Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations of the Lifestyle for Brain Health Index With Structural Brain Changes and Cognition

Background and Objectives Observational research has shown that a substantial proportion of all dementia cases worldwide are attributable to modifiable risk factors. Dementia risk scores might be useful to identify high-risk individuals and monitor treatment adherence. The objective of this study was to investigate whether a dementia risk score, the Lifestyle for Brain Health (LIBRA) index, is associated with MRI markers and cognitive functioning/impairment in the general population. Methods Cross-sectional data were used from the observational population-based cohort of The Maastricht Study. The weighted compound score of LIBRA (including 12 dementia risk and protective factors, e.g., hypertension, physical inactivity) was calculated, with higher scores indicating higher dementia risk. Standardized volumes of white matter, gray matter, and CSF (as proxy for general brain atrophy), white matter hyperintensities, and presence of cerebral small vessel disease were derived from 3T MRI. Cognitive functioning was tested in 3 domains: memory, information processing speed, and executive function and attention. Values ≤1.5 SDs below the average were defined as cognitive impairment. Multiple regression analyses and structural equation modeling were used, adjusted for age, sex, education, intracranial volume, and type 2 diabetes. Results Participants (n = 4,164; mean age 59 years; 49.7% men) with higher LIBRA scores (mean 1.19, range −2.7 to 9.2), denoting higher dementia risk, had higher volumes of white matter hyperintensities (β = 0.051, p = 0.002) and lower scores on information processing speed (β = −0.067, p = 0.001) and executive function and attention (β = −0.065, p = 0.004). Only in men, associations between LIBRA score and volumes of gray matter (β = −0.093, p < 0.001) and CSF (β = 0.104, p < 0.001) and memory (β = −0.054, p = 0.026) were found. White matter hyperintensities and CSF volume partly mediated the association between LIBRA score and cognition. Discussion Higher health- and lifestyle-based dementia risk is associated with markers of general brain atrophy, cerebrovascular pathology, and worse cognition, suggesting that LIBRA meaningfully summarizes individual lifestyle-related brain health. Improving LIBRA factors on an individual level might improve population brain health. Sex differences in lifestyle-related pathology and cognition need to be further explored. Classification of Evidence This study provides Class II evidence that higher LIBRA scores are significantly associated with lower scores in some cognitive domains and a higher risk of cognitive impairment.
SPR-Based Kinetic Analysis of the Early Stages of Infection in Cells Infected with Human Coronavirus and Treated with Hydroxychloroquine

Cell-based assays are a valuable tool for examination of virus–host cell interactions and drug discovery processes, allowing for a more physiological setting compared to biochemical assays. Despite the fact that cell-based SPR assays are label-free and thus provide all the associated benefits, they have never been used to study viral growth kinetics and to predict drug antiviral response in cells. In this study, we prove the concept that the cell-based SPR assay can be applied in the kinetic analysis of the early stages of viral infection of cells and the antiviral drug activity in the infected cells. For this purpose, cells immobilized on the SPR slides were infected with human coronavirus HCov-229E and treated with hydroxychloroquine. The SPR response was measured at different time intervals within the early stages of infection. Methyl Thiazolyl Tetrazolium (MTT) assay was used to provide the reference data. We found that the results of the SPR and MTT assays were consistent, and SPR is a reliable tool in investigating virus–host cell interaction and the mechanism of action of viral inhibitors. SPR assay was more sensitive and accurate in the first hours of infection within the first replication cycle, whereas the MTT assay was not so effective. After the second replication cycle, noise was generated by the destruction of the cell layer and by the remnants of dead cells, and masks useful SPR signals.
Personal Values in Relation to Risk Intelligence: Evidence from a Multi-Mediation Model

