A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate.

The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response1. Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and-concomitantly-protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model2 and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.

YF17D-based vaccines - standing on the shoulders of a giant.

Live-attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark for vaccines made today. YF17D triggers a particularly broad and polyfunctional response engaging multiple arms of innate, humoral and cellular immunity. This unique immunogenicity translates into an extraordinary vaccine efficacy and outstanding longevity of protection, possibly by single-dose immunization. More recently, progress in molecular virology and synthetic biology allowed engineering of YF17D as a powerful vector and promising platform for the development of novel recombinant live vaccines, including two licensed vaccines against Japanese encephalitis and dengue, even in paediatric use. Likewise, numerous chimeric and transgenic preclinical candidates have been described. These include prophylactic vaccines against emerging viral infections (e.g. Lassa, Zika and SARS-CoV-2) and parasitic diseases (e.g. malaria), as well as therapeutic applications targeting persistent infections (e.g. HIV and chronic hepatitis), and cancer. Efforts to overcome historical safety concerns and manufacturing challenges are ongoing and pave the way for wider use of YF17D-based vaccines. In this review, we summarize recent insights regarding YF17D as vaccine platform, and how YF17D-based vaccines may complement as well as differentiate from other emerging modalities in response to unmet medical needs and for pandemic preparedness.

Competency based curriculum for cardiovascular magnetic resonance: A position statement of the Society for Cardiovascular Magnetic Resonance.

This position statement guides cardiovascular magnetic resonance (CMR) imaging program directors and learners on the key competencies required for Level II and III CMR practitioners, whether trainees come from a radiology or cardiology background. This document is built upon existing curricula and was created and vetted by an international panel of cardiologists and radiologists on behalf of the Society for Cardiovascular Magnetic Resonance (SCMR).

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. METHODS: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. RESULTS: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. CONCLUSIONS: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

Effect of dietary inclusion of microalgae (Nannochloropsis gaditana and Schizochytrium spp) on non-specific immunity and erythrocyte maturity in Atlantic salmon fingerlings.

The parr-smolt transformation in salmonids involves a critical period characterized by systemic changes associated with the fish's immune response. In this context, as a dietary ingredient in functional diets, microalgae offer an alternative due to their nutritional and bioactive compounds that could strengthen the immune status. This study evaluated the effect of a diet supplemented with Schizochytrium spp and Nannochloropsis gaditana on the expression of genes associated with the antibacterial response. Additionally, the study assessed the effect on the leukocyte population and erythrocyte maturity in Salmo salar blood. Fish were fed for 30 days with a microalgal mixture (1:1) at a 10% inclusion. Each diet was randomly assigned to a tank using a completely randomized design (CRD) with four replications. Each tank was stocked with 70 Atlantic salmon fingerlings with an initial mean weight of 78.87 ± 0.84. Transcription levels were quantified and analyzed by qRT-PCR from cell isolates and mucus tissue. Furthermore, cell count and identification of leukocytes and classification of cellular maturity of erythrocytes using a neural network with a multilayer perceptron (MLP) were performed. Our results showed a significant (p < 0.05) increase in fold change expression of C3 (2.54 ± 0.65) and NK-Lysine (6.84 ± 0.94) in erythrocytes of microalgae-supplemented fish. Moreover, a significant increase of 1.59 and 2.35 times in monocytes and immature erythrocytes, respectively, was observed in the same group of fish (p < 0.05). This study's results indicate that dual microalgae (Schizochytrium spp and N. gaditana) supplementation can increase innate humoral antibacterial components, particularly in erythrocyte tissue, and increase phagocytic cells and immature erythrocytes in S. salar blood.

Modal Frustration and Periodicity Breaking in Artificial Spin Ice.

Here, an artificial spin ice lattice is introduced that exhibits unique Ising and non-Ising behavior under specific field switching protocols because of the inclusion of coupled nanomagnets into the unit cell. In the Ising regime, a magnetic switching mechanism that generates a uni- or bimodal distribution of states dependent on the alignment of the field is demonstrated with respect to the lattice unit cell. In addition, a method for generating a plethora of randomly distributed energy states across the lattice, consisting of Ising and Landau states, is investigated through magnetic force microscopy and micromagnetic modeling. It is demonstrated that the dispersed energy distribution across the lattice is a result of the intrinsic design and can be finely tuned through control of the incident angle of a critical field. The present manuscript explores a complex frustrated environment beyond the 16-vertex Ising model for the development of novel logic-based technologies.

