Miracle-dz/UniFAR-FTUs huggingface dataset:
Late sodium current and calcium homeostasis in arrhythmogenesis

ABSTRACT The cardiac late sodium current (INa,late) is the small sustained component of the sodium current active during the plateau phase of the action potential. Several studies demonstrated that augmentation of the current can lead to cardiac arrhythmias; therefore, INa,late is considered as a promising antiarrhythmic target. Fundamentally, enlarged INa,late increases Na+ influx into the cell, which, in turn, is converted to elevated intracellular Ca2+ concentration through the Na+/Ca2+ exchanger. The excessive Ca2+ load is known to be proarrhythmic. This review describes the behavior of the voltage-gated Na+ channels generating INa,late in health and disease and aims to discuss the physiology and pathophysiology of Na+ and Ca2+ homeostasis in context with the enhanced INa,late demonstrating also the currently accessible antiarrhythmic choices.
Genotypic Characteristics and Correlation of Epidemiology of Staphylococcus aureus in Healthy Pigs, Diseased Pigs, and Environment

China is one of the largest producers of pigs and pork in the world. However, large-scale studies on pig-associated Staphylococcus aureus in relation to healthy pigs, diseased pigs and environment are scarce. The objective of the present study was to characterize and compare S. aureus isolates from healthy pigs, diseased pigs and environment through antimicrobial susceptibility testing, multiple locus sequence typing, spa typing, and antimicrobial resistance gene screening. Results showed all isolates were susceptible to linezolid and vancomycin. However, 66.7% (104/156) isolates were multidrug-resistant by displaying resistance to three or more antibiotics and high rates of resistance to penicillin, tetracycline, clindamycin, and clarithromycin were observed. Of the 20 multilocus sequence types (STs) identified among the isolates, ST9, ST188, and ST7 were most commonly isolated from healthy pigs and environment, while ST1 was most commonly isolated from diseased pigs. In total, 17 spa types were represented among the isolates, while t4792 was most commonly isolated from diseased pigs and t899, t189 were most commonly isolated from healthy pigs and environment. In conclusion, the genotypic and epidemiology characteristics observed among the isolates suggest pigs and pork could be important players in S. aureus dissemination.
Maternal Docosahexaenoic Acid Status during Pregnancy and Its Impact on Infant Neurodevelopment

Dietary components are essential for the structural and functional development of the brain. Among these, docosahexaenoic acid, 22:6n-3 (DHA), is critically necessary for the structure and development of the growing fetal brain in utero. DHA is the major n-3 long-chain polyunsaturated fatty acid in brain gray matter representing about 15% of all fatty acids in the human frontal cortex. DHA affects neurogenesis, neurotransmitter, synaptic plasticity and transmission, and signal transduction in the brain. Data from human and animal studies suggest that adequate levels of DHA in neural membranes are required for maturation of cortical astrocyte, neurovascular coupling, and glucose uptake and metabolism. Besides, some metabolites of DHA protect from oxidative tissue injury and stress in the brain. A low DHA level in the brain results in behavioral changes and is associated with learning difficulties and dementia. In humans, the third trimester-placental supply of maternal DHA to the growing fetus is critically important as the growing brain obligatory requires DHA during this window period. Besides, DHA is also involved in the early placentation process, essential for placental development. This underscores the importance of maternal intake of DHA for the structural and functional development of the brain. This review describes DHA’s multiple roles during gestation, lactation, and the consequences of its lower intake during pregnancy and postnatally on the 2019 brain development and function.
The Predicted Functional Compartmentation of Rice Terpenoid Metabolism by Trans-Prenyltransferase Structural Analysis, Expression and Localization

