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A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 μg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020–004272–17) and ClinicalTrials.gov (NCT04672395). 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3–76·8), 83·7% (97·86% CI 55·9–95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3–100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3–90·4) for delta, 91·8% (44·9–99·8) for gamma, and 58·6% (13·3–81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63–103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups. Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant. Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.

The rise in antibiotic resistance is a major threat for human health. Basidiomycete fungi represent an untapped source of underexploited antimicrobials, with pleuromutilin—a diterpene produced by Clitopilus passeckerianus —being the only antibiotic from these fungi leading to commercial derivatives. Here we report genetic characterisation of the steps involved in pleuromutilin biosynthesis, through rational heterologous expression in Aspergillus oryzae coupled with isolation and detailed structural elucidation of the pathway intermediates by spectroscopic methods and comparison with synthetic standards. A. oryzae was further established as a platform for bio-conversion of chemically modified analogues of pleuromutilin intermediates, and was employed to generate a semi-synthetic pleuromutilin derivative with enhanced antibiotic activity. These studies pave the way for future characterisation of biosynthetic pathways of other basidiomycete natural products in ascomycete heterologous hosts, and open up new possibilities of further chemical modification for the growing class of potent pleuromutilin antibiotics. Pleuromutilin derivatives are potent antibacterial drugs obtained from Basidiomycete fungi. Here, the authors report the genetic characterisation of the steps involved in pleuromutilin biosynthesis through heterologous expression and generate a semi-synthetic pleuromutilin derivative with enhanced antibiotic activity.

Retrieved from the Moderate Resolution Imaging Spectroradiometer (MODIS) on-board the Aqua satellite, 12 years (2003–2014) of aerosol and cloud properties were used to statistically quantify aerosol–cloud interaction (ACI) over the Baltic Sea region, including the relatively clean Fennoscandia and the more polluted central–eastern Europe. These areas allowed us to study the effects of different aerosol types and concentrations on macro- and microphysical properties of clouds: cloud effective radius (CER), cloud fraction (CF), cloud optical thickness (COT), cloud liquid water path (LWP) and cloud-top height (CTH). Aerosol properties used are aerosol optical depth (AOD), Ångström exponent (AE) and aerosol index (AI). The study was limited to low-level water clouds in the summer. The vertical distributions of the relationships between cloud properties and aerosols show an effect of aerosols on low-level water clouds. CF, COT, LWP and CTH tend to increase with aerosol loading, indicating changes in the cloud structure, while the effective radius of cloud droplets decreases. The ACI is larger at relatively low cloud-top levels, between 900 and 700 hPa. Most of the studied cloud variables were unaffected by the lower-tropospheric stability (LTS), except for the cloud fraction. The spatial distribution of aerosol and cloud parameters and ACI, here defined as the change in CER as a function of aerosol concentration for a fixed LWP, shows positive and statistically significant ACI over the Baltic Sea and Fennoscandia, with the former having the largest values. Small negative ACI values are observed in central–eastern Europe, suggesting that large aerosol concentrations saturate the ACI.

Runner bean (Phaseolus coccineus L.) is a crop of significant economic importance in Mexico, but its inclusion in diets remains limited to certain regions. The bioprocessing of legumes through germination expands their consumption possibilities. Applying oxidative stress during germination has been suggested to improve the functional qualities of legume seeds. In this study, response surface methodology (RSM) with a central composite rotatable design (13 treatments) was used to identify the optimal hydrogen peroxide soaking concentration ([H₂O₂]; 0–35 mM) and germination time (Gt; 0–96 h) to enhance germination percentage (GP), free phenolic content (FPC), free flavonoid content (FFC), and antioxidant capacity in black runner bean sprouts. Regression analysis generated predictive models for each response. Optimal conditions were identified as [H₂O₂] of 30 mM and Gt of 92 h, achieving a GP of 95.7%. Under these conditions, sprouts exhibited increases in FPC from 67.6 to 72.7 mg GAE/100 g dry weight (DW), FFC from 26.4 to 28.6 mg CE/100 g DW, ABTS•+ scavenging activity from 3,028 to 3,782 μmol TE/100 g DW, and oxygen radical absorbance capacity (ORAC) from 5,793 to 6,573 μmol TE/100 g DW compared to those germinated without H₂O₂ stress. Soaking with 30 mM H₂O₂ enhanced the content of ferulic and p-coumaric acids in free and bound phenolic fractions, whereas catechin and quercetin showed notable reductions in both fractions as a result of H₂O₂ treatment. These findings reveal that H₂O₂ treatment can modify the phenolic profile of runner bean sprouts, thereby boosting their nutraceutical value.