Evaluating the More Suitable ISM Frequency Band for IoT-Based Smart Grids: A Quantitative Study of 915 MHz vs. 2400 MHz.

IoT has begun to be employed pervasively in industrial environments and critical infrastructures thanks to its positive impact on performance and efficiency. Among these environments, the Smart Grid (SG) excels as the perfect host for this technology, mainly due to its potential to become the motor of the rest of electrically-dependent infrastructures. To make this SG-oriented IoT cost-effective, most deployments employ unlicensed ISM bands, specifically the 2400 MHz one, due to its extended communication bandwidth in comparison with lower bands. This band has been extensively used for years by Wireless Sensor Networks (WSN) and Mobile Ad-hoc Networks (MANET), from which the IoT technologically inherits. However, this work questions and evaluates the suitability of such a "default" communication band in SG environments, compared with the 915 MHz ISM band. A comprehensive quantitative comparison of these bands has been accomplished in terms of: power consumption, average network delay, and packet reception rate. To allow such a study, a dual-band propagation model specifically designed for the SG has been derived, tested, and incorporated into the well-known TOSSIM simulator. Simulation results reveal that only in the absence of other 2400 MHz interfering devices (such as WiFi or Bluetooth) or in small networks, is the 2400 MHz band the best option. In any other case, SG-oriented IoT quantitatively perform better if operating in the 915 MHz band.

Conceptual Design of a Nano-Networking Device.

Nanotechnology is an emerging scientific area whose advances, among many others, have a positive direct impact on the miniaturization of electronics. This unique technology enables the possibility to design and build electronic components as well as complete devices (called nanomachines or nanodevices) at the nano scale. A nanodevice is expected to be an essential element able to operate in a nanonetwork, where a huge number of them would coordinate to acquire data, process the information gathered, and wirelessly transmit those data to end-points providing innovative services in many key scenarios, such as the human body or the environment. This paper is aimed at studying the feasibility of this type of device by carefully examining their main component parts, namely the nanoprocessor, nanomemory, nanoantenna, and nanogenerator. To this end, a thorough state-of-the-art review is conveyed to discuss, substantiate, and select the most suitable current technology (commercial or pre-commercial) for each component. Then, we further contribute by developing a complete conceptual nanodevice layout taking into consideration its ultra-small size (similar to a blood cell) and its very restricted capabilities (e.g., processing, memory storage, telecommunication, and energy management). The required resources as well as the power consumption are realistically estimated.

On the Feasibility of Wireless Multimedia Sensor Networks over IEEE 802.15.5 Mesh Topologies.

Wireless Multimedia Sensor Networks (WMSNs) are a special type of Wireless Sensor Network (WSN) where large amounts of multimedia data are transmitted over networks composed of low power devices. Hierarchical routing protocols typically used in WSNs for multi-path communication tend to overload nodes located within radio communication range of the data collection unit or data sink. The battery life of these nodes is therefore reduced considerably, requiring frequent battery replacement work to extend the operational life of the WSN system. In a wireless sensor network with mesh topology, any node may act as a forwarder node, thereby enabling multiple routing paths toward any other node or collection unit. In addition, mesh topologies have proven advantages, such as data transmission reliability, network robustness against node failures, and potential reduction in energy consumption. This work studies the feasibility of implementing WMSNs in mesh topologies and their limitations by means of exhaustive computer simulation experiments. To this end, a module developed for the Synchronous Energy Saving (SES) mode of the IEEE 802.15.5 mesh standard has been integrated with multimedia tools to thoroughly test video sequences encoded using H.264 in mesh networks.

[Usefulness of upper gastrointestinal series to detect leaks in the early postoperative period of bariatric surgery]. / Utilidad del estudio contrastado precoz del tracto digestivo superior después de cirugía bariátrica: ¿se justifica su uso rutinario?