Most terpenoids are derived from the basic terpene skeletons of geranyl pyrophosphate (GPP, C10), farnesyl-PP (FPP, C15) and geranylgeranyl-PP (GGPP, C20). The trans-prenyltransferases (PTs) mediate the sequential head-to-tail condensation of an isopentenyl-PP (C5) with allylic substrates. The in silico structural comparative analyses of rice trans-PTs with 136 plant trans-PT genes allowed twelve rice PTs to be identified as GGPS_LSU (OsGGPS1), homomeric G(G)PS (OsGPS) and GGPS_SSU-II (OsGRP) in Group I; two solanesyl-PP synthase (OsSPS2 and 3) and two polyprenyl-PP synthases (OsSPS1 and 4) in Group II; and five FPSs (OsFPS1, 2, 3, 4 and 5) in Group III. Additionally, several residues in “three floors” for the chain length and several essential domains for enzymatic activities specifically varied in rice, potentiating evolutionarily rice-specific biochemical functions of twelve trans-PTs. Moreover, expression profiling and localization patterns revealed their functional compartmentation in rice. Taken together, we propose the predicted topology-based working model of rice PTs with corresponding terpene metabolites: GPP/GGPPs mainly in plastoglobuli, SPPs in stroma, PPPs in cytosol, mitochondria and chloroplast and FPPs in cytosol. Our findings could be suitably applied to metabolic engineering for producing functional terpene metabolites in rice systems.
Nanoencapsulated Clove Oil Applied as an Anesthetic at Slaughtering Decreases Stress, Extends the Freshness, and Lengthens Shelf Life of Cultured Fish

In the aquaculture industry, fish are stunned using a wide range of methods, but all of them trigger stress responses and affect the fish flesh quality. Chilled water is considered one of the most efficient methods, but even this is not a stress-free experience for the fish. Anesthetics included in the ice slurry or in water could decrease this stress and delay the loss of flesh quality. In this work, we analyze the effect of clove oil (CO) nanoencapsulated in β-cyclodextrins (β-CD) (CO + β-CD), incorporated in the stunning bath, on the stress response and the organoleptic attributes of fresh marine and freshwater fish from four economically important fish species: Atlantic salmon, European seabass, Nile tilapia, and Rainbow trout. CO + β-CD reduces the time required to induce anesthesia, independently of water salinity, habitat or water temperature. The plasmatic glucose and cortisol levels decreased in all four species, although the concentrations of CO varied between species. Moreover, plasmatic lactate level differed between the marine and freshwater fish. The use of CO + β-CD extended the shelf life of fish from all the species studied (by 3–7 days). In conclusion, using CO encapsulated in β-CD for anesthetizing fish can be regarded as an improved fish-stunning technique that reduces the anesthesia-induction time, decreases the stress response, and extends the shelf life of fresh fish.
Aloperine protects human retinal pigment epithelial cells against hydrogen peroxide–induced oxidative stress and apoptosis through activation of Nrf2/HO-1 pathway

Abstract Age-related macular degeneration (AMD) is a complex multifactorial disease associated with the dysfunction of retinal pigment epithelium (RPE). Aloperine is a quinolizidine alkaloid that has been proven to possess broad pharmacological activities. However, the effects of aloperine on AMD remain unclear. In the present study, we used hydrogen peroxide (H2O2) to induce oxidative injury in human RPE cells (ARPE-19 cells). ARPE-19 cells were pretreated with different concentrations of aloperine for 2 h, followed by H2O2 exposure. Cell cytotoxicity was determined using lactate dehydrogenase (LDH) release assay. Cell viability was measured using Cell Counting Kit-8 (CCK-8) assay. The reactive oxygen species (ROS) generation, malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-PX) activity were detected to reflect oxidative status. Western blot was performed to detect the expressions of bcl-2, bax, nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). The activity of caspase-3 was also assessed to indicate cell apoptosis. In addition, ARPE-19 cells were transfected with siNrf2 to knock down Nrf2. Our results showed that pretreatment with aloperine elevated the reduced cell viability of H2O2-induced ARPE-19 cells in a dose-dependent manner. Aloperine greatly decreased the production of ROS and MDA, and increased the activities of SOD and GSH-PX in H2O2-stimulated ARPE-19 cells. H2O2-caused a decrease in bcl-2 expression and increases in bax expression and caspase-3 activity were mitigated by aloperine. Moreover, aloperine treatment enhanced the expression levels of Nrf2 in nuclear fraction and the HO-1 expression in lysates. Knockdown of Nrf2 reversed the protective effects of aloperine on H2O2-induced ARPE-19 cells. In conclusion, these findings demonstrated that aloperine protected ARPE-19 cells from H2O2-induced oxidative stress and apoptosis in part via activating the Nrf2/HO-1 signaling pathway. The findings suggested a therapeutic potential of aloperine for the treatment of ADM.
Molecular epidemiology and surveillance of circulating rotavirus among children with gastroenteritis in Bangladesh during 2014–2019

