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Environmental sampling around a landfill site in the UK previously identified the methylimidazolium ionic liquid, 1-octyl-3-methylimidazolium (M8OI), in the soil. More recently, M8OI was shown to be detectable in sera from 5/20 PBC patients and 1/10 controls and to be oxidised on the alkyl chain in the human liver. The objective of this study was to examine the metabolism of M8OI in humans in more detail. In human hepatocytes, M8OI was mono-oxygenated to 1-(8-Hydroxyoctyl)-3-methyl-imidazolium (HO8IM) then further oxidised to 1-(7-carboxyheptyl)-3-methyl-1H-imidazol-3-ium (COOH7IM). The addition of ketoconazole—in contrast to a range of other cytochrome P450 inhibitors—blocked M8OI metabolism, suggesting primarily CYP3A-dependent mono-oxygenation of M8OI. Hepatocytes from one donor produced negligible and low levels of HO8IM and COOH7IM, respectively, on incubation with M8OI, when compared to hepatocytes from other donors. This donor had undetectable levels of CYP3A4 protein and low CYP3A enzyme activity. Transcript expression levels for other adult CYP3A isoforms—CYP3A5 and CYP3A43—suggest that a lack of CYP3A4 accounted primarily for this donor’s low rate of M8OI oxidation. Insect cell (supersome) expression of various human CYPs identified CYP3A4 as the most active CYP mediating M8OI mono-oxygenation, followed by CYP3A5. HO8IM and COOH7IM were not toxic to human hepatocytes, in contrast to M8OI, and using a pooled preparation of human hepatocytes from five donors, ketoconazole potentiated M8OI toxicity. These data demonstrate that CYP3A initiates the mono-oxygenation and detoxification of M8OI in adult human livers and that CYP3A4 likely plays a major role in this process.

Abstract Precision in grazing management is highly dependent on accurate pasture monitoring. Typically, this is often overlooked because existing approaches are labour-intensive, need calibration, and are commonly perceived as inaccurate. Machine-learning processes harnessing big data, including remote sensing, can offer a new era of decision-support tools (DST) for pasture monitoring. Its application on-farm remains poor because of a lack of evidence about its accuracy. This study aimed at evaluating and quantifying the minimum data required to train a machine-learning satellite-based DST focusing on accurate pasture biomass prediction using this approach. Management data from 14 farms in New South Wales, Australia and measured pasture biomass throughout 12 consecutive months using a calibrated rising plate meter (RPM) as well as pasture biomass estimated using a DST based on high temporal/spatial resolution satellite images were available. Data were balanced according to farm and week of each month and randomly allocated for model evaluation (20%) and for progressive training (80%) as follows: 25% training subset (1W: week 1 in each month); 50% (2W: week 1 and 3); 75% (3W: week 1, 3, and 4); and 100% (4W: week 1 to 4). Pasture biomass estimates using the DST across all training datasets were evaluated against a calibrated rising plate meter (RPM) using mean-absolute error (MAE, kg DM/ha) among other statistics. Tukey’s HSD test was used to determine the differences between MAE across all training datasets. Relative to the control (no training, MAE: 498 kg DM ha−1) 1W did not improve the prediction accuracy of the DST (P > 0.05). With the 2W training dataset, the MAE decreased to 342 kg DM ha−1 (P 0.05). This study accounts for minimal training data for a machine-learning DST to monitor pastures from satellites with comparable accuracy to a calibrated RPM which is considered the ‘gold standard’ for pasture biomass monitoring.

Abstract The continued evolution of SARS-CoV-2 underscores the need to understand qualitative aspects of the humoral immune response elicited by spike immunization. Here, we combine monoclonal antibody (mAb) isolation with deep B cell receptor (BCR) repertoire sequencing of rhesus macaques immunized with prefusion-stabilized spike glycoprotein. Longitudinal tracing of spike-sorted B cell lineages in multiple immune compartments demonstrates increasing somatic hypermutation and broad dissemination of vaccine-elicited B cells in draining and non-draining lymphoid compartments, including the bone marrow, spleen and, most notably, periaortic lymph nodes. Phylogenetic analysis of spike-specific monoclonal antibody lineages identified through deep repertoire sequencing delineates extensive intra-clonal diversification that shaped neutralizing activity. Structural analysis of the spike in complex with a broadly neutralizing mAb provides a molecular basis for the observed differences in neutralization breadth between clonally related antibodies. Our findings highlight that immunization leads to extensive intra-clonal B cell evolution where members of the same lineage can both retain the original epitope specificity and evolve to recognize additional spike variants not previously encountered.

Background: Cystic, sporadic hemangioblastomas (HBLs) represent a unique, therapeutically challenging subset of central nervous system tumors, mainly due to their unpredictable growth patterns and potential for symptomatic progression. This study aims to explore the complexities surrounding the diagnosis, treatment, and long-term management of these lesions. Methods: A comprehensive literature review was performed, and a detailed case study of a 56-year-old patient with a cystic, sporadic cerebellar HBL was produced. Results: The case highlights the multiphasic growth pattern typical of cystic, sporadic HBLs, characterized by periods of dormancy and subsequent rapid expansion. An initial surgical intervention offered temporary control. Tumor recurrence, mainly through cystic enlargement, was treated by SRS. A subsequent recurrence, again caused by cystic growth, eventually led to the patient’s death. The intricacies of treatment modalities, focusing on the transition from surgical resection to stereotactic radiosurgery (SRS) upon recurrence, are discussed. Parameters indicating impending tumor growth, coupled with symptomatic advances, are also explored. Conclusions: The management of cystic, sporadic cerebellar HBLs requires a strategic approach that can be informed by radiological characteristics and tumoral behavior. This study underscores the importance of a proactive, individualized management plan and suggests guidelines that could inform clinical decision making.

Abstract The recent SarsCov2 pandemic has disrupted healthcare system notably impacting intensive care units (ICU). In severe cases, the immune system is dysregulated, associating signs of hyperinflammation and immunosuppression. In the present work, we investigated, using a joint modeling approach, whether the trajectories of cellular immunological parameters were associated with survival of COVID‐19 ICU patients. This study is based on the REA‐IMMUNO‐COVID cohort including 538 COVID‐19 patients admitted to ICU between March 2020 and May 2022. Measurements of monocyte HLA‐DR expression (mHLA‐DR), counts of neutrophils, of total lymphocytes, and of CD4+ and CD8+ subsets were performed five times during the first month after ICU admission. Univariate joint models combining survival at day 28 (D28), hospital discharge and longitudinal analysis of those biomarkers’ kinetics with mixed‐effects models were performed prior to the building of a multivariate joint model. We showed that a higher mHLA‐DR value was associated with a lower risk of death. Predicted mHLA‐DR nadir cutoff value that maximized the Youden index was 5414 Ab/C and led to an AUC = 0.70 confidence interval (95%CI) = [0.65; 0.75] regarding association with D28 mortality while dynamic predictions using mHLA‐DR kinetics until D7, D12 and D20 showed AUCs of 0.82 [0.77; 0.87], 0.81 [0.75; 0.87] and 0.84 [0.75; 0.93]. Therefore, the final joint model provided adequate discrimination performances at D28 after collection of biomarker samples until D7, which improved as more samples were collected. After severe COVID‐19, decreased mHLA‐DR expression is associated with a greater risk of death at D28 independently of usual clinical confounders.

Abstract Genetic support for a drug target has been shown to increase the probability of success in drug development, with the potential to reduce attrition in the pharmaceutical industry alongside discovering novel therapeutic targets. It is therefore important to maximise the detection of genetic associations that affect disease susceptibility. Conventional statistical methods such as genome-wide association studies (GWAS) only identify some of the genetic contribution to disease, so novel analytical approaches are required to extract additional insights. C4X Discovery has developed Taxonomy3, a unique method for analysing genetic datasets based on mathematics that is novel in drug discovery. When applied to a previously published rheumatoid arthritis GWAS dataset, Taxonomy3 identified many additional novel genetic signals associated with this autoimmune disease. Follow-up studies using tool compounds support the utility of the method in identifying novel biology and tractable drug targets with genetic support for further investigation.