Digital health interventions, such as electronic immunization registries (eIRs) and electronic logistic management information systems (eLMIS), have the potential to significantly improve immunization data management and vaccine logistics in low- and middle-income countries (LMICs). Despite their growing adoption, there is limited evidence of the financial and economic costs associated with their implementation compared to traditional paper-based systems. We aimed to measure the costs of implementing eIR and eLMIS systems in LMICs and to estimate their economic costs as compared to the previous paper-based registries. The study was conducted across four countries-Guinea, Honduras, Rwanda, and Tanzania-which implemented the tools in 2018, 2012, 2019, and 2014, respectively. A combination of primary and secondary data sources was used for the analysis. Retrospective cost data regarding the design, development, and implementation of the tools were directly obtained from implementers and National Immunization Program offices in all countries. Primary survey data were collected to gauge the operational expenses of immunization information systems, both with and without electronic tools, using an activity-based costing approach in 275 facilities. The annual cost of the immunization information system at the national level was then extrapolated and compared to national spending on immunization as a measure of affordability. Costs were reported in 2023 international dollars (I$). The total costs of designing, developing, and deploying eIR, eLMIS, or both were I$ 2.2, 6.4, 6.8, and 44.3 million in Guinea, Honduras, Rwanda, and Tanzania, respectively. Design costs were greatly affected by the degree of customization of the tool, whereas rollout costs were mostly driven by the costs of purchasing hardware and training health workers. Overall, the implementation of the electronic systems was associated with higher costs in Honduras (I$626 per facility, 95% CI 516-821) and Rwanda (I$399, 95% CI I$108-I$691), a cost reduction in Tanzania (-I$2539, 95% CI -I$4290 to -I$789) and no significant cost difference in Guinea. The percentage weight of the cost of managing data with the electronic systems over the total national immunization budgets was estimated at 0.7%, 7.7%, 3.3%, and 4.8% for Guinea, Honduras, Rwanda, and Tanzania, respectively. Digital health interventions such as eIR and eLMIS can potentially reduce costs and improve the efficiency of immunization data management and vaccine logistics in LMICs. However, the extent of cost savings depends on how effectively these digital systems replace traditional paper-based methods and the extent of their use in decision-making, especially at the facility level. Careful planning and investment are essential to unlocking the full economic potential of digital health in LMICs.

Australian smoke from the extraordinary biomass burning in December 2019 was observed over Marambio, Antarctica from the 7th to the 10th January, 2020. The smoke plume was transported thousands of kilometers over the Pacific Ocean, and reached the Antarctic Peninsula at a hight of 13 km, as determined by satellite lidar observations. The proposed origin and trajectory of the aerosol are supported by back-trajectory model analyses. Ground-based Sun–Sky–Moon photometer belonging to the Aerosol Robotic Network (AERONET) measured aerosol optical depth (500 nm wavelength) above 0.3, which is unprecedented for the site. Inversion of sky radiances provide the optical and microphysical properties of the smoke over Marambio. The AERONET data near the fire origin in Tumbarumba, Australia, was used to investigate the changes in the measured aerosol properties after transport and ageing. The analysis shows an increase in the fine mode particle radius and a reduction in absorption (increase in the single scattering albedo). The available long-term AOD data series at Marambio suggests that smoke particles could have remained over Antarctica for several weeks after the analyzed event.

Digital environments are increasingly used to study social and pain-related behaviors. Empathy and contextual factors influence observationally induced placebo analgesia. We tested whether state empathy (i.e., immediate affective and cognitive responses to another’s experience) differs when observing a demonstrator in immersive VR versus 2D video, and whether this modulation affects placebo hypoalgesia. Forty-seven participants observed a human or avatar demonstrator receiving painful stimulation with or without placebo, then experienced the same stimulations. Observation induced significant placebo hypoalgesia for pain intensity and unpleasantness. Human demonstrators evoked greater cognitive empathy, while placebo treatments reduced empathy across contexts. Analgesic effects were stronger in 2D after observing humans, but in VR, avatars induced greater placebo effects. Placebo responsiveness was related to trait empathy in the VR-Human condition; however, state empathy did not mediate the effect. Our findings highlight that demonstrator characteristics and immersion critically shape the social transfer of placebo effects.