Acute gastroenteritis is one of the major health problems in children aged <5 years around the world. Rotavirus A (RVA) is an important pathogen of acute gastroenteritis. The burden of rotavirus disease in the pediatric population is still high in Bangladesh. This study investigated the prevalence of group A, B, and C rotavirus (RAV, RBV, RCV), norovirus, adenovirus (AdV) and human bocavirus (HBoV) infections in children with acute gastroenteritis in Bangladesh from February 2014 to January 2019. A total of 574 fecal specimens collected from children with diarrhea in Bangladesh during the period of February 2014-January 2019 were examined for RAV, RBV and RCV by reverse transcriptase- multiplex polymerase chain reaction (RT- multiplex PCR). RAV was further characterized to G-typing and P-typing by RT-multiplex PCR and sequencing method. It was found that 24.4% (140 of 574) fecal specimens were positive for RVA followed by AdV of 4.5%. RBV and RCV could not be detected in this study. Genotype G1P[8] was the most prevalent (43%), followed by G2P[4] (18%), and G9P[8] (3%). Among other genotypes, G9P[4] was most frequent (12%), followed by G1P[6] (11%), G9P[6] (3%), and G11P[25] (3%). We found that 7% RVA were nontypeable. Mutations at antigenic regions of the VP7 gene were detected in G1P[8] and G2P[4] strains. Incidence of rotavirus infection had the highest peak (58.6%) during November to February with diarrhea (90.7%) as the most common symptom. Children aged 4–11 months had the highest rotavirus infection percentage (37.9%). By providing baseline data, this study helps to assess efficacy of currently available RVA vaccine. This study revealed a high RVA detection rate, supporting health authorities in planning strategies such as introduction of RVA vaccine in national immunization program to reduce the disease burden.
Evaluation of Bone Gain and Complication Rates after Guided Bone Regeneration with Titanium Foils: A Systematic Review

Guided bone regeneration techniques are increasingly used to enable the subsequent placement of dental implants. This systematic review aims to analyze the success rate of these techniques in terms of bone gain and complications rate using titanium membranes as a barrier element. Electronic and hand searches were conducted in PubMed/Medline, Scielo, Scopus and Cochrane Library databases for case reports, case series, cohort studies and clinical trials in humans published up to and including 19 September 2020. Thirteen articles were included in the qualitative analysis. Bone gain both horizontally and vertically was comparable to that obtained with other types of membranes more commonly used. The postoperative complication rate was higher that of native collagen membranes and non-resorbable titanium-reinforced membranes, and similar that of crosslinked collagen membranes and titanium meshes. The survival rate of the implants was similar to that of implants placed in native bone. Due to the limited scientific literature published on this issue, more randomized clinical trials comparing occlusive titanium barriers and other types of membranes are necessary to reach more valid conclusions.
Dynamic follow‐up of smoldering multiple myeloma identifies a subset of patients at high risk of progression

onstrate that absolute increase exhibited a better discriminatory ability compared to a relative increase. It could be argued that relative increases could overestimate the impact of a dynamic biomarker, particularly in patients with low levels at diagnoses. Anemia is one of the hallmark symptoms in symptomatic MM. Hence, a decrease in hemoglobin during the first year of diagnosis as a RF of progression in SMM has been suggested in previous studies (Table S3B in Appendix S1). We could not confirm that the decrease of hemoglobin by ≥ 5 g/L during the first year of follow-up as a RF. Moreover, this cut-off could include values within the intraindividual variation of hemoglobin. The findings in our retrospective study support that dynamic changes in MP can identify patients at high risk of progression. In conclusion, BMPCs > 20% and MP > 20 g/L at diagnosis, were independent RFs for the progression. Moreover, eMP > 5 g/L and eFLCr > 4.5 were significant predictors of progression during the follow-up. With a median TTP of 5 months after an evolving pattern is observed, patients with evolving RF should be closely monitored. However, as these findings are exploratory, they should be validated in future prospective studies. The observed high risk of progression in patients with either or both evolving biomarkers may advocate a closer monitoring of these patients as well as possibly inclusion in future prospective early intervention trials.
Sex-based Approach for the Clinical Impact of the Increased Hemoglobin on Incident AF in the General Population

