Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Cardiovascular changes in dipper and nondipper hypertension in perimenopausal women ( time-dependent effects of antihypertensives)

Background The lack of a decrease in nocturnal blood pressure to up to 10% of the daytime measure is termed as nondipper (ND) hypertension. It is a cardiovascular (CV) risk factor with increased CV morbidity and accelerated target organ damage especially in women. The beneficial effect of restoring the ND state by administering antihypertensives (chronotherapy) at bedtime rather than on awakening is still debated. Objectives The aim of this study was to determine the extent of ND hypertension and the magnitude of CV morbidities among perimenopausal women in comparison with an identical dipper group. The study also intended to determine the administration time-dependent effect on the ND state. Study designThe study included a cross-sectional part and a prospective randomized part. Patients and methods One hundred and thirty perimenopausal women who were not known to be hypertensive, with an office blood pressure repeatedly exceeding 140/90 mmHg were included. After obtaining informed consents, complete history was taken and clinical examination was carried out. The included patients underwent 12-lead ECG and echocardiography, and the carotid intima-media thickness was measured. Besides the routine urine and blood analysis, analyses to obtain levels of lipids, HbA1-c, serum thyroid stimulating hormone, coagulation factors (factor VIII, fibrinogen), urinary albumin excretion, and C reactive protein were also carried out. Ambulatory blood pressure of all patients on a nonworking day was monitored. The studied patients were classified as dippers and NDs. The ND patients were randomly assigned to treatment with angiotensin receptor blockers (ARBs). Half of the ND patients received their dosage at bedtime and the others received the same dosage on awakening for 6 months, after which the ambulatory blood pressure was remeasured. Results ND hypertension was detected in 61.5% of patients, its occurrence being significantly higher among women with hot flashes, those with postural hypotension, obese women, and among women with elevated HbA1-c, fibrinogen, cholesterol, C reactive protein and urinary albumin excretion levels. There was significant prolongation of the QTc interval and QT dispersion with a significant increase in the interventricular septal dimension and carotid artery intima-media thickness in the ND group. Disappearance of the ND phenomenon occurred in 80% of patients receiving therapy with ARBs at bedtime. Conclusion ND hypertension is common among perimenopausal women, especially those with hot flashes, postural hypotension, and higher BMIs and HbA1-c levels, and is associated with many CV risk factors. Chronotherapy with ARBs at bedtime is more efficient in restoring the circadian rhythm of blood pressure compared with that on awakening

Synthesis of alpha-aminophosphonate functionalized chitosan sorbents: Effect of methyl vs phenyl group on uranium sorption

International audienceA one-pot synthesis procedure was used for preparing two derivatives of chitosan bearing α-aminophosphonate moieties. Chitosan functionalization was performed by reacting chitosan with glutaraldehyde and triphenylphosphite or trimethylphosphite under selected experimental conditions. The materials (CS-Ph and CS-Me, respectively) were characterized using different analytical procedures for confirming their suggested structures: scanning electron microscopy (coupled to energy dispersive X-ray analysis), Fourier-transform infra-red spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy analyses, thermogravimetric analysis and elemental analysis. The sorption properties of these materials were compared for U(VI) recovery through the study of pH effect, sorption isotherms, thermodynamics, uptake kinetics and sorbent recycling (metal desorption and sorbent re-use). The sorption isotherms were modeled using the Langmuir and the Sips equations while the kinetic profiles were preferentially fitted by the pseudo-second order rate equation. The comparison of sorption properties shows that the methyl α-aminophosphonate derivative is much more effective in uranium recovery than the phenyl derivative: maximum sorption capacities reached at pH 5 around 245 mg U g−1 and 114 mg U g−1, respectively. Tentative explanations are suggested associated to the acid-base properties, the steric hindrance and the donor/acceptor behavior of reactive groups. Experimental data show that uranyl sorption process proceeds via an exothermic and spontaneous reaction for the two sorbents. Metal desorption was successfully tested using sodium bicarbonate solutions and the sorbent was recycled four times: the sorption and desorption efficiencies progressively decreased but remained relatively high at the fourth cycle (sorption: 88–90% of initial sorption and desorption decreasing by 5% between the first and the fourth cycles). Finally, the sorbents were efficiently tested on acidic ore leachate

Preparation and Characterization of Silymarin-Conjugated Gold Nanoparticles with Enhanced Anti-Fibrotic Therapeutic Effects against Hepatic Fibrosis in Rats: Role of MicroRNAs as Molecular Targets

