Miracle-dz/UniFAR-FTUs huggingface dataset:
Automated Classification of Significant Prostate Cancer on MRI: A Systematic Review on the Performance of Machine Learning Applications

Significant prostate carcinoma (sPCa) classification based on MRI using radiomics or deep learning approaches has gained much interest, due to the potential application in assisting in clinical decision-making. Objective: To systematically review the literature (i) to determine which algorithms are most frequently used for sPCa classification, (ii) to investigate whether there exists a relation between the performance and the method or the MRI sequences used, (iii) to assess what study design factors affect the performance on sPCa classification, and (iv) to research whether performance had been evaluated in a clinical setting Methods: The databases Embase and Ovid MEDLINE were searched for studies describing machine learning or deep learning classification methods discriminating between significant and nonsignificant PCa on multiparametric MRI that performed a valid validation procedure. Quality was assessed by the modified radiomics quality score. We computed the median area under the receiver operating curve (AUC) from overall methods and the interquartile range. Results: From 2846 potentially relevant publications, 27 were included. The most frequent algorithms used in the literature for PCa classification are logistic regression (22%) and convolutional neural networks (CNNs) (22%). The median AUC was 0.79 (interquartile range: 0.77–0.87). No significant effect of number of included patients, image sequences, or reference standard on the reported performance was found. Three studies described an external validation and none of the papers described a validation in a prospective clinical trial. Conclusions: To unlock the promising potential of machine and deep learning approaches, validation studies and clinical prospective studies should be performed with an established protocol to assess the added value in decision-making.
Are Household Potato Frying Habits Suitable for Preventing Acrylamide Exposure?

A survey was conducted of 730 Spanish households to identify culinary practices which might influence acrylamide formation during the domestic preparation of french fries and their compliance with the acrylamide mitigation strategies described in the 2017/2158 Regulation. Spanish household practices conformed with the majority of recommendations for the selection, storing and handling of potatoes, with the exception of soaking potato strips. Olive oil was the preferred frying oil (78.7%) and frying pans were the most common kitchen utensils used for frying (79.0%), leading to a higher oil replacement rate than with a deep-fryer. Although frying temperature was usually controlled (81.0%), participants were unaware of the maximum temperature recommended for preventing acrylamide formation. For french fries, color was the main criteria when deciding the end-point of frying (85.3%). Although a golden color was preferred by respondents (87.3%), color guidelines are recommended in order to unify the definition of “golden. ” The results conclude that habits of the Spanish population are in line with recommendations to mitigate acrylamide during french fry preparation. Furthermore, these habits do not include practices that risk increasing acrylamide formation. Nevertheless, educational initiatives tailored towards consumers would reduce the formation of this contaminant and, consequently, exposure to it in a domestic setting.
Porcine Reproductive and Respiratory Syndrome Virus Antagonizes PCSK9’s Antiviral Effect via Nsp11 Endoribonuclease Activity

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry worldwide. Our previous study had indicated that proprotein convertase subtilisin/kexin type 9 (PCSK9) was a responsive gene in porcine alveolar macrophages (PAMs) upon PRRSV infection. However, whether PCSK9 impacts the PRRSV replication and how the PRRSV modulates host PCSK9 remains elusive. Here, we demonstrated that PCSK9 protein suppressed the replication of both type-1 and type-2 PRRSV species. More specifically, the C-terminal domain of PCSK9 was responsible for the antiviral activity. Besides, we showed that PCSK9 inhibited PRRSV replication by targeting the virus receptor CD163 for degradation through the lysosome. In turn, PRRSV could down-regulate the expression of PCSK9 in both PAMs and MARC-145 cells. By screening the nonstructural proteins (nsps) of PRRSV, we showed that nsp11 could antagonize PCSK9’s antiviral activity. Furthermore, mutagenic analyses of PRRSV nsp11 revealed that the endoribonuclease activity of nsp11 was critical for antagonizing the antiviral effect of PCSK9. Collectively, our data provide further insights into the interaction between PRRSV and the cell host and offer a new potential target for the antiviral therapy of PRRSV.
Effect of Bentonite Characteristics on Wine Proteins, Polyphenols, and Metals under Conditions of Different pH

