Miracle-dz/UniFAR-FTUs huggingface dataset:
Global and regional incidence, mortality and disability-adjusted life-years for Epstein-Barr virus-attributable malignancies, 1990–2017

Objective To determine the global and regional burden of Epstein-Barr virus (EBV)-attributed malignancies. Design An international comparative study based on the Global Burden of Disease (GBD) Study estimates. Setting Global population by age, sex, region, demographic index and time. Methods and outcome measures The burden of EBV-attributed Burkitt lymphoma (BL), Hodgkin lymphoma (HL), nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC) was estimated in a two-step process. In the first step, the fraction of each malignancy attributable to EBV was estimated based on published studies; this was then applied to the GBD estimates to determine the global and regional incidence, mortality and disability-adjusted life-years (DALYs) for each malignancy by age, sex, geographical region and social demographic index (SDI) from 1990 to 2017. Results The combined global incidence of BL, HL, NPC and GC in 2017 was 1.442 million cases, with over 973 000 deaths. An estimated 265 000 (18%) incident cases and 164 000 (17%) deaths were due to the EBV-attributed fraction. This is an increase of 36% in incidence and 19% in mortality from 1990. In 2017, EBV-attributed malignancies caused 4.604 million DALYs, of which 82% was due to NPC and GC alone. The incidence of both of these malignancies was higher in high and middle-high SDI regions and peaked in adults aged between 50 and 70 years. All four malignancies were more common in males and the highest burden was observed in East Asia. Conclusions This study provides comprehensive estimates of the burden of EBV-attributed BL, HL, NPC and GC. The overall burden of EBV-related malignancies is likely to be higher since EBV is aetiologically linked to several other malignancies not included in this analysis. Increasing global population and life expectancy is expected to further raise this burden in the future. The urgency for developing an effective vaccine to prevent these malignancies cannot be overstated.
Intracellular Organization by Jumbo Bacteriophages

Since their discovery more than 100 years ago, the viruses that infect bacteria (bacteriophages) have been widely studied as model systems. Largely overlooked, however, have been “jumbo phages,” with genome sizes ranging from 200 to 500 kbp. Jumbo phages generally have large virions with complex structures and a broad host spectrum. While the majority of jumbo phage genes are poorly functionally characterized, recent work has discovered many unique biological features, including a conserved tubulin homolog that coordinates a proteinaceous nucleus-like compartment that houses and segregates phage DNA. ABSTRACT Since their discovery more than 100 years ago, the viruses that infect bacteria (bacteriophages) have been widely studied as model systems. Largely overlooked, however, have been “jumbo phages,” with genome sizes ranging from 200 to 500 kbp. Jumbo phages generally have large virions with complex structures and a broad host spectrum. While the majority of jumbo phage genes are poorly functionally characterized, recent work has discovered many unique biological features, including a conserved tubulin homolog that coordinates a proteinaceous nucleus-like compartment that houses and segregates phage DNA. The tubulin spindle displays dynamic instability and centers the phage nucleus within the bacterial host during phage infection for optimal reproduction. The shell provides robust physical protection for the enclosed phage genomes against attack from DNA-targeting bacterial immune systems, thereby endowing jumbo phages with broad resistance. In this review, we focus on the current knowledge of the cytoskeletal elements and the specialized nuclear compartment derived from jumbo phages, and we highlight their importance in facilitating spatial and temporal organization over the viral life cycle. Additionally, we discuss the evolutionary relationships between jumbo phages and eukaryotic viruses, as well as the therapeutic potential and drawbacks of jumbo phages as antimicrobial agents in phage therapy.
Brucella abortus-Stimulated Platelets Activate Brain Microvascular Endothelial Cells Increasing Cell Transmigration through the Erk1/2 Pathway