In a risk society, personal values can be important resources, useful for managing uncertainty and guiding people in the perception of risk. The goal of this article is to explore the relationship between risk intelligence and personal values. The participants were 731 Italian adults aged between 18 and 65 years (M = 30.25; DS = 10.71). The survey was composed of the following measures: Subjective Risk Intelligence Scale and Portrait Values Questionnaire. Data analyses have found significant relationships between some types of personal values and risk intelligence: subjective risk intelligence is negatively related to conservation and positively related to openness to change and self-transcendence, but it was not related to self-enhancement. Furthermore, values of openness to change and self-transcendence mediate the relationship between age and subjective risk intelligence, while conservation values and self-enhancement values did not mediate the same relationship. Implication for practice and future research will be discussed.
Herb–Drug Interactions: Worlds Intersect with the Patient at the Center

Abstract: Background This review examines three bodies of literature related to herb–drug interactions: case reports, clinical studies, evaluations found in six drug interaction checking resources. The aim of the study is to examine the congruity of resources and to assess the degree to which case reports signal for further study. A qualitative review of case reports seeks to determine needs and perspectives of case report authors. Methods: Systematic search of Medline identified clinical studies and case reports of interacting herb–drug combinations. Interacting herb–drug pairs were searched in six drug interaction resources. Case reports were analyzed qualitatively for completeness and to identify underlying themes. Results: Ninety-nine case-report documents detailed 107 cases. Sixty-five clinical studies evaluated 93 mechanisms of interaction relevant to herbs reported in case studies, involving 30 different herbal products; 52.7% of these investigations offered evidence supporting reported reactions. Cohen’s kappa found no agreement between any interaction checker and case report corpus. Case reports often lacked full information. Need for further information, attitudes about herbs and herb use, and strategies to reduce risk from interaction were three primary themes in the case report corpus. Conclusions: Reliable herb–drug information is needed, including open and respectful discussion with patients.
GP trainees' experiences of training

Understanding the experience of training in an authentic and rich way can be a powerful driver to reviewing teaching and learning practice. GP educators in the Health Education England Wessex region decided to take this a step further and examine the equity of the experience of training, including trainees' thoughts and views about how that experience could be improved.
A dual role for DNA binding by Runt in activation and repression of sloppy paired transcription

This work investigates the role of DNA binding by Runt in regulating the sloppy paired 1 (slp1) gene and in particular two distinct cis-regulatory elements that mediate regulation by Runt and other pair-rule transcription factors during Drosophila segmentation. We find that a DNA-binding–defective form of Runt is ineffective at repressing both the distal (DESE) and proximal (PESE) early stripe elements of slp1 and is also compromised for DESE-dependent activation. The function of Runt-binding sites in DESE is further investigated using site-specific transgenesis and quantitative imaging techniques. When DESE is tested as an autonomous enhancer, mutagenesis of the Runt sites results in a clear loss of Runt-dependent repression but has little to no effect on Runt-dependent activation. Notably, mutagenesis of these same sites in the context of a reporter gene construct that also contains the PESE enhancer results in a significant reduction of DESE-dependent activation as well as the loss of repression observed for the autonomous mutant DESE enhancer. These results provide strong evidence that DNA binding by Runt directly contributes to the regulatory interplay of interactions between these two enhancers in the early embryo.
Selectin Dependence of Allergic Skin Inflammation Is Diminished by Maternal Atopy

Allergic skin inflammation requires the influx of inflammatory cells into the skin. Extravasation of leukocytes into the skin requires interactions between endothelial selectins and their glycan ligands on the surface of leukocytes. Selectin-ligand formation requires the activity of several glycosyltransferases, including Fut7. In this report, we tested the importance of Fut7 for the development of allergic skin inflammation in the Stat6VT transgenic mouse model. We observed that Fut7 deficiency was protective but did not eliminate disease. Segregation of the data by gender of the parent that transmitted the Stat6VT transgene, but not by gender of the pups, which were analyzed for disease, revealed that the protective effects of Fut7 deficiency were significantly greater when dams were Stat6VT negative. In contrast, in mice from litters of Stat6VT+ dams, Fut7 deficiency resulted in only modest protection. These findings indicate that pups from atopic dams exhibit a greater propensity for allergic disease, similar to observations in humans, and that the effect of maternal atopy is due to enhanced selectin-independent mechanisms of leukocyte recruitment in their offspring. Together, these results demonstrate that Fut7 deficiency can be protective in a model of atopic dermatitis but that maternal atopy diminishes these protective effects, suggesting alternative pathways for leukocyte recruitment in the absence of Fut7 enzyme activity. These observations have implications for understanding how the environment in utero predisposes for the development of allergic disease.
Acyl-Coenzyme A: Cholesterol Acyltransferase (ACAT) in Cholesterol Metabolism: From Its Discovery to Clinical Trials and the Genomics Era