Satellite-based aerosol products are routinely validated against ground-based reference data, usually obtained from sun photometer networks such as AERONET (AEROsol RObotic NETwork). In a typical validation exercise a spatial sample of the instantaneous satellite data is compared against a temporal sample of the point-like ground-based data. The observations do not correspond to exactly the same column of the atmosphere at the same time, and the representativeness of the reference data depends on the spatiotemporal variability of the aerosol properties in the samples. The associated uncertainty is known as the collocation mismatch uncertainty (CMU). The validation results depend on the sampling parameters. While small samples involve less variability, they are more sensitive to the inevitable noise in the measurement data. In this paper we study systematically the effect of the sampling parameters in the validation of AATSR (Advanced Along-Track Scanning Radiometer) aerosol optical depth (AOD) product against AERONET data and the associated collocation mismatch uncertainty. To this end, we study the spatial AOD variability in the satellite data, compare it against the corresponding values obtained from densely located AERONET sites, and assess the possible reasons for observed differences. We find that the spatial AOD variability in the satellite data is approximately 2 times larger than in the ground-based data, and the spatial variability correlates only weakly with that of AERONET for short distances. We interpreted that only half of the variability in the satellite data is due to the natural variability in the AOD, and the rest is noise due to retrieval errors. However, for larger distances (∼ 0.5∘) the correlation is improved as the noise is averaged out, and the day-to-day changes in regional AOD variability are well captured. Furthermore, we assess the usefulness of the spatial variability of the satellite AOD data as an estimate of CMU by comparing the retrieval errors to the total uncertainty estimates including the CMU in the validation. We find that accounting for CMU increases the fraction of consistent observations.

SARS-CoV-2 is an emerging infectious disease of zoonotic origin that caused the coronavirus disease in late 2019 and triggered a pandemic that has severely affected human health and caused millions of deaths. Early and massive diagnosis of SARS-CoV-2 infected patients is the key to preventing the spread of the virus and controlling the outbreak. Lateral flow immunoassays (LFIA) are the simplest biosensors. These devices are clinical diagnostic tools that can detect various analytes, including viruses and antibodies, with high sensitivity and specificity. This review summarizes the advantages, limitations, and evolution of LFIA during the SARS-CoV-2 pandemic and the challenges of improving these diagnostic devices.

Identification of new sources of compounds with anticancer and antioxidant potential is essential for cancer treatment. Rhizospheric bacteria have emerged as a promising source of these agents. This study is aimed at investigating the anticancer and antioxidant properties of bacteria isolated from the rhizosphere of Lophocereus marginatus . Six rhizobacteria of L. marginatus were isolated and molecularly identified by sequencing the 16S rRNA gene and MALDI‐TOF. We evaluated the inhibitory activity of methanol (MeOH) and ethyl acetate (EtOAc) extracts obtained from rhizobacteria against the murine lymphoma cell line L5178Y‐R, as well as normal Vero monkey kidney cells and peripheral blood mononuclear cells (PBMCs). Compared with those of normal cells, the MeOH extract of Paenibacillus sp. PMS‐B023 showed selective anticancer activity against lymphoma, with 50% inhibitory concentration (IC 50 ) values of 117.5 μ g/mL and a selectivity index (SI) > 2.1, as compared with those of normal cells. L‐Pro‐L‐Val cycle, gageostatin B, cinnamic acid, parvifloracin, daidzein, genistein, actinomycin D, actinomycin Y4, and surfactin C were detected in the MeOH extract, which may be responsible for its antilymphoma activity. We did not find significant antioxidant activity in any of the extracts evaluated using the 2,2‐diphenyl‐1‐picrylhydrazyl technique (IC 50 > 250 μ g/mL). The results showed that Paenibacillus sp. PMS‐B023 has antitumor potential and selective activity against L5178Y‐R lymphoma cells. The presence of anticancer compounds was also demonstrated, as previously described in the literature.