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Under GFAP promoter control, the U251 stable clone exhibited GCV sensitivity, while the neuronal N2A clones were nonreactive. During GCV treatment, cells underwent apoptosis on day 3 and dying cells were identified after day 5. Nestin was increasingly expressed in surviving cells, indicating that the population of neural stem-like cells was enriched. Lower levels of GFAP expression were detected in surviving cells. Furthermore, βIII-tubulin-positive neuron-like cells were identified after GCV treatment. This study established pGFAP-HSVtk-P2A-EGFP plasmids that successfully ablated GFAP-positive glioblastoma cells, but left neuronal N2A cells intact. These data suggest that the neural differentiation of glioblastoma cells can be promoted by treatment with the HSVtk/GCV system.Ammonia is a pollutant frequently found in aquatic ecosystems. In fish, ammonia can cause physical damage, alter its behaviour, and even cause death. Exposure to ammonia also increases fish physiological stress, which can be measured through biomarkers. In this study, we analysed the effect of sublethal ammonia concentrations on the behaviour and the oxidative stress of Barbus meridionalis that had been pre-exposed to this compound in the wild. Wild-caught fish from a polluted site (pre-exposed fish) and from an unpolluted site (non-pre-exposed fish) were exposed, under experimental conditions, to total ammonia concentrations (TAN) of 0, 1, 5, and 8 mg/L. Swimming activity, feeding behaviour, and oxidative stress response based on biomarkers were analysed. Pre-exposed fish showed both an altered behaviour and an altered oxidative stress response in the control treatment (0 mg/L). Differences in swimming activity were also found as pre-exposed fish swam less. Lower feeding activity (voracity and satiety) and altered response to oxidative stress were also observed at ≥ 1 mg/L TAN. Biomarker results confirmed pre-exposed fish suffer from a reduction in their antioxidant defences and, hence, showed increased oxidative tissue damage. In summary, pre-exposed fish showed more sensitivity to ammonia exposure than fish from a pristine site.Over the last decade the availability of SNP-trait associations from genome-wide association studies has led to an array of methods for performing Mendelian randomization studies using only summary statistics. A common feature of these methods, besides their intuitive simplicity, is the ability to combine data from several sources, incorporate multiple variants and account for biases due to weak instruments and pleiotropy. With the advent of large and accessible fully-genotyped cohorts such as UK Biobank, there is now increasing interest in understanding how best to apply these well developed summary data methods to individual level data, and to explore the use of more sophisticated causal methods allowing for non-linearity and effect modification. In this paper we describe a general procedure for optimally applying any two sample summary data method using one sample data. Our procedure first performs a meta-analysis of summary data estimates that are intentionally contaminated by collider bias between the genetic instruments and unmeasured confounders, due to conditioning on the observed exposure. These estimates are then used to correct the standard observational association between an exposure and outcome. Simulations are conducted to demonstrate the method's performance against naive applications of two sample summary data MR. We apply the approach to the UK Biobank cohort to investigate the causal role of sleep disturbance on HbA1c levels, an important determinant of diabetes. Our approach can be viewed as a generalization of Dudbridge et al. (Nat. IWP-4 concentration Comm. 10 1561), who developed a technique to adjust for index event bias when uncovering genetic predictors of disease progression based on case-only data. Our work serves to clarify that in any one sample MR analysis, it can be advantageous to estimate causal relationships by artificially inducing and then correcting for collider bias.
During uncertainties associated with the COVID-19 pandemic, effectively improving people's health literacy is more important than ever. Drawing knowledge maps of health literacy research through data mining and visualized measurement technology helps systematically present the research status and development trends in global academic circles.

This paper uses CiteSpace to carry out a metric analysis of 9,492 health literacy papers included in Web of Science through mapping knowledge domains. First, based on the production theory of scientific knowledge and the data mining of citations, the main bodies (country, institution and author) that produce health literacy knowledge as well as their mutual cooperation (collaboration network) are both clarified. Additionally, based on the quantitative framework of cocitation analysis, this paper introduces the interdisciplinary features, development trends and hot topics of the field. Finally, by using burst detection technology in the literature, it further reveals ld will expand in two directions, namely, mental health literacy and eHealth literacy, both of which are closely linked to social development and issues. The results of this study provide references for future applied research in health literacy.
A systematic approach is needed to address the challenges of health literacy, and the network framework of cooperation on health literacy at regional, national and global levels should be strengthened to further promote the application of health literacy research. In the future, we anticipate that this research field will expand in two directions, namely, mental health literacy and eHealth literacy, both of which are closely linked to social development and issues. The results of this study provide references for future applied research in health literacy.
Patient-reported outcome measures (PROMs) can provide valuable insights on the impact of a disease or treatment on a patient's health-related quality of life. In ophthalmology, particularly in dry eye disease (DED) and ocular surface disease (OSD), it is unclear whether the available PROMs were developed using comprehensive guidelines. To address this, we evaluated the methodological quality of studies assessing the psychometric properties of PROMs in DED and OSD [PROSPERO registration number CRD42019142328].