Objective and Approach Understanding vaccine hesitancy among distinct communities is crucial to ensuring equitable uptake of vaccination. The objective was to examine the influence of psychological antecedents of vaccine uptake, known as the “5Cs”, on COVID-19 vaccination among Métis Nation of Ontario (MNO) citizens. The Métis people are one of three Indigenous peoples in Canada. A population-based online survey was implemented by the MNO, including the short version of the “5C” (confidence, complacency, constraint, calculation, collective responsibility) psychological antecedents of vaccination scale. Census sampling achieved a 39% response rate and respondents were linked to the COVID-19 vaccine database (COVAX) in Ontario (n=4,012). Analyses included logistic regression models (adjusted for sociodemographics) and exploratory latent class analyses. Results In logistic regression models, MNO citizens who were less confident that COVID-19 vaccines were safe (OR=0.04; 95% CI=0.03-0.06) and did not agree vaccination was a collective action to prevent the spread of disease (OR=0.11, 95% CI: 0.07-0.17) had lower odds of being vaccinated. MNO citizens who disagreed the risk of COVID-19 was small (OR=14.87, 95% CI: 9.99-22.13) had a higher odds of being vaccinated. Vaccine hesitancy profiles with (i) lower confidence in availability/safety of COVID-19 vaccines, (ii) lower perceptions about severity of COVID-19 and (iii) higher everyday life constraints/stressors were associated with lower vaccination rates (males, OR: 4.69; CI: 3.18–6.92; females, OR: 4.77, CI: 3.03–7.51) in latent class analyses. Conclusions and Implications Métis-specific analyses enabled a community-driven response, resulting in low vaccine hesitancy and high uptake.

Abstract Estimates of the energy potential of the different energy sources are essential for modelling energy systems. However, the potential of biomass is debatable due to the numerous dimensions and assumptions embedded. It is thus important to investigate further the final potential to understand their implications. Therefore, this study analyses European studies assessing biomass potential and proposes a critical discussion on the different results to converge to a realistic range of potentials for 2030. Biomass is divided into four categories: forestry products, agricultural residues, energy crops and other waste, each with sub-categories. Belgium is used as a case study to highlight the convergences and divergences of the studies. Having a national case study allows for more precise analyses through in-depth comparisons with national data and reports. The potential estimates are compared with the current production for each category in order to have a better view of the gap to be bridged. From these national perspectives, the European potential can be better apprehended. The results show that the realistic potentials for 2030 for Belgium and Europe are somewhat in the lower range of the estimates of the different studies: from 30 to 41 TWh and from 2000 to 2500 TWh, respectively. The forestry biomass is already well exploited with a slight potential increase, while the agricultural residues present the most significant potential increase. The realistic potential for energy crops in Belgium turned out to be close to the minimum estimates. Indeed, the implications of those crops are considerable regarding the agricultural structure and logistics. This article emphasises that no energy potential is neutral, as it involves a specific system in terms of agriculture, forestry or waste management, with broader social, economic or environmental implications. Consequently, using one estimate rather than another is not a trivial matter; it has an impact on the system being modelled from the outset.

The InBIO Barcoding Initiative (IBI) Dataset - DS-IBILP08 contains records of 2350 specimens of moths (Lepidoptera species that do not belong to the superfamily Papilionoidea). All specimens have been morphologically identified to species or subspecies level and represent 1158 species in total. The species of this dataset correspond to about 42% of mainland Portuguese Lepidoptera species. All specimens were collected in mainland Portugal between 2001 and 2022. All DNA extracts and over 96% of the specimens are deposited in the IBI collection at CIBIO, Research Center in Biodiversity and Genetic Resources.The authors enabled "The InBIO Barcoding Initiative Database: DNA barcodes of Portuguese moths" in order to release the majority of data of DNA barcodes of Portuguese moths within the InBIO Barcoding Initiative. This dataset increases the knowledge on the DNA barcodes of 1158 species from Portugal belonging to 51 families. There is an increase in DNA barcodes of 205% in Portuguese specimens publicly available. The dataset includes 61 new Barcode Index Numbers. All specimens have their DNA barcodes publicly accessible through BOLD online database and the distribution data can be accessed through the Global Biodiversity Information Facility (GBIF).

Abstract Background A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented. Results To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30–6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09–4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72–13.57), p = 0.001). Conclusions By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches.

Introduction: Acquired perforating dermatosis (APD) is a frequent disorder in hemodialysis patients and the effect on the quality of life is poorly described. We investigated the prevalence of APD in hemodialysis patients, measured and compared APD-associated quality of life. Methods: We developed a prospective, observational, and descriptive study. We invited patients over the age of 18 in hemodialysis. Data was obtained from their electronic file and a dermatological examination was performed. The Dermatology Life Quality Index (DLQI) was applied. Descriptive analysis of demographic variables, clinical features, and dermoscopy findings, as well as comparison of DLQI scores, was made. Results: The sample consisted of 46 patients, with a prevalence of APD of 11%. Patients with APD were leaner and younger compared to patients without APD. The time on hemodialysis was longer in patients with APD compared to those without APD, with a median of 90 versus 32 months (p = 0.015). The impact on quality of life was greater in patients with APD compared to those without APD, with some effect in all patients with APD and 33% in patients without APD (p = 0.001). Patients with APD had more frequent pruritus compared to those without APD (p = 0.007). Conclusions: Age, time on hemodialysis and BMI are associated with the presence of APD. Patients with APD had a higher prevalence of pruritus and a greater impact on quality of life in dermatology compared to patients without APD. Resumen: Introducción: La dermatosis perforante adquirida (DPA) es un trastorno frecuente en pacientes en hemodiálisis y el efecto en la calidad de vida está poco descrito. Investigamos la prevalencia de DPA en pacientes en hemodiálisis, medimos y comparamos la calidad de vida asociada a DPA. Métodos: Desarrollamos un estudio prospectivo, observacional y descriptivo. Invitamos a pacientes mayores de 18 años en hemodiálisis. Se obtuvieron datos de su expediente electrónico y se realizó exploración dermatológica. Se aplicó el Índice de Calidad de Vida en Dermatología (DLQI). Se hizo un análisis descriptivo de las variables demográficas, características clínicas y hallazgos de dermatoscopia, así como la comparación de los puntajes de DLQI. Resultados: La muestra fue de 46 pacientes, con una prevalencia de DPA del 11%. Los pacientes con DPA eran más delgados y jóvenes en comparación con los pacientes sin DPA. El tiempo en hemodiálisis fue mayor en los pacientes con DPA en comparación a los pacientes sin DPA, con una mediana de 90 versus 32 meses (p = 0,015). La afección en calidad de vida fue mayor en los pacientes con DPA en comparación a los pacientes sin DPA, con algún efecto en todos los pacientes con DPA y un 33% en los pacientes sin DPA (p = 0,001). Los pacientes con DPA tuvieron con más frecuencia prurito en comparación con los pacientes sin DPA (p = 0,007). Conclusiones: La edad, el tiempo en hemodiálisis y el IMC se asocian con la presencia de DPA. Pacientes con DPA tuvieron una prevalencia más alta de prurito y mayor afección en la calidad de vida en dermatología en comparación con pacientes sin DPA.

