Miracle-dz/UniFAR-FTUs huggingface dataset:
Reproducibility of echocardiographic indices of left atrial size in dogs with subclinical myxomatous mitral valve disease

Abstract Background Reliability of echocardiographic measurements of left atrial (LA) size, an important marker of disease severity, has not been reported in dogs with myxomatous mitral valve disease (MMVD). Objectives To define and compare reliability of left atrial dimension/diameter (LAD), LAD indexed to aortic valve diameter (LAD/AoD), left atrium‐to‐aortic root ratio (LA/Ao), left atrial volume acquired from a right parasternal long‐axis (LAVRPLx), and left apical view (LAVLAP) in dogs with subclinical MMVD. Animals Nine dogs with subclinical MMVD. Methods Prospective reproducibility study. Dogs underwent 12 echocardiographic examinations by 2 operators on the mornings and afternoons of 3 nonconsecutive days within 1 week. Reliability (measurement variability) was quantified using coefficients of variation (CV) and 95% repeatability/reproducibility coefficients (95% RC). A mixed‐model analysis of variance (ANOVA) was used to determine if time of day, day, and operator were significant sources of variability for each index. Results Linear measurements (LAD, LAD/AoD, and LA/Ao) exhibited less within‐day, between‐day, and interoperator variability (CVs, 3.9%‐12.5%) than did volume estimate measurements (LAVRPLx and LAVLAP; CVs, 11.8%‐17.9%). Of the linear measurements, LA/Ao exhibited greater variability (CVs, 9.9%‐12.5%) compared to LAD and LAD/AoD (CVs, 3.9%‐4.9%). Operator was a significant (P = .005) source of variability for LA/Ao. Conclusions and Clinical Importance Compared to other linear measurements, LA/Ao was the least reproducible and most dependent on operator. The 95% RC for each LA size index are provided to help identify clinically relevant changes (beyond intraoperator or interoperator variability) during serial echocardiographic examinations of dogs with subclinical MMVD.
Proteome-wide data analysis reveals tissue-specific network associated with SARS-CoV-2 infection

Abstract For patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the damages to multiple organs have been clinically observed. Since most of current investigations for virus–host interaction are based on cell level, there is an urgent demand to probe tissue-specific features associated with SARS-CoV-2 infection. Based on collected proteomic datasets from human lung, colon, kidney, liver, and heart, we constructed a virus-receptor network, a virus-interaction network, and a virus-perturbation network. In the tissue-specific networks associated with virus–host crosstalk, both common and different key hubs are revealed in diverse tissues. Ubiquitous hubs in multiple tissues such as BRD4 and RIPK1 would be promising drug targets to rescue multi-organ injury and deal with inflammation. Certain tissue-unique hubs such as REEP5 might mediate specific olfactory dysfunction. The present analysis implies that SARS-CoV-2 could affect multi-targets in diverse host tissues, and the treatment of COVID-19 would be a complex task.
Esophageal Hematoma Associated with the Bolus Ingestion of Hot Coffee

A 59-year-old woman presented with pharyngeal discomfort and dysphagia starting the previous day. Esophagogastroduodenoscopy revealed a longitudinal reddish area and hematoma mainly on the left wall of the esophagus. On the previous day, she had felt a piece of meat sticking in her throat while eating; she therefore rapidly gulped down some hot coffee to hasten the passage of the meat. Based on the history, we diagnosed her endoscopic findings as esophageal hematoma and thermal injury associated with hot coffee. We herein describe a case of an acute esophageal hematoma and thermal injury and the clinical course following endoscopy.
Food deserts and cardiovascular health among young adults

