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Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) affects approximately 1% of the general population. It is a chronic, disabling, multi-system disease for which there is no effective treatment. This is probably related to the limited knowledge about its origin. Here, we summarized the current knowledge about the pathogenesis of ME/CFS and revisit the immunopathobiology of Epstein-Barr virus (EBV) infection. Given the similarities between EBV-associated autoimmune diseases and cancer in terms of poor T cell surveillance of cells with EBV latency, expanded EBV-infected cells in peripheral blood and increased antibodies against EBV, we hypothesize that there could be a common etiology generated by cells with EBV latency that escape immune surveillance. Albeit inconclusive, multiple studies in patients with ME/CFS have suggested an altered cellular immunity and augmented Th2 response that could result from mechanisms of evasion to some pathogens such as EBV, which has been identified as a risk factor in a subset of ME/CFS patients. Namely, cells with latency may evade the immune system in individuals with genetic predisposition to develop ME/CFS and in consequence, there could be poor CD4 T cell immunity to mitogens and other specific antigens, as it has been described in some individuals. Ultimately, we hypothesize that within ME/CFS there is a subgroup of patients with DRB1 and DQB1 alleles that could confer greater susceptibility to EBV, where immune evasion mechanisms generated by cells with latency induce immunodeficiency. Accordingly, we propose new endeavors to investigate if anti-EBV therapies could be effective in selected ME/CFS patients.

Arm and finger paralysis, e.g. due to brain stem stroke, often results in the inability to perform activities of daily living (ADLs) such as eating and drinking. Recently, it was shown that a hybrid electroencephalography/electrooculography (EEG/EOG) brain/neural hand exoskeleton can restore hand function to quadriplegics, but it was unknown whether such control paradigm can be also used for fluent, reliable and safe operation of a semi-autonomous whole-arm exoskeleton restoring ADLs. To test this, seven abled-bodied participants (seven right-handed males, mean age 30 ± 8 years) were instructed to use an EEG/EOG-controlled whole-arm exoskeleton attached to their right arm to perform a drinking task comprising multiple sub-tasks (reaching, grasping, drinking, moving back and releasing a cup). Fluent and reliable control was defined as average ‘time to initialize’ (TTI) execution of each sub-task below 3 s with successful initializations of at least 75% of sub-tasks within 5 s. During use of the system, no undesired side effects were reported. All participants were able to fluently and reliably control the vision-guided autonomous whole-arm exoskeleton (average TTI 2.12 ± 0.78 s across modalities with 75% successful initializations reached at 1.9 s for EOG and 4.1 s for EEG control) paving the way for restoring ADLs in severe arm and hand paralysis.

The sera from pigs infected with virulent classical swine fever virus (CSFV) contain substantial amounts of tumor necrosis factor (TNF), a prototype proinflammatory cytokine with pleiotropic activities. TNF limits the replication of CSFV in cell culture. In order to investigate the signaling involved in the antiviral activity of TNF, we employed small-molecule inhibitors to interfere specifically with JAK/STAT and NF-κB signaling pathways in near-to-primary endothelial PEDSV.15 cells. In addition, we knocked out selected factors of the interferon (IFN) induction and signaling pathways using CRISPR/Cas9. We found that the anti-CSFV effect of TNF was sensitive to JAK/STAT inhibitors, suggesting that TNF induces IFN signaling. Accordingly, we observed that the antiviral effect of TNF was dependent on intact type I IFN signaling as PEDSV.15 cells with the disrupted type I IFN receptor lost their capacity to limit the replication of CSFV after TNF treatment. Consequently, we examined whether TNF activates the type I IFN induction pathway. With genetically modified PEDSV.15 cells deficient in functional interferon regulatory factor 1 or 3 (IRF1 or IRF3), we observed that the anti-CSFV activity exhibited by TNF was dependent on IRF1, whereas IRF3 was dispensable. This was distinct from the lipopolysaccharide (LPS)-driven antiviral effect that relied on both IRF1 and IRF3. In agreement with the requirement of IRF1 to induce TNF- and LPS-mediated antiviral effects, intact IRF1 was also essential for TNF- and LPS-mediated induction of IFN-β mRNA, while the activation of NF-κB was not dependent on IRF1. Nevertheless, NF-κB activation was essential for the TNF-mediated antiviral effect. Finally, we observed that CSFV failed to counteract the TNF-mediated induction of the IFN-β mRNA in PEDSV.15 cells, suggesting that CSFV does not interfere with IRF1-dependent signaling. In summary, we report that the proinflammatory cytokine TNF limits the replication of CSFV in PEDSV.15 cells by specific induction of an IRF1-dependent antiviral type I IFN response.