Abstract This paper describes the instrumentation and the first results of an upper atmospheric observing project conducted in New Zealand. We operate an all-sky aurora camera and a 64-Hz sampling induction magnetometer at Middlemarch, as well as 1-Hz sampling fluxgate magnetometers which have been operative at three stations in New Zealand, Middlemarch, Eyrewell and Te Wharau. Green and red auroras corresponding to the 557.7 nm and 630.0 nm emissions, respectively, were observed on the night of 5 August 2019. Pc1 pulsations were observed in the frequency range of ~ 0.2–1 Hz before and after a small (minimum Dst = − 40 nT) geomagnetic storm during 4–6 October 2020. Before the geomagnetic storm, Pc1 pulsations with several center frequencies were observed regardless of local time. During the recovery phase, an IPDP (interval of pulsations of diminishing period) type of Pc1 and four subsequent intervals of Pc1s were detected. The Ionospheric Alfvén Resonator (IAR) was also identified with spectral resonance structures during this magnetic storm. Lower harmonic modes of the IAR were present throughout the local nighttime, but higher harmonic modes with frequency of 5–15 Hz seemed to disappear at the onset time of substorms. This is the first report of the IAR at such a high frequency range and this is the first IAR observation in the southern hemisphere. Examples of applying cross-phase analysis to observation data of fluxgate magnetometers are also given. Graphical Abstract

Resumen: Introducción: La dermatosis perforante adquirida (DPA) es un trastorno frecuente en pacientes en hemodiálisis, y el efecto en la calidad de vida está poco descrito. Investigamos la prevalencia de DPA en pacientes en hemodiálisis, medimos y comparamos la calidad de vida asociada a DPA. Métodos: Desarrollamos un estudio prospectivo, observacional y descriptivo. Invitamos a pacientes mayores de 18 años en hemodiálisis. Se obtuvieron datos de su expediente electrónico, y se realizó exploración dermatológica. Se aplicó el Índice de Calidad de Vida en Dermatología (DLQI). Se hizo un análisis descriptivo de las variables demográficas, de las características clínicas y de los hallazgos de dermatoscopia, así como la comparación de los puntajes del DLQI. Resultados: La muestra fue de 46 pacientes, con una prevalencia de DPA del 11%. Los pacientes con DPA eran más delgados y jóvenes en comparación con los pacientes sin DPA. El tiempo en hemodiálisis fue mayor en los pacientes con DPA en comparación a los pacientes sin DPA, con una mediana de 90 versus 32 meses (p = 0,015). La afección en calidad de vida fue mayor en los pacientes con DPA en comparación a los pacientes sin DPA, con un algún efecto en todos los pacientes con DPA y un 33% en los pacientes sin DPA (p = 0,001). Los pacientes con DPA tuvieron con más frecuencia prurito en comparación con los pacientes sin DPA (p = 0,007). Conclusiones: La edad, el tiempo en hemodiálisis y el índice de masa corporal se asocian con la presencia de DPA. Los pacientes con DPA tuvieron una prevalencia más alta de prurito y mayor afección en la calidad de vida en dermatología en comparación con los pacientes sin DPA. Abstract: Introduction: Acquired perforating dermatosis (APD) is a frequent disorder in hemodialysis patients and the effect on the quality of life is poorly described. We investigated the prevalence of APD in hemodialysis patients, measured and compared APD-associated quality of life. Methods: We developed a prospective, observational, and descriptive study. We invited patients over the age of 18 in hemodialysis. Data was obtained from their electronic file and a dermatological examination was performed. The Dermatology Life Quality Index (DLQI) was applied. Descriptive analysis of demographic variables, clinical features, and dermoscopy findings, as well as comparison of DLQI scores, was made. Results: The sample consisted of 46 patients, with a prevalence of APD of 11%. Patients with APD were leaner and younger compared to patients without APD. The time on hemodialysis was longer in patients with APD compared to those without APD, with a median of 90 versus 32 months (P=.015). The impact on quality of life was greater in patients with APD compared to those without APD, with some effect in all patients with APD and 33% in patients without APD (P=.001). Patients with APD had more frequent pruritus compared to those without APD (P=.007). Conclusions: Age, time on hemodialysis and BMI are associated with the presence of APD. Patients with APD had a higher prevalence of pruritus and a greater impact on quality of life in dermatology compared to patients without APD.

IntroductionHistorically, low-and middle-income countries have been scarce producers of biomedical research; only 2% of the global scientific output is produced by these countries despite accounting for 92% of the global burden of disease. In addition, few low-and middle-income countries have exhaustively mapped and analyzed their scientific production in health and its association with main local burden of disease.ObjectiveTo evaluate the evolution of biomedical research in Ecuador over the last 100 years and its relationship with the main causes of mortality.MethodsA bibliometric study embedded in a systematic review design was carried out using biomedical publications indexed in Scopus and Web of Science (WoS) during the period 1920–2021. Information from the National Institute of Statistics and Census was used to identify the main causes of mortality.ResultsOur search strategy identified 16,697 publications related to biomedicine in Ecuador. Of these 3,225 articles met the criteria for this study. Since 2010, there has been an exponential increase in scientific production in biomedicine. This increase was predominantly based on cross-sectional observational studies (49.67%). During the period analyzed (1920–2021), biomedical production was distributed with 52.43% in clinical research, 37.79% in public health, and 9.77% in basic sciences. The research focus with the highest number of publications was epidemiology and surveillance system of diseases (23.44%). Additionally, private universities are the largest producers of biomedical research compared to public universities, 40.12% vs. 19.60%, respectively. Of the total biomedical research produced, 18.54% is associated with the main causes of mortality, and the Ecuadorian private university is the largest contributor to these studies compared to public universities, 39.97% vs. 16.72%.ConclusionIn one century, Ecuador produced 3,225 articles in biomedicine, according to our criteria. 18.54% of the total produced is aimed at solving the main causes of mortality in the country. Private universities are the leaders in scientific production related to health in Ecuador.

As we learn more about the multi-scale interstellar medium (ISM) of our Galaxy, we develop a greater understanding for the complex relationships between the large-scale diffuse gas and dust in Giant Molecular Clouds (GMCs), how it moves, how it is affected by the nearby massive stars, and which portions of those GMCs eventually collapse into star forming regions. The complex interactions of those gas, dust and stellar populations form what has come to be known as the ecology of our Galaxy. Because we are deeply embedded in the plane of our Galaxy, it takes up a significant fraction of the sky, with complex dust lanes scattered throughout the optically recognizable bands of the Milky Way. These bands become bright at (sub-)millimetre wavelengths, where we can study dust thermal emission and the chemical and kinematic signatures of the gas. To properly study such large-scale environments, requires deep, large area surveys that are not possible with current facilities. Moreover, where stars form, so too do planetary systems, growing from the dust and gas in circumstellar discs, to planets and planetesimal belts. Understanding the evolution of these belts requires deep imaging capable of studying belts around young stellar objects to Kuiper belt analogues around the nearest stars. Here we present a plan for observing the Galactic Plane and circumstellar environments to quantify the physical structure, the magnetic fields, the dynamics, chemistry, star formation, and planetary system evolution of the galaxy in which we live with AtLAST; a concept for a new, 50m single-dish sub-mm telescope with a large field of view which is the only type of facility that will allow us to observe our Galaxy deeply and widely enough to make a leap forward in our understanding of our local ecology.

Abstract The Energy Return On Investment (EROI) is a recognised indicator for assessing the relevance of an energy project in terms of net energy delivered to society. For woody biomass divergences remain on the right methodology to assess the EROI leading to large variations in the published estimates. This article presents an in‐depth discussion about the EROI of woody biomass in three different forms: woodchips, pellets and liquid fuels. The conceptualisation of EROI is further developed to reach a consistent definition for biomass post‐processed fuels. It considers, on top of the external energy investments, the grey energy associated with the energy used to enrich the fuel. With the proposed methodology, all woodchips have an EROI of the same order of magnitude, between 20 and 37, depending on forestry types, operations and machineries. For secondary residues, the first estimate is 170 if, as co‐products, no energy investment is allocated to the forestry operations and transport. On the basis of a mass allocation for forestry operations and transport, the EROI for secondary residues becomes of the same order of magnitude as that for wood chips. Woodchips can be further post‐processed into pellets or liquid fuels. Pellets have an EROI of 4–7 if the heat is externally supplied and 8–23 if internally supplied (self‐consumption of part of the raw material). Liquid fuels derived from primary wood and residues through gasification and Fischer‐Tropsch synthesis have an EROI between 4 and 16. Fuel enhancement with hydrogen (Power & Biomass to Liquids) impacts negatively the EROI due to the low EROI of hydrogen produced from renewable electricity. However, these fuels offer other advantages such as improved carbon efficiency. A correct estimate of EROI for forestry biomass, as proposed in this work, is a necessary dimension in assessing the suitability of a project.