Abstract Objective: This study assesses the association between living in a food desert and cardiovascular health risk among young adults in the USA, as well as evaluates whether personal and area socioeconomic status moderates this relationship. Design: A cross-sectional analysis was performed using data from Wave I (1993–1994) and Wave IV (2008) from the National Longitudinal Study of Adolescent to Adult Health. Ordinary least squares regression models assessing the association between living in a food desert and cardiovascular health were performed. Mediation and moderation analyses assessed the degree to which this association was conditioned by area and personal socioeconomic status. Setting: Sample of respondents living in urban census tracts in the USA in 2008. Participants: Young adults (n 8896) aged 24–34 years. Results: Net of covariates living in a food desert had a statistically significant association with cardiovascular health risk (range 0–14) (β = 0·048, P < 0·01). This association was partially mediated by area and personal socioeconomic status. Further analyses demonstrate that the adverse association between living in a food desert and cardiovascular health is concentrated among low socioeconomic status respondents. Conclusions: The findings from this study suggest a complex interplay between food deserts and economic conditions for the cardiovascular health of young adults. Developing interventions that aim to improve health behaviour among lower-income populations may yield benefits for preventing the development of cardiovascular health problems.
KINETICS OF NITRATE, AMMONIUM, AND UREA UPTAKE BY FOUR INTERTIDAL SEAWEEDS FROM NEW ZEALAND 1

The competitive ability for N uptake by four intertidal seaweeds, Stictosiphonia arbuscula (Harvey) King et Puttock, Apophlaea lyallii Hook. f. et Harvey, Scytothamnus australis Hook. f. et Harvey, and Xiphophora gladiata (Labillardière) Montagne ex Harvey, from New Zealand is described by the uptake kinetics for NO3−, NH4+, and urea. This is the first study to report uptake kinetics for N uptake by a range of southern hemisphere intertidal seaweeds in relation to season and zonation. Species growing at the highest shore positions had higher NO3− and urea uptake at both high and low concentrations and had unsaturable NH4+ uptake in both summer and winter. Although there was evidence of some feedback inhibition of Vmax for NO3− uptake by Stictosiphonia arbuscula growing at the lower vertical limits of its range, rates were high compared with species growing lower on the shore. Our results highlight the superior competitive ability for N uptake of certain high intertidal seaweeds, and consistent with our previous findings we can conclude that intertidal seaweeds in southeast New Zealand are adapted to maximizing N acquisition in a potentially N‐limiting environment.
Characterization of humoral and cellular immune features of gamma-irradiated influenza vaccine

ABSTRACT The most widely used influenza vaccines are prepared by chemical inactivation. However, chemical, especially formalin, treatment-induced modifications of the antigenic structure of the virus are frequently associated with adverse effects including low efficacy of protection, unexpected immune responses, or exacerbation of disease. Gamma-irradiation was suggested as an alternative influenza virus inactivation method due to its great features of completely inactivating virus while not damaging the structures of protein antigens, and cross-protective ability against heterologous strains. However, immunological features of gamma radiation-inactivated influenza vaccine have not been fully understood. In this study, we aimed to investigate the humoral and cellular immune responses of gamma radiation-inactivated influenza vaccine. The gamma irradiation-inactivated influenza vaccine (RADVAXFluA) showed complete viral inactivation but retained normal viral structure with functional activities of viral protein antigens. Intranasal immunization of RADVAXFluA provided better protection against influenza virus infection than formalin-inactivated influenza virus (FIV) in mice. RADVAXFluA greatly enhanced the production of virus-specific serum IgG and alveolar mucosal IgA, which effectively neutralized HA (hemagglutinin) and NA (neuraminidase) activities, and blocked viral binding to the cells, respectively. Further analysis of IgG subclasses showed RADVAXFluA-immunized sera had higher levels of IgG1 and IgG2a than those of FIV-immunized sera. In addition, analysis of cellular immunity found RADVAXFluA induced strong dendritic cells (DC) activation resulting in higher DC-mediated activation of CD8+ T cells than FIV. The results support improved immunogenicity by RADVAXFluA.
Hepatoprotective, cytotoxic, antimicrobial and antioxidant activities of Dioon spinulosum leaves Dyer Ex Eichler and its isolated secondary metabolites