The purification and cloning of the acyl-coenzyme A: cholesterol acyltransferase (ACAT) enzymes and the sterol O-acyltransferase (SOAT) genes has opened new areas of interest in cholesterol metabolism given their profound effects on foam cell biology and intestinal lipid absorption. The generation of mouse models deficient in Soat1 or Soat2 confirmed the importance of their gene products on cholesterol esterification and lipoprotein physiology. Although these studies supported clinical trials which used non-selective ACAT inhibitors, these trials did not report benefits, and one showed an increased risk. Early genetic studies have implicated common variants in both genes with human traits, including lipoprotein levels, coronary artery disease, and Alzheimer’s disease; however, modern genome-wide association studies have not replicated these associations. In contrast, the common SOAT1 variants are most reproducibly associated with testosterone levels.
In Silico Identification of Cholesterol Binding Motifs in the Chemokine Receptor CCR3

CC motif chemokine receptor 3 (CCR3) is a Class A G protein-coupled receptor (GPCR) mainly responsible for the cellular trafficking of eosinophils. As such, it plays key roles in inflammatory conditions, such as asthma and arthritis, and the metastasis of many deadly forms of cancer. However, little is known about how CCR3 functionally interacts with its bilayer environment. Here, we investigate cholesterol binding sites in silico through Coarse-Grained Molecular Dynamics (MD) and Pylipid analysis using an extensively validated homology model based on the crystal structure of CCR5. These simulations identified several cholesterol binding sites containing Cholesterol Recognition/Interaction Amino Acid Consensus motif (CRAC) and its inversion CARC motifs in CCR3. One such site, a CARC site in TM1, in conjunction with aliphatic residues in TM7, emerged as a candidate for future investigation based on the cholesterol residency time within the binding pocket. This site forms the core of a cholesterol binding site previously observed in computational studies of CCR2 and CCR5. Most importantly, these cholesterol binding sites are conserved in other chemokine receptors and may provide clues to cholesterol regulation mechanisms in this subfamily of Class A GPCRs.
Acute effects of hypouricemia on endothelium, oxidative stress, and arterial stiffness: A randomized, double‐blind, crossover study

We hypothesized acute moderate and drastic reductions in uric acid concentration exert different effects on arterial function in healthy normotensive and hypertensive adults. Thirty‐six adults (aged 58 [55;63] years) with or without primary hypertension participated in a three‐way, randomized, double‐blind, crossover study in which [placebo] and [febuxostat] and [febuxostat and rasburicase] were administered. Febuxostat and rasburicase reduce the uric acid concentration by xanthine oxidoreductase inhibition and uric acid degradation into allantoin, respectively. Endothelial function was assessed in response to acetylcholine, sodium nitroprusside, heating (with and without nitric oxide synthase inhibition) using a laser Doppler imager. Arterial stiffness was determined by applanation tonometry, together with blood pressure, renin–angiotensin system activity, oxidative stress, and inflammation. Uric acid concentration was 5.1 [4.1;5.9], 1.9 [1.2;2.2] and 0.2 [0.2;0.3] mg/dL with [placebo], [febuxostat] and [febuxostat–rasburicase] treatments, respectively (p < 0.0001). Febuxostat improved endothelial response to heat particularly when nitric oxide synthase was inhibited (p < 0.05) and reduced diastolic and mean arterial pressure (p = 0.008 and 0.02, respectively). The augmentation index decreased with febuxostat (ANOVA p < 0.04). Myeloperoxidase activity profoundly decreased with febuxostat combined with rasburicase (p < 0.0001). When uric acid dropped, plasmatic antioxidant capacity markedly decreased, while superoxide dismutase activity increased (p < 0.0001). Other inflammatory and oxidant markers did not differ. Acute moderate hypouricemia encompasses minor improvements in endothelial function, blood pressure, and arterial stiffness.
Photobleached Oxidative Degradation of Melanins: Chemical Characterization of Melanins Present in Alpaca Fiber