Studies have yet to evaluate how bentonite properties may affect the protein profile, polyphenol content, metal concentration, and heat stability of a white wine at different pH values. Therefore, this work assessed the proteins, polyphenols, metals, and haze forming tendency when heating white wine samples before and after a fining treatment with four activated sodium bentonites in a typical wine pH range (3.00 to 3.60). Soluble wine proteins were separated by sodium dodecyl sulfate - polyacrylamide gel electrophoresis, and gel images were compared using the Quantity One software package (Bio-Rad Laboratories, Inc., Hercules, CA). The wine haze forming tendency, metals, and polyphenols were measured using heat tests and International Organisation of Vine and Wine (OIV) methods. Low molecular mass proteins were efficiently removed by all of the bentonites, regardless of the pH. High and medium molecular mass proteins were less likely to be removed and the efficiency, which depended on the pH, was variable. Reductions of vacuolar invertase (GIN1) and VVTL1 fractions of the thaumatin-like proteins were induced by bentonites with pH values less than 10. These bentonites were affected to a lesser extent by the negative effect of acidic pH. The reduction in haze forming tendency of the unfined Erbaluce wine was particularly noticeable in bentonite fined samples heated at 50 to 60°C, 60 to 80°C, and 70 to 80°C at pH 3.17, pH 3.30, and pH 3.60, respectively. The poor removal of glycoproteins (YGP1 and Hmp1) at higher pH values contributed to an increased thermal stability. The exchange of cationic species, notably sodium and potassium, between the bentonites and the wine was related more to the wine pH than to the clay type. Finally, the extent of polyphenol removal correlated with the amount of protein removed. When protein removal did not occur, the reduction of polyphenols was driven by the specific surface area and the surface charge density of the bentonite.
The Epidemiology of SARS-CoV-2 in a Pediatric Healthcare Network in the United States.

BACKGROUND Understanding the prevalence and clinical presentation of COVID-19 in pediatric patients can help healthcare providers and systems prepare and respond to this emerging pandemic. METHODS Retrospective case series of patients tested for SARS-CoV-2 across a pediatric healthcare network, including the clinical features and outcomes of those with positive test results. RESULTS Of 7,256 unique children tested for SARS-CoV-2, 424 (5.8%) tested positive. Patients 18-21 years of age had the highest test positive rate (11.2%) while those 1-5 years of age had the lowest (3.9%). By race, 10.6% (226/2132) of Black children tested positive vs. 3.3% (117/3592) of White children. Of those with an indication for testing, 21.1% (371/1756) of patients with reported exposures or clinical symptoms tested positive vs. 3.8% (53/1410) of those undergoing pre-procedural or pre-admission testing. Of the 424 patients who tested positive for SARS-CoV-2, 182 (42.9%) had no comorbid medical conditions, 87 (20.5%) had asthma, 55 (13.0% had obesity, and 38 (9.0%) had mental health disorders. Overall, 52.1% had cough, 51.2% fever, and 14.6% shortness of breath. Seventy-seven (18.2%) SARS-CoV-2 positive patients were hospitalized, of which 24 (31.2%) required any respiratory support. SARS-CoV-2-targeted antiviral therapy was given to 9 patients, and immunomodulatory therapy to 18 patients. Twelve (2.8%) SARS-CoV-2 positive patients developed critical illness requiring mechanical ventilation and 2 patients required extracorporeal membrane oxygenation. Two patients died. CONCLUSIONS In this large cohort of pediatric patients tested for SARS-CoV-2, the rate of infection was low, but varied by testing indication. The majority of cases were mild, few children had critical illness, and two patients died.
Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling

Molecular profiling from liquid biopsy, in particular cell-free DNA (cfDNA), represents an attractive alternative to tissue biopsies for the detection of actionable targets and tumor monitoring. In addition to PCR-based assays, Next Generation Sequencing (NGS)-based cfDNA assays are now commercially available and are being increasingly adopted in clinical practice. However, the validity of these products as well as the clinical utility of cfDNA in the management of patients with cancer has yet to be proven. Within framework of the Innovative Medicines Initiative (IMI) program CANCER-ID we evaluated the use of commercially available reference materials designed for ctDNA testing and cfDNA derived from Diagnostic Leukaphereses (DLA) for inter- and intra-assay as well as intra- and inter-laboratory comparisons. In three experimental setups, a broad range of assays including ddPCR, MassARRAY and various NGS-based assays were tested. We demonstrate that both reference materials with predetermined VAFs and DLA samples are extremely useful for the performance assessment of mutation analysis platforms. Moreover, our data indicate a substantial variability of NGS assays with respect to sensitivity and specificity highlighting the importance of extensive validation of the test performance before offering these tests in clinical routine practice.
Organize, Don’t Agonize: Strategic Success of Phytophthora Species