Abstract Given the lack of adequate research on Dioon spinulosum (D. spinulosum) Dyer Ex Eichler, this study was conducted focusing on different biological activities and phytochemical investigation of D. spinulosum for the first time. D. spinulosum showed strong protective activity against DNA damage and potent activity against VERO cell line. It also presented antimicrobial and hepatoprotective activity. Phytochemical investigation of the leaves resulted in isolation of two new flavonoids, apigenin 7-O-α-d-glucopyranoside (15) and amentoflavone 7-O-α-l-rhamnopyranoside (16), in addition to fifteen known compounds: phytone (1), trans-phytol (2), β-sitosterol (3), stigmasterol (4), oliveriflavone (5), 7,4′,7″,4″′-tetramethylamentoflavone (6), 7,4',7''-trimethylamentoflavone (7), scaidopitysin (8), bilobetin (9), isoginkgetin (10), aromadendrin (11), sotusflavone (12), engeletin (14) and eriocitrin (17) for the first time together with amentoflavone (13). Compounds (11) and (13) displayed very strong cytotoxic activity and showed the highest protective activity against DNA damage. Graphical Abstract
“Take My Bone Away?” Hypoxia and bone: A narrative review

To maintain normal cellular and physiological function, sufficient oxygen is required. Recently, evidence has suggested that hypoxia, either pathological or environmental, may influence bone health. It appears that bone cells are distinctly responsive to hypoxic stimuli; for better or worse, this is still yet to be elucidated. Hypoxia has been shown to offer potentially therapeutic effects for bone by inducing an osteogenic–angiogenic response, although, others have noted excessive osteoclastic bone resorption instead. Much evidence suggests that the hypoxic‐inducible pathway is integral in mediating the changes in bone metabolism. Furthermore, many factors associated with hypoxia including changes in energy metabolism, acid–base balance and the increased generation of reactive oxygen species, are known to influence bone metabolism. This review aims to examine some of the putative mechanisms responsible for hypoxic‐induced alterations of bone metabolism, with regard to osteoclasts and osteoblasts, both positive and negative.
S‐adenosylmethionine and methylthioadenosine boost cellular productivities of antibody forming Chinese hamster ovary cells

The improvement of cell specific productivities for the formation of therapeutic proteins is an important step towards intensified production processes. Among others, the induction of the desired production phenotype via proper media additives is a feasible solution provided that said compounds adequately trigger metabolic and regulatory programs inside the cells. In this study, S‐(5′‐adenosyl)‐ l‐methionine (SAM) and 5′‐deoxy‐5′‐(methylthio)adenosine (MTA) were found to stimulate cell specific productivities up to approx. 50% while keeping viable cell densities transiently high and partially arresting the cell cycle in an anti‐IL‐8‐producing CHO‐DP12 cell line. Noteworthy, MTA turned out to be the chemical degradation product of the methyl group donor SAM and is consumed by the cells.
Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial

Introduction The rapid worldwide spread of COVID-19 has caused a global health crisis. To date, symptomatic supportive care has been the most common treatment. It has been reported that the mechanism of COVID-19 is related to cytokine storms and subsequent immunogenic damage, especially damage to the endothelium and alveolar membrane. Vitamin C (VC), also known as L-ascorbic acid, has been shown to have antimicrobial and immunomodulatory properties. A high dose of intravenous VC (HIVC) was proven to block several key components of cytokine storms, and HIVC showed safety and varying degrees of efficacy in clinical trials conducted on patients with bacterial-induced sepsis and acute respiratory distress syndrome (ARDS). Therefore, we hypothesise that HIVC could be added to the treatment of ARDS and multiorgan dysfunction related to COVID-19. Methods and analysis The investigators designed a multicentre prospective randomised placebo-controlled trial that is planned to recruit 308 adults diagnosed with COVID-19 and transferred into the intensive care unit. Participants will randomly receive HIVC diluted in sterile water or placebo for 7 days once enrolled. Patients with a history of VC allergy, end-stage pulmonary disease, advanced malignancy or glucose-6-phosphate dehydrogenase deficiency will be excluded. The primary outcome is ventilation-free days within 28 observational days. This is one of the first clinical trials applying HIVC to treat COVID-19, and it will provide credible efficacy and safety data. We predict that HIVC could suppress cytokine storms caused by COVID-19, help improve pulmonary function and reduce the risk of ARDS of COVID-19. Ethics and dissemination The study protocol was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (identifiers: Clinical Ethical Approval No. 2020001). Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. Trial registration number NCT04264533.
Occurrence and bioacessibility of mycotoxins in fish feed

