Principal role of fungi in soil carbon stabilization during early pedogenesis in the high Arctic.

Climate warming is causing widespread deglaciation and pioneer soil formation over glacial deposits. Melting glaciers expose rocky terrain and glacial till sediment that is relatively low in biomass, oligotrophic, and depleted in nutrients. Following initial colonization by microorganisms, glacial till sediments accumulate organic carbon and nutrients over time. However, the mechanisms driving soil nutrient stabilization during early pedogenesis after glacial retreat remain unclear. Here, we traced amino acid uptake by microorganisms in recently deglaciated high-Arctic soils and show that fungi play a critical role in the initial stabilization of the assimilated carbon. Pioneer basidiomycete yeasts were among the predominant taxa responsible for carbon assimilation, which were associated with overall high amino acid use efficiency and reduced respiration. In intermediate- and late-stage soils, lichenized ascomycete fungi were prevalent, but bacteria increasingly dominated amino acid assimilation, with substantially decreased fungal:bacterial amino acid assimilation ratios and increased respiration. Together, these findings demonstrate that fungi are important drivers of pedogenesis in high-Arctic ecosystems that are currently subject to widespread deglaciation from global warming.

Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: VLA1553 is a live-attenuated vaccine candidate for active immunisation and prevention of disease caused by chikungunya virus. We report safety and immunogenicity data up to day 180 after vaccination with VLA1553. METHODS: This double-blind, multicentre, randomised, phase 3 trial was done in 43 professional vaccine trial sites in the USA. Eligible participants were healthy volunteers aged 18 years and older. Patients were excluded if they had history of chikungunya virus infection or immune-mediated or chronic arthritis or arthralgia, known or suspected defect of the immune system, any inactivated vaccine received within 2 weeks before vaccination with VLA1553, or any live vaccine received within 4 weeks before vaccination with VLA1553. Participants were randomised (3:1) to receive VLA1553 or placebo. The primary endpoint was the proportion of baseline negative participants with a seroprotective chikungunya virus antibody level defined as 50% plaque reduction in a micro plaque reduction neutralisation test (µPRNT) with a µPRNT50 titre of at least 150, 28 days after vaccination. The safety analysis included all individuals who received vaccination. Immunogenicity analyses were done in a subset of participants at 12 pre-selected study sites. These participants were required to have no major protocol deviations to be included in the per-protocol population for immunogenicity analyses. This trial is registered at ClinicalTrials.gov, NCT04546724. FINDINGS: Between Sept 17, 2020 and April 10, 2021, 6100 people were screened for eligibility. 1972 people were excluded and 4128 participants were enrolled and randomised (3093 to VLA1553 and 1035 to placebo). 358 participants in the VLA1553 group and 133 participants in the placebo group discontinued before trial end. The per-protocol population for immunogenicity analysis comprised 362 participants (266 in the VLA1553 group and 96 in the placebo group). After a single vaccination, VLA1553 induced seroprotective chikungunya virus neutralising antibody levels in 263 (98·9%) of 266 participants in the VLA1553 group (95% CI 96·7-99·8; p<0·0001) 28 days post-vaccination, independent of age. VLA1553 was generally safe with an adverse event profile similar to other licensed vaccines and equally well tolerated in younger and older adults. Serious adverse events were reported in 46 (1·5%) of 3082 participants exposed to VLA1553 and eight (0·8%) of 1033 participants in the placebo arm. Only two serious adverse events were considered related to VLA1553 treatment (one mild myalgia and one syndrome of inappropriate antidiuretic hormone secretion). Both participants recovered fully. INTERPRETATION: The strong immune response and the generation of seroprotective titres in almost all vaccinated participants suggests that VLA1553 is an excellent candidate for the prevention of disease caused by chikungunya virus. FUNDING: Valneva, Coalition for Epidemic Preparedness Innovation, and EU Horizon 2020.