BACKGROUND: Postoperative leaks are the most undesirable complication of bariatric surgery and upper gastrointestinal (GI) series are routinely ordered to rule them out. Despite the published literature recommending against its routine use, it is still being customarily used in Chile. AIM: To examine the usefulness of routine upper GI series using water-soluble iodinated contrast media for the detection of early postoperative leaks in patients undergoing bariatric surgery. MATERIAL AND METHODS: A cohort of 328 patients subjected to bariatric surgery was followed from October 2012 to October 2013. Most of them underwent sleeve gastrectomy. RESULTS: Upper GI series on the first postoperative day were ordered to 308 (94%) patients. Postoperative leaks were observed in two patients, with an incidence of 0.6%. The sensitivity for upper GI series detection of leak was 0% and the negative predictive value was 99%. CONCLUSIONS: Routine upper GI series after bariatric surgery is not useful for the diagnosis of postoperative leak, given the low incidence of this complication and the low sensitivity of the technique.

Entry of Newcastle Disease Virus into the host cell: role of acidic pH and endocytosis.

Most paramyxoviruses enter the cell by direct fusion of the viral envelope with the plasma membrane. Our previous studies have shown the colocalization of Newcastle Disease Virus (NDV) with the early endosome marker EEA1 and the inhibition of NDV fusion by the caveolin-phosphorylating drug phorbol 12-myristate 13-acetate (PMA) prompted us to propose that NDV enters the cells via endocytosis. Here we show that the virus-cell fusion and cell-cell fusion promoted by NDV-F are increased by about 30% after brief exposure to low pH in HeLa and ELL-0 cells but not in NDV receptor- deficient cell lines such as GM95 or Lec1. After a brief low-pH exposure, the percentage of NDV fusion at 29 °C was similar to that at 37 °C without acid-pH stimulation, meaning that acid pH would decrease the energetic barrier to enhance fusion. Furthermore, preincubation of cells with the protein kinase C inhibitor bisindolylmaleimide led to the inhibition of about 30% of NDV infectivity, suggesting that a population of virus enters cells through receptor-mediated endocytosis. Moreover, the involvement of the GTPase dynamin in NDV entry is shown as its specific inhibitor, dynasore, also impaired NDV fusion and infectivity. Optimal infection of the host cells was significantly affected by drugs that inhibit endosomal acidification such as concanamycin A, monensin and chloroquine. These results support our hypothesis that entry of NDV into ELL-0 and HeLa cells occurs through the plasma membrane as well as by dynamin- low pH- and receptor- dependent endocytosis.

Modulation of hepatitis C virus genome replication by glycosphingolipids and four-phosphate adaptor protein 2.

UNLABELLED: Hepatitis C virus (HCV) assembles its replication complex on cytosolic membrane vesicles often clustered in a membranous web (MW). During infection, HCV NS5A protein activates PI4KIIIα enzyme, causing massive production and redistribution of phosphatidylinositol 4-phosphate (PI4P) lipid to the replication complex. However, the role of PI4P in the HCV life cycle is not well understood. We postulated that PI4P recruits host effectors to modulate HCV genome replication or virus particle production. To test this hypothesis, we generated cell lines for doxycycline-inducible expression of short hairpin RNAs (shRNAs) targeting the PI4P effector, four-phosphate adaptor protein 2 (FAPP2). FAPP2 depletion attenuated HCV infectivity and impeded HCV RNA synthesis. Indeed, FAPP2 has two functional lipid-binding domains specific for PI4P and glycosphingolipids. While expression of the PI4P-binding mutant protein was expected to inhibit HCV replication, a marked drop in replication efficiency was observed unexpectedly with the glycosphingolipid-binding mutant protein. These data suggest that both domains are crucial for the role of FAPP2 in HCV genome replication. We also found that HCV significantly increases the level of some glycosphingolipids, whereas adding these lipids to FAPP2-depleted cells partially rescued replication, further arguing for the importance of glycosphingolipids in HCV RNA synthesis. Interestingly, FAPP2 is redistributed to the replication complex (RC) characterized by HCV NS5A, NS4B, or double-stranded RNA (dsRNA) foci. Additionally, FAPP2 depletion disrupts the RC and alters the colocalization of HCV replicase proteins. Altogether, our study implies that HCV coopts FAPP2 for virus genome replication via PI4P binding and glycosphingolipid transport to the HCV RC. IMPORTANCE: Like most viruses with a positive-sense RNA genome, HCV replicates its RNA on remodeled host membranes composed of lipids hijacked from various internal membrane compartments. During infection, HCV induces massive production and retargeting of the PI4P lipid to its replication complex. However, the role of PI4P in HCV replication is not well understood. In this study, we have shown that FAPP2, a PI4P effector and glycosphingolipid-binding protein, is recruited to the HCV replication complex and is required for HCV genome replication and replication complex formation. More importantly, this study demonstrates, for the first time, the crucial role of glycosphingolipids in the HCV life cycle and suggests a link between PI4P and glycosphingolipids in HCV genome replication.

