Miracle-dz/UniFAR-FTUs huggingface dataset:
Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial.

AIMS Statins are pivotal to the secondary prevention of major adverse cardiovascular events, but some patients are statin-intolerant. We examined the effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab on the risk of major adverse cardiovascular events according to the intensity of background statin treatment. METHODS AND RESULTS The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with acute coronary syndrome and dyslipidaemia despite intensive or maximum-tolerated statin treatment (including no statin if intolerance was documented). The primary outcome (major adverse cardiovascular events) comprised coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina. Median follow-up was 2.8 years. Baseline statin treatment was high-intensity (88.8%), low/moderate-intensity (8.7%) or none (2.4%). Median baseline low-density lipoprotein cholesterol was 86, 89 and 139 mg/dL (P < 0.001) in these statin treatment categories, respectively. Alirocumab produced similar relative reductions in low-density lipoprotein cholesterol from baseline across statin treatment subgroups, but the mean absolute reductions differed (52.9, 56.7 and 86.1 mg/dL, respectively; P < 0.001). With placebo, the incidence of major adverse cardiovascular events was highest in the no statin subgroup (10.8%, 10.7% and 26.0% respectively). Alirocumab reduced major adverse cardiovascular events in each statin subgroup (hazard ratio 0.88, 95% confidence interval (CI) 0.80-0.96; 0.68, 0.49-0.94; and 0.65, 0.44-0.97, respectively; Pinteraction = 0.14) with a gradient of absolute risk reduction: 1.25%, 95% CI 0.34-2.16; 3.16%, 0.38-5.94; 7.97%, 0.42-15.51; Pinteraction = 0.106). CONCLUSIONS PCSK9 inhibition with alirocumab reduces the relative risk of major adverse cardiovascular events after acute coronary syndrome irrespective of background statin treatment. However, patients on no statin are at high absolute risk for recurrent major adverse cardiovascular events; alirocumab substantially reduces that risk. PCSK9 inhibition may be an important therapeutic strategy for statin-intolerant patients with acute coronary syndrome.
Commercial Saccharomyces cerevisiae as a starter culture in “Wanergao”: A traditional fermented food in China

To explore the effect of commercial Saccharomyces cerevisiae on the quality of traditional “Wanergao” for reasonable consuming guidance, the dominant microbes, physicochemical property, free amino acid content, texture, and sensory properties during fermentation of “Wanergao” were illustrated in this paper. Compared with the samples in the control group, “Wanergao” samples in the two groups that were subjected to S. cerevisiae inoculation had weaker acidity (the pH values dropped from 4.39 ± 0.08 to 4.36 ± 0.07 and 4.36 ± 0.07 within 2 h during fermentation), higher fermenting rate (volume increased from 100 ± 1.31 to 305 ± 4.61 and 316 ± 4.93 mL separately within 3 h), and the dominant lactic acid bacteria and yeast being leukonid and S. cerevisiae. More amylose, ethanol, and free amino acid were detected in “Wanergao” produced with S. cerevisiae inoculation compared with “Wanergao” produced by sourdough. The two kinds of “Wanergao” presented various hardness (2318 ± 112, 2279 ± 103), springiness (0.76 ± 0.03, 0.71 ± 0.03), chewiness (1.43 ± 0.05, 1.41 ± 0.06), and cohesiveness (0.68 ± 0.03, 0.62 ± 0.03) after fermentation. The result of sensory analysis revealed that “Wanergao” in the S. cerevisiae group had higher elasticity, aroma, and restoring force. The experiment demonstrated that “Wanergao” produced by using S. cerevisiae is a kind of fermented rice product with rich fragrance, high amount of nutrients, and strong elasticity.
Improvement of plankton biovolume estimates derived from image-based automatic sampling devices: application to FlowCAM