[Post-colonoscopy colorectal cancer: Evaluation of a cohort in its clinical and colonoscopic characteristics, survival and its causes according to the World Endoscopy Organization]. / Cáncer colorrectal post-colonoscopia: Evaluación de una cohorte en sus características clínicas, colonoscópicas, sobrevida y sus causas según la Organización Mundial de Endoscopia.

Post-colonoscopy colorectal cancer (PCCRC) is a tumor that appears after a normal colonoscopy before the established time for the endoscopic follow up. Its origin reflects the quality of the colonoscopy and the different tumoral biologics between the CRC and the CRCPC. Our aim is to describe the characteristics of the PCCRC in our region, to identify risk factors, to discriminate the potential causes according to the World Endoscopý Organization (WEO) and to determine its impact in the patient's survival. We studied patients with colorectal cancer (CRC) attended at the gastro-oncology clinic of two institutions of Medellin-Colombia, between January 2012 and December 2021 that had been submitted to a colonoscopy between 6-36 months before the colonoscopy in which the CRC was diagnosed. 919 patients during 10 years for CRC, 68 cases of PCCRC (6.9%); It was more frequent in older patients (74 vs. 66 years; p=0.03), with background of adenomatous polyps (36.8% vs. 20.1%; p=0.01) and in right colon (57.4% vs. 40.6%; p=0.006), with a tendency in patients with diverticulosis (41.2% vs. 31.3%; p=0.05) and diabetes (25% vs. 14%; p=0.06); less survival at 5 and 10 years (58% and 55.2% vs. 67% and 63%; p < 0.001). According to the WEO, the PCCRC presents in 61.3% because of abnormal findings omitted in inadequate colonoscopies, 29% in a suitable colonoscopy and 9.7% incomplete resections of adenomas. In conclusion, the rate of PCCRC was 6.9% with more propension in older patients, a background of polyp resection, and proximal colon. According to the WEO, the abnormal findings omitted more frequently were related with inadequate colonoscopies. The patients with PCCRC had less survival.

Structure and ecological function of the soil microbiome affecting plant-soil feedbacks in the presence of a soil-borne pathogen.

Interactions between plants and soil microbes are important for plant growth and resistance. Through plant-soil-feedbacks, growth of a plant is influenced by the previous plant that was growing in the same soil. We performed a plant-soil feedback study with 37 grass, forb and legume species, to condition the soil and then tested the effects of plant-induced changes in soil microbiomes on the growth of the commercially important cut-flower Chrysanthemum in presence and absence of a pathogen. We analysed the fungal and bacterial communities in these soils using next-generation sequencing and examined their relationship with plant growth in inoculated soils with or without the root pathogen, Pythium ultimum. We show that a large part of the soil microbiome is plant species-specific while a smaller part is conserved at the plant family level. We further identified clusters of plant species creating plant growth promoting microbiomes that suppress concomitantly plant pathogens. Especially soil inocula with higher relative abundances of arbuscular mycorrhizal fungi caused positive effects on the Chrysanthemum growth when exposed to the pathogen. We conclude that plants differ greatly in how they influence the soil microbiome and that plant growth and protection against pathogens is associated with a complex soil microbial community.

The influence of sulfur configuration in 1 H NMR chemical shifts of diasteromeric five-membered cyclic sulfites.

The effect of the stereochemistry of the sulfur atom on 1 H chemical shifts of the diasteromeric pair of cyclic sulfites of 4-[methoxy(4-nitrophenyl)methyl]-5-phenyl-1,3,2-dioxathiolan-2-oxide was investigated. The complete 1 H and 13 C NMR spectral assignment was achieved by the use of one-dimensional and two-dimensional NMR techniques in combination with X-ray data. A correlation of experimental data with theoretical calculations of chemical shift tensors using density functional theory and topological theory of atoms in molecules was made. Copyright © 2016 John Wiley & Sons, Ltd.

Performance Characterization of an xy-Stage Applied to Micrometric Laser Direct Writing Lithography.