Objetivo: Presentar una serie de casos de pacientes con fracturas cervicales de tipo “masa lateral flotante” con énfasis en describir el rol de la lesión discal en la potencial inestabilidad segmentaria. Materiales y Métodos: Se realizó un estudio descriptivo y retrospectivo de una serie de pacientes con fracturas facetarias de tipo “masa lateral flotante”, aisladas, diagnosticadas entre el 1 de enero de 2016 y el 1 de enero de 2022. Se incluyeron pacientes con lesiones de tipo “masa lateral flotante” según la clasificación AO, diagnosticadas por tomografía computarizada y, al menos, 6 meses de seguimiento. Se excluyó a aquellos con fracturas patológicas, lesiones por fragilidad ósea y registros incompletos. Resultados: Se analizó a 16 pacientes (media de la edad 42.86; DE 12,396), con predominio del sexo masculino (81,25%). El 68,75% tenía una lesión del disco intervertebral en el segmento fracturado y el 18,75%, anterolistesis. A 11 pacientes se les propuso un tratamiento conservador durante 12 semanas. La fractura consolidó en el 45,4% y 6 (54,6%) evolucionaron con traslación. El fracaso del tratamiento conservador se asoció con lesión del disco intervertebral. Once pacientes fueron operados, en su mayoría, con artrodesis cervical anterior monosegmentaria. Conclusiones: En esta serie de casos, la presencia de una lesión asociada del disco intervertebral fue más frecuente cuando el tratamiento conservador fracasó y cuando se decidió una artrodesis como tratamiento inicial. La mayoría de las cirugías se realizaron por vía anterior con discectomía y artrodesis cervical anterior en un único nivel, y se lograron buenos resultados.

Abstract Background Staining tissue samples to visualise cellular detail and tissue structure is at the core of pathology diagnosis, but variations in staining can result in significantly different appearances of the tissue sample. While the human visual system is adept at compensating for stain variation, with the growth of digital imaging in pathology, the impact of this variation can be more profound. Despite the ubiquity of haematoxylin and eosin staining in clinical practice worldwide, objective quantification is not yet available. We propose a method for quantitative haematoxylin and eosin stain assessment to facilitate quality assurance of histopathology staining, enabling truly quantitative quality control and improved standardisation. Methods The stain quantification method comprises conventional microscope slides with a stain-responsive biopolymer film affixed to one side, called stain assessment slides. The stain assessment slides were characterised with haematoxylin and eosin, and implemented in one clinical laboratory to quantify variation levels. Results Stain assessment slide stain uptake increased linearly with duration of haematoxylin and eosin staining (r = 0.99), and demonstrated linearly comparable staining to samples of human liver tissue (r values 0.98–0.99). Laboratory implementation of this technique quantified intra- and inter-instrument variation of staining instruments at one point in time and across a five-day period. Conclusion The proposed method has been shown to reliably quantify stain uptake, providing an effective laboratory quality control method for stain variation. This is especially important for whole slide imaging and the future development of artificial intelligence in digital pathology.

Abstract High-entropy alloy (HEA) nanoparticles (NPs) exhibit unusual combinations of functional properties. However, their scalable synthesis remains a significant challenge requiring extreme fabrication conditions. Metal salts are often employed as precursors because of their low decomposition temperatures, yet contain potential impurities. Here, we propose an ultrafast ( 5000 K) is employed for rapid heating/cooling (103 − 105 K s−1), and demonstrates the synthesis of CrFeCoNiMo HEA NPs ( ~ 50 nm) at a high rate approaching 35 g h−1 with a conversion efficiency of 42%. Our thermofluid simulation reveals that the properties of HEA NPs can be tailored by the plasma gas which affects the thermal history of NPs. The HEA NPs demonstrate an excellent light absorption of > 96% over a wide spectrum, representing great potential for photothermal conversion of solar energy at large scales. Our work shows that the thermal plasma process developed could provide a promising route towards industrial scale production of HEA NPs.

Abstract Background Inhaled sedation during invasive mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) has received increasing attention. However, inhaled sedation devices increase dead-space ventilation and an undesirable effect is the increase in minute ventilation needed to maintain CO2 removal. A consequence of raising minute ventilation is an increase in mechanical power (MP) that can promote lung injury. However, the effect of inhaled sedation devices on MP remains unknown. Methods We conducted a bench study to assess and compare the effects of three devices delivering inhaled sevoflurane currently available in ICU (AnaConDa-50 mL (ANA-50), AnaConDa-100 mL (ANA-100), and MIRUS) on MP by using a test lung model set with three compliances (20, 40, and 60 mL/cmH2O). We simulated lung-protective ventilation using a low tidal volume and two levels of positive end-expiratory pressure (5 and 15 cmH2O) under ambient temperature and dry conditions. Following the insertion of the devices, either the respiratory rate or tidal volume was increased in 15%-steps until end-tidal CO2 (EtCO2) returned to the baseline value. MP was calculated at baseline and after EtCO2 correction using a simplified equation. Results Following device insertion, the EtCO2 increase was significantly greater with MIRUS (+ 78 ± 13%) and ANA-100 (+ 100 ± 11%) than with ANA-50 (+ 49 ± 7%). After normalizing EtCO2 by adjusting minute ventilation, MP significantly increased by more than 50% with all inhaled sedation devices compared to controls. The lowest increase in MP was observed with ANA-50 (p 50% with all devices after normalizing EtCO2 by adjusting minute ventilation. Conclusion Inhaled sedation devices substantially increased MP in this bench model of protective ventilation, which might limit their benefits in ARDS.

Abstract Objectives The current literature provides limited guidance on the management of positive margins (PMs) following transoral laser microsurgery (TLM) for glottic squamous cell carcinoma (SCC). Long‐term data exploring the treatment of PMs with both initial observation and re‐resection are limited. Our objective was to determine the optimal treatment for PM patients following TLM for glottic SCC. Methods Clinical information on glottic SCC patients with PMs following treatment with TLM was prospectively collected at our institution from 2007 to 2018. We use a laryngeal template during the initial TLM where the area of resection is outlined for future reference. Data were compared with univariate analysis and survival plots were generated using the Kaplan–Meier method. Results A total of 29 patients with PMs were treated with either re‐resection (19 patients), close observation (6 patients), or adjuvant radiation alone (4 patients). Re‐resection patients had SCC or severe dysplasia on initial margin pathology and 23% with early‐stage disease had recurrence (T1–T2). Five (83%) patients who underwent close observation required re‐resection based on clinical suspicion of recurrence (confirmed on final pathology), which was significantly different from the re‐resection patients (p

Background: Bias, whether implicit (unconscious) or explicit (conscious), can lead to preferential treatment of specific social groups and antipathy towards others. When healthcare professionals (HCPs), including pharmacists, act on these biases, patient care and health outcomes can be adversely affected. This study aims to estimate implicit and explicit racial/ethnic bias towards Black and Arab people among community pharmacists in Ontario, Canada. Methods: Community pharmacists participated in a secure, web-based survey using a cross-sectional design that included Harvard’s Race and Arab Implicit Association Tests (IATs) to examine bias towards Black and Arab people. Explicit (stated) preferences were measured by self-report. Data were analyzed using descriptive and inferential statistics. Results: The study surveyed 407 community pharmacists, 56.1 % of whom were women with an average age of 46.9. Implicit Association Test (IAT) results showed a statistically significant moderate preference for white people over both Black (mean IAT = 0.41) and Arab people (mean IAT = 0.35). However, most pharmacists explicitly stated that they had no racial/ethnic preference, with 75.7 % expressing a neutral preference between Black and white and 66.6 % neutral between Arab and white. However, a slight preference for white individuals was observed. Demographic factors such as age, place of birth, race/ethnicity, and experience significantly impacted IAT scores. For example, older, Canadian-born, white pharmacists with more experience displayed higher implicit bias scores. A mild correlation was found between implicit and explicit bias, indicating as implicit bias increases, explicit bias tends to become more negative. Conclusions: This study is the first to explore the issue of pharmacist bias in Canada and concentrate on anti-Arab bias. Our findings reveal that Ontario community pharmacists tend to have an unconscious inclination towards white people, which calls for further understanding of this matter. Additionally, we discovered a moderate degree of anti-Arab bias, indicating that studies on other HCPs should consider bias against this social group. Educational interventions are needed to address the implicit biases among community pharmacists in Ontario, Canada. These findings should aim to raise self-awareness of biases, educate about the potential implications of these biases on patient care, and provide strategies to reduce bias.

