Miracle-dz/UniFAR-FTUs huggingface dataset:
Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice

Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contributes to angiotensin II (Ang II)-induced aortic stiffening and endothelial dysfunction in females via increased pro-inflammatory (M1) macrophage polarization. Female mice lacking MR in myeloid cells (MyMRKO) were infused with Ang II (500 ng/kg/min) for 4 weeks. This was followed by determinations of aortic stiffness and vasomotor responses, as well as measurements of markers of inflammation and macrophage infiltration/polarization in different adipose tissue compartments. MyMRKO mice were protected against Ang II-induced aortic endothelial stiffening, as assessed via atomic force microscopy in aortic explants, and vasorelaxation dysfunction, as measured by aortic wire myography. In alignment, MyMRKO mice were protected against Ang II-induced macrophage infiltration and M1 polarization in visceral adipose tissue (VAT) and thoracic perivascular adipose tissue (tPVAT). Collectively, this study demonstrates a critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females associated with pro-inflammatory macrophage polarization in VAT and tPVAT. Our data have potential clinical implications for the prevention and management of cardiovascular disease in women, who are disproportionally at higher risk for poor outcomes.
Effect of Liraglutide on Cardiometabolic Risk Profile in People with Coronary Artery Disease with or without Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Whether liraglutide use improves cardiometabolic risk factors in different subsets of subjects with coronary artery disease (CAD) remains unclear. In a systematic review and meta-analysis, we quantified the effects of liraglutide on cardiometabolic risk profile in subjects with CAD with or without type 2 diabetes mellitus (T2D). Methods: Online database searches were conducted in PubMed, Scopus, EMBASE, Web of Science, Cochrane library, and Google Scholar from incept up to 15th January 2021. We identified randomized controlled trials (RCTs) assessing the effects of liraglutide compared to placebo on cardiometabolic risk profile. We used the random- or fixed-effect models to pool the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Results: Out of a total of 7,320 citations, six articles (seven RCTs) with 294 subjects with CAD (mean age, 61.21 years; 19% women) were included. Our findings presented as WMD and 95% CI showed a statistical significant decrease in hemoglobin A1c (HbA1c) [−0.36%; −0.47; −0.26, p < 0.001; I 2 = 0.0% (with 6 RCTs)], body mass index (BMI) [−0.61 kg/m2; −1.21; −0.01, p = 0.047; I 2 = 72.2% (with five RCTs)], and waist circumference [−2.41 cm; −3.47; −1.36, p < 0.001; I 2 = 0.0% (with three RCTs)]. Through a set of subgroup analyses, we found a significant reduction in BMI in CAD patients with T2D [WMD = −1.06; 95% CI, −1.42, −0.70, p < 0.001; I 2 = 0.0% (with three RCTs)] compared to CAD only patients [WMD = −0.08; 95% CI, −0.45, 0.29, p = 0.66; I 2 = 0.0% (with two RCTs)] in the liraglutide group compared with the placebo group. No significant changes in heart rate, blood pressure, and lipid profiles were observed. Conclusions: Among people with established CAD, liraglutide significantly improved HbA1c, BMI, and waist circumference values. The effect of liraglutide on BMI was more robust in individuals with T2D compared to those without.
Deciphering Myostatin’s Regulatory, Metabolic, and Developmental Influence in Skeletal Diseases