This article concerns the characterization of the stability and performance of a motorized stage used in laser direct writing lithography. The system was built from commercial components and commanded by G-code. Measurements use a pseudo-periodic-pattern (PPP) observed by a camera and image processing is based on Fourier transform and phase measurement methods. The results report that the built system has a stability against vibrations determined by peak-valley deviations of 65 nm and 26 nm in the x and y directions, respectively, with a standard deviation of 10 nm in both directions. When the xy-stage is in movement, it works with a resolution of 0.36 µm, which is an acceptable value for most of research and development (R and D) microtechnology developments in which the typical feature size used is in the micrometer range.

Impact of plant domestication on rhizosphere microbiome assembly and functions.

The rhizosphere microbiome is pivotal for plant health and growth, providing defence against pests and diseases, facilitating nutrient acquisition and helping plants to withstand abiotic stresses. Plants can actively recruit members of the soil microbial community for positive feedbacks, but the underlying mechanisms and plant traits that drive microbiome assembly and functions are largely unknown. Domestication of plant species has substantially contributed to human civilization, but also caused a strong decrease in the genetic diversity of modern crop cultivars that may have affected the ability of plants to establish beneficial associations with rhizosphere microbes. Here, we review how plants shape the rhizosphere microbiome and how domestication may have impacted rhizosphere microbiome assembly and functions via habitat expansion and via changes in crop management practices, root exudation, root architecture, and plant litter quality. We also propose a "back to the roots" framework that comprises the exploration of the microbiome of indigenous plants and their native habitats for the identification of plant and microbial traits with the ultimate goal to reinstate beneficial associations that may have been undermined during plant domestication.

Detection of all four dengue serotypes in Aedes aegypti female mosquitoes collected in a rural area in Colombia.

The Aedes aegypti vector for dengue virus (DENV) has been reported in urban and periurban areas. The information about DENV circulation in mosquitoes in Colombian rural areas is limited, so we aimed to evaluate the presence of DENV in Ae. aegypti females caught in rural locations of two Colombian municipalities, Anapoima and La Mesa. Mosquitoes from 497 rural households in 44 different rural settlements were collected. Pools of about 20 Ae. aegypti females were processed for DENV serotype detection. DENV in mosquitoes was detected in 74% of the analysed settlements with a pool positivity rate of 62%. The estimated individual mosquito infection rate was 4.12% and the minimum infection rate was 33.3/1,000 mosquitoes. All four serotypes were detected; the most frequent being DENV-2 (50%) and DENV-1 (35%). Two-three serotypes were detected simultaneously in separate pools. This is the first report on the co-occurrence of natural DENV infection of mosquitoes in Colombian rural areas. The findings are important for understanding dengue transmission and planning control strategies. A potential latent virus reservoir in rural areas could spill over to urban areas during population movements. Detecting DENV in wild-caught adult mosquitoes should be included in the development of dengue epidemic forecasting models.

The branched mitochondrial respiratory chain from Debaryomyces hansenii: components and supramolecular organization.

The branched respiratory chain in mitochondria from the halotolerant yeast Debaryomyces hansenii contains the classical complexes I, II, III and IV plus a cyanide-insensitive, AMP-activated, alternative-oxidase (AOX). Two additional alternative oxidoreductases were found in this organism: an alternative NADH dehydrogenase (NDH2e) and a mitochondrial isoform of glycerol-phosphate dehydrogenase (MitGPDH). These monomeric enzymes lack proton pump activity. They are located on the outer face of the inner mitochondrial membrane. NDH2e oxidizes exogenous NADH in a rotenone-insensitive, flavone-sensitive, process. AOX seems to be constitutive; nonetheless, most electrons are transferred to the cytochromic pathway. Respiratory supercomplexes containing complexes I, III and IV in different stoichiometries were detected. Dimeric complex V was also detected. In-gel activity of NADH dehydrogenase, mass spectrometry, and cytochrome c oxidase and ATPase activities led to determine the composition of the putative supercomplexes. Molecular weights were estimated by comparison with those from the yeast Y. lipolytica and they were IV2, I-IV, III2-IV4, V2, I-III2, I-III2-IV, I-III2-IV2, I-III2-IV3 and I-III2-IV4. Binding of the alternative enzymes to supercomplexes was not detected. This is the first report on the structure and organization of the mitochondrial respiratory chain from D. hansenii.

