Efficient self-supervised metric information retrieval: A bibliography based method applied to covid literature

The literature on coronaviruses counts more than 300,000 publications. Finding relevant papers concerning arbitrary queries is essential to discovery helpful knowledge. Current best information retrieval (IR) use deep learning approaches and need supervised train sets with labeled data, namely to know a priori the queries and their corresponding relevant papers. Creating such labeled datasets is time-expensive and requires prominent experts’ efforts, resources insufficiently available under a pandemic time pressure. We present a new self-supervised solution, called SUBLIMER, that does not require labels to learn to search on corpora of scientific papers for most relevant against arbitrary queries. SUBLIMER is a novel efficient IR engine trained on the unsupervised COVID-19 Open Research Dataset (CORD19), using deep metric learning. The core point of our self-supervised approach is that it uses no labels, but exploits the bibliography citations from papers to create a latent space where their spatial proximity is a metric of semantic similarity; for this reason, it can also be applied to other domains of papers corpora. SUBLIMER, despite is self-supervised, outperforms the Precision@5 (P@5) and Bpref of the state-of-the-art competitors on CORD19, which, differently from our approach, require both labeled datasets and a number of trainable parameters that is an order of magnitude higher than our

Plant Essential Oils as Healthy Functional Ingredients of Nutraceuticals and Diet Supplements: A Review

Essential oils (EOs) are mixtures of volatile molecules endowed with health-promoting biological activities that go beyond their role as aromas and natural preservatives and can be exploited to develop functional foods and diet supplements. Their composition is briefly addressed along with regulatory aspects. The potential health benefit of human diet supplementation with EOs is outlined through a review of the recent literature on available clinical trials and preclinical research concerning EOs activity towards: (1) irritable bowel syndrome; (2) inflammatory bowel disease; (3) regulation of microbiota; (4) gastroprotection; (5) hepatoprotection; (6) protection of the urinary tract and diuresis; (7) management of metabolic disorders including hyperglycemia and hyperlipidemia; (8) anti-inflammatory and pain control; (9) immunomodulation and protection from influenza; and (10) neuroprotection and modulation of mood and cognitive performance. The emerging potential in such activities of selected EOs is given focus, particularly green and black cumin, bergamot, orange, myrtle, peppermint, sage, eucalyptus, lavender, thyme, lemon balm, ginger, and garlic

Efficient Memory-Enhanced Transformer for Long-Document Summarization in Low-Resource Regimes

Long document summarization poses obstacles to current generative transformer-based models because of the broad context to process and understand. Indeed, detecting long-range dependencies is still challenging for today’s state-of-the-art solutions, usually requiring model expansion at the cost of an unsustainable demand for computing and memory capacities. This paper introduces Emma, a novel efficient memory-enhanced transformer-based architecture. By segmenting a lengthy input into multiple text fragments, our model stores and compares the current chunk with previous ones, gaining the capability to read and comprehend the entire context over the whole document with a fixed amount of GPU memory. This method enables the model to deal with theoretically infinitely long documents, using less than 18 and 13 GB of memory for training and inference, respectively. We conducted extensive performance analyses and demonstrate that Emma achieved competitive results on two datasets of different domains while consuming significantly less GPU memory than competitors do, even in low-resource settings

Potent Antioxidant and Anti-Tyrosinase Activity of Butein and Homobutein Probed by Molecular Kinetic and Mechanistic Studies †

Butein (BU) and homobutein (HB) are bioactive polyhydroxylated chalcones widespread in dietary plants, whose antioxidant properties require mechanistic definition. They were investigated by inhibited autoxidation kinetic studies of methyl linoleate in TritonTM X-100 micelles at pH 7.4, 37 °C. Butein had kinh = (3.0 ± 0.9) × 104 M−1s−1 showing a chain-breaking mechanism with higher antioxidant activity than reference α-tocopherol (kinh = (2.2 ± 0.6) × 104 M−1s−1), particularly concerning the stoichiometry or peroxyl radical trapping n = 3.7 ± 1.1 vs. 2.0 for tocopherol. Homobutein had kinh = (2.8 ± 0.9) × 103 M−1s−1, pairing the relative BDEOH measured by radical equilibration EPR as 78.4 ± 0.2 kcal/mol for BU and estimated as 82.6 kcal/mol for HB. The inhibition of mushroom tyrosinase (mTYR) by HB and BU was also investigated. BU gives a reversible uncompetitive inhibition of monophenolase reaction with KI′ = 9.95 ± 2.69 μM and mixed-type diphenolase inhibition with KI = 3.30 ± 0.75 μM and KI′ = 18.75 ± 5.15 μM, while HB was nearly competitive toward both mono- and diphenolase with respective KI of 2.76 ± 0.70 μM and 2.50 ± 1.56 μM. IC50 values (monophenolase/diphenolase at 1 mM substrate) were 10.88 ± 2.19 μM/15.20 ± 1.25 μM, 14.78 ± 1.05 μM/12.36 ± 2.00 μM, and 33.14 ± 5.03 μM/18.27 ± 3.42 μM, respectively, for BU, HB, and reference kojic acid. Molecular docking studies confirmed the mechanism. Results indicate very potent antioxidant activity for BU and potent anti-tyrosinase activity for both chalcones, which is discussed in relation to bioactivity toward protection from skin disorders and food oxidative spoilage

A synergic nanoantioxidant based on covalently modified halloysite-trolox nanotubes with intra-lumen loaded quercetin