Background and Objectives Although the adverse cardiovascular effect of anemia has been well described, the effect of polycythemia on the incident atrial fibrillation (AF) remain unclear. The objective of this study is to identify the association between increased hemoglobin and incident AF. Methods This was a retrospective-cohort study with 434,269 subjects who underwent national health examinations from the Korean National Sample Cohort. We estimated the risk of incident AF according to hemoglobin-based four-categories. Results During 3.9-year of follow-up, polycythemia group showed higher incidences of AF (hazard ratio[HR] with 95% confidence interval[CI], 1.50 [1.28–1.76] and 1.69 [1.13–2.56]; in men and women, respectively) than normal hemoglobin group (each p<0.001). In the normal hemoglobin and polycythemia groups, a 1 g/dL increase in hemoglobin level was associated with increased risks of incident AF (1.12 [1.07–1.17] and 1.18 [1.10–1.26] in men and women, each p<0.001). To investigate the specific hemoglobin concentration related to greater AF incidence, we analyzed the sensitivity/specificity of different hemoglobin levels: ≥16.0 g/dL in men and ≥14.5 g/dL in women showed the highest Youden's index, with c-indices of 0.83 and 0.82, respectively. Kaplan-Meier cumulative-event curves according to these specific hemoglobin levels (≥16.0 g/dL in men and ≥14.5 g/dL in women) also showed consistent results in both sexes (each p<0.05). Conclusions Even in the Korean general population, increased hemoglobin was significantly associated with higher rate of incident AF. Especially, subjects with hemoglobin levels ≥14.5 g/dL in women and ≥16.0 g/dL among men were associated with increased risk of incident AF.
Rapid Profiling of the Volatilome of Cooked Meat by PTR-ToF-MS: Underlying Latent Explanatory Factors

Volatile organic compounds (VOCs) are important contributors to meat aroma and are variably correlated with each other. To study the sources of variation and the correlations among meat VOCs, meat cuts from five animal species/categories (chicken, turkey, pork, veal, and beef; two animals/species/retailer: 100 meat cuts) were obtained by 10 retailers. Each cut was processed into four burgers, two of which were grilled and two were cooked in a water bath (400 meat burgers). VOCs were detected by Proton-Transfer-Reaction Time-of-Flight Mass-Spectrometry (PTR-ToF-MS). From these, 129 peaks were selected, of which 72 were tentatively identified as relevant VOCs. Pearson correlations revealed a large number of positive and negative relationships among the VOCs. A multivariate statistical analysis revealed that 87% of the matrix covariance was explained by 17 independent Latent Explanatory Factors (LEFs), which have been described and characterized. LEFs identified may be valuable tools for reducing the dimensionality of results from VOC analyses and can be useful for better understanding and interpreting the variation in the meat aroma profile, although further study is required to characterize their sensory meaning.
Anthocyanins in Brassicaceae: composition, stability, bioavailability, and potential health benefits

Abstract Brassicaceae family includes various economic plants for edible or ornamental purposes. Brassicaceae vegetables are considered to be a major part of human diet as sources rich in phytochemicals. Among them, anthocyanins provide red to blue colors in Brassicaceae plants and as well have nutritional value and pharmaceutical potential. This review aims to summarize the chemical composition, stability, bioaccessibility, bioavailability, potential health benefits, and applications of anthocyanins from Brassicaceae. Additionally, the potential for incorporation of Brassicaceae anthocyanins in food systems as food additives and functional ingredients was demonstrated.
Gemcitabine-Loaded Magnetically Responsive Poly(ε-caprolactone) Nanoparticles against Breast Cancer