Current research findings in humans and other mammalian and non-mammalian species support the potent regulatory role of myostatin in the morphology and function of muscle as well as cellular differentiation and metabolism, with real-life implications in agricultural meat production and human disease. Myostatin null mice (mstn−/−) exhibit skeletal muscle fiber hyperplasia and hypertrophy whereas myostatin deficiency in larger mammals like sheep and pigs engender muscle fiber hyperplasia. Myostatin’s impact extends beyond muscles, with alterations in myostatin present in the pathophysiology of myocardial infarctions, inflammation, insulin resistance, diabetes, aging, cancer cachexia, and musculoskeletal disease. In this review, we explore myostatin’s role in skeletal integrity and bone cell biology either due to direct biochemical signaling or indirect mechanisms of mechanotransduction. In vitro, myostatin inhibits osteoblast differentiation and stimulates osteoclast activity in a dose-dependent manner. Mice deficient in myostatin also have decreased osteoclast numbers, increased cortical thickness, cortical tissue mineral density in the tibia, and increased vertebral bone mineral density. Further, we explore the implications of these biochemical and biomechanical influences of myostatin signaling in the pathophysiology of human disorders that involve musculoskeletal degeneration. The pharmacological inhibition of myostatin directly or via decoy receptors has revealed improvements in muscle and bone properties in mouse models of osteogenesis imperfecta, osteoporosis, osteoarthritis, Duchenne muscular dystrophy, and diabetes. However, recent disappointing clinical trial outcomes of induced myostatin inhibition in diseases with significant neuromuscular wasting and atrophy reiterate complexity and further need for exploration of the translational application of myostatin inhibition in humans.
RHEOLOGICAL PROPERTIES OF SOME KETCHUPS ON THE POLISH MARKET

A b s t r a c t . The paper presents the results of rheological measurements of five selected ketchups available on the Polish market. Rheological identification was carried out in rotary shear conditions and using forced oscillation. The equilibrium flow curves (shear at constant and stepwise increasing values of shear rate) were determined, and the thixotropic effect in the form of shear hysteresis loop under conditions of shear at increasing and then decreasing shear rates. The values of the dynamic storage modulus, the loss modulus and the complex viscosity modulus were determined in dynamic measurements. The water content was also measured, and qualitative characterisation of the structure was made on the basis of photographs taken under conditions of shear interferometry. The research revealed significant differences in rheological properties and structure of the ketchups examined. All the media showed a significant thixotropic effect. The values of apparent viscosity of the ketchups did not depend on water content but primarily on the consistency stabiliser used. The presence of modified starch had a significant impact on the flow curves, and thus on the rheological properties. The presence of tomato cell walls in ketchup structure caused the appearance of discontinuity in the flow curves at low shear rates and lower storage modulus values. It was also demonstrated that the ketchups studied did not meet the Cox-Merz equation. K e y w o r d s : rheological properties of ketchup, apparent viscosity, thixotropic effect
Current Concepts in Fluid Therapy in Horses

Despite the frequent inclusion of fluid therapy in the treatment of many conditions in horses, there are limited studies available to provide evidenced-based, species-specific recommendations. Thus, equine fluid therapy is based on the application of physiology and extrapolation from evidence in other veterinary species and human medicine. The physiologic principles that underly the use of fluids in medicine are, at first glance, straightforward and simple to understand. However, in the past 20 years, multiple studies in human medicine have shown that creating recommendations based on theory in combination with experimental and/or small clinical studies does not consistently result in best practice. As a result, there are ongoing controversies in human medicine over fluid types, volumes, and routes of administration. For example, the use of 0.9% NaCl as the replacement fluid of choice is being questioned, and the theoretical benefits of colloids have not translated to clinical cases and negative effects are greater than predicted. In this review, the current body of equine research in fluid therapy will be reviewed, connections to the controversies in human medicine and other veterinary species will be explored and, where appropriate, recommendations for fluid therapy in the adult horse will be made based on the available evidence. This review is focused on the decisions surrounding developing a fluid plan involving crystalloids, synthetic colloids, and plasma.
Infodemic Pathways: Evaluating the Role That Traditional and Social Media Play in Cross-National Information Transfer

The COVID-19 pandemic has occurred alongside a worldwide infodemic where unprecedented levels of misinformation have contributed to widespread misconceptions about the novel coronavirus. Conspiracy theories, poorly sourced medical advice, and information trivializing the virus have ignored national borders and spread quickly. This information spread has occurred despite generally strong preferences for domestic national media and social media networks that tend to be geographically bounded. How, then, is (mis)information crossing borders so rapidly? Using social media and survey data, we evaluate the extent to which consumption and propagation patterns of domestic and international traditional news and social media can help inform theorizing about cross-national information spread. In a detailed case study of Canada, we employ a large multi-wave survey and a massive data set of Canadian Twitter users. We show that the majority of misinformation circulating on Twitter that is shared by Canadian accounts is retweeted from U.S.-based accounts. Moreover, exposure to U.S.-based media outlets is associated with COVID-19 misperceptions and increased exposure to U.S.-based information on Twitter is associated with an increased likelihood to post misinformation. We thus theorize and empirically identify a key globalizing infodemic pathway: disregard for national origin of social media posting.
Antibiotics and Antibiotic Resistance Genes in Animal Manure – Consequences of Its Application in Agriculture