Narrow Magnonic Waveguides Based on Domain Walls.

The channeling of spin waves with domain walls in ultrathin ferromagnetic films is demonstrated theoretically and through micromagnetics simulations. It is shown that propagating excitations localized to the wall, which appear in the frequency gap of bulk spin wave modes, can be guided in curved geometries and propagate in close proximity to other channels. For Néel-type walls arising from a Dzyaloshinskii-Moriya interaction, the channeling is strongly nonreciprocal and group velocities can exceed 1 km/s in the long wavelength limit for certain propagation directions. The channeled modes represent an unusual analogy of whispering gallery waves that are one dimensional and nonreciprocal with this interaction. Moreover, a sufficiently strong Dzyaloshinskii-Moriya interaction can create a degeneracy of channeled and propagating modes at a critical wave vector.

A comprehensive WSN-based approach to efficiently manage a Smart Grid.

The Smart Grid (SG) is conceived as the evolution of the current electrical grid representing a big leap in terms of efficiency, reliability and flexibility compared to today's electrical network. To achieve this goal, the Wireless Sensor Networks (WSNs) are considered by the scientific/engineering community to be one of the most suitable technologies to apply SG technology to due to their low-cost, collaborative and long-standing nature. However, the SG has posed significant challenges to utility operators-mainly very harsh radio propagation conditions and the lack of appropriate systems to empower WSN devices-making most of the commercial widespread solutions inadequate. In this context, and as a main contribution, we have designed a comprehensive ad-hoc WSN-based solution for the Smart Grid (SENSED-SG) that focuses on specific implementations of the MAC, the network and the application layers to attain maximum performance and to successfully deal with any arising hurdles. Our approach has been exhaustively evaluated by computer simulations and mathematical analysis, as well as validation within real test-beds deployed in controlled environments. In particular, these test-beds cover two of the main scenarios found in a SG; on one hand, an indoor electrical substation environment, implemented in a High Voltage AC/DC laboratory, and, on the other hand, an outdoor case, deployed in the Transmission and Distribution segment of a power grid. The results obtained show that SENSED-SG performs better and is more suitable for the Smart Grid than the popular ZigBee WSN approach.

[Aortitis: report of three cases]. / Aortitis, causas infrecuentes en Reumatología: presentación de casos.

Aortitis is a nonspecific term that describes an inflammation of the aortic wall caused by inflammatory, infectious, paraneoplastic and idiopathic diseases. The symptoms are variable and nonspecific; therefore a high level of clinical suspicion is required to diagnose it. It is often an incidental finding while looking for other diagnoses and it is confirmed mainly through imaging studies. We report three cases of aortitis: A 29-year-old woman presenting with alopecia, oral and nasal ulcers and positive antinuclear antibodies. A CAT scan showed a segmental thickening of thoracic aorta, with dilated and stenotic areas. She was successfully treated with steroids, hydroxychloroquine, cyclophosphamide and azathioprine. A 41-year-old male presenting with dorsal pain and cough. The CAT scan showed an extra-intimal thickening of the descending aorta and stenosis of the celiac artery. The final diagnosis was a polyangiitis and was treated with steroids, cyclophosphamide and azathioprine. A 28-year-old woman presenting with pain in the left upper abdomen. Imaging studies showed a thickening of the aortic arch and subclavian artery. The final diagnosis was sarcoidosis and the patient was treated with prednisone.

Analyzing the intrastate and interstate swine movement network in the United States.

Identifying and restricting animal movements is a common approach used to mitigate the spread of diseases between premises in livestock systems. Therefore, it is essential to uncover between-premises movement dynamics, including shipment distances and network-based control strategies. Here, we analyzed three years of between-premises pig movements, which include 197,022 unique animal shipments, 3973 premises, and 391,625,374 pigs shipped across 20 U.S. states. We constructed unweighted, directed, temporal networks at 180-day intervals to calculate premises-to-premises movement distances, the size of connected components, network loyalty, and degree distributions, and, based on the out-going contact chains, identified network-based control actions. Our results show that the median distance between premises pig movements was 74.37 km, with median intrastate and interstate movements of 52.71 km and 328.76 km, respectively. On average, 2842 premises were connected via 6705 edges, resulting in a weak giant connected component that included 91 % of the premises. The premises-level network exhibited loyalty, with a median of 0.65 (IQR: 0.45 - 0.77). Results highlight the effectiveness of node targeting to reduce the risk of disease spread; we demonstrated that targeting 25 % of farms with the highest degree or betweenness limited spread to 1.23 % and 1.7 % of premises, respectively. While there is no complete shipment data for the entire U.S., our multi-state movement analysis demonstrated the value and the needs of such data for enhancing the design and implementation of proactive- disease control tactics.

Cholesterol dependence of Newcastle Disease Virus entry.

Lipid rafts are membrane microdomains enriched in cholesterol, sphingolipids, and glycolipids that have been implicated in many biological processes. Since cholesterol is known to play a key role in the entry of some other viruses, we investigated the role of cholesterol and lipid rafts in the host cell plasma membrane in Newcastle Disease Virus (NDV) entry. We used methyl-ß-cyclodextrin (MßCD) to deplete cellular cholesterol and disrupt lipid rafts. Our results show that the removal of cellular cholesterol partially reduces viral binding, fusion and infectivity. MßCD had no effect on the expression of sialic acid containing molecule expression, the NDV receptors in the target cell. All the above-described effects were reversed by restoring cholesterol levels in the target cell membrane. The HN viral attachment protein partially localized to detergent-resistant membrane microdomains (DRMs) at 4°C and then shifted to detergent-soluble fractions at 37°C. These results indicate that cellular cholesterol may be required for optimal cell entry in NDV infection cycle.

Current trends in wireless mesh sensor networks: a review of competing approaches.

Finding a complete mesh-based solution for low-rate wireless personal area networks (LR-WPANs) is still an open issue. To cope with this concern, different competing approaches have emerged in the Wireless Mesh Sensor Networks (WMSNs) field in the last few years. They are usually supported by the IEEE 802.15.4 standard, the most commonly adopted LR-WPAN recommendation for point-to-point topologies. In this work, we review the most relevant and up-to-date WMSN solutions that extend the IEEE 802.15.4 standard to multi-hop mesh networks. To conduct this review, we start by identifying the most significant WMSN requirements (i.e., interoperability, robustness, scalability, mobility or energy-efficiency) that reveal the benefits and shortcomings of each proposal. Then, we re-examine thoroughly the group of proposals following different design guidelines which are usually considered by end-users and developers. Among all of the approaches reviewed, we highlight the IEEE 802.15.5 standard, a recent recommendation that, in its LR-WPAN version, fully satisfies the greatest number of WMSN requirements. As a result, IEEE 802.15.5 can be an appropriate solution for a wide-range of applications, unlike the majority of the remaining solutions reviewed, which are usually designed to solve particular problems, for instance in the home, building and industrial sectors. In this sense, a description of IEEE 802.15.5 is also included, paying special attention to its efficient energy-saving mechanisms. Finally, possible improvements of this recommendation are pointed out in order to offer hints for future research.

On maximizing the lifetime of Wireless Sensor Networks by optimally assigning energy supplies.

The extension of the network lifetime of Wireless Sensor Networks (WSN) is an important issue that has not been appropriately solved yet. This paper addresses this concern and proposes some techniques to plan an arbitrary WSN. To this end, we suggest a hierarchical network architecture, similar to realistic scenarios, where nodes with renewable energy sources (denoted as primary nodes) carry out most message delivery tasks, and nodes equipped with conventional chemical batteries (denoted as secondary nodes) are those with less communication demands. The key design issue of this network architecture is the development of a new optimization framework to calculate the optimal assignment of renewable energy supplies (primary node assignment) to maximize network lifetime, obtaining the minimum number of energy supplies and their node assignment. We also conduct a second optimization step to additionally minimize the number of packet hops between the source and the sink. In this work, we present an algorithm that approaches the results of the optimization framework, but with much faster execution speed, which is a good alternative for large-scale WSN networks. Finally, the network model, the optimization process and the designed algorithm are further evaluated and validated by means of computer simulation under realistic conditions. The results obtained are discussed comparatively.