Plants are constantly challenged by various environmental stressors ranging from abiotic—sunlight, elevated temperatures, drought, and nutrient deficits, to biotic factors—microbial pathogens and insect pests. These not only affect the quality of harvest but also the yield, leading to substantial annual crop losses, worldwide. Although plants have a multi-layered immune system, phytopathogens such as species of the oomycete genus Phytophthora, can employ elaborate mechanisms to breach this defense. For the last two decades, researchers have focused on the co-evolution between Phytophthora and interacting hosts to decouple the mechanisms governing their molecular associations. This has provided a comprehensive understanding of the pathobiology of plants affected by oomycetes. Ultimately, this is important for the development of strategies to sustainably improve agricultural production. Therefore, this paper discusses the present-day state of knowledge of the strategic mode of operation employed by species of Phytophthora for successful infection. Specifically, we consider motility, attachment, and host cell wall degradation used by these pathogenic species to obtain nutrients from their host. Also discussed is an array of effector types from apoplastic (hydrolytic proteins, protease inhibitors, elicitins) to cytoplastic (RxLRs, named after Arginine-any amino acid-Leucine-Arginine consensus sequence and CRNs, for CRinkling and Necrosis), which upon liberation can subvert the immune response and promote diseases in plants.
Evaluation of wild red clover (Trifolium pratense L.) ecotypes and hybrid populations (Trifolium pratense L. × Trifolium diffusum Ehrh.) for clover rot resistance (Sclerotinia trifoliorum Erikss.)

Forage grass breeders are intensively searching for qualitatively novel initial breeding material, more attention is being paid to wild ecotypes’ phenomenon of polymorphism within the species, and the application of interspecific hybridisation is becoming increasingly widespread. The present study was designed to investigate the variability of clover rot resistance (Sclerotinia trifoliorum Erikss.) in wild red clover (Trifolium pratense L.) ecotypes and hybrid populations (Trifolium pratense L. × Trifolium diffusum Ehrh.). Red clover ecotypes were found to possess a different resistance to the clover rot causal agent: 38.5% of the ecotypes were attributed to the moderately resistant clover group, whereas the plants of the standard variety ‘Liepsna’ were found to be non-resistant. Compared with non-resistant ecotypes, moderately resistant wild ecotypes exhibited a better overwinter survival and better digestibility characteristics, however, they accumulated lower contents of crude protein and green material. Interspecific hybrids, compared with the plants of the standard varieties ‘Liepsna’ and ‘Vyliai’, were characterised by increased (on average 1.4 times higher) resistance to the causal agent of clover rot.
CB1 receptor‐dependent desensitisation of TRPV1 channels contributes to the analgesic effect of dipyrone in sensitised primary sensory neurons

While dipyrone is a widely used analgesic, its mechanism of action is not completely understood. Recently, we have reported that the dipyrone metabolite 4‐aminoantipyrine (4‐AA) reduces PGE2‐induced pain‐related behaviour through cannabinoid CB1 receptors. Here, we ascertained, in naive and PGE2‐induced “inflamed” conditions, both in vivo and in vitro, the molecular mechanisms involved in the 4‐AA‐induced analgesic effects.
Long-Term Phenotypic and Proteomic Changes Following Vitrified Embryo Transfer in the Rabbit Model

Simple Summary This study was conducted to demonstrate how a vitrified embryo transfer procedure incurs phenotypic and molecular changes throughout life. This study reports the first evidence describing that embryonic manipulation during a vitrified embryo transfer cycle induced molecular modifications, concerning oxidative phosphorylation and dysregulations in zinc and lipid metabolism in liver tissue, which has been reported as responsible for postnatal variations of the phenotype. Abstract Nowadays, assisted reproductive technologies (ARTs) are considered valuable contributors to our past, but a future without their use is inconceivable. However, in recent years, several studies have evidenced a potential impact of ART on long-term development in mammal species. To date, the long-term follow-up data are still limited. So far, studies have mainly focused on in vitro fertilization or in vitro culture, with information from gametes/embryos cryopreservation field being practically missing. Herein, we report an approach to determine whether a vitrified embryo transfer procedure would have long-term consequences on the offspring. Using the rabbit as a model, we compared animals derived from vitrified-transferred embryos versus those naturally conceived, studying the growth performance, plus the weight throughout life, and the internal organs/tissues phenotype. The healthy status was assessed over the hematological and biochemical parameters in peripheral blood. Additionally, a comparative proteomic analysis was conducted in the liver tissue to investigate molecular cues related to vitrified embryo transfer in an adult tissue. After vitrified embryo transfer, birth weight was increased, and the growth performance was diminished in a sex-specific manner. In addition, vitrified-transferred animals showed significantly lower body, liver and heart weights in adulthood. Molecular analyses revealed that vitrified embryo transfer triggers reprogramming of the liver proteome. Functional analysis of the differentially expressed proteins showed changes in relation to oxidative phosphorylation and dysregulations in the zinc and lipid metabolism, which has been reported as possible causes of a disturbed growth pattern. Therefore, we conclude that vitrified embryo transfer is not a neutral procedure, and it incurs long-term effects in the offspring both at phenotypic and molecular levels. These results described a striking example of the developmental plasticity exhibited by the mammalian embryo.
Statins: Could an old friend help in the fight against COVID‐19?

The COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID‐19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID‐19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS‐CoV‐2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well‐known anti‐inflammatory properties of statins, by blocking several molecular mechanisms, including NF‐κB and NLRP3 inflammasomes, could limit the “cytokine storm” in severe COVID‐19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID‐19 outcomes.
Haematological cancers and the risk of severe COVID‐19: Exploration and critical evaluation of the evidence to date

From the outset of the COVID‐19 pandemic, patients and healthcare professionals have been concerned that a history of haematological malignancy will lead to an increased risk of severe COVID‐19. This led to the UK government advising patients with blood cancers to shield, massive re‐organisation of NHS haematology and cancer services, and changes in treatment plans for thousands of patients. Given the unknown effects that relaxation of social‐distancing measures will have on the infection rate, we review the evidence to date to see whether a history of haematological malignancy is associated with increased risk of COVID‐19. Multivariable analysis of large population studies, taking other known risk factors into account, do indicate that patients with haematological malignancy, especially those diagnosed recently, are at increased risk of death from COVID‐19 compared to the general population. The evidence that this risk is higher than for those with solid malignancies is conflicting. There is suggestive evidence from smaller cohort studies that those with myeloid malignancy may be at increased risk within the blood cancer population, but this needs to be confirmed on larger studies. Ongoing large collaborative efforts are required to gain further evidence regarding specific risk factors for severe complications of COVID‐19.
Morphology and ontogeny of conidia in Wilsonomyces carpophilus, gen. nov. and Comb. nov., causal pathogen of shot hole disease of Prunus species

The new genus Wilsonomyces is described and the new combination W. carpophilus is proposed based on colony characteristics, morphology of conidia, and conidial ontogeny. Cultures, living plant material, and herbarium specimens were examined using bright-field, phase contrast, scanning, and transmission electron microscopy
Covid-19 Confinement and Changes of Adolescent’s Dietary Trends in Italy, Spain, Chile, Colombia and Brazil

Confinement due to the COVID-19 pandemic can influence dietary profiles, especially those of adolescents, who are highly susceptible to acquiring bad eating habits. Adolescents’ poor dietary habits increase their subsequent risk of degenerative diseases such as obesity, diabetes, cardiovascular pathologies, etc. Our aim was to study nutritional modifications during COVID-19 confinement in adolescents aged 10 to 19 years, compare them with their usual diet and dietary guidelines, and identify variables that may have influenced changes. Data were collected by an anonymous online questionnaire on food intake among 820 adolescents from Spain, Italy, Brazil, Colombia, and Chile. The results show that COVID-19 confinement did influence their dietary habits. In particular, we recorded modified consumption of fried food, sweet food, legumes, vegetables, and fruits. Moreover, gender, family members at home, watching TV during mealtime, country of residence, and maternal education were diversely correlated with adequate nutrition during COVID-19 confinement. Understanding the adolescents’ nutrition behavior during COVID-19 lockdown will help public health authorities reshape future policies on their nutritional recommendations, in preparation for future pandemics.
Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes

Phospholipase A2 (PLA2) enzymes are important toxins found in many snake venoms, and they can exhibit a variety of toxic activities including causing hemolysis and/or anticoagulation. In this study, the inhibiting effects of the small molecule PLA2 inhibitor varespladib on snake venom PLA2s was investigated by nanofractionation analytics, which combined chromatography, mass spectrometry (MS), and bioassays. The venoms of the medically important snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus, Echis ocellatus, and Oxyuranus scutellatus were separated by liquid chromatography (LC) followed by nanofractionation and interrogation of the fractions by a coagulation assay and a PLA2 assay. Next, we assessed the ability of varespladib to inhibit the activity of enzymatic PLA2s and the coagulopathic toxicities induced by fractionated snake venom toxins, and identified these bioactive venom toxins and those inhibited by varespladib by using parallel recorded LC-MS data and proteomics analysis. We demonstrated here that varespladib was not only capable of inhibiting the PLA2 activities of hemotoxic snake venoms, but can also effectively neutralize the coagulopathic toxicities (most profoundly anticoagulation) induced by venom toxins. While varespladib effectively inhibited PLA2 toxins responsible for anticoagulant effects, we also found some evidence that this inhibitory molecule can partially abrogate procoagulant venom effects caused by different toxin families. These findings further emphasize the potential clinical utility of varespladib in mitigating the toxic effects of certain snakebites.