The study of planets and small bodies within our Solar System is fundamental for understanding the formation and evolution of the Earth and other planets. Compositional and meteorological studies of the giant planets provide a foundation for understanding the nature of the most commonly observed exoplanets, while spectroscopic observations of the atmospheres of terrestrial planets, moons, and comets provide insights into the past and present-day habitability of planetary environments, and the availability of the chemical ingredients for life. While prior and existing (sub)millimeter observations have led to major advances in these areas, progress is hindered by limitations in the dynamic range, spatial and temporal coverage, as well as sensitivity of existing telescopes and interferometers. Here, we summarize some of the key planetary science use cases that factor into the design of the Atacama Large Aperture Submillimeter Telescope (AtLAST), a proposed 50-m class single dish facility: (1) to more fully characterize planetary wind fields and atmospheric thermal structures, (2) to measure the compositions of icy moon atmospheres and plumes, (3) to obtain detections of new, astrobiologically relevant gases and perform isotopic surveys of comets, and (4) to perform synergistic, temporally-resolved measurements in support of dedicated interplanetary space missions. The improved spatial coverage (several arcminutes), resolution (~ 1.2′′ − 12′′), bandwidth (several tens of GHz), dynamic range (~ 105) and sensitivity (~ 1 mK km s−1) required by these science cases would enable new insights into the chemistry and physics of planetary environments, the origins of prebiotic molecules and the habitability of planetary systems in general.

We present a genome assembly from an individual Notothenia rossii (the marbled rockcod; Chordata; Actinopterygii; Perciformes; Nototheniidae). The genome sequence is 1,042.9 megabases in span. Most of the assembly is scaffolded into 12 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 21.68 kilobases in length. Gene annotation of this assembly on Ensembl identified 24,432 protein coding genes.

Introduction There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk.Methods and analysis Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis.Ethics and dissemination The London—Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee.Trial registration number ISRCTN72104369.

Myoelectric prostheses have recently shown significant promise for restoring hand function in individuals with upper limb loss or deficiencies, driven by advances in machine learning and increasingly accessible bioelectrical signal acquisition devices. Here, we first introduce and validate a novel experimental paradigm using a virtual reality headset equipped with hand-tracking capabilities to facilitate the recordings of synchronized EMG signals and hand pose estimation. Using both the phasic and tonic EMG components of data acquired through the proposed paradigm, we compare hand gesture classification pipelines based on standard signal processing features, convolutional neural networks, and covariance matrices with Riemannian geometry computed from raw or xDAWN-filtered EMG signals. We demonstrate the performance of the latter for gesture classification using EMG signals. We further hypothesize that introducing physiological knowledge in machine learning models will enhance their performances, leading to better myoelectric prosthesis control. We demonstrate the potential of this approach by using the neurophysiological integration of the “move command" to better separate the phasic and tonic components of the EMG signals, significantly improving the performance of sustained posture recognition. These results pave the way for the development of new cutting-edge machine learning techniques, likely refined by neurophysiology, that will further improve the decoding of real-time natural gestures and, ultimately, the control of myoelectric prostheses.

Abstract Objective Millions of Americans are infected by influenza annually. A minority seek care in the emergency department (ED) and, of those, only a limited number experience severe disease or death. ED clinicians must distinguish those at risk for deterioration from those who can be safely discharged. Methods We developed random forest machine learning (ML) models to estimate needs for critical care within 24 h and inpatient care within 72 h in ED patients with influenza. Predictor data were limited to those recorded prior to ED disposition decision: demographics, ED complaint, medical problems, vital signs, supplemental oxygen use, and laboratory results. Our study population was comprised of adults diagnosed with influenza at one of five EDs in our university health system between January 1, 2017 and May 18, 2022; visits were divided into two cohorts to facilitate model development and validation. Prediction performance was assessed by the area under the receiver operating characteristic curve (AUC) and the Brier score. Results Among 8032 patients with laboratory‐confirmed influenza, incidence of critical care needs was 6.3% and incidence of inpatient care needs was 19.6%. The most common reasons for ED visit were symptoms of respiratory tract infection, fever, and shortness of breath. Model AUCs were 0.89 (95% CI 0.86–0.93) for prediction of critical care and 0.90 (95% CI 0.88–0.93) for inpatient care needs; Brier scores were 0.026 and 0.042, respectively. Importantpredictors included shortness of breath, increasing respiratory rate, and a high number of comorbid diseases. Conclusions ML methods can be used to accurately predict clinical deterioration in ED patients with influenza and have potential to support ED disposition decision‐making.

High-content imaging approaches, in combination with the use of perturbing agents such as small molecules or CRISPR-driven gene editing, have widely contributed to the identification of new therapeutic compounds. Thanks to recent advances in image-analysis methods, the use of high-content screens is increasingly gaining popularity and thus accelerating the discovery of new therapeutics. However, due to the lack of fully biocompatible fluorescent markers, large-scale high-content screens are mostly performed on fixed cells, which complicates the monitoring of changes in cell physiology over time.Here we present a novel fluorescent nontoxic dye that displays intensity and staining pattern changes in response to different physiological states. With multiparametric image analysis, these unique properties allow not only for the detection of distinct phenotypic fingerprints, but also for the quantification of more traditional disease-relevant phenotypes such as apoptosis, autophagy, ER stress and more. Since the dye only gets fluorescent when incorporated into cellular membranes, it is typically used without washing steps, therefore making it ideal to include in automation workflows. In this work, we present ​​relevant data on its biocompatibility and its potential to quantitatively assess subtle cellular phenotypes. Applications such as live kinetic imaging, and live image-based morphological profiling are also discussed. The rich information this fluorescent probe provides facilitates unbiased quantitative phenotypic analysis at larger scale, and ultimately paves the way for more discoveries of new therapeutic agents.

Summary: Background: Despite more than 50 years of research and parallel improvements in hepatology and oncology, there is still today neither a treatment to prevent disease progression in primary sclerosing cholangitis (PSC), nor reliable early diagnostic tools for the associated hepatobiliary cancers. Importantly, the limited understanding of the underlying biological mechanisms in PSC and its natural history not only affects the identification of new drug targets but implies a lack of surrogate markers that hampers the design of clinical trials and the evaluation of drug efficacy. The lack of easy access to large representative well-characterised prospective resources is an important contributing factor to the current situation. Methods: We here present the SUPRIM cohort, a national multicentre prospective longitudinal study of unselected PSC patients capturing the representative diversity of PSC phenotypes. We describe the 10-year effort of inclusion and follow-up, an intermediate analysis report including original results, and the associated research resource. All included patients gave written informed consent (recruitment: November 2011–April 2016). Findings: Out of 512 included patients, 452 patients completed the five-year follow-up without endpoint outcomes. Liver transplantation was performed in 54 patients (10%) and hepatobiliary malignancy was diagnosed in 15 patients (3%). We draw a comprehensive landscape of the multidimensional clinical and biological heterogeneity of PSC illustrating the diversity of PSC phenotypes. Performances of available predictive scores are compared and perspectives on the continuation of the SUPRIM cohort are provided. Interpretation: We envision the SUPRIM cohort as an open-access collaborative resource to accelerate the generation of new knowledge and independent validations of promising ones with the aim to uncover reliable diagnostics, prognostic tools, surrogate markers, and new treatment targets by 2040. Funding: This work was supported by the Swedish Cancer Society, Stockholm County Council, and the Cancer Research Funds of Radiumhemmet.