This paper analyzes Altmetric.com, one of the most important altmetric data providers currently used. We have analyzed a set of publications with doi number indexed in the Web of Science during the period 2011-2013 and collected their data with the Altmetric API. 19% of the original set of papers was retrieved from Altmetric.com including some altmetric data. We identified 16 different social media sources from which Altmetric.com retrieves data. However five of them cover 95.5% of the total set. Twitter (87.1%) and Mendeley (64.8%) have the highest coverage. We conclude that Altmetric.com is a transparent, rich and accurate tool for altmetric data. Nevertheless, there are still potential limitations on its exhaustiveness as well as on the selection of social media sources that need further research.

Japanese encephalitis virus (JEV), a main cause of severe viral encephalitis in humans, has a complex ecology, composed of a cycle involving primarily waterbirds and mosquitoes, as well as a cycle involving pigs as amplifying hosts. To date, JEV transmission has been exclusively described as being mosquito-mediated. Here we demonstrate that JEV can be transmitted between pigs in the absence of arthropod vectors. Pigs shed virus in oronasal secretions and are highly susceptible to oronasal infection. Clinical symptoms, virus tropism and central nervous system histological lesions are similar in pigs infected through needle, contact or oronasal inoculation. In all cases, a particularly important site of replication are the tonsils, in which JEV is found to persist for at least 25 days despite the presence of high levels of neutralizing antibodies. Our findings could have a major impact on the ecology of JEV in temperate regions with short mosquito seasons. Japanese encephalitis virus (JEV) is primarily transmitted between mosquitoes and birds but can also infect pigs. Here the authors demonstrate that JEV, which was thought to be spread exclusively by mosquitoes, can be transmitted between pigs through a direct contact.

Live-attenuated influenza vaccines (LAIV) offer advantages over the commonly used inactivated split influenza vaccines. However, finding the optimal balance between sufficient attenuation and immunogenicity has remained a challenge. We recently developed an alternative LAIV based on the 2009 pandemic H1N1 virus with a truncated NS1 protein and lacking PA-X protein expression (NS1(1–126)-ΔPAX). This virus showed a blunted replication and elicited a strong innate immune response. In the present study, we evaluated the efficacy of this vaccine candidate in the porcine animal model as a pertinent in vivo system. Immunization of pigs via the nasal route with the novel NS1(1–126)-ΔPAX LAIV did not cause disease and elicited a strong mucosal immune response that completely blocked replication of the homologous challenge virus in the respiratory tract. However, we observed prolonged shedding of our vaccine candidate from the upper respiratory tract. To improve LAIV safety, we developed a novel prime/boost vaccination strategy combining primary intramuscular immunization with a haemagglutinin-encoding propagation-defective vesicular stomatitis virus (VSV) replicon, followed by a secondary immunization with the NS1(1–126)-ΔPAX LAIV via the nasal route. This two-step immunization procedure significantly reduced LAIV shedding, increased the production of specific serum IgG, neutralizing antibodies, and Th1 memory cells, and resulted in sterilizing immunity against homologous virus challenge. In conclusion, our novel intramuscular prime/intranasal boost regimen interferes with virus shedding and transmission, a feature that will help combat influenza epidemics and pandemics.

The impacts of the accelerated glacier retreat in recent decades on glacier runoff changes are still unknown in most Andean catchments, increasing uncertainties in estimating water availability. This particularly affects the outer tropics and Dry Andes, heavily impacted by prolonged droughts. Current global estimates overlook climatic and morphometric disparities, which significantly influence model parameters, among Andean glaciers. Meanwhile, local studies have used different approaches to estimate glacier runoff in a few catchments. Improving 21st-century glacier runoff projections relies on calibrating and validating models using corrected historical climate inputs and calibrated parameters across diverse glaciological zones. Here, we simulate glacier evolution and related runoff changes between the periods 2000–2009 and 2010–2019 across 786 Andean catchments (11 282 km2 of glacierized area, 11° N to 55° S) using the Open Global Glacier Model (OGGM). TerraClimate atmospheric variables were corrected using in situ data, getting a mean temperature bias by up to 2.1 °C and enhanced monthly precipitation. Glacier mass balance and volume were calibrated, where melt factor and the Glen A parameter exhibited significant alignment with varying environmental conditions. Simulation outcomes were validated against in situ data in three documented catchments (with a glacierized area > 8 %) and monitored glaciers. Our results at the Andes scale reveal an average reduction of 8.3 % in glacier volume and a decrease of 2.2 % in surface area between the periods 2000–2009 and 2010–2019. Comparing these two periods, glacier and climate variations have led to a 12 % increase in mean annual glacier melt (86.5 m3 s−1) and a decrease in rainfall on glaciers of −2 % (−7.6 m3 s−1) across the Andes, with both variables comprising the glacier runoff. We confirmed the utility of our corrected regional simulations of glacier runoff contribution at the catchment scale, where our estimations align with previous studies (e.g., Maipo 34° S, Chile) as well as provide new insights on the seasonal glaciers' largest contribution (e.g., La Paz 16° S, Bolivia) and new estimates of glacier runoff contribution (e.g., Baker 47° S, Chile).