Schools as Potential Risk Sites for Vector-Borne Disease Transmission: Mosquito Vectors in Rural Schools in Two Municipalities in Colombia.

Dengue and other vector-borne diseases are of great public health importance in Colombia. Vector surveillance and control activities are often focused at the household level. Little is known about the importance of nonhousehold sites, including schools, in maintaining vector-borne disease transmission. The objectives of this paper were to determine the mosquito species composition in rural schools in 2 municipalities in Colombia and to assess the potential risk of vector-borne disease transmission in school settings. Entomological surveys were carried out in rural schools during the dry and rainy seasons of 2011. A total of 12 mosquito species were found: Aedes aegypti, Anopheles pseudopunctipennis, Culex coronator, Cx. quinquefasciatus, and Limatus durhamii in both immature and adult forms; Ae. fluviatilis, Cx. nigripalpus, Cx. corniger, and Psorophora ferox in immature forms only; and Ae. angustivittatus, Haemagogus equinus, and Trichoprosopon lampropus in adult forms only. The most common mosquito species was Cx. quinquefasciatus. Classrooms contained the greatest abundance of adult female Ae. aegypti and Cx. quinquefasciatus. The most common Ae. aegypti breeding sites were containers classified as "others" (e.g., cans), followed by containers used for water storage. A high level of Ae. aegypti infestation was found during the wet season. Our results suggest that rural schools are potentially important foci for the transmission of dengue and other mosquito-borne diseases. We propose that public health programs should be implemented in rural schools to prevent vector-borne diseases.

Retrocecal Appendicitis Post-blunt Abdominal Trauma: A Case Report.

Appendicitis, characterized by inflammation and obstruction of the appendiceal lumen, is a common surgical emergency often attributed to various factors. We present the case of an 18-year-old female who developed retrocecal appendicitis following blunt abdominal trauma, a rare occurrence with significant diagnostic challenges. Initial symptoms mimicked upper abdominal trauma, evolving to classic signs of appendicitis within hours. Despite a negative pre-trauma history of abdominal pain, clinical evaluation led to a suspicion of appendicitis. Contrast-enhanced CT scan confirmed the thickening of the cecal appendix, prompting urgent surgical intervention. An open appendectomy revealed a congested retrocecal appendix, supporting the diagnosis. Our case underscores the importance of considering trauma as a potential trigger for appendicitis, especially in the absence of typical pre-trauma symptoms. Diagnostic criteria for post-trauma appendicitis are evolving, and we underscore a comprehensive clinical assessment alongside imaging modalities. While surgical management remains standard, newer approaches like endoscopic retrograde appendicitis therapy warrant exploration. Further research is essential to refine diagnostic and therapeutic strategies for this uncommon presentation, ensuring timely intervention and improved patient outcomes.

Identifying Areas of Invasion Risk and Changes in the Ecological Niche Occupied by the Coffee Leaf Miner Leucoptera coffeella (Lepidoptera: Lyonetiidae).

Insects of economic importance such as Leucoptera coffeella can cause high defoliation in plants and reduce crop yields. We aimed to identify changes in the ecological niche and potential zones of the invasion. Occurrence records were obtained from databases and bibliography. WorldClim V2.0 bioclimatic layers were used. For the modeling of the potential distribution, the kuenm R package was used by executing the Maxent algorithm. The potential distribution models suggested greatest environmental suitability extends from Europe, South Asia, and Central and South Africa, showing the "tropical and subtropical moist broadleaf forests" as the ecoregion that presents the greatest probability of the presence of L. coffeella. The potential distribution model projected in the invaded area agrees with the known distribution in the region (America), although the results show that it is occupying environmental spaces not present in the area of origin. This species presented a large proportion of the invaded niche that overlaps the native niche and is colonizing new environmental conditions in the invaded area relative to its native distribution (Africa). This information could be used in the planning of coffee crops on the American continent.

Simulation of the fluid dynamic and thermal behavior of an experimental passive cooling system of photovoltaic panels.