Desde a década de 1990, a pesca demersal do Sudeste e Sul do Brasil tem se diversificado, incorporando uma ampla gama de espécies de peixes e invertebrados existentes na Margem Meridional Brasileira. O processo de ordenamento dessa atividade, por outro lado, manteve-se focado em poucas espécies-alvo e nunca evoluiu para acomodar a diversificação de espécies e pescarias. Esse cenário permitiu o desenvolvimento de uma pescaria “multiespécies – multifrotas” submetida a pouco controle, que tem mantido os recursos pressionados e suscetíveis à sobrepesca e depleções localizadas. Entre 2018 e 2022, uma rede formada por 19 pesquisadores de 10 instituições de pesquisa se debruçou sobre os diversos aspectos desse cenário, identificando a premente demanda para reformar o modelo de gestão da pesca demersal no sentido de (a) abandonar o uso de espécies/estoques como alvo da gestão, e (b) aumentar a importância dada a elementos que evitem a degradação dos ecossistemas marinhos. Reunida no âmbito de uma chamada governamental que fomentou a pesquisa científica voltada à gestão pesqueira em todo o país, essa rede de pesquisadores desenvolveu as bases conceituais e empíricas para uma gestão pesqueira baseada em “unidades geográficas de gestão” e na implementação de um manejo pesqueiro “baseado no ecossistema”. Este ensaio descreve o processo de reflexão que motivou a proposta de reforma da gestão pesqueira demersal do Sudeste e Sul do Brasil, tendo, como fundamento, aspectos críticos e passíveis de mudança a partir da inserção do conhecimento científico e de experiências nacionais e internacionais.

El texto analiza la circulación, entre Italia y América Latina, de los debates en torno de la relación entre socialismo y democracia suscitados en el marco del gobierno de la Unidad Popular en Chile (1970-1973). Se analiza cómo las “lecciones de Chile” animaron el debate italiano de su tiempo y contribuyeron a configurar la estrategia eurocomunista adoptada por el Partido Comunista en los años 70. Asimismo, se indaga en el hecho de que una zona de la intelectualidad latinoamericana no registrara significativamente los dilemas de la experiencia chilena pero sí reservara atención privilegiada a esos mismos temas en su versión italiana.

Abstract Background Out-of-hospital cardiac arrest (OHCA) is a heterogeneous entity with multiple origins and prognoses. An early, reliable assessment of the prognosis is useful to adapt therapeutic strategy, tailor intensity of care, and inform relatives. We aimed primarily to undertake a prospective multicentric study to evaluate predictive performance of the Cardiac Arrest Prognosis (CAHP) Score as compare to historical dataset systematically collected after OHCA (Utstein style criteria). Our secondary aim was to evaluate other dedicated scores for predicting outcome after OHCA and to compare them to Utstein style criteria. Methods We prospectively collected data from 24 French and Belgium Intensive Care Units (ICUs) between August 2020 and June 2022. All cases of non-traumatic OHCA (cardiac and non-cardiac causes) patients with stable return of spontaneous circulation (ROSC) and comatose at ICU admission (defined by Glasgow coma score ≤ 8) on ICU admission were included. The primary outcome was the modified Rankin scale (mRS) at day 90 after cardiac arrest, assessed by phone interviews. A wide range of developed scores (CAHP, OHCA, CREST, C-Graph, TTM, CAST, NULL-PLEASE, and MIRACLE2) were included, and their accuracies in predicting poor outcome at 90 days after OHCA (defined as mRS ≥ 4) were determined using the area under the receiving operating characteristic curve (AUROC) and the calibration belt. Results During the study period, 907 patients were screened, and 658 were included in the study. Patients were predominantly male (72%), with a mean age of 61 ± 15, most having collapsed from a supposed cardiac cause (64%). The mortality rate at day 90 was 63% and unfavorable neurological outcomes were observed in 66%. The performance (AUROC) of Utstein criteria for poor outcome prediction was moderate at 0.79 [0.76–0.83], whereas AUROCs from other scores varied from 0.79 [0.75–0.83] to 0.88 [0.86–0.91]. For each score, the proportion of patients for whom individual values could not be calculated varied from 1.4% to 17.4%. Conclusions In patients admitted to ICUs after a successfully resuscitated OHCA, most of the scores available for the evaluation of the subsequent prognosis are more efficient than the usual Utstein criteria but calibration is unacceptable for some of them. Our results show that some scores (CAHP, sCAHP, mCAHP, OHCA, rCAST) have superior performance, and that their ease and speed of determination should encourage their use. Trial registration https://clinicaltrials.gov/ct2/show/NCT04167891

Abstract Electrocatalytic CO2 reduction into value-added multicarbon products offers a means to close the anthropogenic carbon cycle using renewable electricity. However, the unsatisfactory catalytic selectivity for multicarbon products severely hinders the practical application of this technology. In this paper, we report a cascade AgCu single-atom and nanoparticle electrocatalyst, in which Ag nanoparticles produce CO and AgCu single-atom alloys promote C-C coupling kinetics. As a result, a Faradaic efficiency (FE) of 94 ± 4% toward multicarbon products is achieved with the as-prepared AgCu single-atom and nanoparticle catalyst under ~720 mA cm−2 working current density at −0.65 V in a flow cell with alkaline electrolyte. Density functional theory calculations further demonstrate that the high multicarbon product selectivity results from cooperation between AgCu single-atom alloys and Ag nanoparticles, wherein the Ag single-atom doping of Cu nanoparticles increases the adsorption energy of *CO on Cu sites due to the asymmetric bonding of the Cu atom to the adjacent Ag atom with a compressive strain.

Abstract Objectives This release note describes the Maize GxE project datasets within the Genomes to Fields (G2F) Initiative. The Maize GxE project aims to understand genotype by environment (GxE) interactions and use the information collected to improve resource allocation efficiency and increase genotype predictability and stability, particularly in scenarios of variable environmental patterns. Hybrids and inbreds are evaluated across multiple environments and phenotypic, genotypic, environmental, and metadata information are made publicly available. Data description The datasets include phenotypic data of the hybrids and inbreds evaluated in 30 locations across the US and one location in Germany in 2020 and 2021, soil and climatic measurements and metadata information for all environments (combination of year and location), ReadMe, and description files for each data type. A set of common hybrids is present in each environment to connect with previous evaluations. Each environment had a collaborator responsible for collecting and submitting the data, the GxE coordination team combined all the collected information and removed obvious erroneous data. Collaborators received the combined data to use, verify and declare that the data generated in their own environments was accurate. Combined data is released to the public with minimal filtering to maintain fidelity to the original data.

The Pfizer-BioNTech vaccine was one of the essential tools in curtailing the COVID-19 pandemic. Unlike conventional vaccines, this newly approved mRNA vaccine is taken up by cells, which leads to the synthesis of the specific viral Spike antigen. The vaccine was initially introduced for adults, and the immunological profile of adult recipients is well-characterized. The vaccine was approved for paediatric use much later after its efficacy and safety had been confirmed in children. However, the complete picture of how the paediatric immune system in children reacts to the vaccine is not well documented. Therefore, in order to better understand the immune response in children, we analysed the humoral response, immune cell count, and interferon signalling in paediatric vaccine recipients ranging between 5 and 17 years of age. Our findings suggest that the paediatric recipients elicit a robust humoral response that is sustained for at least three months. We also found that the vaccine triggered a transient lymphocytopenia similar to that observed during viral infection. Interestingly, we also found that the vaccine may sensitise the interferon signalling pathway, priming the cells to mount a potent response when exposed to interferons during a subsequent infection. The study offers new insights into the workings of the paediatric immune system and innate immunity, thereby opening the doors for further research in this field.