Antibiotic resistance genes (ARGs) are a relatively new type of pollutant. The rise in antibiotic resistance observed recently is closely correlated with the uncontrolled and widespread use of antibiotics in agriculture and the treatment of humans and animals. Resistant bacteria have been identified in soil, animal feces, animal housing (e.g., pens, barns, or pastures), the areas around farms, manure storage facilities, and the guts of farm animals. The selection pressure caused by the irrational use of antibiotics in animal production sectors not only promotes the survival of existing antibiotic-resistant bacteria but also the development of new resistant forms. One of the most critical hot-spots related to the development and dissemination of ARGs is livestock and poultry production. Manure is widely used as a fertilizer thanks to its rich nutrient and organic matter content. However, research indicates that its application may pose a severe threat to human and animal health by facilitating the dissemination of ARGs to arable soil and edible crops. This review examines the pathogens, potentially pathogenic microorganisms and ARGs which may be found in animal manure, and evaluates their effect on human health through their exposure to soil and plant resistomes. It takes a broader view than previous studies of this topic, discussing recent data on antibiotic use in farm animals and the effect of these practices on the composition of animal manure; it also examines how fertilization with animal manure may alter soil and crop microbiomes, and proposes the drivers of such changes and their consequences for human health.
Clopidogrel Plus Aspirin in Patients With Different Types of Single Small Subcortical Infarction

Background: We aim to investigate the effects and safety of clopidogrel plus aspirin in patients with different types of single small subcortical infarction (SSSI) in the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Methods: SSSI was defined as single DWI lesion of ≤2.0 cm. Patients with SSSI were divided into SSSI + PAD (parent artery disease) and SSSI – PAD, according to the stenosis of the parent artery. The efficacy outcome was stroke recurrence during 90-day follow-up. Cox proportional hazards models or logistic regression models were used to assess the interaction of the treatment effects of clopidogrel plus aspirin vs. aspirin alone among patients with and without PAD. Results: Among 338 patients with SSSI included in the subanalysis, 105 were with PAD and 233 without. The efficacy of clopidogrel plus aspirin compared with aspirin alone on any stroke was consistent between patients with [adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI), 0.25–2.75] and without PAD (adjusted HR 1.03; 95% CI, 0.40–2.68, interaction P = 0.83). In patients with SSSI + PAD, the rate of stroke recurrence in those treated with dual antiplatelet therapy and mono antiplatelet therapy was not significantly different (10.9 vs. 13.6%, P = 0.77). The number of bleeding events was similar between the clopidogrel-aspirin group and aspirin group regardless of SSSI + PAD or SSSI – PAD. Conclusions: There was no significant difference in the efficacy of clopidogrel plus aspirin compared with aspirin alone between patients with SSSI + PAD and SSSI – PAD in the CHANCE trial. Studies in other populations and with adequate power are needed to further verify such findings.
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype

Cellular senescence is a stable cell cycle arrest that can be triggered in normal cells in response to various intrinsic and extrinsic stimuli, as well as developmental signals. Senescence is considered to be a highly dynamic, multi-step process, during which the properties of senescent cells continuously evolve and diversify in a context dependent manner. It is associated with multiple cellular and molecular changes and distinct phenotypic alterations, including a stable proliferation arrest unresponsive to mitogenic stimuli. Senescent cells remain viable, have alterations in metabolic activity and undergo dramatic changes in gene expression and develop a complex senescence-associated secretory phenotype. Cellular senescence can compromise tissue repair and regeneration, thereby contributing toward aging. Removal of senescent cells can attenuate age-related tissue dysfunction and extend health span. Senescence can also act as a potent anti-tumor mechanism, by preventing proliferation of potentially cancerous cells. It is a cellular program which acts as a double-edged sword, with both beneficial and detrimental effects on the health of the organism, and considered to be an example of evolutionary antagonistic pleiotropy. Activation of the p53/p21WAF1/CIP1 and p16INK4A/pRB tumor suppressor pathways play a central role in regulating senescence. Several other pathways have recently been implicated in mediating senescence and the senescent phenotype. Herein we review the molecular mechanisms that underlie cellular senescence and the senescence associated growth arrest with a particular focus on why cells stop dividing, the stability of the growth arrest, the hypersecretory phenotype and how the different pathways are all integrated.
Online Survey of the Impact of COVID-19 Risk and Cost Estimates on Worry and Health Behavior Compliance in Young Adults

The novel coronavirus COVID-19 pandemic is associated with elevated rates of anxiety and relatively lower compliance with public health guidelines in younger adults. To develop strategies for reducing anxiety and increasing adherence with health guidelines, it is important to understand the factors that contribute to anxiety and health compliance in the context of COVID-19. Earlier research has shown that greater perceived risk of negative events and their costs are associated with increased anxiety and compliance with health behaviors, but it is unclear what role they play in a novel pandemic surrounded by uncertainty. In the present study we measured (1) perceived risk as the self-reported probability of being infected and experiencing serious symptoms due to COVID-19 and (2) perceived cost as financial, real-world, physical, social, and emotional consequences of being infected with COVID-19. Worry was assessed using the Penn State Worry Questionnaire (PWSQ) and health compliance was measured as endorsement of the World Health Organization (WHO) health directives for COVID-19. Our results showed that greater perceived risk and costs of contracting the COVID-19 virus were associated with greater worry and while only costs were associated with greater compliance with health behaviors. Neither self-reported worry nor its interaction with cost estimates was associated with increased engagement in health behaviors. Our results provide important insight into decision making mechanisms involved in both increased anxiety and health compliance in COVID-19 and have implications for developing psychoeducational and psychotherapeutic strategies to target both domains.
uhrf1 and dnmt1 Loss Induces an Immune Response in Zebrafish Livers Due to Viral Mimicry by Transposable Elements

Activation of transposable elements (TEs) can cause cellular damage. Cytoplasmic nucleic acid sensing pathways evolved to detect pathogens, but can also serve to cull cells with inappropriate TE activation as TEs can be viral mimetics. Epigenetic silencing of TEs is mediated in part by DNA methylation, but it is not clear if TE activation or the immune system contribute to the cellular damage caused by loss of DNA methylation. Here, we provide mechanistic insight into the observation of an activated interferon response in the liver of zebrafish larvae with deletion in critical components of the DNA methylation machinery, uhrf1 and dnmt1. We focus on dissecting the relationship between DNA methylation, TE activation and induction of an immune response through cytoplasmic DNA and double stranded RNA sensing pathways and identify tnfa as a mediator of cell death in the liver of these mutants. Integrated RNAseq and methylome analysis identified LTR transposons as the most upregulated in these mutants and also the most methylated in control larvae, indicating a direct role of DNA methylation in suppressing this TE subclass. RNAseq analysis from these same samples revealed expression signatures of a type-I interferon response and of tnfa activation, mimicking the pattern of gene expression in virally infected cells. CRISPR/Cas9 mediated depletion of the cellular antiviral sensors sting and mavs reduced expression of interferon response genes and tnfa depletion dramatically reduced cell death in uhrf1 mutant livers. This suggests that the antiviral response induced by DNA hypomethylation and TE activation in the liver is mediated by the signaling pathways activated by both cytoplasmic double stranded RNA and DNA and that tnfa mediates cell death as a potential mechanism to eliminate these damaged cells.
Effect of Sodium Hydroxide on the Fast Synthesis of Superhydro-phobic Powder from Polymethylhydrosiloxane