Four databases were searched; reference list and citation searching of included studies was also conducted. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to appraise the quality of the studies evaluating the psychometric properties of PROMs used in DED and OSD.

The search strategy (S3 Table) retrieved 5,761 records, 573 duplicates were removed, 5,188 abstracts were screened and 127 full-text articles were retrieved for further review. sing the COSMIN standards. The majority of the studies evaluating PROMs included in this review did not meet the recommended COSMIN criteria and the quality of the PROMs evaluated is not assured. Further evaluation of their psychometric properties is required if these are going to be used in clinical practice or research.The accurate detection of foot-strike and toe-off is often critical in the assessment of running biomechanics. The gold standard method for step event detection requires force data which are not always available. Although kinematics-based algorithms can also be used, their accuracy and generalisability are limited, often requiring corrections for speed or foot-strike pattern. The purpose of this study was to develop FootNet, a novel kinematics and deep learning-based algorithm for the detection of step events in treadmill running. Five treadmill running datasets were gathered and processed to obtain segment and joint kinematics, and to identify the contact phase within each gait cycle using force data. The proposed algorithm is based on a long short-term memory recurrent neural network and takes the distal tibia anteroposterior velocity, ankle dorsiflexion/plantar flexion angle and the anteroposterior and vertical velocities of the foot centre of mass as input features to predict the contact phase within a given gait cycle. The chosen model architecture underwent 5-fold cross-validation and the final model was tested in a subset of participants from each dataset (30%). Non-parametric Bland-Altman analyses (bias and [95% limits of agreement]) and root mean squared error (RMSE) were used to compare FootNet against the force data step event detection method. The association between detection errors and running speed, foot-strike angle and incline were also investigated. FootNet outperformed previously published algorithms (foot-strike bias = 0 [-10, 7] ms, RMSE = 5 ms; toe-off bias = 0 [-10, 10] ms, RMSE = 6 ms; and contact time bias = 0 [-15, 15] ms, RMSE = 8 ms) and proved robust to different running speeds, foot-strike angles and inclines. We have made FootNet's source code publicly available for step event detection in treadmill running when force data are not available.
In the absence of a vaccine or pharmacological treatment, prevention and control of Guinea worm disease is dependent on timely identification and containment of cases to interrupt transmission. The Chad Guinea Worm Eradication Program (CGWEP) surveillance system detects and monitors Guinea worm disease in both humans and animals. Although Guinea worm cases in humans has declined, the discovery of canine infections in dogs in Chad has posed a significant challenge to eradication efforts. A foundational information system that supports the surveillance activities with modern data management practices is needed to support continued program efficacy.

We sought to assess the current CGWEP surveillance and information system to identify gaps and redundancies and propose system improvements. We reviewed documentation, consulted with subject matter experts and stakeholders, inventoried datasets to map data elements and information flow, and mapped data management processes. We used the Information Value Cycle (IVthese findings, we proposed a four-phased roadmap for centralizing data systems and transitioning to an electronic data capture system. These included development of a data governance plan, transition to electronic data entry and centralized data storage, transition to a relational database, and cloud-based integration. The method and outcome of this assessment could be used by other neglected tropical disease programs looking to transition to modern electronic data capture systems.Plasmodium vivax, a major contributor to the malaria burden in India, has the broadest geographic distribution and shows higher genetic diversity than P. falciparum. Here, we investigated the genetic diversity of two leading P. vivax vaccine candidate antigens, at three geographically diverse malaria-endemic regions in India. Pvama1 and Pvmsp119 partial coding sequences were generated from one hundred P. vivax isolates in India (Chennai n = 28, Nadiad n = 50 and Rourkela n = 22) and ~1100 published sequences from Asia, South America, North America, and Oceania regions included. These data were used to assess the genetic diversity and potential for vaccine candidacy of both antigens on a global scale. A total of 44 single nucleotide polymorphism (SNPs) were identified among 100 Indian Pvama1 sequences, including 10 synonymous and 34 nonsynonymous mutations. Nucleotide diversity was higher in Rourkela and Nadiad as compared to Chennai. Nucleotide diversity measures showed a strong balancing selection in Indian and global population for domain I of Pvama1, which suggests that it is a dominant target of the protective immune response.
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