In order to characterize the phenotype and to examine the effects of sun exposure on the color and structure of eumelanin (EM) and pheomelanin (PM) in alpaca fibers, we applied Soluene‐350 solubilization, alkaline hydrogen peroxide oxidation (AHPO) and hydroiodic acid (HI) hydrolysis to the base and tip fibers of 20 true‐black (TB) and 20 warm‐black (WB) alpacas. We analyzed absorbances at 500 nm (A500) and 650 nm (A650), Free and Total pyrrole‐2,3,5‐tricarboxylic acid (PTCA), 2,3,4,5‐tetracarboxylic acid (PTeCA) as degradative products from EM, and 4‐amino‐3‐hydroxyphenylalanine (4‐AHP), 3‐amino‐4‐hydroxyphenylalanine (3‐AHP) and thiazole‐2,4,5‐tricarboxylic acid (TTCA) as degradative products from PM. We found that the ratio of PTeCA/Total PTCA increased significantly from the base to the tip in both colors of alpaca fibers, while the ratios of A650/A500 and 4‐AHP/3‐AHP decreased significantly. These results show that structures made of both EM and PM in alpaca fibers are modified significantly by sun exposure inducing color change. This study indicates that the ratios of A650/A500, PTeCA/Total PTCA and 4‐AHP/3‐AHP are highly sensitive markers of color change and photodegradation of EM and PM, respectively.
Metabolomic Studies for the Evaluation of Toxicity Induced by Environmental Toxicants on Model Organisms

Environmental pollution causes significant toxicity to ecosystems. Thus, acquiring a deeper understanding of the concentration of environmental pollutants in ecosystems and, clarifying their potential toxicities is of great significance. Environmental metabolomics is a powerful technique in investigating the effects of pollutants on living organisms in the environment. In this review, we cover the different aspects of the environmental metabolomics approach, which allows the acquisition of reliable data. A step-by-step procedure from sample preparation to data interpretation is also discussed. Additionally, other factors, including model organisms and various types of emerging environmental toxicants are discussed. Moreover, we cover the considerations for successful environmental metabolomics as well as the identification of toxic effects based on data interpretation in combination with phenotype assays. Finally, the effects induced by various types of environmental toxicants in model organisms based on the application of environmental metabolomics are also discussed.
MiR-146b-5p targets IFI35 to inhibit inflammatory response and apoptosis via JAK1/STAT1 signalling in lipopolysaccharide-induced glomerular cells

Abstract The dysregulated microRNAs (miRNAs) are implicated in the malignancy of lupus nephritis (LN). This work aims to analyse the effect and mechanism of miR-146b-5p in lipopolysaccharides (LPS)-induced model of LN in vitro. The serum samples of LN patients and normal volunteers were collected. HK-2 cells were challenged via LPS. miR-146b-5p and interferon-induced protein 35 (IFI35) abundances were detected via quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The inflammatory response was assessed via inflammatory cytokines levels via qRT-PCR and enzyme-linked immunosorbent assay. Cell apoptosis was analysed via flow cytometry and apoptotic protein levels. The protein levels of JAK1/STAT1 signalling were detected via western blot. The relationship of miR-146b-5p and IFI35 was analysed via bioinformatics and dual-luciferase reporter assays. This study revealed that miR-146b-5p level was declined and IFI35 abundance was elevated in serum of LN patients and LPS-challenged HK-2 cells. Functionally, IFI35 overexpression promoted LPS-caused inflammatory response and cell apoptosis, and knockdown of IFI35 caused an opposite trend. Meanwhile, miR-146b-5p targeted IFI35 to suppress inflammatory response and cell inflammatory response and apoptosis via inactivating the JAK1/STAT1 pathway. MiR-146b-5p suppressed inflammatory response and cell apoptosis by IFI35 mediated-JAK1/STAT1 signalling in HK-2 cells, which provided a new mechanism for understanding the pathogenesis of LN.
Recent Development of Nanomaterials-Based Cytosensors for the Detection of Circulating Tumor Cells

