Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in gliclazide‐associated genes may predict poor bladder cancer prognosis

In recent years, an increasing number of patients have had diabetes and cancer simultaneously; thus, it is crucial for physicians to select hypoglycemic drugs with the lowest risk of inducing cancer. Gliclazide is a widely used sulfonylurea hypoglycemic drug, but its cancer risk remains controversial. Here, we explored the primary targets of gliclazide and its associated genes by querying an available database to construct a biological network. By using DrugBank and STRING, we found two primary targets of gliclazide and 50 gliclazide‐associated genes, which were then enrolled for Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using WebGestalt. From this analysis, we obtained the top 15 KEGG pathways. Accurate analysis of these KEGG pathways revealed that two pathways, one linked to bladder cancer and the other linked to the phosphoinositide 3‐kinase–AKT signaling pathway, are functionally associated with gliclazide, and from these we identified four overlapping genes. Finally, genomic analysis using cBioPortal showed that genomic alterations of these four overlapping genes predict poor prognosis for patients with bladder cancer. In conclusion, gliclazide should be used with caution as a hypoglycemic drug for diabetic patients with cancer, especially bladder cancer. In addition, this study provides a functional network analysis to flexibly explore drug interaction systems and estimate their safety.
Pharmacokinetics and Pharmacodynamics of Remimazolam (CNS 7056) after Continuous Infusion in Healthy Male Volunteers

Background: Remimazolam (CNS 7056) is a new ultra-short acting benzodiazepine for IV sedation. This study aimed to investigate the electroencephalogram (EEG) pharmacodynamics of remimazolam infusion. Methods: Twenty healthy male volunteers received remimazolam as continuous IV infusion of 5 mg/min for 5 min, 3 mg/min for the next 15 min, and 1 mg/min for further 15 min. Continuous EEG monitoring was performed by a neurophysiologic system with electrodes placed at F3, F4, C3, C4, O1, O2, Cz, and Fp1 (10/20 system) and using the Narcotrend Index. Sedation was assessed clinically by using the Modified Observer’s Assessment of Alertness and Sedation scale. Pharmacodynamic models were developed for selected EEG variables and Narcotrend Index. Results: EEG changes during remimazolam infusion were characterized by an initial increase in beta frequency band and a late increase in delta frequency band. The EEG beta ratio showed a prediction probability of Modified Observer’s Assessment of Alertness and Sedation score of 0.79, and could be modeled successfully using a standard sigmoid Emax model. Narcotrend Index showed a prediction probability of Modified Observer’s Assessment of Alertness and Sedation score of 0.74. The time course of Narcotrend Index was described by an extended sigmoid Emax model with two sigmoid terms and different plasma–effect equilibration times. Conclusions: Beta ratio was identified as a suitable EEG variable for monitoring remimazolam sedation. Narcotrend Index appeared less suitable than the beta ratio for monitoring the sedative effect if remimazolam is administered alone. Electroencephalogram changes during remimazolam infusion in 20 adult male volunteers were characterized by an initial increase in the beta frequency band and a late increase in the delta frequency band. Beta ratio had a monotonic relationship to Modified Observer’s Assessment of Alertness and Sedation scores and could be modeled using a standard sigmoid Emax pharmacodynamic model. The standard sigmoid Emax model failed to describe the time course of the Narcotrend Index appropriately; it was necessary to extend the model by adding a second sigmoid term with a second effect site concentration. Supplemental Digital Content is available in the text.
Effect of morphology and temperature treatment control on the photocatalytic and photoluminescence properties of SrWO_4 crystals

This work reports the combined effect of the morphology and crystallization degree of the strontium tungstate (SrWO_4) scheelite structure on its photocatalytic and photoluminescence properties. The difference in the precursor ratio leads to two morphologies, spindle and sphere, which remain unchanged with heat treatment up to 500 °C. However, the crystallite sizes of the as-obtained samples and samples treated at 300 and 500 °C are about 50–74 nm for spindles and 44–110 nm for spheres. Both morphologies and thermal treatments lead to the variation in the photoluminescence and photodegradation of rhodamine (RhB) and methylene blue (MB) dyes under UV irradiation. A stronger photodegradation efficiency was found for RhB (90%) than for MB (72%). The photoinduced mechanism is more significant for RhB and becomes more efficient for samples treated at high temperature, while the photocatalysis of MB is weak due to the adsorption process. A broad visible photoluminescence band was observed at room temperature and chromaticity coordinates were identified, which confirmed the emission wavelength. The most intense photoluminescence was obtained for samples treated at 300 °C, corresponding to the optimal disordered structures and accompanied by a redshift wavelength for both spheres and spindles. In this case, the spindles showed the most intense photoluminescence, almost ten times higher than that in spheres.
Preventive Effect of Lactobacillus fermentum CQPC08 on 4-Nitroquineline-1-Oxide Induced Tongue Cancer in C57BL/6 Mice