We describe the preparation and properties of the first example of a synergic nanoantioxidant, obtained by different functionalizations of the external surface and the inner lumen of halloysite nanotubes (HNTs). Trolox, a mimic of natural α-tocopherol, was selectively grafted on the HNT external surface; while quercetin, a natural polyphenolic antioxidant, was loaded into the inner lumen to afford a bi-functional nanoantioxidant, HNT-Trolox/Que, which was investigated for its reactivity with transient peroxyl radicals and a persistent 1,1-diphenyl-2-picrylhydrazyl (DPPH•) radical in comparison with the corresponding mono-functional analogues HNT-Trolox and HNT/Que. Both HNT-Trolox and HNT/Que showed good antioxidant performance in the inhibited autoxidation of organic substrates; however HNT-Trolox/Que protection by reaction with peroxyl radicals was 35% higher in acetonitrile and 65% in chlorobenzene, as compared to the expected performance based on the sum of contributions of NHT-Trolox and NHT/Que. Similar enhancement was observed also in the trapping of DPPH• radicals. Synergism between the distinct antioxidant functions was based on the rapid reaction of externally exposed Trolox (rate constant with peroxyl radicals was 1.1 × 106 M-1 s-1 and 9 × 104 M-1 s-1 respectively in chlorobenzene and acetonitrile, at 30 °C), followed by its regeneration by quercetin released from the HNT lumen. The advantages of this novel nanoantioxidant are discussed

From the dual function lead AP2238 to AP2469, a multi-target-directed ligand for the treatment of Alzheimer\u2019s disease

The development of drugs with different pharmacological properties appears to be an innovative therapeutic approach for Alzheimer\u2019s disease. In this article, we describe a simple structural modification of AP2238, a first dual function lead, in particular the introduction of the catechol moiety performed in order to search for multi-target ligands. The new compound AP2469 retains antiacetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme (BACE)1 activities compared to the reference, and is also able to inhibit Ab42 self aggregation, Ab42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Ab42 oligomer-binding to neuron and microglial cell membrane gives this molecule both neuroprotective and antiinflammatory properties. These findings, together with its strong chain-breaking antioxidant performance, make AP2469 a potential drug able to modify the course of the diseas

Perturbation of cytochrome P450, generation of oxidative stress and induction of DNA damage in Cyprinus carpio exposed in situ to potable surface water

Epidemiological evidence suggests a link between consumption of chlorinated drinking water and various cancers. Chlorination of water rich in organic chemicals produces carcinogenic organochlorine by-products (OBPs) such as trihalomethanes and haloacetic acids. Since the discovery of the first OBP in the 1970s, there have been several investigations designed to determine the biological effects of single chemicals or small artificial OBP combinations. However, there is still insufficient information regarding the general biological response to these compounds, and further studies are still needed to evaluate their potential genotoxic effects. In the current study, we evaluated the effect of three drinking water disinfectants on the activity of cytochrome P450 (CYP)-linked metabolizing enzymes and on the generation of oxidative stress in the livers of male and female Cyprinus carpio fish (carp). The fish were exposed in situ for up 20 days to surface water obtained from the Trasmene lake in Italy. The water was treated with 1-2 mg/L of either sodium hypochlorite (NaClO) or chlorine dioxide (ClO2) as traditional disinfectants or with a relatively new disinfectant product, peracetic acid (PAA). Micronucleus (MN) frequencies in circulating erythrocytes from the fish were also analysed as a biomarker of genotoxic effect. In the CYP-linked enzyme assays, a significant induction (up to a 57-fold increase in the deethylation of ethoxyresorufin with PAA treatment) and a notable inactivation (up to almost a 90% loss in hydroxylation of p-nitrophenol with all disinfectants, and of testosterome 2 beta-hydroxylation with NaClO) was observed in subcellular liver preparations from exposed fish. Using the electron paramagnetic resonance (EPR) spectroscopy radical-probe technique, we also observed that CYP-modulation was associated with the production of reactive oxygen species (ROS). In addition, we found a significant increase in MN frequency in circulating erythrocytes after 10 days of exposure of fish to water treated with ClO2, while a non-significant six-fold increase in MN frequency was observed with NaClO, but not with PAA. Our data suggest that the use of ClO2 and NaClO to disinfect drinking water could generate harmful OBP mixtures that are able to perturb CYP-mediated reactions, generate oxidative stress and induce genetic damage. These data may provide a mechanistic explanation for epidemiological studies linking consumption of chlorinated drinking water to increased risk of urinary, gastrointestinal and bladder cancers. (c) 2006 Elsevier B.V. All rights reserved

Current Concepts on Antiplatelet Therapy: Focus on the Novel Thienopyridine and Non-Thienopyridine Agents

Thienopyridines are a class of drug targeting the platelet adenosine diphosphate (ADP) 2 receptor. They significantly reduce platelet activity and are therefore clinically beneficial in settings where platelet activation is a key pathophysiological feature, particularly myocardial infarction. Ticlopidine, the first of the class introduced to clinical practice, was soon challenged and almost completely replaced by clopidogrel for its better tolerability. More recently, prasugrel and ticagrelor have been shown to provide a more powerful antiplatelet action compared to clopidogrel but at a cost of higher risk of bleeding complications. Cangrelor, a molecule very similar to ticagrelor, is currently being evaluated against clopidogrel. Considering the key balance of ischemic protection and bleeding risk, this paper discusses the background to the development of prasugrel, ticagrelor, and cangrelor and aims to characterise their risk-benefit profile and possible implementation in daily practice

Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease : a prospective cohort study

Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function. Patients and methods : In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates. Results : During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1. Conclusion : sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease