article will talk about culture experience medical undergraduates' scientific thinking skills, hoping to help students form a correct view of science and values, and improve the quality of their own research.
Sleep deprivation induces fragmented memory loss

Sleep deprivation increases rates of forgetting in episodic memory. Yet, whether an extended lack of sleep alters the qualitative nature of forgetting is unknown. We compared forgetting of episodic memories across intervals of overnight sleep, daytime wakefulness, and overnight sleep deprivation. Item-level forgetting was amplified across daytime wakefulness and overnight sleep deprivation, as compared to sleep. Importantly, however, overnight sleep deprivation led to a further deficit in associative memory that was not observed after daytime wakefulness. These findings suggest that sleep deprivation induces fragmentation among item memories and their associations, altering the qualitative nature of episodic forgetting.
Improving the Heading Accuracy in Indoor Pedestrian Navigation Based on a Decision Tree and Kalman Filter

In pedestrian inertial navigation, multi-sensor fusion is often used to obtain accurate heading estimates. As a widely distributed signal source, the geomagnetic field is convenient to provide sufficiently accurate heading angles. Unfortunately, there is a broad presence of artificial magnetic perturbations in indoor environments, leading to difficulties in geomagnetic correction. In this paper, by analyzing the spatial distribution model of the magnetic interference field on the geomagnetic field, two quantitative features have been found to be crucial in distinguishing normal magnetic data from anomalies. By leveraging these two features and the classification and regression tree (CART) algorithm, we trained a decision tree that is capable of extracting magnetic data from distorted measurements. Furthermore, this well-trained decision tree can be used as a reject gate in a Kalman filter. By combining the decision tree and Kalman filter, a high-precision indoor pedestrian navigation system based on a magnetically assisted inertial system is proposed. This system is then validated in a real indoor environment, and the results show that our system delivers state-of-the-art positioning performance. Compared to other baseline algorithms, an improvement of over 70% in the positioning accuracy is achieved.
Metabolic Syndrome Is Associated with Oxidative Stress and Proinflammatory State

Metabolic syndrome (MetS) is associated with increased risk of developing diabetes and cardiovascular diseases. MetS is also characterized by an increase of oxidative stress which contributes to impaired inflammation, vascular function, and atherosclerosis. The aim was to assess the oxidative stress and inflammatory markers in plasma and PBMCs in adults with or without MetS. Antioxidant and inflammatory parameters were measured in peripheral blood mononuclear cells (PBMCs) of 80 men and 80 women over 55 to 80-years-old residing in the Balearic Islands without previously documented cardiovascular disease. Circulating leukocytes, neutrophils, lymphocytes, basophils, and monocytes were higher in MetS subjects with respect to those without MetS. Plasma levels of malondialdehyde, tumor necrosis factor α (TNFα), and interleukin 6 (IL-6) levels were higher in MetS subjects in both genders, but the superoxide dismutase activity was lower. The myeloperoxidase plasma activity was higher in the MetS male subjects. Higher activities and protein levels of catalase and glutathione reductase in PBMCs were observed in MetS subjects in both genders. Obtained data show that MetS is associated with oxidative stress and a proinflammatory state and with high antioxidant defenses in PBMCs probably derived from a pre-activation state of immune cells.
Maximizing the Amount of Deposited Particles During a Severe Asthma Attack Using the Stochastic Lung Model

Abstract Background: The aim of this study was to use a computerized lung model to simulate the deposition of inhaled particles in the human airways during a severe asthma attack, in order to find the combination of breathing- and particle-related parameters which leads to the highest deposited fractions in the target areas of the airways. Material and Method: A stochastic lung model was used to simulate the deposition of 1 nm – 100 μm particles during a severe asthma attack in bronchial generations 9-16. Breathing parameters were chosen to reflect the use of a therapeutic inhalation device, with a 10 s symmetrical breathing cycle and 2000 ml tidal volume. To maximize the deposited fraction in the target areas, further simulations were carried out changing the tidal volume (750-3000 ml), the length of the breathing cycle (2-20 s) and the length of breathing pause following inhalation (0-10 s). Results: The highest deposited fraction of 51.50% in bronchial generations 9–16 was obtained in the case of 0.01 μm particles, this value being more than4 times higher compared to the highest deposition of 3–6 μm particles currently used in inhalation devices (11.81% in the case of 5 μm particles). Modifying breathing-related parameters did not lead to valuable increases in the deposited fractions in the investigated region. Conclusions: Deposition fractions in the therapeutically important areas of the airways may be more than4 times higher in the case of 0.01 μm particles, compared to particles currently used in the treatment of asthma bronchiale.
Proteomic Profiling of Zebrafish Challenged by Spring Viremia of Carp Virus Provides Insight into Skin Antiviral Response.

Spring viremia of carp virus (SVCV) causes the skin hemorrhagic disease in cyprinid species, but its molecular mechanism of skin immune response remains unclear at the protein level. In the present study, the differential proteomics of the zebrafish (Danio rerio) skin in response to SVCV infection were examined by isobaric tags for relative and absolute quantitation and quantitative polymerase chain reaction (qPCR) assays. A total of 3999 proteins were identified, of which 320 and 181 proteins were differentially expressed at 24 and 96 h postinfection, respectively. The expression levels of 16 selected immune-related differentially expressed proteins (DEPs) were confirmed by qPCR analysis. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that DEPs were significantly associated with complement, inflammation, and antiviral response. The protein-protein interaction network of cytoskeleton-associated proteins, ATPase-related proteins, and parvalbumins from DEPs was shown to be involved in skin immune response. This is first report on the skin proteome profiling of zebrafish against SVCV infection, which will contribute to understand the molecular mechanism of local mucosal immunity in fish.
FAK-targeted and combination therapies for the treatment of cancer: an overview of phase I and II clinical trials

ABSTRACT Introduction: Focal adhesion kinase (FAK) is a promising target for the treatment of solid tumors because its expression has been linked to tumor progression, invasion, and drug resistance. Several FAK inhibitors have been developed and tested for efficacy in treating advanced cancers. Four FAK inhibitors have shown promising preclinical data and have advanced to clinical development in solid tumors. Areas covered: This article provides a systematic review on FAK inhibitors that have been tested or are currently in clinical trials in advanced solid tumors. We discuss the efficacy of GSK2256098, PF-00562271, VS-6063, and BI 853520 in the preclinical setting and summarize the results of phase I/II clinical trials evaluating these compounds. Expert opinion: The FAK inhibitors examined in clinical trials thus far have been shown to have manageable toxicity profiles and have demonstrated cytostatic effects as single agents, extending progression-free survival without producing a clinical or radiographic response. Trials are currently underway to strengthen the efficacy of treatment by combining FAK inhibitors with cytotoxic chemotherapy, targeted therapy, or immunotherapy. In the future, prognostic markers must be identified to carefully select patients who could benefit from FAK inhibitor treatment alone or in combination strategies.
The Role of Leptin Levels in Adaptation to Cold Climates

Currently, adipose tissue is considered an endocrine organ that produces hormone-active substances, including leptin, which can play a key role in thermoregulation processes. Therefore, we performed a meta-analysis to investigate the influence of the climatic environment on leptin levels. A systematic literature search in the databases was carried out on 10 January 2020. Finally, 22 eligible articles were included in the current meta-analysis and a total of 13,320 participants were covered in the final analysis. It was shown that males of the “North” subgroup demonstrated significantly higher levels of leptin (10.02 ng/mL; CI: 7.92–12.13) than males of the “South” subgroup (4.9 ng/mL; CI: 3.71–6.25) (p = 0.0001). On the contrary, in the female group, a similar pattern was not detected (p = 0.91). Apparently, in order to maintain body temperature, higher leptin levels are required. The results of the study indicate that such effects are most pronounced in males and to a smaller extent in females, apparently due to a relatively high initial concentration of leptin in females. The correlation between leptin levels and climatic environment data support the hypothesis of leptin-mediated thermoregulation as an adaptive mechanism to cold climates.
Insights into the Cathode-electrolyte Interphases of High-energy-density Cathodes in Lithium-ion Batteries.

We present a comprehensive study of cycled high-Ni (LiNi1-xMxO2, M = metals), Li-rich (Li1+xMnyM1-x-yO2), and high-voltage spinel (LiMn1.5Ni0.5O4) electrodes with time-of-flight secondary ion mass spectrometry (TOF-SIMS) and X-ray pho-toelectron spectroscopy (XPS) in conjunction with electrochemical techniques to better understand their evolving cath-ode-electrolyte interphase (CEI) structure during cycling. TOF-SIMS provides fragment-specific information regarding the surface film content for each of the electrodes. High-Ni cathodes show thick surface films initially containing Li2CO3, later developing oxidized organic carbonates throughout cycling. Li-rich electrode surface films develop strong characteristics during their first activation cycles, where released O2 oxidizes organic carbonates to form polymeric carbons and decom-pose LiPF6. High-voltage spinel electrodes operate outside the standard electrolyte stability window, generating reactive oxidized electrolyte species that further decompose LiPF6. The distribution and concentration of these different chemical fragments measured by TOF-SIMS are finally summarized by color-coded high resolution images of cycled high-Ni, Li-rich, and high-voltage spinel electrodes.
Antithrombotic Therapy After Transcatheter Aortic Valve Implantation