Central nervous system invasion by bacteria of the genus Brucella results in an inflammatory disorder called neurobrucellosis. A common feature associated with this pathology is blood–brain barrier (BBB) activation. However, the underlying mechanisms involved with such BBB activation remain unknown. The aim of this work was to investigate the role of Brucella abortus-stimulated platelets on human brain microvascular endothelial cell (HBMEC) activation. Platelets enhanced HBMEC activation in response to B. abortus infection. Furthermore, supernatants from B. abortus-stimulated platelets also activated brain endothelial cells, inducing increased secretion of IL-6, IL-8, CCL-2 as well as ICAM-1 and CD40 upregulation on HBMEC compared with supernatants from unstimulated platelets. Outer membrane protein 19, a B. abortus lipoprotein, recapitulated B. abortus-mediated activation of HBMECs by platelets. In addition, supernatants from B. abortus-activated platelets promoted transendothelial migration of neutrophils and monocytes. Finally, using a pharmacological inhibitor, we demonstrated that the Erk1/2 pathway is involved in the endothelial activation induced by B. abortus-stimulated platelets and also in transendothelial migration of neutrophils. These results describe a mechanism whereby B. abortus-stimulated platelets induce endothelial cell activation, promoting neutrophils and monocytes to traverse the BBB probably contributing to the inflammatory pathology of neurobrucellosis.
Current use of cardiac biomarkers in various heart conditions.

Biomarkers are increasingly recognized to have significant clinical value in early identification and progression of various cardiovascular diseases. There are many heart conditions such as Congestive heart failure (CHF), ischemic heart diseases (IHD), and diabetic cardiomyopathy (DCM) and cardiac remodeling in which the severity of the cardiac pathology can be mirrored through these biomarker or cardiac biomarkers. From the emergency department (ED) evaluation of acute coronary syndromes (ACS) or suspected acute myocardial infarction (AMI) with cardiac marker Troponin to the diagnosis of chronic conditions like Heart Failure (HF) with natriuretic peptides, like B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and mid regional pro-atrial natriuretic peptide (MR-proANP), their use is con-tinuously increasing. Their clinical importance has led to the discovery of newer biomarkers such as the soluble source of tumorigenicity 2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15) and various micro ribonucleic acids (miRNAs). Since cardiac pathophysiology involves a complex interplay between inflammatory, genetic, neurohormonal, and biochemical levels, these biomarkers could be enzymes, hormones, and biologic substances showing cardiac injury, stress, and malfunction. Therefore, multi-marker approaches with different combinations of novel cardiac biomarkers, con-tinual assessment of cardiac biomarkers are likely to improve cardiac risk prediction, stratification, and overall patient well-being. On the other hand, these biomarkers may reflect coexisting or isolated disease processes in different organ systems other than the cardiovascular system. Therefore, knowledge of cardiac biomarkers is imperative. In this article, we have re-viewed the role of cardiac biomarkers and their use in the diagnosis and prognosis of various cardiovascular diseases from different investigations conducted in recent years.
Mutational Analysis of Root Gravitropism and Phototropism of Arabidopsis thaliana Seedlings

Root gravitropism and phototropism were analysed in young seedlings of Arabidopsis thaliana by a simple procedure using agar plates, by changing the position of plates or by covering the plates with black opaque sheet. Roots of A. thaliana seedlings growing on the surface of agar medium showed clear responses to gravity and light stimuli. A set of mutants with abnormal gravitropism or phototropism was isolated. Gravitropic mutants were separated into two types, reduced-response type and non-response type. The mutants were genetically divided into two complementation groups, aux1 and agr1. In both groups the reduced-response type mutants carried weaker genetic lesions, whereas the non-response type mutants carried heavier genetic lesions. Mutants with no phototropic response were classified into two complementation groups, rpt1 and rpt2. The root tropism mutants showed normal tropic responses in shoots, indicating that genetic regulation pathways are different in roots and shoots.
Criteria for lactic acid bacteria screening to enhance silage quality