Solar energy capacity has increased significantly globally, with values above 800 GW produced by different systems. Among these, PVT panels can generate either electricity, heat, or both. As these systems present various issues associated with excessive temperature increases, cooling systems have been developed to control the temperature using fluids such as water. The article uses previous data from the Technologic Institute of Sonora, which analyzed various cooling device configurations and selected the best two options (B1 and B4) based on the panel efficiency. Using the boundary conditions and the predicted streamlines, a simulation was made in CFD programs, determining the correct parameters to replicate the system fluid dynamics. Several simulations were carried out using different turbulence models. After comparing the temperature contour diagram and the streamline, it was obtained that the k-ω turbulence model best describes the fluid's behavior. The transient analysis simulations allow us to determine that the B1 configuration delivers the best cooling effect as it presents the most homogeneous temperature profile. BIAS and RMSE were calculated to validate and contrast the results obtained experimentally, obtaining values of 0.8675 and 1.8981, respectively.

A randomized, double-blinded Phase 3 study to demonstrate lot-to-lot consistency and to confirm immunogenicity and safety of the live-attenuated chikungunya virus vaccine candidate VLA1553 in healthy adults†.

BACKGROUND: The global spread of the chikungunya virus (CHIKV) increases the exposure risk for individuals travelling to or living in endemic areas. This Phase 3 study was designed to demonstrate manufacturing consistency between three lots of the single shot live-attenuated CHIKV vaccine VLA1553, and to confirm the promising immunogenicity and safety data obtained in previous trials. METHODS: This randomized, double-blinded, lot-to-lot consistency, Phase 3 study, assessed immunogenicity and safety of VLA1553 in 408 healthy adults (18-45 years) in 12 sites across the USA. The primary endpoint was a comparison of the geometric mean titre (GMT) ratios of CHIKV-specific neutralizing antibodies between three VLA1553 lots at 28 days post-vaccination. Secondary endpoints included immunogenicity and safety over 6 months post-vaccination. RESULTS: GMTs were comparable between the lots meeting the acceptance criteria for equivalence. The average GMT (measured by 50% CHIKV micro plaque neutralization test; µPRNT50) peaked with 2643 at 28 days post-vaccination and decreased to 709 at 6 months post-vaccination. An excellent seroresponse rate (defined as µPRNT50 titre ≥ 150 considered protective) was achieved in 97.8% of participants at 28 days post-vaccination and still persisted in 96% at 6 months after vaccination. Upon VLA1553 immunization, 72.5% of participants experienced adverse events (AEs), without significant differences between lots (related solicited systemic AE: 53.9% of participants; related solicited local AE: 19.4%). Overall, AEs were mostly mild or moderate and resolved without sequela, usually within 3 days. With 3.9% of participants experiencing severe AEs, 2.7% were classified as related, whereas none of the six reported serious adverse events was related to the administration of VLA1553. CONCLUSIONS: All three lots of VLA1553 recapitulated the safety and immunogenicity profiles of a preceding Phase 3 study, fulfilling pre-defined consistency requirements. These results highlight the manufacturability of VLA1553, a promising vaccine for the prevention of CHIKV disease for those living in or travelling to endemic areas.

Metagenome-assembled genomes (MAGs) suggest an acetate-driven protective role in gut microbiota disrupted by Clostridioides difficile.

Clostridioides difficile may have a negative impact on gut microbiota composition in terms of diversity and abundance, thereby triggering functional changes supported by the differential presence of genes involved in significant metabolic pathways, such as short-chain fatty acids (SCFA). This work has evaluated shotgun metagenomics data regarding 48 samples from four groups classified according to diarrhea acquisition site (community- and healthcare facility-onset) and positive or negative Clostridioides difficile infection (CDI) result. The metagenomic-assembled genomes (MAGs) obtained from each sample were taxonomically assigned for preliminary comparative analysis concerning differences in composition among groups. The predicted genes involved in metabolism, transport, and signaling remained constant in microbiota members; characteristic patterns were observed in MAGs and genes involved in SCFA butyrate and acetate metabolic pathways for each study group. A decrease in genera and species, as well as relative MAG abundance with the presence of the acetate metabolism-related gene, was evident in the HCFO/- group. Increased antibiotic resistance markers (ARM) were observed in MAGs along with the genes involved in acetate metabolism. The results highlight the need to explore the role of acetate in greater depth as a potential protector of the imbalances produced by CDI, as occurs in other inflammatory intestinal diseases.