The most commonly used biomass estimate for microalgae is obtained from cell biovolume, usually calculated from microscopically measured linear dimensions. Although reliable, this is a highly time-consuming and specialized technique. Automated sampling devices that acquire images of cells and use pattern recognition techniques to identify the images have been developed as an alternative to microscopy-based methods. There are some aspects of automatic sampling and classification methods, however, which can be improved for the analysis of field samples including living and non-living particles. In this work, we demonstrate how the accuracy of a state-of the-art technique for plankton classification (Support Vector Machine) can be improved up to 86% if a previous automated step designed to remove non-living images is included. There is a tendency with the currently applied automatic methods to misestimate cell biovolume due to the two-dimensionality of the images. Here, we present a data set of more than 500 samples to show that the greatest effect is caused by the incorrect estimation of biovolume of the chain-forming diatoms. This results in an overestimate of biomass of between 20 and 100% where chain-forming diatoms represent more than the 20% of the biomass of the sample. We show how the classification method can be adapted to provide not only taxonomic but also the morphological classification of cells in order to obtain a more reliable estimate of biovolume according to the predicted cell shape, in a way comparable with microscopy-based estimates.
Immunogenic SARS-CoV-2 Epitopes: In Silico Study Towards Better Understanding of COVID-19 Disease—Paving the Way for Vaccine Development

The emergence of the COVID-19 outbreak at the end of 2019, caused by the novel coronavirus SARS-CoV-2, has, to date, led to over 13.6 million infections and nearly 600,000 deaths. Consequently, there is an urgent need to better understand the molecular factors triggering immune defense against the virus and to develop countermeasures to hinder its spread. Using in silico analyses, we showed that human major histocompatibility complex (MHC) class I cell-surface molecules vary in their capacity for binding different SARS-CoV-2-derived epitopes, i.e., short sequences of 8-11 amino acids, and pinpointed five specific SARS-CoV-2 epitopes that are likely to be presented to cytotoxic T-cells and hence activate immune responses. The identified epitopes, each one of nine amino acids, have high sequence similarity to the equivalent epitopes of SARS-CoV virus, which are known to elicit an effective T cell response in vitro. Moreover, we give a structural explanation for the binding of SARS-CoV-2-epitopes to MHC molecules. Our data can help us to better understand the differences in outcomes of COVID-19 patients and may aid the development of vaccines against SARS-CoV-2 and possible future outbreaks of novel coronaviruses.
Structural and Functional Refinement of the Axon Initial Segment in Avian Cochlear Nucleus during Development

The axon initial segment (AIS) is involved in action potential initiation. Structural and biophysical characteristics of the AIS differ among cell types and/or brain regions, but the underlying mechanisms remain elusive. Using immunofluorescence and electrophysiological methods, combined with super-resolution imaging, we show in the developing nucleus magnocellularis of the chicken in both sexes that the AIS is refined in a tonotopic region-dependent manner. This process of AIS refinement differs among cells tuned to different frequencies. At hearing onset, the AIS was ∼50 µm long with few voltage-gated sodium channels regardless of tonotopic region. However, after hatching, the AIS matured and displayed an ∼20-µm-long structure with a significant enrichment of sodium channels responsible for an increase in sodium current and a decrease in spike threshold. Moreover, the shortening was more pronounced, while the accumulation of channels was not, in neurons tuned to higher frequency, creating tonotopic differences in the AIS. We conclude that AIS shortening is mediated by disassembly of the cytoskeleton at the distal end of the AIS, despite intact periodicity of the submembranous cytoskeleton across the AIS. Importantly, deprivation of afferent input diminished the shortening in neurons tuned to a higher frequency to a larger extent in posthatch animals, with little effect on the accumulation of sodium channels. Thus, cytoskeletal reorganization and sodium channel enrichment at the AIS are differentially regulated depending on tonotopic region, but work synergistically to optimize neuronal output in the auditory nucleus. SIGNIFICANCE STATEMENT The axon initial segment (AIS) plays fundamental roles in determining neuronal output. The AIS varies structurally and molecularly across tonotopic regions in avian cochlear nucleus. However, the mechanism underlying these variations remains unclear. The AIS is immature around hearing onset, but becomes shorter and accumulates more sodium channels during maturation, with a pronounced shortening and a moderate channel accumulation at higher tonotopic regions. Afferent input adjusts sodium conductance at the AIS by augmenting AIS shortening (via disassembly of cytoskeletons at its distal end) specifically at higher-frequency regions. However, this had little effect on channel accumulation. Thus, cytoskeletal structure and sodium channel accumulation at the AIS are regulated differentially but work synergistically to optimize the neuronal output.
Impact of troponin I level on coronary artery bypass grafting outcomes