The main challenge of ensiling is conserving the feed through a fermentative process that results in high nutritional and microbiological quality while minimizing fermentative losses. This challenge is of growing interest to farmers, industry and research and involves the use of additives to improve the fermentation process and preserve the ensiled material. Most studies involved microbial additives; lactic acid bacteria (LAB) have been the focus of much research and have been widely used. Currently, LABs are used in modern and sustainable agriculture because of their considerable potential for enhancing human and animal health. Although the number of studies evaluating LABs in silages has increased, the potential use of these micro‐organisms in association with silage has not been adequately studied. Fermentation processes using the same strain produce very different results depending on the unique characteristics of the substrate, so the choice of silage inoculant for different starting substrates is of extreme importance to maximize the nutritional quality of the final product. This review describes the current scenario of the bioprospecting and selection process for choosing the best LAB strain as an inoculant for ensiling. In addition, we analyse developments in the fermentation process and strategies and methods that will assist future studies on the selection of new strains of LAB as a starter culture or inoculant.
Development and Characterization of Clay–Nanocomposites for Water Purification

In this work we propose a facile method of preparing cost-effective clay-metaloxide/metal (CuO/Ag and ZnO/Ag) composite pellets for an efficient water purification technique. Clay, with intrinsic antibacterial activity, served as a membrane support for different metaloxide/Ag nanoparticles (NPs) concentrations (2.5, 5 and 10 wt.%), as the active fillers. The effect of time (24 and 48 h) on the bactericidal activity of these pellets was also monitored. The clay–nanocomposite pellets were characterized using: X-ray diffraction, X-ray fluorescence, scanning electron microscopy, transmission electron microscopy, ultraviolet–visible (UV–Vis) spectrophotometry and nitrogen desorption analysis. The antibacterial activity performance was tested using E. coli and S. aureus strains of ATCC25922 and ATCC25923, respectively, in two aqueous media (nutrient broth and nutrient-free) by the colony-forming unit method. The results showed that the clay-CuO/Ag composite with a bandgap (1.24 eV) exhibited overall best performance under all conditions and time factors of ~100% efficiency in nutrient-free medium for all concentrations and times and 20–40% efficiency in nutrient broth for 24 h. The clay-ZnO/Ag with a bandgap of 2.88 eV showed no bactericidal activity in both media, except for that with 10 wt. % ZnO/Ag which showed 100% efficiency in nutrient-free medium after 24 h. All the synthesized composites showed 100% bactericidal efficiency in nutrient free medium after 48 h. These results indicate that, the clay/metaloxide/Ag could serve as efficient water purification technique, with a potential for large-scale commercialization.
Antibiotic Tolerance of Staphylococcus aureus Biofilm in Periprosthetic Joint Infections and Antibiofilm Strategies

The need for bone and joint prostheses is currently growing due to population aging, leading to an increase in prosthetic joint infection cases. Biofilms represent an adaptive and quite common bacterial response to several stress factors which confer an important protection to bacteria. Biofilm formation starts with bacterial adhesion on a surface, such as an orthopedic prosthesis, further reinforced by matrix synthesis. The biofilm formation and structure depend on the immediate environment of the bacteria. In the case of infection, the periprosthetic joint environment represents a particular interface between bacteria, host cells, and the implant, favoring biofilm initiation and maturation. Treating such an infection represents a huge challenge because of the biofilm-specific high tolerance to antibiotics and its ability to evade the immune system. It is crucial to understand these mechanisms in order to find new and adapted strategies to prevent and eradicate implant-associated infections. Therefore, adapted models mimicking the infectious site are of utmost importance to recreate a relevant environment in order to test potential antibiofilm molecules. In periprosthetic joint infections, Staphylococcus aureus is mainly involved because of its high adaptation to the human physiology. The current review deals with the mechanisms involved in the antibiotic resistance and tolerance of Staphylococcus aureus in the particular periprosthetic joint infection context, and exposes different strategies to manage these infections.
Some ASOs that bind in the coding region of mRNAs and induce RNase H1 cleavage can cause increases in the pre-mRNAs that may blunt total activity