Safety and immunogenicity against ancestral, Delta and Omicron virus variants following a booster dose of an inactivated whole-virus COVID-19 vaccine (VLA2001): Interim analysis of an open-label extension of the randomized, controlled, phase 3 COV-COMPARE trial.

OBJECTIVES: Booster doses for COVID-19 vaccinations have been shown to amplify the waning immune response after primary vaccination and to enhance protection against emerging variants of concern (VoCs). Here, we aimed to assess the immunogenicity and safety of a booster dose of an inactivated whole-virus COVID-19 vaccine (VLA2001) after primary vaccination with 2 doses of either VLA2001 or ChAdOx1-S (Oxford-Astra Zeneca), including the cross-neutralization capacity against the Delta and Omicron VoCs. METHODS: This interim analysis of an open-label extension of a randomized, controlled phase 3 trial assessed a single booster dose of an inactivated whole-virus COVID-19 vaccine (VLA2001) in healthy or medically stable adults aged 18 years and above, recruited in 21 clinical sites in the UK, who had previously received two doses of either VLA2001 or ChAdOx1-S. Safety outcomes were frequency and severity of solicited injection site and systemic reactions within 7 days after booster vaccination as well as frequency and severity of any unsolicited adverse events (AE) after up to 6 months. Immunogenicity outcomes were the immune response to ancestral SARS-CoV-2 assessed 14 days post booster expressed as geometric mean titres (GMT), GMT fold ratios and seroconversion of specific neutralizing antibodies and S-protein binding IgG antibodies. Immunogenicity against the Delta and Omicron VoCs was assessed as a post-hoc outcome with a pseudovirus neutralization antibody assay. This study is registered with ClinicalTrials.gov, NCT04864561, and is ongoing. RESULTS: A booster dose of VLA2001 was administered to 958 participants, of whom 712 had been primed with VLA2001, and 246 with ChAdOx1-S. Within 7 days following these booster doses, 607 (63.4%) participants reported solicited injection site reactions, and 487 (50.8%) reported solicited systemic reactions. Up to 14 days post booster, 751 (78.4%) participants reported at least one adverse event. The tolerability profile of a booster dose of VLA2001 was similar in VLA2001-primed and ChAdOx1-S-primed participants. In VLA2001-primed participants, the GMT (95% CI) of neutralizing antibodies increased from 32.5 (22.8, 46.3) immediately before to 521.5 (413.0, 658.6) 2 weeks after administration of the booster dose, this corresponds to a geometric mean fold rise (GMFR) of 27.7 (20.0, 38.5). Compared to 2 weeks after the second priming dose, the GMFR was 3.6 (2.8, 4.7). In the ChAdOx1-S primed group, the GMT (95% CI) of neutralizing antibodies increased from 65.8 (43.9, 98.4) immediately before to 188.3 (140.3, 252.8) 2 weeks after administration of the booster dose, a geometric mean fold rise (GMFR) of 3.0 (2.2, 4.0). Compared to 2 weeks after the second priming dose, the GMFR was 1.6 (1.1, 2.2). For S-protein binding IgG antibodies, the pre- versus post-booster GMT fold ratio (95% CI) was 34.6 (25.0, 48.0) in the VLA2001-primed group and 4.0 (3.0, 5.2) in the ChAdOx1-S-primed group. Compared to 2 weeks after the second priming dose, the GMT fold rise of IgG antibodies was 3.8 (3.2, 4.6) in the VLA2001-primed group and 1.2 (0.9, 1.6) in the ChAdOx1-S-primed group. The GMT against Delta (B.1.617.2) and Omicron (BA.4/5) increased from 4.2 to 260, and from 2.7 to 56.7, respectively, when boosting subjects previously primed with VLA2001. Following the boost, 97% of subjects primed with VLA2001 had detectable Delta- and 94% Omicron-neutralizing antibodies. In subjects primed with ChAdOx1-S, the GMT against Delta and Omicron titres increased from 9.1 to 92.5, and from 3.6 to 12.3, respectively. After boosting, 99% of subjects primed with ChAdOx1-S had detectable Delta- and 70% Omicron-neutralizing antibodies. In both VLA2001 and ChAdOx1-S primed subjects, the additional VLA2001 dose boosted T cell responses against SARS-CoV-2 antigens to levels above those observed before the booster dose. CONCLUSION: A booster dose of VLA2001 was safe and well tolerated after primary immunization with VLA2001 and ChAdOx1-S. The tolerability of a booster dose of VLA2001 was similar to the favourable profile observed after the first and second priming doses. Both in a homologous and a heterologous setting, boosting resulted in higher neutralizing antibody titres than after primary immunization and significant increases in cross-neutralization titres against Delta and Omicron were observed after the booster dose. These data support the use of VLA2001 in booster programmes in ChadOx1-S primed groups.