The paper reports the role of sodium hydroxide in the synthesis of a superhydrophobic powder from polymethylhydrosiloxane (PMHS) in the presence of ethanol and water. The effects of other basic and acidic solutions as well as the absence of water were also investigated. PMHS exhibited rapid gelation (from 8 h to 2 h) by increasing the concentration of sodium hydroxide in the presence of ethanol and water. In contrast, gelation did not occur in the absence of sodium hydroxide or water or in the presence of acidic solutions. Delayed gelation (96 h to 120 h) occurred as a result of the introduction of dipotassium hydrogen phosphate trihydrate. Superhydrophobic powder was obtained by the evaporation of solvents from the gelated sol at 150 °C. The surface properties of the superhydrophobic powder were examined by scanning electron microscopy, high resolution transmission electron microscopy, N 2 sorption isotherm, and X-ray diffraction. The particle size, functional groups and thermal stability of the powder were analyzed by dynamic light scattering spectroscopy, Fourier transform infrared spectroscopy, 29 Si cross polarization magic angle spinning nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. The surface properties of the powder were also assessed by contact angle measurements. The results showed that increasing the concentration of sodium hydroxide added to PMHS or increasing the drying temperature of the gelated sol resulted in the more rapid formation of superhydrophobic powder.
Clinical Utility of Automatable Prediction Models for Improving Palliative and End-Of-Life Care Outcomes: Towards Routine Decision Analysis Before Implementation

Objective To evaluate the clinical utility of automatable prediction models for increasing goals-of-care discussions among hospitalized patients at the end-of-life. Materials and Methods We developed three Random Forest models and updated the Modified Hospital One-year Mortality Risk model: alternative models to predict one-year mortality (proxy for EOL status) using admission-time data. Admissions from July 2011-2016 were used for training and those from July 2017-2018 were used for temporal validation. We simulated alerts for admissions in the validation cohort and modelled alternative scenarios where alerts lead to code status orders (CSOs) in the EHR. We linked actual CSOs and calculated the expected risk difference (eRD), the number needed to benefit (NNB) and the net benefit (NB) of each model for the patient-centered outcome of a CSO among EOL hospitalizations. Results Models had a C-statistic of 0.79-0.86 among unique patients. A CSO was documented during 2599 of 3773 hospitalizations at the EOL (68.9%). At a threshold that identified 10% of eligible admissions, the eRD ranged from 5.4% to 10.7% (NNB 5.4-10.9 alerts). Under usual care, a CSO had a 34% PPV for EOL status. Using this to inform the relative cost of FPs, only two models improved NB over usual care. A RF model with diagnostic predictors had the highest clinical utility by either measure, including in sensitivity analyses. Discussion Automatable prediction models with acceptable temporal validity differed meaningfully in their expected ability to improve patient-centered outcomes over usual care. Conclusion Decision-analysis should precede implementation of automated prediction models for improving palliative and EOL care outcomes.
Nine Unique Iridoids and Iridoid Glycosides From Patrinia scabiosaefolia

Patrinia scabiosaefolia is a medical and edible Chinese herb with high nutritional and medicinal value. The continuing study of its chemical constituents led to the discovery of nine unique iridoids and iridoid glycosides, including three new iridoids (1-3) and six previously unknown irioid glycosides (5-10), and one known compound (4). Among them, compound 1 was a deformed iridoid, while compounds 3, 5-7, and 10 formed a new ring in their skeletons which was uncommon in this genus. For compound 3, the new ring existed between C-3 and C-10, while a 1,3-dioxane appeared between C-7 and C-10 in compounds 5-7 and 10. Moreover, compound 10 was a bis-iridoid glycoside, which was the first reported in P. scabiosaefolia. And the sugar of irioid glycosides (5-10) was glucose at C-11, except in 9 which had a 5-deoxyglucose moiety. All their structures were confirmed based on the extensive spectroscopic analysis, including IR, UV, HR-ESI-MS, ECD, and 1D- and 2D-NMR experiments. Their cytotoxic activities against HL-60, A-549, SMMC-7721, MCF-7, SW480 were also tested.