Abstract Antisense oligonucleotide (ASO) drugs that trigger RNase H1 cleavage of target RNAs have been developed to treat various diseases. Basic pharmacological principles suggest that the development of tolerance is a common response to pharmacological interventions. In this manuscript, for the first time we report a molecular mechanism of tolerance that occurs with some ASOs. Two observations stimulated our interest: some RNA targets are difficult to reduce with RNase H1 activating ASOs and some ASOs display a shorter duration of activity than the prolonged target reduction typically observed. We found that certain ASOs targeting the coding region of some mRNAs that initially reduce target mRNAs can surprisingly increase the levels of the corresponding pre-mRNAs. The increase in pre-mRNA is delayed and due to enhanced transcription and likely also slower processing. This process requires that the ASOs bind in the coding region and reduce the target mRNA by RNase H1 while the mRNA resides in the ribosomes. The pre-mRNA increase is dependent on UPF3A and independent of the NMD pathway or the XRN1-CNOT pathway. The response is consistent in multiple cell lines and independent of the methods used to introduce ASOs into cells.
Design and Evaluation of Anti-SARS-Coronavirus Agents Based on Molecular Interactions with the Viral Protease

Three types of new coronaviruses (CoVs) have been identified recently as the causative viruses for the severe pneumonia-like respiratory illnesses, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and corona-virus disease 2019 (COVID-19). Neither therapeutic agents nor vaccines have been developed to date, which is a major drawback in controlling the present global pandemic of COVID-19 caused by SARS coronavirus 2 (SARS-CoV-2) and has resulted in more than 20,439,814 cases and 744,385 deaths. Each of the 3C-like (3CL) proteases of the three CoVs is essential for the proliferation of the CoVs, and an inhibitor of the 3CL protease (3CLpro) is thought to be an ideal therapeutic agent against SARS, MERS, or COVID-19. Among these, SARS-CoV is the first corona-virus isolated and has been studied in detail since the first pandemic in 2003. This article briefly reviews a series of studies on SARS-CoV, focusing on the development of inhibitors for the SARS-CoV 3CLpro based on molecular interactions with the 3CL protease. Our recent approach, based on the structure-based rational design of a novel scaffold for SARS-CoV 3CLpro inhibitor, is also included. The achievements summarized in this short review would be useful for the design of a variety of novel inhibitors for corona-viruses, including SARS-CoV-2.
Depression and Change in Caregiver Burden Among Family Members of Intensive Care Unit Survivors.

BACKGROUND Family members of patients in intensive care units may experience psychological distress and substantial caregiver burden. OBJECTIVE To evaluate whether change in caregiver burden from intensive care unit admission to 3-month follow-up is associated with caregiver depression at 3 months. METHODS Caregiver burden was assessed at enrollment and 3 months later, and caregiver depression was assessed at 3 months. Depression was measured with the Hospital Anxiety and Depression Score. The primary analysis was the association between depression at 3 months and change in caregiver burden, controlling for a history of caregiver depression. RESULTS One hundred one participants were enrolled; 65 participants had a surviving loved one and completed 3-month follow-up. At 3-month follow-up, 12% of participants met criteria for depression. Increased caregiver burden over time was significantly associated with depression at follow-up (Fisher exact test, P = .004), although this association was not significant after controlling for self-reported history of depression at baseline (Cochran-Mantel-Haenszel test, P = .23). CONCLUSIONS Family members are increasingly recognized as a vulnerable population susceptible to negative psychological outcomes after a loved one's admission to the intensive care unit. In this small sample, no significant association was found between change in caregiver burden and depression at 3 months after controlling for baseline depression.
Erenumab does not alter cerebral hemodynamics and endothelial function in migraine without aura