Three new coordination geometries of homoleptic Zn complexes of curcuminoids and their high antiproliferative potential.

To our previously reported first crystal structure of a homoleptic zinc curcuminoid complex with square pyramidal geometry, we add herein three new geometries of homoleptic type complexes i.e. octahedral, trigonal-pyramidal, and trigonal-bipyramidal. Octahedral geometry was observed in the new pseudo-polymorph of the DAC-Zn complex resulting from crystallization in DMF, while square-pyramidal geometry was obtained in DMSO. Improving crystallinity involved suppressing the phenolic interactions by etherification and esterification. The complete characterization of these complexes was carried out using SCXRD, IR, MS, EA, liquid, and solid-state NMR. Moreover, the cytotoxic activity of all complexes was evaluated. The IC50 values for the DiMeOC-Zn (7) complex were 8 or 22 times higher than for cisplatin in the U251 and HCT-15 cell lines, indicating a high antiproliferative and therapeutic potential.

Unveiling the relevance of traffic enforcement cameras on the severity of vehicle-pedestrian collisions in an urban environment with machine learning models.

PURPOSE: One of the leading causes of violent fatalities around the world is road traffic collisions, and pedestrians are among the most vulnerable road users with respect to such incidents. Since walking is highly promoted in urban areas to alleviate motor-vehicle externalities, it is paramount to understand the causes associated with vehicle-pedestrian collisions and their severity to provide safe environments. Although traffic enforcement cameras can address vehicle-vehicle collisions, little is known about their effectiveness with respect to vehicle-pedestrian incidents. METHODOLOGY: In this study, we trained a set of machine learning models to forecast if a vehicle-pedestrian collision will turn into an injury or fatality, and the most suitable model was used to investigate the contributing features associated with such events with emphasis on the impact of traffic enforcement cameras. In addition to traffic enforcement camera proximity, features associated with the collision, weather, vehicle, victim, and infrastructure are included in the model to reduce unobserved heterogeneity. RESULTS: Results show that a Linear Discriminant Analysis model surpasses other machine learning models considering the evaluation metrics. Results reveal that the age and gender of the victim, the involvement of larger vehicles in the collision, and the quality of the illumination are the causes associated with pedestrian fatalities. On the other hand, involvement of motorcycles and collisions that occurred in densely populated locations are the causes associated with pedestrian injuries. CONCLUSIONS: This investigation demonstrates how to articulate machine learning into a vehicle-pedestrian crash analysis to understand the direction and magnitude of covariates in the corresponding severity outcome. Furthermore, it highlights the remarkable effect that traffic enforcement cameras and other features have on vehicle-pedestrian crash severity. These results provide actionable guidance for educational campaigns, enhanced traffic engineering, and infrastructure improvements that could be implemented in the analyzed region to provide safer transportation.