ABSTRACT In this study Aflatoxin B1 (AFB1), ochratoxin A (OTA) and zearalenone (ZEN) occurrence in fish feed, regarding its chemical composition, were investigated. Besides, AFB1 bioaccessibility to fish was evaluated by in vitro digestion. Mycotoxins were extracted by QuEChERS and quantified by HPLC-FLD. Results showed that 93.3% of the samples were contaminated at maximum levels of 16.5, 31.6, and 322 µg/kg in the cases of AFB1, OTA, and ZEN, respectively. A positive correlation between OTA, ZEN contamination, and lipid content was observed. Risk estimation of feed consumption by fish at the highest levels of AFB1, OTA, and ZEN shows that the younger the fish, the higher the risk of exposure to mycotoxins. The AFB1 bioaccessibility assay showed that 85% of this mycotoxin may be absorbed by fish. Therefore, establishing maximum levels in the fishing sector is fundamental to contribute to feed quality and nutritional safety of fish species.
Increased risk of Ventriculostomy-Associated hemorrhage in patients treated with antiplatelet agents for stent-assisted coiling of ruptured intracranial aneurysms

Abstract Purpose The aim of this study is to evaluate the impact of antiplatelet agents for stent-assisted coiling, including intravenous (IV) tirofiban as an antiplatelet premedication, on rates of external ventricular drain (EVD)-related hemorrhage in acutely ruptured intracranial aneurysms. The impact of IV tirofiban in particular was also evaluated. Methods Rates of radiographically identified hemorrhage associated with EVD placement were compared between patients who received an antiplatelet agent for stent-assisted coil embolization (SACE), and patients who did not receive an antiplatelet agent between June 2013 and June 2019. Results 78 patients treated for a ruptured aneurysm which required an EVD were included. A total of 46 patients who underwent stent-assisted coiling and received IV tirofiban and oral asipirin and clopidogrel (DAPT) were included in the antiplatelet group, while 32 who underwent single coiling and received no antiplatelet therapy were included in the control group. Overall, EVD-related hemorrhage occurred in 13 patients (16.67%): 11 (23.91%) in the antiplatelet group and 2 (6.25%) in the control group (p = 0.040). Of 37 patients who underwent computed tomography after SACE, but before the use of DAPT, 8 (21.62%) exhibited EVD-related hemorrhage after IV tirofiban therapy (p = 0.070 vs. control group). EVD-related hemorrhage was not significantly different between patients with EVD placement after coil embolization versus before coil embolization (p = 0.124). In the subgroup analysis for the antiplatelet group, we did not observed increased EVD-related hemorrhage in patients receiving EVD placement after administration of antiplatelet agents (8/27 [29.63%]) versus before administration of antiplatelet agents (3/19 [15.79%]). Conclusion Patients with ruptured aneurysm who receive an antiplatelet agent for stent-assisted coiling are at a higher risk for EVD-related hemorrhage. The order of EVD placement and EVT, as well as the order of EVD placement and antiplatelet initiation do not appear to be significantly different regarding the outcome of EVD-related hemorrhage. Highlights Patients with ruptured aneurysm who receive an antiplatelet agent for stent-assisted coiling are at a higher risk for EVD-related hemorrhage. There was a trend towards higher EVD related haemorrhage when tirofiban was used but it did not reach statisitical significance. The order of EVD—whether before vs after endovascular treatment, or before vs after antiplatelet therapy did not influence the EVD-related hemorrhage rates.
Antioxidant and antidiabetic activities of peptides isolated from a hydrolysate of an egg-yolk protein by-product prepared with a proteinase from Asian pumpkin (Cucurbita ficifolia)