Objective To assess whether erenumab influences cerebral vasomotor reactivity and flow-mediated dilation in migraine patients. Methods Consecutive migraineurs prescribed erenumab at our Headache Centre and age and sex-matching controls were invited to participate in this observational longitudinal study. Patients were evaluated for cerebral vasomotor reactivity to hypercapnia (breath-holding index) in middle and posterior cerebral arteries and for brachial corrected flow mediated dilation at baseline (T0), after 2 weeks from the first erenumab injection (T2) and after 2 weeks from the fourth Erenumab injection (T18). Patients displaying a reduction of at least 50% in monthly migraine days after completing the fourth month of therapy were classified as responders. Results Sixty patients and 25 controls agreed to participate. Middle and posterior cerebral artery mean flow velocities, breath-holding index and flow-mediated dilation did not differ at T0 and from T0 to T2 in patients and controls. In patients, we neither observed a variation of the explored variables from T0 to T18 nor an interaction between evaluation times (T0–T2 or T0–T18) and chronic condition at T0, responder state or erenumab fourth dose. Conclusions Our findings demonstrate that erenumab preserves cerebral vasomotor reactivity and flow-mediated dilation in migraineurs without aura.
Cholinergic transmission in C. elegans: Functions, diversity, and maturation of ACh‐activated ion channels

Acetylcholine is an abundant neurotransmitter in all animals. Effects of acetylcholine are excitatory, inhibitory, or modulatory depending on the receptor and cell type. Research using the nematode C. elegans has made ground‐breaking contributions to the mechanistic understanding of cholinergic transmission. Powerful genetic screens for behavioral mutants or for responses to pharmacological reagents identified the core cellular machinery for synaptic transmission. Pharmacological reagents that perturb acetylcholine‐mediated processes led to the discovery and also uncovered the composition and regulators of acetylcholine‐activated channels and receptors. From a combination of electrophysiological and molecular cellular studies, we have gained a profound understanding of cholinergic signaling at the levels of synapses, neural circuits, and animal behaviors. This review will begin with a historical overview, then cover in‐depth current knowledge on acetylcholine‐activated ionotropic receptors, mechanisms regulating their functional expression and their functions in regulating locomotion.
Evaluation of the Efficiency of Detection and Capture of Manganese in Aqueous Solutions of FeCeOx Nanocomposites Doped with Nb2O5

The main purpose of this work is to study the effectiveness of using FeCeOx nanocomposites doped with Nb2O5 for the purification of aqueous solutions from manganese. X-ray diffraction, energy–dispersive analysis, scanning electron microscopy, vibrational magnetic spectroscopy, and mössbauer spectroscopy were used as research methods. It is shown that an increase in the dopant concentration leads to the transformation of the shape of nanoparticles from spherical to cubic and rhombic, followed by an increase in the size of the nanoparticles. The spherical shape of the nanoparticles is characteristic of a structure consisting of a mixture of two phases of hematite (Fe2O3) and cerium oxide CeO2. The cubic shape of nanoparticles is typical for spinel-type FeNbO4 structures, the phase contribution of which increases with increasing dopant concentration. It is shown that doping leads not only to a decrease in the concentration of manganese in model solutions, but also to an increase in the efficiency of adsorption from 11% to 75%.
Functional Dependence of the Power for Hovering on Wing Disc Loading in Hummingbirds

The mass-specific power input (metabolic cost) of hovering is independent of body mass but is proportional to the 0.5 exponent of wing disc loading for the sample considered here. The efficiency of converting energy metabolism to aerodynamic power is approximately constant at 6.23% in hummingbirds with a wide range of body mass and wing disc loading. Actuator wing disc theory of helicopter aerodynamics appears adequate for comparing the energetic cost of hovering flight among hummingbirds. Differences in the power input for hovering due to differences in wing disc loading are greater for larger hummingbirds than for smaller ones. Impaired integrity of the outer portion of the wing disc caused by molt or breaking primaries 8, 9, or 10 greatly increases the required power for hovering. The unusual nonsequential pattern of primary-feather molt in hummingbirds may be of adaptive value in that it results in the most rapid restoration of the integrity of the wing disc.