The accurate analysis of circulating tumor cells (CTCs) holds great promise in early diagnosis and prognosis of cancers. However, the extremely low abundance of CTCs in peripheral blood samples limits the practical utility of the traditional methods for CTCs detection. Thus, novel and powerful strategies have been proposed for sensitive detection of CTCs. In particular, nanomaterials with exceptional physical and chemical properties have been used to fabricate cytosensors for amplifying the signal and enhancing the sensitivity. In this review, we summarize the recent development of nanomaterials-based optical and electrochemical analytical techniques for CTCs detection, including fluorescence, colorimetry, surface-enhanced Raman scattering, chemiluminescence, electrochemistry, electrochemiluminescence, photoelectrochemistry and so on.
The PPIP5K Family Member Asp1 Controls Inorganic Polyphosphate Metabolism in S. pombe

Inorganic polyphosphate (polyP) which is ubiquitously present in both prokaryotic and eukaryotic cells, consists of up to hundreds of orthophosphate residues linked by phosphoanhydride bonds. The biological role of this polymer is manifold and diverse and in fungi ranges from cell cycle control, phosphate homeostasis and virulence to post-translational protein modification. Control of polyP metabolism has been studied extensively in the budding yeast Saccharomyces cerevisiae. In this yeast, a specific class of inositol pyrophosphates (IPPs), named IP7, made by the IP6K family member Kcs1 regulate polyP synthesis by associating with the SPX domains of the vacuolar transporter chaperone (VTC) complex. To assess if this type of regulation was evolutionarily conserved, we determined the elements regulating polyP generation in the distantly related fission yeast Schizosaccharomyces pombe. Here, the VTC machinery is also essential for polyP generation. However, and in contrast to S. cerevisiae, a different IPP class generated by the bifunctional PPIP5K family member Asp1 control polyP metabolism. The analysis of Asp1 variant S. pombe strains revealed that cellular polyP levels directly correlate with Asp1-made IP8 levels, demonstrating a dose-dependent regulation. Thus, while the mechanism of polyP synthesis in yeasts is conserved, the IPP player regulating polyP metabolism is diverse.
Performance of methods to detect genetic variants from bisulphite sequencing data in a non‐model species

The profiling of epigenetic marks like DNA methylation has become a central aspect of studies in evolution and ecology. Bisulphite sequencing is commonly used for assessing genome‐wide DNA methylation at single nucleotide resolution but these data can also provide information on genetic variants like single nucleotide polymorphisms (SNPs). However, bisulphite conversion causes unmethylated cytosines to appear as thymines, complicating the alignment and subsequent SNP calling. Several tools have been developed to overcome this challenge, but there is no independent evaluation of such tools for non‐model species, which often lack genomic references. Here, we used whole‐genome bisulphite sequencing (WGBS) data from four female great tits (Parus major) to evaluate the performance of seven tools for SNP calling from bisulphite sequencing data. We used SNPs from whole‐genome resequencing data of the same samples as baseline SNPs to assess common performance metrics like sensitivity, precision, and the number of true positive, false positive, and false negative SNPs for the full range of variant and genotype quality values. We found clear differences between the tools in either optimizing precision (Bis‐SNP), sensitivity (biscuit), or a compromise between both (all other tools). Overall, the choice of SNP caller strongly depends on which performance parameter should be maximized and whether ascertainment bias should be minimized to optimize downstream analysis, highlighting the need for studies that assess such differences.