The effect of preoperative cardiac troponin level on outcomes after coronary artery bypass grafting (CABG) is unclear. We investigated the impact of preoperative cardiac troponin I (cTnI) level as well as the time interval between maximum cTnI and surgery on CABG outcomes.
The first study in pediatric: Population pharmacokinetics of sirolimus and its application in Chinese children with immune cytopenia

The narrow therapeutic index and large inter-individual variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring (TDM) necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with immune cytopenia. The objective of this study was to characterize the PK of sirolimus in pediatric patients with immune cytopenia and to develop a population PK model in Chinese children and evaluate its utility for dose individualization. A total of 27 children with either acquired or congenital immune cytopenia aged 8.16 ± 3.60 years (range: 1–15 years) were included. TDM data for sirolimus were collected. The population PK model of sirolimus was described using the nonlinear mixed-effects modeling (Phoenix NLME 1.3 software) approach. Covariate analysis was applied to select candidate factors associated with PK parameters. The final model was validated using bootstrap (1000 runs) and visual predictive check (VPC) method. A one-compartment model with first-order absorption and elimination was developed. The outcome parameters were as follows: apparent clearance (CL/F) 5.63 L/h, apparent distribution volume (V/F) 144.16 L. Inter-individual variabilities for CL/F and V/F were 3.53% and 7.27%, respectively. The intra-individual variability of proportional error model was 22.45%. The covariate test found that body weight and total bilirubin were strongly associated with clearance; however, we did not find the relevance between the covariate and volume of distribution of sirolimus. Personalized dosage regimens were provided based on Bayesian method. The oral dose should be adjusted according to weight and total bilirubin. This is the first study to describe a population PK model of sirolimusin pediatric patients with immune cytopenia. Population pharmacokinetic (PPK) model–based dose individualization of sirolimus and the design of future clinical studies in children will be facilitated by the developed model in this study.
Cryptic diversity within the rotifer Polyarthra dolichoptera along an altitudinal gradient

Summary Cryptic species (species that are difficult or impossible to distinguish morphologically) are found worldwide and neglecting them may hamper our understanding of species-environment relationships. The rotifer Polyarthra dolichoptera occurs across wide environmental gradients, indicating the potential for a cryptic species complex. We used P. dolichoptera as a model to investigate spatial patterns and relationships of cryptic species with environmental variables along a broad altitudinal gradient. We sequenced 575 specimens of Polyarthra from 42 waterbodies from Germany, Hungary and Italy sampled in summer. Thirty-five lakes were distributed along an altitudinal gradient (250–2564 m a.s.l.) in a geographically restricted area, the Trentino–South Tyrol region, Italy, and one lake (Lake Tovel) was sampled in two basins and at different depths year-round to investigate temporal and spatial patterns of cryptic species. We used the Generalised Mixed Yule Coalescent model to delimit cryptic species (GMYC entities) based on a phylogenetic tree and related their presence/absence to space and the environment by applying Mantel tests and variance partitioning. We found twelve GMYC entities of P. dolichoptera. In variance partitioning, most explained variability was attributed to the interaction between space and altitude and by environmental variables and geographical space alone. However, by splitting the data into sets of low- and high-altitude lakes, the strong effect of altitude was removed; conductivity and silica played a major role in high-altitude lakes, whereas neither environment nor space were related to entity occurrence in low-altitude lakes. In Lake Tovel, three cryptic entities were found that did not show spatial segregation; however, two entities showed temporal segregation while the third one occurred throughout the year. Our study showed that P. dolichoptera is a complex of species which distribution is driven by geography and environmental parameters whose importance is different in low- and high-altitude lakes. Considerable unexplained variability points to a major contribution of other variables, potentially in-lake properties such as competition, predation and species behaviour.
Human Interferon-γ Enhances the Expression of Class I and Class II Major Histocompatibility Complex Products in Neoplastic Cells More Effectively than Interferon-α and Interferon-β