The development of transcatheter aortic valve implantation has represented one of the greatest advances in the cardiology field in recent years and has changed clinical practice for patients with aortic stenosis. Despite the continuous improvement in operators’ experience and techniques, and the development of new generation devices, thromboembolic and bleeding complications after transcatheter aortic valve implantation remain frequent, and are a major concern due to their negative impact on prognosis in this vulnerable population. In addition, the optimal antithrombotic regimen in this scenario is not known, and current recommendations are mostly empirical and not evidence based. The present review aims to provide an overview of the current status of knowledge, including relevant on-going randomised trials, on antithrombotic treatment strategies after transcatheter aortic valve implantation.
On the Stability of Discrete Models of Compressed Beams in Elastic Media

The equilibrium configurations of compressed elastic beams in an elastic medium are investigated. The analysis is performed on discrete models by means of a geometric non linear treatment. The effect of the elastic stiffness of the medium on the overall stability of the structural system is taken into account through a parameter which represents the ratio between the elastic medium stiffness and the beam stiffness. This parameter shows to have a great influence on the buckling and post-buckling behaviour of the structure.
Endogenous Wnt/β-catenin signaling in Müller cells protects retinal ganglion cells from excitotoxic damage

Purpose To analyze whether activation of endogenous wingless (Wnt)/β-catenin signaling in Müller cells is involved in protection of retinal ganglion cells (RGCs) following excitotoxic damage. Methods Transgenic mice with a tamoxifen-dependent β-catenin deficiency in Müller cells were injected with N-methyl-D-aspartate (NMDA) into the vitreous cavity of one eye to induce excitotoxic damage of the RGCs, while the contralateral eye received PBS only. Retinal damage was quantified by counting the total number of RGC axons in cross sections of optic nerves and measuring the thickness of the retinal layers on meridional sections. Then, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was performed to identify apoptotic cells in retinas of both genotypes. Western blot analyses to assess the level of retinal β-catenin and real-time RT-PCR to quantify the retinal expression of neuroprotective factors were performed. Results Following NMDA injection of wild-type mice, a statistically significant increase in retinal β-catenin protein levels was observed compared to PBS-injected controls, an effect that was blocked in mice with a Müller cell-specific β-catenin deficiency. Furthermore, in mice with a β-catenin deficiency in Müller cells, NMDA injection led to a statistically significant decrease in RGC axons as well as a substantial increase in TUNEL-positive cells in the RGC layer compared to the NMDA-treated controls. Moreover, in the retinas of the control mice a NMDA-mediated statistically significant induction of leukemia inhibitory factor (Lif) mRNA was detected, an effect that was substantially reduced in mice with a β-catenin deficiency in Müller cells. Conclusions Endogenous Wnt/β-catenin signaling in Müller cells protects RGCs against excitotoxic damage, an effect that is most likely mediated via the induction of neuroprotective factors, such as Lif.
Microcellular Environmental Regulation of Silver Nanoparticles in Cancer Therapy: A Critical Review

Silver nanoparticles (AgNPs) play significant roles in various cancer cells such as functional heterogeneity, microenvironmental differences, and reversible changes in cell properties (e.g., chemotherapy). There is a lack of targets for processes involved in tumor cellular heterogeneity, such as metabolic clampdown, cytotoxicity, and genotoxicity, which hinders microenvironmental biology. Proteogenomics and chemical metabolomics are important tools that can be used to study proteins/genes and metabolites in cells, respectively. Chemical metabolomics have many advantages over genomics, transcriptomics, and proteomics in anticancer therapy. However, recent studies with AgNPs have revealed considerable genomic and proteomic changes, particularly in genes involved in tumor suppression, apoptosis, and oxidative stress. Metabolites interact biochemically with energy storage, neurotransmitters, and antioxidant defense systems. Mechanobiological studies of AgNPs in cancer metabolomics suggest that AgNPs may be promising tools that can be exploited to develop more robust and effective adaptive anticancer therapies. Herein, we present a proof-of-concept review for AgNPs-based proteogenomics and chemical metabolomics from various tumor cells with the help of several technologies, suggesting their promising use as drug carriers for cancer therapy.