Lactobacillus fermentum CQPC08 (LF-CQPC08) is a newly discovered strain of bacteria isolated and identified from traditional pickled vegetables in Sichuan, China. We used 4-nitroquinoline 1-oxide to establish an experimental tongue cancer mouse model to evaluate the preventive effect of LF-CQPC08 on tongue cancer in vivo. Lactobacillus delbruechii subsp. bulgaricus, is a common commercial strain and is used as a positive control to compare the effect with LF-CQPC08. The preventive strength and mechanism of LF-CQPC08 on tongue cancer were determined by measuring the biochemical indicators in mouse serum and tissues. Our results showed LF-CQPC08 inhibits the decline of splenic index, thymus index, percentage of phagocytic macrophages, and phagocytic index effectively. LF-CQPC08 also increased levels of mouse serum granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), immunoglobulin (Ig)G, IgM levels of serum interleukin (IL)-4, IL-12, tumor necrosis factor-alpha, and interferon-gamma levels, thereby inhibiting the decline in immunity caused by tongue cancer. It also increased the activity levels of superoxide dismutase and glutathione peroxidase and decreased the levels of malondialdehyde in the tissues of the tongue cancer mouse model, thereby suppressing the oxidative stress damage in the tissue caused by tongue cancer. Through quantitative PCR, LF-CQPC08 upregulated the mRNA expression of nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione-S-transferases-π (GST-π), and Bcl-2-associated X protein (Bax), and downregulated the mRNA expression of p53, p63, p73, phosphatase and tensin homolog (PTEN), B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL) in the tongue tissues of the tongue cancer mouse. These results indicated that LF-CQPC08 reduced the influence of tongue cancer on the immune system and oxidative balance and improved the immunity and enhanced antioxidant capacity of the mouse model, thereby preventing tongue cancer. LF-CQPC08 could be used as a microbial resource with a preventive effect on tongue cancer.
Precision exercise medicine: understanding exercise response variability

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability. In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels—a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability.
Expression Dynamics of Core RNAi Machinery Genes in Pea Aphids Upon Exposure to Artificially Synthesized dsRNA and miRNAs

The pea aphid is an important pest of vegetables and causes serious losses worldwide. RNA interference (RNAi) is an effective pest control tool, and three sub-pathways have been described: The miRNA pathway, siRNA pathway, and piRNA pathway. A large number of genes in miRNA pathway and piRNA pathway are found to be expanded. To study the roles of these genes, the expression of 25 core RNAi genes was screened in spatiotemporal samples, artificially synthesized dsRNA and miRNA treated samples. The 25 genes were all expressed during different development stages and in different tissues. In dsRNA-treated samples and miRNA-treated samples, the expressions of genes in these three pathways were induced, especially the expanded genes. This suggests a complex network of RNAi core genes in the three sub-pathways. Treatment of miRNA seems to induce gene expression in a dosage-dependent manner. These results increase our knowledge of the siRNA pathway and related factors from RNAi pathway in aphids and promote the use of RNAi for the control of aphid pests.
Comparing 22 popular phosphoproteomics pipelines for peptide identification and site localization.

Phosphorylation-driven cell signaling governs most biological functions and is widely studied using mass spectrometry-based phosphoproteomics. Identifying the peptides and localizing the phosphorylation sites within them from the raw data is challenging and can be performed by several algorithms that return scores that are not directly comparable. This increases the heterogeneity among published phosphoproteomics data sets and prevents their direct integration. Here, we compare 22 pipelines implemented in the main software tools used for bottom-up phosphoproteomics analysis (MaxQuant, Proteome Discoverer, PeptideShaker). We test six search engines (Andromeda, Comet, Mascot, MS Amanda, SequestHT, and X! Tandem) in combination with several localization scoring algorithms (delta score, D-score, PTM-score, phosphoRS, and Ascore). We show that these follow very different score distributions, which can lead to different false localization rates for the same threshold. We provide a strategy to discriminate correctly from incorrectly localized phosphorylation sites in a consistent manner across the tested pipelines. The results presented here can help users choose the most appropriate pipeline and cutoffs for their phosphoproteomics analysis.
Defective regression models for cure rate modeling with interval‐censored data