A reproducible and efficient interfacial polymer disposition method has been used to formulate magnetite/poly(ε-caprolactone) (core/shell) nanoparticles (average size ≈ 125 nm, production performance ≈ 90%). To demonstrate that the iron oxide nuclei were satisfactorily embedded within the polymeric solid matrix, a complete analysis of these nanocomposites by, e.g., electron microscopy visualizations, energy dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, electrophoresis, and contact angle goniometry was conducted. The magnetic responsive behaviour of these nanoparticles was quantitatively characterized by the hysteresis cycle and qualitatively investigated by visualization of the colloid under exposure to a 0.4 T magnet. Gemcitabine entrapment into the polymeric shell reported adequate drug loading values (≈11%), and a biphasic and pH-responsive drug release profile (≈four-fold faster Gemcitabine release at pH 5.0 compared to pH 7.4). Cytotoxicity studies in MCF-7 human breast cancer cells proved that the half maximal inhibitory concentration of Gem-loaded nanocomposites was ≈two-fold less than that of the free drug. Therefore, these core/shell nanoparticles could have great possibilities as a magnetically targeted Gemcitabine delivery system for breast cancer treatment.
Disordered eating among college students: The effects of parental attachment and the mediating role of emotion dysregulation

Abstract Objectives The current study explored the relationship between parental attachment and disordered eating among college students. This study also explored the potential mediating role of factors associated with emotion regulation. Participants: One hundred sixty-seven undergraduates (M = 18.93 years, SD = 1.02) participated in the current study. Methods: Participants completed an anonymous questionnaire reporting their perceptions of their parental attachment relationships, emotional reactivity, difficulty regulating emotions, and disordered eating. Results: Analyses using structural equation modeling indicated that difficulty regulating emotions mediated the relationship between maternal attachment and disordered eating, but not between paternal attachment and disordered eating. Emotional reactivity did not emerge as a significant mediator. Conclusions: These findings suggest that maternal attachment relationships may be associated with difficulty regulating emotions in adulthood, which may in turn impact disordered eating attitudes and behaviors.
Pre-Trained Deep Convolutional Neural Network for Clostridioides Difficile Bacteria Cytotoxicity Classification Based on Fluorescence Images

Clostridioides difficile infection (CDI) is an enteric bacterial disease that is increasing in incidence worldwide. Symptoms of CDI range from mild diarrhea to severe life-threatening inflammation of the colon. While antibiotics are standard-of-care treatments for CDI, they are also the biggest risk factor for development of CDI and recurrence. Therefore, novel therapies that successfully treat CDI and protect against recurrence are an unmet clinical need. Screening for novel drug leads is often tested by manual image analysis. The process is slow, tedious and is subject to human error and bias. So far, little work has focused on computer-aided screening for drug leads based on fluorescence images. Here, we propose a novel method to identify characteristic morphological changes in human fibroblast cells exposed to C. difficile toxins based on computer vision algorithms supported by deep learning methods. Classical image processing algorithms for the pre-processing stage are used together with an adjusted pre-trained deep convolutional neural network responsible for cell classification. In this study, we take advantage of transfer learning methodology by examining pre-trained VGG-19, ResNet50, Xception, and DenseNet121 convolutional neural network (CNN) models with adjusted, densely connected classifiers. We compare the obtained results with those of other machine learning algorithms and also visualize and interpret them. The proposed models have been evaluated on a dataset containing 369 images with 6112 cases. DenseNet121 achieved the highest results with a 93.5% accuracy, 92% sensitivity, and 95% specificity, respectively.
Application of Differential Network Enrichment Analysis for Deciphering Metabolic Alterations

Modern analytical methods allow for the simultaneous detection of hundreds of metabolites, generating increasingly large and complex data sets. The analysis of metabolomics data is a multi-step process that involves data processing and normalization, followed by statistical analysis. One of the biggest challenges in metabolomics is linking alterations in metabolite levels to specific biological processes that are disrupted, contributing to the development of disease or reflecting the disease state. A common approach to accomplishing this goal involves pathway mapping and enrichment analysis, which assesses the relative importance of predefined metabolic pathways or other biological categories. However, traditional knowledge-based enrichment analysis has limitations when it comes to the analysis of metabolomics and lipidomics data. We present a Java-based, user-friendly bioinformatics tool named Filigree that provides a primarily data-driven alternative to the existing knowledge-based enrichment analysis methods. Filigree is based on our previously published differential network enrichment analysis (DNEA) methodology. To demonstrate the utility of the tool, we applied it to previously published studies analyzing the metabolome in the context of metabolic disorders (type 1 and 2 diabetes) and the maternal and infant lipidome during pregnancy.