Immunogenicity and safety of an inactivated whole-virus COVID-19 vaccine (VLA2001) compared with the adenoviral vector vaccine ChAdOx1-S in adults in the UK (COV-COMPARE): interim analysis of a randomised, controlled, phase 3, immunobridging trial.

BACKGROUND: The Valneva COVID-19 vaccine (VLA2001; Valneva Austria, Vienna, Austria) is an inactivated whole-virus, adjuvanted SARS-CoV-2 vaccine. We aimed to assess the safety and immunogenicity of primary vaccination with VLA2001 versus the ChAdOx1-S (Oxford-AstraZeneca) adenoviral-vectored vaccine. METHODS: In this immunobridging phase 3 trial (COV-COMPARE), participants aged 18 years and older who were medically stable (as determined by an investigator) were enrolled at 26 sites in the UK. In the double-blind, randomised, controlled arm of the trial, participants aged 30 years and older were randomly assigned (2:1) to receive two doses of VLA2001 (0·5 mL; with 33 antigen units [AU] per dose) or ChAdOx1-S (0·5 mL; with 2·5 × 108 infectious units per dose) on days 1 and 29. In another arm, participants aged 18-29 years received two doses of VLA2001 (same dose) open label on days 1 and 29. The primary immunogenicity outcome was the immune response of a two-dose schedule of VLA2001 on day 43, in adults aged 30 years and older, versus two doses of ChAdOx1-S via superiority of geometric mean titres (GMTs) of neutralising antibodies (GMT ratio of >1 at a two-sided significance level of 5%) and non-inferiority of the seroconversion rate (non-inferiority margin of -10% for the lower limit of the 95% CI for the difference between groups). The primary safety outcome was the frequency and severity of any adverse events in all participants up to day 43. Safety was assessed in all participants who received at least one dose of vaccine. GMTs were assessed in a subset of participants aged 30 years and older who were seronegative at baseline, had at least one evaluable antibody titre measurement after vaccination, and had no confirmed COVID-19 during the study (immunogenicity population); and seroconversion was assessed in the per-protocol population, which comprised the immunogenicity population but excluding any participants with major protocol violations. For each timepoint, only participants with available data were included in the analysis. This study is registered with ClinicalTrials.gov, NCT04864561, and is ongoing. FINDINGS: Between April 28 and June 3, 2021, 4181 individuals were screened and 4017 enrolled, of whom 2975 (74%) were aged 30 years or older and randomly assigned to receive VLA2001 (n=1978) or ChAdOx1-S (n=997), and 1042 (26%) were aged 18-29 years (all received open-label VLA2001). 4012 participants received at least one dose of vaccine (1040 in the open-label VLA2001 group, 1977 in the randomised VLA2001 group, and 995 in the ChAdOx1-S group). The immunogenicity population comprised 492 participants in the randomised VLA2001 group and 498 in the ChAdOx1-S group; three participants in the VLA2001 group were excluded from the per-protocol population. VLA2001 induced higher neutralising GMTs than did ChAdOx1-S (803·5 [95% CI 748·5-862·6] vs 576·6 [543·6-611·7]; GMT ratio 1·39 [95% CI 1·25-1·56]; p<0·0001), and non-inferior seroconversion rates (444 [97·4%] of 456 participants vs 444 [98·9%] of 449; difference -1·5% [95% CI -3·3 to 0·2]. Any adverse event was reported in 963 (92·6%) participants in the open-label VLA2001 group, 1755 (88·8%) in the randomised VLA2001 group, and 976 (98·1%) in the ChAdOx1-S group. Most adverse events reported were mild or moderate in severity. INTERPRETATION: VLA2001 has a favourable tolerability profile and met superiority criteria for neutralising antibodies and non-inferiority criterion for seroconversion rates compared with ChAdOx1-S. The data presented here formed the basis of successful marketing approval for use of VLA2001 in primary vaccination in the EU, the UK, Bahrain, and United Arab Emirates. FUNDING: UK Department of Health and Social Care and Valneva Austria.