Regression models in survival analysis are most commonly applied for right‐censored survival data. In some situations, the time to the event is not exactly observed, although it is known that the event occurred between two observed times. In practice, the moment of observation is frequently taken as the event occurrence time, and the interval‐censored mechanism is ignored. We present a cure rate defective model for interval‐censored event‐time data. The defective distribution is characterized by a density function whose integration assumes a value less than one when the parameter domain differs from the usual domain. We use the Gompertz and inverse Gaussian defective distributions to model data containing cured elements and estimate parameters using the maximum likelihood estimation procedure. We evaluate the performance of the proposed models using Monte Carlo simulation studies. Practical relevance of the models is illustrated by applying datasets on ovarian cancer recurrence and oral lesions in children after liver transplantation, both of which were derived from studies performed at A.C. Camargo Cancer Center in São Paulo, Brazil.
Effects of toll-like receptor-7 agonists on feeding behaviour, voluntary activity, cloacal temperature and crop emptying in chicks

ABSTRACT 1. The purpose of the present study was to determine if an intraperitoneal injection of two toll-like receptor-7 (TLR7) agonists, imiquimod and resiquimod, affect feed intake, voluntary activity, cloacal temperature, crop-emptying rate, plasma corticosterone (CORT) and glucose concentrations, and splenic gene expression of cytokines in chicks (Gallus gallus). 2. Although intraperitoneal injection of 100 µg imiquimod significantly increased splenic gene expression of interleukin-1β (IL-1β), IL-6, IL-8, and interferon-γ (IFN-γ), it did not affect feed intake, voluntary activity, cloacal temperature, crop-emptying rate or plasma constituents. 3. Intraperitoneal injection of 100 µg resiquimod significantly decreased feed intake, voluntary activity, cloacal temperature, crop-emptying rate and increased plasma corticosterone concentrations. 4. Intraperitoneal injection of resiquimod significantly increased splenic gene expression of IL-1β, IL-6, IL-8, IFN-γ, and tumour necrosis factor-like cytokine 1A. 5. The results showed that activation of TLR7 is associated with anorexia, hypoactivity, hypothermia, disturbance of feed passage in the digestive tract and the response to stress in chicks.
Estimating Social Influence Using Latent Space Adjusted Approach in R

Social influence, sometimes referred to as spillover or contagion, have been extensively studied in various empirical social network research. However, there are various estimation challenges in identifying social influence effects, as they are often entangled with other factors, such as homophily in the selection process, the individual's preference for the same social settings, etc. Methods currently available either do not solve these problems or require strong assumptions. Recent works by Xu 2018 and others show that a latent-space adjusted approach based on the latent space model has potential to disentangle the influence from other processes, and the simulation evidence shows the approach performs better than other state-of-the-art approaches in terms of recovering the true social influence effect when there is an unobserved trait co-determining influence and selection. In this paper we illustrate how latent space adjusted approach accounts for bias in the estimation of the social influence effect, and demonstrate how this approach can be implemented to estimate various social influence models with an empirical example in R.
What Makes Research Software Sustainable? An Interview Study with Research Software Engineers

Software is now a vital scientific instrument, providing the tools for data collection and analysis across disciplines from bioinformatics and computational physics, to the humanities. The software used in research is often home-grown and bespoke: it is constructed for a particular project, and rarely maintained beyond this, leading to rapid decay, and frequent 'reinvention of the wheel'. Understanding how to develop sustainable research software, such that it is suitable for future reuse, is therefore of interest to both researchers and funders, but how to achieve this remains an open question. Here we report the results of an interview study examining how research software engineers – the people actively developing software in an academic research environment – subjectively define software sustainability. Thematic analysis of the data reveals two interacting dimensions: intrinsic sustainability, which relates to internal qualities of software, such as modularity, encapsulation and testability, and extrinsic sustainability, concerning cultural and organisational factors, including how software is resourced, supported and shared. Research software engineers believe an increased focus on quality and discoverability are key factors in increasing the sustainability of academic research software.
How can memories last for days, years, or a lifetime? Proposed mechanisms for maintaining synaptic potentiation and memory

With memory encoding reliant on persistent changes in the properties of synapses, a key question is how can memories be maintained from days to months or a lifetime given molecular turnover? It is likely that positive feedback loops are necessary to persistently maintain the strength of synapses that participate in encoding. Such feedback may occur within signal-transduction cascades and/or the regulation of translation, and it may occur within specific subcellular compartments or within neuronal networks. Not surprisingly, numerous positive feedback loops have been proposed. Some posited loops operate at the level of biochemical signal-transduction cascades, such as persistent activation of Ca2+/calmodulin kinase II (CaMKII) or protein kinase Mζ. Another level consists of feedback loops involving transcriptional, epigenetic and translational pathways, and autocrine actions of growth factors such as BDNF. Finally, at the neuronal network level, recurrent reactivation of cell assemblies encoding memories is likely to be essential for late maintenance of memory. These levels are not isolated, but linked by shared components of feedback loops. Here, we review characteristics of some commonly discussed feedback loops proposed to underlie the maintenance of memory and long-term synaptic plasticity, assess evidence for and against their necessity, and suggest experiments that could further delineate the dynamics of these feedback loops. We also discuss crosstalk between proposed loops, and ways in which such interaction can facilitate the rapidity and robustness of memory formation and storage.
Implementation of Fall Preventions Over the Past 15 Years