Human interferon-γ was more effective than interferon-β or -α in stimulating production of immunoassociated antigens; HLA-A, -B, and -C; and β2-microglobulin in human M14 and Namalva cells. The comparison was made on the basis of antiviral units, and the stimulation could be abolished by treatment of the interferon-γ preparation with pH 2 or anti-interferon-γ serum.
Antidiabetic Food-Derived Peptides for Functional Feeding: Production, Functionality and In Vivo Evidences

Bioactive peptides released from the enzymatic hydrolysis of food proteins are currently a trending topic in the scientific community. Their potential as antidiabetic agents, by regulating the glycemic index, and thus to be employed in food formulation, is one of the most important functions of these peptides. In this review, we aimed to summarize the whole process that must be considered when talking about including these molecules as a bioactive ingredient. In this regard, at first, the production, purification and identification of bioactive peptides is summed up. The detailed metabolic pathways described included carbohydrate hydrolases (glucosidase and amylase) and dipeptidyl-peptidase IV inhibition, due to their importance in the food-derived peptides research field. Then, their characterization, concerning bioavailability in vitro and in situ, stability and functionality in food matrices, and ultimately, the in vivo evidence (from invertebrate animals to humans), was described. The future applicability that these molecules have due to their biological potential as functional ingredients makes them an important field of research, which could help the world population avoid suffering from several diseases, such as diabetes.
Antibody Binding and Complement-Mediated Killing of Invasive Haemophilus influenzae Isolates from Spain, Portugal, and the Netherlands

Haemophilus influenzae is a Gram-negative bacterium that can be classified into typeable (types a through f) and nontypeable (NTHi) groups. This opportunistic pathogen asymptomatically colonizes the mucosal epithelium of the upper respiratory tract, from where it spreads to other neighboring regions, potentially leading to disease. Infection with NTHi can cause otitis media, sinusitis, conjunctivitis, exacerbations of chronic obstructive pulmonary disease, and pneumonia, but it is increasingly causing invasive disease, including bacteremia and meningitis. ABSTRACT Haemophilus influenzae is a Gram-negative bacterium that can be classified into typeable (types a through f) and nontypeable (NTHi) groups. This opportunistic pathogen asymptomatically colonizes the mucosal epithelium of the upper respiratory tract, from where it spreads to other neighboring regions, potentially leading to disease. Infection with NTHi can cause otitis media, sinusitis, conjunctivitis, exacerbations of chronic obstructive pulmonary disease, and pneumonia, but it is increasingly causing invasive disease, including bacteremia and meningitis. Invasive NTHi strains are more resistant to complement-mediated killing. However, the mechanisms of complement resistance have never been studied in large numbers of invasive NTHi strains. In this study, we determined the relationship between binding of IgG or IgM and the bacterial survival in normal human serum for 267 invasive H. influenzae strains from Spain, Portugal, and the Netherlands, of which the majority (200 [75%]) were NTHi. NTHi bacteria opsonized with high levels of IgM had the lowest survival in human serum. IgM binding to the bacterial surface, but not IgG binding, was shown to be associated with complement-mediated killing of NTHi strains. We conclude that evasion of IgM binding by NTHi strains increases survival in blood, thereby potentially contributing to their ability to cause severe invasive diseases.
Diagnostic Value of Imaging Modalities for COVID-19: Scoping Review