Abstract The research focused on digital learning environments has identified various challenges for learners, such as technical problems, lack of community, motivation, self-regulation, self-efficacy, and social anxiety. Social anxiety is conceptualized as an emotional disorder that may impede achievement in higher education. The project reported here investigates N = 666 students' social anxiety in digital learning environments at four higher education institutions located in Australia, Germany, Latvia, and Turkey. This range of contexts allowed the research to cover a wide variety of cultural and institutional idiosyncrasies. Findings revealed different levels of social anxiety in higher education digital learning environments across countries and their cultural contexts. In addition, gender plays a significant role in social anxiety for peer interactions with female students reporting higher social anxiety than male students. The findings suggest that it is worth tertiary educators pausing to consider social anxiety's role in reducing interactions within digital learning environments. Additional research is required to establish the causes of social anxiety in digital learning environments and, as a result, to develop strategies to minimise its effect. Graphical Abstract

Abstract Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) induces higher levels of RABV-G specific plasmablasts and T cells in blood, and plasma cells in the bone marrow compared to two doses of Rabipur in non-human primates. The mRNA vaccine also generates higher RABV-G binding and neutralizing antibody titers than Rabipur, while the degree of somatic hypermutation and clonal diversity of the response are similar for the two vaccines. The higher overall antibody titers induced by the mRNA vaccine translates into improved cross-neutralization of related lyssavirus strains, suggesting that this platform has potential for the development of a broadly protective vaccine against these viruses.

Abstract Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries. The evolution and geographical distribution of S. Concord remained unclear. Here, we provide a genomic overview of the population structure and antimicrobial resistance (AMR) of S. Concord by analysing genomes from 284 historical and contemporary isolates obtained between 1944 and 2022 across the globe. We demonstrate that S. Concord is a polyphyletic serovar distributed among three Salmonella super-lineages. Super-lineage A is composed of eight S. Concord lineages, of which four are associated with multiple countries and low levels of AMR. Other lineages are restricted to Ethiopia and horizontally acquired resistance to most antimicrobials used for treating invasive Salmonella infections in low- and middle-income countries. By reconstructing complete genomes for 10 representative strains, we demonstrate the presence of AMR markers integrated in structurally diverse IncHI2 and IncA/C2 plasmids, and/or the chromosome. Molecular surveillance of pathogens such as S. Concord supports the understanding of AMR and the multi-sector response to the global AMR threat. This study provides a comprehensive baseline data set essential for future molecular surveillance.

IntroductionAnalysis of an individual’s immunoglobulin (IG) gene repertoire requires the use of high-quality germline gene reference sets. When sets only contain alleles supported by strong evidence, AIRR sequencing (AIRR-seq) data analysis is more accurate and studies of the evolution of IG genes, their allelic variants and the expressed immune repertoire is therefore facilitated.MethodsThe Adaptive Immune Receptor Repertoire Community (AIRR-C) IG Reference Sets have been developed by including only human IG heavy and light chain alleles that have been confirmed by evidence from multiple high-quality sources. To further improve AIRR-seq analysis, some alleles have been extended to deal with short 3’ or 5’ truncations that can lead them to be overlooked by alignment utilities. To avoid other challenges for analysis programs, exact paralogs (e.g. IGHV1-69*01 and IGHV1-69D*01) are only represented once in each set, though alternative sequence names are noted in accompanying metadata.Results and discussionThe Reference Sets include less than half the previously recognised IG alleles (e.g. just 198 IGHV sequences), and also include a number of novel alleles: 8 IGHV alleles, 2 IGKV alleles and 5 IGLV alleles. Despite their smaller sizes, erroneous calls were eliminated, and excellent coverage was achieved when a set of repertoires comprising over 4 million V(D)J rearrangements from 99 individuals were analyzed using the Sets. The version-tracked AIRR-C IG Reference Sets are freely available at the OGRDB website (https://ogrdb.airr-community.org/germline_sets/Human) and will be regularly updated to include newly observed and previously reported sequences that can be confirmed by new high-quality data.

Abstract Objectives The caecum bridges the small and large intestine and plays a front‐line role in discriminating gastrointestinal antigens. Although dysregulated in acute and chronic conditions, the tissue is often overlooked immunologically. Methods To address this issue, we applied single‐cell transcriptomic‐V(D)J sequencing to FACS‐isolated CD45+ caecal patch/lamina propria leukocytes from a healthy (5‐year‐old) female rhesus macaque ex vivo and coupled these data to VDJ deep sequencing reads from haematopoietic tissues. Results We found caecal NK cells and ILC3s to co‐exist with a spectrum of effector T cells partially derived from SOX4+ recent thymic emigrants. Tolerogenic Vγ8Vδ1‐T cells, plastic CD4+ T helper cells and GZMK+EOMES+ and TMIGD2+ tissue‐resident memory CD8+ T cells were present and differed metabolically. An IL13+GATA3+ Th2 subset expressing eicosanoid pathway enzymes was accompanied by IL1RL1+GATA3+ regulatory T cells and a minor proportion of IgE+ plasma cells (PCs), illustrating tightly regulated type 2 immunity devoid of ILC2s. In terms of B lymphocyte lineages, caecal patch antigen‐presenting memory B cells sat alongside germinal centre cells undergoing somatic hypermutation and differentiation into IGF1+ PCs. Prototypic gene expression signatures decreased across PC clusters, and notably, expanded IgA clonotypes could be traced in VDJ deep sequencing reads from additional compartments, including the bone marrow, supporting that these cells contribute a steady stream of systemic antibodies. Conclusions The data advance our understanding of caecal immunological function, revealing processes involved in barrier maintenance and molecular networks relevant to disease.

ObjectivesLeft atrial appendage occlusion during cardiac surgery is a therapeutic option for stroke prevention in patients with atrial fibrillation. The effectiveness and safety of left atrial appendage occlusion have been evaluated in several studies, including the LAAOS-III trial. While these studies have demonstrated efficacy and safety, the long-term economic impact of this surgical technique has not yet been assessed. Here, we aimed to evaluate the cost-effectiveness and cost-utility of left atrial appendage occlusion during cardiac surgery over a long-term time horizon.MethodsOur study was based on a model representing an hypothetical cohort with the same characteristics as LAAOS-III trial patients. We modelled the incidence of ischemic strokes and systemic embolisms in each intervention arm: "occlusion" and "no-occlusion," using a one-month cycle length with a 20-year time horizon. Regarding occlusion devices, sutures, staples, or an approved surgical occlusion device (AtriClip™-AtriCure, Ohio, USA) could be used.ResultsOur model generated an average cost savings of 607 euros per patient and an incremental gain of 0.062 quality-adjusted life years (QALYs), resulting an incremental cost-utility ratio (ICUR) of €-9,775/QALY. The scenario analysis in which occlusion was systematically performed using the AtriClip™ device generated an ICUR of €3,952/QALY gained.ConclusionsIn the base-case analysis, the strategy proved to be more effective and less costly, confirming left atrial appendage occlusion during cardiac surgery as an economically dominant strategy. The scenario analysis also appeared cost-effective, although it did not result in cost savings. This study provides a new perspective on the assessment of the cost-effectiveness of these techniques.

BackgroundAnomalous origin of the middle meningeal artery (MMA) from the basilar artery is a rare congenital neurological variant that has been detected in both children and adults with diagnoses ranging from intracranial haemorrhage to ependymoma. This review aims to investigate the anatomical course of an anomalous basilar-middle meningeal artery and its clinical presentation.MethodsA systematic search was performed in PubMed using the keywords (middle meningeal artery) and (basilar artery). Ninety-four papers were identified, of which seven were included. One paper was further identified through cross-referencing.ResultsThe average age of presentation was 43 years with a male predominance (7/9). In most cases, the MMA arose between the superior cerebellar artery and the anterior inferior cerebellar artery (8/9) (versus 1 case between the anterior inferior cerebellar artery and the posterior inferior cerebellar artery). The anomaly mostly presented on the left side (6/11), but was bilateral in one case. Most of the cases showed a pontine artery branching from the basilar artery arising 5 mm to 10 mm proximal to the superior cerebellar artery, which would then assume the trajectory of the MMA. In three cases, the vessel increased in calibre near the trigeminal ganglion. Foramen spinosum absence in the anomalous side was noted in 3/6 of the patients.ConclusionTo avoid unexpected complications during neurosurgical and neuroradiointerventional procedures, it is essential to have a clear understanding of the anomalous routes of the MMA. This is especially important when it proves to be the only available route for embolization.