Supplemental Digital Content is Available in the Text. Background: Hospital fall rates have changed minimally with preventive measures; however, the effect on injury rate is unclear. Purpose: The purpose was to determine whether fall-related injuries have changed over time. Methods: A retrospective comparison was done of 1134 adult inpatient falls in 2017 to 1235 falls in 2001-2002 for injury and fall circumstances. Separate comparisons were made of patient characteristics by service line for 2017. Results: Severe fall injuries declined from 6% to 2.4%. Elimination issues remained the most common circumstance (38.9% and 42%). In 2017, malnutrition (31.6%), low function (61.4%), fall history (26.3%), and use of high-risk medications (83.2%) were common in patients who fell. Predictors of falls with injury by patient population were as follows: surgery—male gender (P = .01), low function (P = .006), elimination issues (P = .04); oncology—low function (P = .04); and neurology—low function (P = .02). Conclusions: Severe fall-related injuries have decreased in the past 15 years. The most common circumstance for falls remains elimination issues.
Variational Estimators for Bayesian Optimal Experimental Design

Bayesian optimal experimental design (BOED) is a principled framework for making efficient use of limited experimental resources. Unfortunately, its applicability is hampered by the difficulty of obtaining accurate estimates of the expected information gain (EIG) of an experiment. To address this, we introduce several classes of fast EIG estimators suited to the experiment design context by building on ideas from variational inference and mutual information estimation. We show theoretically and empirically that these estimators can provide significant gains in speed and accuracy over previous approaches. We demonstrate the practicality of our approach via a number of experiments, including an adaptive experiment with human participants.
Characterisation of antibiotic resistance of Salmonella isolated from dog treats in Japan

Abstract Dog treats might be contaminated with Salmonella. In Canada and the USA, outbreaks of human salmonellosis related to exposure to animal-derived dog treats were reported. Consequently, surveillance data on Salmonella contamination of dog treats have been gathered in many countries, but not in Japan. In the current study, we investigated whether dog treats in Japan were contaminated with Salmonella. Overall, 303 dog treats (of which 255 were domestically produced) were randomly collected and the presence of Salmonella investigated. Seven samples were positive for Salmonella enterica subsp. enterica. Among these isolates, three were identified as serovar 4,5,12:i:–; two were serovar Rissen; and two were serovar Thompson. All serovar 4,5,12:i:– and Thompson isolates were resistant to one or more drugs. Two serovar Rissen isolates were fully susceptible to all tested antimicrobial agents. All Salmonella isolates were susceptible to cefotaxime, ciprofloxacin and nalidixic acid. The gene blaTEM was detected in two serovar 4,5,12:i:– isolates. The blaCTX−M and blaCMY genes were not detected in any isolates. This study demonstrated that dog treats in Japan could constitute a potential source of dog and human Salmonella infections, including multidrug-resistant Salmonella isolates.
MicroRNA Biomarker hsa-miR-195-5p for Detecting the Risk of Lung Cancer

Background Lung cancer is one of the leading diagnosed cancers worldwide, and microRNAs could be used as biomarkers to diagnose lung cancer. hsa-miR-195 has been demonstrated to affect the prognosis of NSCLC (non-small-cell lung cancer) in a previous study. However, the diagnostic value of hsa-miR-195-5p in lung cancer has not been investigated. Methods To evaluate the ability of hsa-miR-195-5p to diagnose lung cancer, we compared the expression of hsa-miR-195-5p in lung cancer patients, COPD patients, and normal controls. Receiver operating characteristic (ROC) curve analysis was performed to investigate the sensitivity and specificity of hsa-miR-195-5p. Coexpression network and pathway analysis were carried out to explore the mechanism. Results We found that hsa-miR-195-5p had lower expression in lung cancer and COPD patients than in normal controls, and the AUC was 0.92 for diagnosing lung cancer. hsa-miR-143 correlated with hsa-miR-195-5p, and by combining these two microRNAs, the AUC was 0.97 for diagnosing lung cancer. Conclusions hsa-miR-195-5p may act as a biomarker that contributes to the diagnosis of lung cancer and the detection of its high-risk population.