Background Coronavirus disease (COVID-19) is a serious infectious disease that causes severe respiratory illness. This pandemic represents a serious public health risk. Therefore, early and accurate diagnosis is essential to control disease progression. Radiological examination plays a crucial role in the early identification and management of infected patients. Objective The aim of this review was to identify the diagnostic value of different imaging modalities used for diagnosis of COVID-19. Methods A comprehensive literature search was conducted using the PubMed, Scopus, Web of Science, and Google Scholar databases. The keywords diagnostic imaging, radiology, respiratory infection, pneumonia, coronavirus infection and COVID-19 were used to identify radiology articles focusing on the diagnosis of COVID-19 and to determine the diagnostic value of various imaging modalities, including x-ray, computed tomography (CT), ultrasound, and nuclear medicine for identification and management of infected patients. Results We identified 50 articles in the literature search. Studies that investigated the diagnostic roles and imaging features of patients with COVID-19, using either chest CT, lung ultrasound, chest x-ray, or positron emission topography/computed tomography (PET/CT) scan, were discussed. Of these imaging modalities, chest x-ray and CT scan are the most commonly used for diagnosis and management of COVID-19 patients, with chest CT scan being more accurate and sensitive in identifying COVID-19 at early stages. Only a few studies have investigated the roles of ultrasound and PET/CT scan in diagnosing COVID-19. Conclusions Chest CT scan remains the most sensitive imaging modality in initial diagnosis and management of suspected and confirmed patients with COVID-19. Other diagnostic imaging modalities could add value in evaluating disease progression and monitoring critically ill patients with COVID-19.
The effects of stylopisation on the sexual development of Javesella dubia (Kirschbaum) (Homoptera: Delphacidae)

This is the first record of the entomophagous parasite Elenchus tenuicornis (Kirby) parasitizing Javesella dubia (Kirschbaum) in England. The effects of E. tenuicornis on the development of (a) the primary, secondary and tertiary sexual organs, and (b) the body characters of J. dubia are discussed in detail.
Race or racial segregation? Modification of the PM2.5 and cardiovascular mortality association

Background Many studies have identified an inequitable distribution of exposure to PM2.5 (particulate matter less than 2.5 microns) by race. We investigated the association of PM2.5 and cardiovascular mortality considering both the decedents’ race and neighborhood racial composition as potential modifiers. Methods We obtained geocoded cardiovascular mortality records of all black and white decedents from urban block-groups in Massachusetts between 2001 and 2011 (n = 130,863). We examined the association between PM2.5 and cardiovascular mortality, and assessed effect modification by three types of racial modifiers: decedents’ race, census block-group percent black and white, and two novel measures of racial segregation. The Racial Residential Segregation (RRS) quantifies the concentration of non-Hispanic blacks and whites in each block-group. The Index of Racial Dissimilarity measures dissimilarity in non-Hispanic black and white racial distribution between the smaller census block-group and larger tract. Results We found a 2.35%(95%CI: 0.92%;3.79%) increase in mortality for each 10μg/m3 increase in two-day average exposure to PM2.5. The effect was modified by the block-group racial composition, with higher risks in block-groups with the highest percentage of black residents (interaction p-value = 0.04), and in block-groups with the lowest RRS (i.e. higher black to white resident ratio, interaction p-value = 0.072). Racial dissimilarity did not modify the associations. Conclusion Current levels of PM2.5 are associated with increased cardiovascular deaths in Massachusetts, with different risks between areas with different racial composition and segregation. This suggests that pollution reductions in neighborhoods with the highest percentage of non-Hispanic blacks would be most beneficial in reducing cardiovascular mortality and disparities.
Calcinosis cutis in a background of chronic viral infection: Report of 2 cases: Diagnosed by fine needle aspiration cytology

Calcinosis cutis is an uncommon entity which develops due to the deposition of hydroxyapatite crystals of calcium phosphate in the skin. As the calcific deposits can clinically mimic a tumor, it is feasible to investigate them by fine-needle aspiration cytology (FNAC). In this study, we describe two cases of calcinosis cutis that were diagnosed by fine needle aspiration (FNA). Both the patients presented with nodular lesions in hand and sacrococcygeal region respectively. Aspiration yielded chalky white material. FNA smears showed flakes of amorphous material indicating calcium along with few macrophages. The presence of amorphous calcium salts along with histiocytes in the appropriate clinical settings is diagnostic of calcinosis cutis. The cases are interesting, since both the patients have positive viral markers and are suffering from debilitating diseases.