Bioactive peptides derived from food have been increasingly popular due to their therapeutic properties. Of particular importance are peptides with a multidirectional activity that can be used in the treatment and prevention of diet-related diseases. This paper attempts to utilize a by-product of phospholipid extraction from egg yolk as a source of peptides with a broad spectrum of biological activity. In addition, in this research we used a non-commercial enzyme obtained from Asian pumpkin, which has not been sufficiently researched in terms of its ability to release biopeptides from food proteins. In the present study the biological properties of peptides, derived from egg-yolk protein by-products (YP) remaining after phospholipid extraction, and their four synthetic analogs were investigated with regard to their antioxidant (radical scavenging capacity, Fe2+ chelating effect, reducing power (FRAP)) and antidiabetic (α-glucosidase and DPP-IV inhibitory activities) properties. One of them, with the sequence LAPSLPGKPKPD, exhibited the highest antioxidant activity (free radical scavenging activity (6.03 μM Troloxeq per mg protein); FRAP (296.07 μg Fe2+ per mg protein)). This peptide also revealed the strongest DPP-IV (361.5 μmol L−1) and α-glucosidase (1065.6 μmol L−1) inhibitory activities, a novel multifunctional effect for peptides from an egg-yolk hydrolysate.
Genetic variability in linseed (Linum usitatissimum L.)

Thirty divergent genotypes of linseed were studied for geneticvariability, heritability and genetic advance during rabi season of 2011–12. The highest magnitude of genotypic variation was observed for number of seeds per plant. High heritability coupled with high genetic advance was observed for number of seeds per plant, number of capsules per plant, number of seeds per capsule, number of secondary branches per plant, 100 seed weight and seed yield per plant, while moderate heritability was observed for number of primary branches per plant.
Detection of Multiple Transgene Fragments in a Mouse Model of Gene Doping Based on Plasmid Vector Using TaqMan-qPCR Assay

The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the augmentation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. Firstly, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan- quantitative real-time PCR(qPCR) assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.
Single‐molecule tracking reveals that the nucleoid‐associated protein HU plays a dual role in maintaining proper nucleoid volume through differential interactions with chromosomal DNA

HU (Histone‐like protein from Escherichia coli strain U93) is the most conserved nucleoid‐associated protein in eubacteria, but how it impacts global chromosome organization is poorly understood. Using single‐molecule tracking, we demonstrate that HU exhibits nonspecific, weak, and transitory interactions with the chromosomal DNA. These interactions are largely mediated by three conserved, surface‐exposed lysine residues (triK), which were previously shown to be responsible for nonspecific binding to DNA. The loss of these weak, transitory interactions in a HUα(triKA) mutant results in an over‐condensed and mis‐segregated nucleoid. Mutating a conserved proline residue (P63A) in the HUα subunit, deleting the HUβ subunit, or deleting nucleoid‐associated naRNAs, each previously implicated in HU’s high‐affinity binding to kinked or cruciform DNA, leads to less dramatically altered interacting dynamics of HU compared to the HUα(triKA) mutant, but highly expanded nucleoids. Our results suggest HU plays a dual role in maintaining proper nucleoid volume through its differential interactions with chromosomal DNA. On the one hand, HU compacts the nucleoid through specific DNA structure‐binding interactions. On the other hand, it decondenses the nucleoid through many nonspecific, weak, and transitory interactions with the bulk chromosome. Such dynamic interactions may contribute to the viscoelastic properties and fluidity of the bacterial nucleoid to facilitate proper chromosome functions.