Background: People living in Australian cities face increased mortality risks from exposure to extreme air pollution events due to bushfires and dust storms. However, the burden of mortality attributable to exceptional PM2.5 levels has not been well characterised. We assessed the burden of mortality due to PM2.5 pollution events in Australian capital cities between 2001 and 2020. Methods: For this health impact assessment, we obtained data on daily counts of deaths for all non-accidental causes and ages from the Australian National Vital Statistics Register. Daily concentrations of PM2.5 were estimated at a 5 km grid cell, using a Random Forest statistical model of data from air pollution monitoring sites combined with a range of satellite and land use-related data. We calculated the exceptional PM2.5 levels for each extreme pollution exposure day using the deviation from a seasonal and trend loess decomposition model. The burden of mortality was examined using a relative risk concentration-response function suggested in the literature. Findings: Over the 20-year study period, we estimated 1454 (95 % CI 987, 1920) deaths in the major Australian cities attributable to exceptional PM2.5 exposure levels. The mortality burden due to PM2.5 exposure on extreme pollution days was considerable. Variations were observed across Australia. Despite relatively low daily PM2.5 levels compared to global averages, all Australian cities have extreme pollution exposure days, with PM2.5 concentrations exceeding the World Health Organisation Air Quality Guideline standard for 24-h exposure. Our analysis results indicate that nearly one-third of deaths from extreme air pollution exposure can be prevented with a 5 % reduction in PM2.5 levels on days with exceptional pollution. Interpretation: Exposure to exceptional PM2.5 events was associated with an increased mortality burden in Australia's cities. Policies and coordinated action are needed to manage the health risks of extreme air pollution events due to bushfires and dust storms under climate change.

The introduction of artificial intelligence (AI) challenges much of our traditional understanding of military ethics. What virtues and what sort of ethics education are needed as we move into an ever more AI-driven military reality? In this article we suggest and discuss key virtues that are needed, including the virtue of prudence and the accompanying virtue of good and proper storytelling. We also reflect on the ideal of “explainable AI,” and philosophize about the role of fear in helping us understand what is actually at stake in a military infused with AI-enabled and AI-driven weapons.

Abstract Background In March 2022, an outbreak investigation was initiated in Ireland after identifying a cluster of monophasic Salmonella Typhimurium cases, affecting primarily small children. Microbiological investigations revealed that the cluster was part of a wider international outbreak. Methods A total of 18 Irish outbreak cases were identified. We undertook a matched case–control study using the case–case method to determine if exposure to the implicated products was associated with illness. Results In univariable analysis, the highest odds of disease due to monophasic S. Typhimurium versus other gastrointestinal disease were obtained for a chocolate Product A of Brand A [matched odds ratio (mOR) = 7.77, 95% confidence intervals (CI): 0.89–67.20]. When grouping the implicated products in a composite variable, the odds of disease due to monophasic S. Typhimurium versus other gastrointestinal disease were 10.5 times higher with a consumption of at least one of the implicated products [mOR = 10.50, 95% CI: 1.24–88.60, p = 0.031]. Conclusion This analytical study supported the internationally generated hypothesis which led to the implementation of control measures. Owing to the high levels of chocolate purchasing with Easter approaching, early outbreak identification and involvement in the internationally coordinated investigation was essential to an efficient response and to minimise the risk of further harm to a particularly vulnerable population group.

Ultrasonography is an excellent investigative tool that can assist with the diagnosis of soft tissue conditions. In human medicine, ultrasonography is a fundamental diagnostic tool for the investigation of suspected vegetal foreign bodies (VFB), with protocol-based ultrasonography providing increased accuracy compared to lesion-focused examinations. Protocol-based ultrasonography is an emerging tool within the veterinary field, however, compared to human medicine is not routinely employed. The objective of this study was to develop a systematic ultrasound protocol to examine the distal limb for the visualization of vegetal foreign bodies (SUEDVEG). A 12 MHz linear and an 18 MHz high-frequency small-footprint linear array transducer was used on cadaver forelimbs (n = 6) and hindlimbs (n = 6) with images obtained from three common foreign body locations within the distal limb; 1; the interdigital webbing, 2; the palmar/plantar aspect of the phalanges and metacarpus and 3; the dorsal region of the phalanges and metacarpus. From these images, a 13-step systematic musculoskeletal protocol was developed and utilized on eight clinical cases or 10 limbs that had signs typical of distal limb VFB to preliminarily validate the proposed method. Vegetal foreign bodies were successfully identified and retrieved in seven (n = 8) clinical cases with method steps 9 and 11 (orthogonal views) identifying the majority of VFBs. The described ultrasound method appears highly useful for visualizing soft tissue locations of the canine distal limb known for tracking foreign bodies. Further studies are required to validate the described systematic examination method as the preferred clinical protocol over currently used lesion-focused exploration techniques.

This paper focuses on the experiences of Indigenous learners at Athabasca University. Having access to online education provided a sense of normalcy for students during the global pandemic while many post-secondary institutions and Indigenous communities were closed. The purpose of the research was two-fold: a) to determine the dynamics of reaching Indigenous learners and measuring their adaptability in learning during the COVID-19 pandemic, and b) to understand the effects of the pandemic on the mind, body, spirit, and social environment of Indigenous distance education learners and their families. This research included qualitative and quantitative methods, specifically, a survey, focus group, and individual interviews. We share the results of online research involving Indigenous students during the first and second waves of the COVID-19 pandemic. We concluded that listening to Indigenous students supported their online education while giving them an outlet to express their experiences. This research identified Indigenous student adaptations towards their spirituality in specific ways inherent to their culture given the reactions to COVID-19, their responses, and reflections.

Cervical cancer is one of the most common types of cancer among women and is largely preventable with regular screening using Papanicolau (Pap) tests. In Canada, all provinces have regular screening programs, although with slightly differing recommendations. Previous research has found that immigrant women, who are a large proportion of the Canadian population, are at higher risk of being under-screened, or non-adherent to the recommended screening frequency.Using data from the 2017 Canadian Community Health Survey, this study examined: (1) the extent to which immigration status and time since immigration are associated with Pap test adherence in Ontario, and (2) predictors of Pap test adherence for immigrants and Canadian born populations in Ontario, Canada’s most populous province, with a focus on the role of racial or ethnic identity among immigrants. Estimates of 3-year test adherence were 71.3 % (95 %CI: 66.9–75.7) among immigrant women and 75.4 % (95 %CI: 73.1–77.1) among non-immigrant women. Recent immigrants (6–10 years in Canada) had lower adherence (63.5 %, 95 %CI: 48.0–80.0). Logistic regression models found that immigrant women had lower adherence than Canadian-born women, controlling for age, household income, education, and having a primary care physician. Subgroup analysis found that South Asian immigrant women were least likely to be adherent.These results support targeted programming to increase screening adherence among recent immigrants and raise concerns regarding potential barriers to screening. Data that allow better disaggregation of racial and ethnic identities are important for better understanding the potential implications of these patterns for racial inequities in health.

We report the case of a 30-year-old female patient with sickle cell disease presenting with an acute chest syndrome and neurological deterioration. Cerebral magnetic resonance imaging revealed a handful of foci of diffusion restriction and numerous microbleeds with marked involvement of corpus callosum and subcortical white matter, with relative sparing of the cortex and deep white matter. Corpus callosum-predominant and juxtacortical microbleeds have been typically documented in cerebral fat embolism syndrome, but also in the so-called “critical-illness-associated cerebral microbleeds”, a recently described entity associated with respiratory failure. We discussed whether these 2 entities may coexist.