Background: The main obstacles of silymarin (SIL) application in liver diseases are its low bioavailability, elevated metabolism, rapid excretion in bile and urine, and inefficient intestinal resorption. The study aimed to synthesize and characterize silymarin-conjugated gold nanoparticles (SGNPs) formulation to improve SIL bioavailability and release for potentiating its antifibrotic action. Methods: Both SGNPs and gold nanoparticles (GNPs) were prepared and characterized using standard characterization techniques. The improved formulation was assessed for in vitro drug release study and in vivo study on rats using CCl4 induced hepatic fibrosis model. SIL, SGNPs, and GNPs were administered by oral gavage daily for 30 days. At the end of the study, rats underwent anesthesia and were sacrificed, serum samples were collected for biochemical analysis. Liver tissues were collected to measure the genes and microRNAs (miRNAs) expressions. Also, histopathological and immunohistochemistry (IHC) examinations of hepatic tissues supported these results. Results: The successful formation and conjugation of SGNPs were confirmed by measurements methods. The synthesized nanohybrid SGNPs showed significant antifibrotic therapeutic action against CCl4-induced hepatic damage in rats, and preserved normal body weight, liver weight, liver index values, retained normal hepatic functions, lowered inflammatory markers, declined lipid peroxidation, and activated the antioxidant pathway nuclear factor erythroid-2-related factor 2 (NRF2). The antifibrotic activities of SGNPs mediated through enhancing the hepatic expression of the protective miRNAs; miR-22, miR-29c, and miR-219a which results in suppressed expression of the main fibrosis mediators; TGFβR1, COL3A1, and TGFβR2, respectively. The histopathology and IHC analysis confirmed the anti-fibrotic effects of SGNPs. Conclusions: The successful synthesis of SGNPs with sizes ranging from 16 up to 20 nm and entrapment efficiency and loading capacity 96% and 38.69%, respectively. In vivo studies revealed that the obtained nano-formulation of SIL boosted its anti-fibrotic effects

Efficacy of the Newcastle Disease Virus Genotype VII.1.1-Matched Vaccines in Commercial Broilers

Class II genotype VII Newcastle disease viruses (NDV) are predominant in the Middle East and Asia despite intensive vaccination programs using conventional live and inactivated NDV vaccines. In this study, the protective efficacies of three commercial vaccine regimes involving genotype II NDV, recombinant genotype VII NDV-matched, and an autogenous velogenic NDV genotype VII vaccine were evaluated against challenge with velogenic NDV genotype VII (accession number MG029120). Three vaccination regimes were applied as follows: group-1 received inactivated genotype II, group-2 received inactivated recombinant genotype VII NDV-matched, and group-3 received velogenic inactivated autogenous NDV genotype VII vaccines given on day 7; for the live vaccine doses, each group received the same live genotype II vaccine. The birds in all of the groups were challenged with NDV genotype VII, which was applied on day 28. Protection by the three regimes was evaluated after infection based on mortality rate, clinical signs, gross lesions, virus shedding, seroconversion, and microscopic changes. The results showed that these three vaccination regimes partially protected commercial broilers (73%, 86%, 97%, respectively, vs. 8.6% in non-vaccinated challenged and 0% in non-vaccinated non-challenged birds) against mortality at 10 days post-challenge (dpc). Using inactivated vaccines significantly reduced the virus shedding at the level of the number of shedders and the amount of virus that was shed in all vaccinated groups (G1-3) compared to in the non-vaccinated group (G-4). In conclusion, using closely genotype-matched vaccines (NDV-GVII) provided higher protection than using vaccines that were not closely genotype-matched and non-genotype-matched. The vaccine seeds that were closely related to genotype VII.1.1 provided higher protection against challenge against this genotype since it circulates in the Middle East region. Updating vaccine seeds with recent and closely related isolates provides higher protection

In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives

This study demonstrates high drug-loading of novel pyridine derivatives (S1–S4) in lipid- and polymer-based core–shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core–shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC50 value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site

Targeting Natural Plant Metabolites for Hunting SARS-CoV-2 Omicron BA.1 Variant Inhibitors: Extraction, Molecular Docking, Molecular Dynamics, and Physicochemical Properties Study

(1) Background: SARS-CoV-2 Omicron BA.1 is the most common variation found in most countries and is responsible for 99% of cases in the United States. To overcome this challenge, there is an urgent need to discover effective inhibitors to prevent the emerging BA.1 variant. Natural products, particularly flavonoids, have had widespread success in reducing COVID-19 prevalence. (2) Methods: In the ongoing study, fifteen compounds were annotated from Echium angustifolium and peach (Prunus persica), which were computationally analyzed using various in silico techniques. Molecular docking calculations were performed for the identified phytochemicals to investigate their efficacy. Molecular dynamics (MD) simulations over 200 ns followed by molecular mechanics Poisson–Boltzmann surface area calculations (MM/PBSA) were performed to estimate the binding energy. Bioactivity was also calculated for the best components in terms of drug likeness and drug score. (3) Results: The data obtained from the molecular docking study demonstrated that five compounds exhibited remarkable potency, with docking scores greater than −9.0 kcal/mol. Among them, compounds 1, 2 and 4 showed higher stability within the active site of Omicron BA.1, with ΔGbinding values of −49.02, −48.07, and −67.47 KJ/mol, respectively. These findings imply that the discovered phytoconstituents are promising in the search for anti-Omicron BA.1 drugs and should be investigated in future in vitro and in vivo research