Enthusiasm for using Twitter as a source of data in the social sciences extends to measuring the impact of research with Twitter data being a key component in the new altmetrics approach. In this paper, we examine tweets containing links to research articles in the field of dentistry to assess the extent to which tweeting about scientific papers signifies engagement with, attention to, or consumption of scientific literature. The main goal is to better comprehend the role Twitter plays in scholarly communication and the potential value of tweet counts as traces of broader engagement with scientific literature. In particular, the pattern of tweeting to the top ten most tweeted scientific dental articles and of tweeting by accounts is examined. The ideal that tweeting about scholarly articles represents curating and informing about state-of-the-art appears not to be realized in practice. We see much presumably human tweeting almost entirely mechanical and devoid of original thought, no evidence of conversation, tweets generated by monomania, duplicate tweeting from many accounts under centralized professional management and tweets generated by bots. Some accounts exemplify the ideal, but they represent less than 10% of tweets. Therefore, any conclusions drawn from twitter data is swamped by the mechanical nature of the bulk of tweeting behavior. In light of these results, we discuss the compatibility of Twitter with the research enterprise as well as some of the financial incentives behind these patterns.

Live-attenuated influenza A viruses (LAIV) may be superior to inactivated or subunit vaccines since they can be administered via mucosal routes to induce local immunity in the respiratory tract. In addition, LAIV are expected to trigger stronger T-cell responses that may protect against a broader range of antigen-drifted viruses. However, the development of LAIV is challenging since a proper balance between immunogenicity and safety has to be reached. In this study, we took advantage of reverse genetics to generate three LAIV based on the pandemic H1N1 2009 (pH1N1/09) virus strain: ΔPA-X, which is defective in the synthesis of the accessory PA-X protein, NS1(1-126) lacking 93 amino acids at the C-terminus of the NS1 protein, and a combination of both. Characterization of these recombinant viruses using a novel porcine bronchiolar epithelial cell line (T3) revealed that the ΔPA-X mutant replicated similar to wild type (WT) virus. However, in contrast to the parental virus the ΔPA-X mutant allowed transcription of genes involved in cell cycle progression and limits apoptosis. The NS1(1-126) mutant also replicated comparable to WT virus, but triggered the release of type I and III IFN and several chemokines and cytokines. Surprisingly, only the NS1(1-126)/ΔPA-X double mutant was significantly attenuated on T3 cells, and this was associated with enhanced transcription of genes of the innate immune system and complete absence of apoptosis induction. In conclusion, these findings indicate that NS1 and PA-X act in a concerted manner to manipulate the host cell response, which may help to develop swine LAIV vaccine with a more favorable balance of safety and immunogenicity.

Dispersive magnetic solid-phase extraction (DMSPE) technique is proposed as a new sensitive and effective sample treatment method for the determination of aflatoxins in paprika samples. DMSPE was followed by ultrahigh-performance liquid chromatography and high-resolution mass spectrometry detection (UHPLC-HRMS) using a non-targeted acquisition mode for the detection of main aflatoxins (aflatoxin G1, G2, B1 and B2) and derivatives. DMSPE was based on the use of magnetic nanocomposite coated with polypyrrole (PPy) polymer and the main experimental parameters influencing the extraction efficiency in adsorption and desorption steps have been studied and optimized. Analyses were performed using 250 µL magnetic PPy nanocomposite into the sample solution, adsorbing the analytes in 30 min and desorbing them with ethyl acetate (2 mL) in 15 min. The method has been validated, obtaining quantification limits between 3.5 and 4.7 µg kg−1 and recoveries between 89.5–97.7%. The high recovery rate, wide detection range and the use for the first time of the reusable Fe3O4@PPy nanomaterial in suspension for solid food matrices, guarantee the usefulness of the method developed for adequate control of aflatoxins levels in paprika. The proposed methodology was applied for the analysis of 31 samples (conventional and organic) revealing the absence of aflatoxins in the samples.