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Abstract Molybdoenzymes are essential in global nitrogen, carbon, and sulfur cycling. To date, the only known bioavailable source of molybdenum (Mo) is molybdate. However, in the sulfidic and anoxic (euxinic) habitats that predominate in modern subsurface environments and that were pervasive prior to Earth’s widespread oxygenation, Mo occurs as soluble tetrathiomolybdate ion and molybdenite mineral that is not known to be bioavailable. This presents a paradox for how organisms obtain Mo to support molybdoenzymes in these environments. Here, we show that tetrathiomolybdate and molybdenite sustain the high Mo demand of a model anaerobic methanogen, Methanococcus maripaludis, grown via Mo-dependent formate dehydrogenase, formylmethanofuran dehydrogenase, and nitrogenase. Cells grown with tetrathiomolybdate and molybdenite have similar growth kinetics, Mo content, and transcript levels of proteins involved in Mo transport and cofactor biosynthesis when compared to those grown with molybdate, implying similar mechanisms of transport and cofactor biosynthesis. These results help to reconcile the paradox of how Mo is acquired in modern and ancient anaerobes and provide new insight into how molybdoenzymes could have evolved prior to Earth’s oxygenation.

Abstract Background Vancomycin is a commonly prescribed antibiotic to treat serious Gram-positive infections in children. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration–time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. In most countries, steady-state plasma concentrations are used as a surrogate parameter for this target AUC/MIC, but this practice has some drawbacks. Hence, AUC-based dosing using model-informed precision dosing (MIPD) tools has been proposed for increasing the target attainment rate and reducing vancomycin-related nephrotoxicity. Solid scientific evidence for these claimed benefits is lacking in children. This randomized controlled trial aims to investigate the large-scale utility of MIPD dosing of vancomycin in critically ill children. Methods Participants from 14 neonatal intensive care, pediatric intensive care, and pediatric hemo-oncology ward units from 7 hospitals are randomly allocated to the intervention or standard-of-care comparator group. In the intervention group, a MIPD dosing calculator is used for AUC-based dosing, in combination with extra sampling for therapeutic drug monitoring in the first hours of treatment, as compared to standard-of-care. An AUC24h between 400 and 600 is targeted, assuming an MIC of 1 mg/L. Patients in the comparator group receive standard-of-care dosing and monitoring according to institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400–600 between 24 and 48 h after the start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury during vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400–600 between 48 and 72 h after the start of vancomycin treatment, time to clinical cure, ward unit length-of-stay, hospital length-of-stay, and 30-day all-cause mortality. Discussion This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children. Trial registration Eudract number: 2019–004538-40. Registered on 2020–09-08 ClinicalTrials.gov NCT046666948. Registered on 2020–11-28

IntroductionThis study evaluated the effect of the COVID-19 pandemic on temporal trends in mental health and addiction–related inpatient hospitalization rates among youth (aged 10–17 years) in Canadian provinces and territories (excluding Quebec) from 1 April 2018 to 5 March 2022. MethodsWe conducted an interrupted time series analysis across three periods: T0 (pre-pandemic: 1 April 2018 to 15 March 2020); T1 (early pandemic: 15 March 2020 to 5 July 2020); and T2 (later pandemic: 6 July 2020 to 5 March 2022). ResultsPre-pandemic mental health and addiction–related hospitalization rates had significant regional variability, with weekly rates from 6.27 to 85.59 events per 100 000 persons in Manitoba and the territories combined, respectively. During T1, the national (excluding Quebec) weekly hospitalization rate decreased from a pre-pandemic level of 12.82 (95% CI: 12.14 to 13.50) to 5.11 (95% CI: 3.80 to 6.41) events per 100 000 persons. There was no statistically significant change in the mental health and addiction– related hospitalization rate across provinces and territories in T2 compared to T0. However, there was a significant increase in the rate of self-harm–related hospitalizations among females Canada-wide and in most provinces during this period. ConclusionAlthough several Canadian studies have reported increases in mental health and addiction–related outpatient and emergency department visits among youth during the COVID-19 pandemic, this did not correspond to an increase in the inpatient hospital burden, with the notable exception of self-harm among young females.

IntroductionCette étude a évalué l’effet de la pandémie de COVID-19 sur l’évolution des taux d’hospitalisation pour des raisons de santé mentale ou de dépendance chez les jeunes (de 10 à 17 ans) dans les provinces et territoires du Canada (à l’exception du Québec) entre le 1er avril 2018 et le 5 mars 2022. MéthodologieNous avons effectué une analyse de séries chronologiques interrompues sur trois périodes : T0 (avant la pandémie : du 1er avril 2018 au 15 mars 2020), T1 (début de la pandémie : du 15 mars 2020 au 5 juillet 2020) et T2 (fin de la pandémie : du 6 juillet 2020 au 5 mars 2022). RésultatsAvant la pandémie, les taux d’hospitalisation pour des raisons de santé mentale ou de dépendance étaient très variables d’une région à l’autre, avec des taux hebdomadaires allant de 6,27 événements pour 100 000 personnes (Manitoba) à 85,59 événements pour 100 000 personnes (trois territoires). Au cours de la période T1, le taux d’hospitalisation hebdomadaire à l’échelle nationale (à l’exception du Québec) est passé de 12,82 événements pour 100 000 personnes avant la pandémie (IC à 95 % : 12,14 à 13,50) à 5,11 événements pour 100 000 personnes (IC à 95 % : 3,80 à 6,41). Il n’y a pas eu de changement statistiquement significatif du taux d’hospitalisation pour des raisons de santé mentale ou de dépendance dans les provinces et les territoires pour la période T2 par rapport à la période T0. Cependant, le taux d’hospitalisation pour automutilation a augmenté de façon considérable chez les filles dans l’ensemble du Canada et dans la plupart des provinces au cours de cette période. ConclusionBien que plusieurs études canadiennes aient fait état d’une augmentation du nombre de consultations externes et de consultations aux urgences pour des raisons de santé mentale ou de dépendance chez les jeunes pendant la pandémie de COVID-19, cette hausse ne s’est pas traduite par une augmentation du nombre de patients hospitalisés, à l’exception notable des cas d’automutilation chez les filles.

Abstract Background The intensive use of social media among adolescents has caused concern about its impact on their mental health, but studies show that social media use is linked to both better and worse mental health. These seemingly contradictory findings may result from the diverse motivations, interactions, and experiences related to social media use, and studies investigating specific facets of social media use in relation to mental health and well-being, beyond general usage metrics, have been called for. Aspects of self-presentation on social media, such as feedback-seeking and upwards social comparison have been linked to worse mental health, however, there is a need for more studies exploring the relationship between self-presentation on social media and adolescent mental health over time. Aim The aim of this study was to explore the cross-sectional and longitudinal relationship between aspects of self-presentation and depression, anxiety, and well-being among adolescents. Methods This study utilised both cross-sectional and longitudinal datasets from the LifeOnSoMe-study, comprising 3,424 and 439 participants, respectively (OSF preregistration https://doi.org/10.17605/OSF.IO/BVPS8 ). Latent Class Analysis (LCA) was used to identify similar response patterns within the Self-Presentation and Upwards Social Comparison Inclination Scale (SPAUSCIS). Regression models and first differencing methods were applied to evaluate the cross-sectional and longitudinal associations between focus on self-presentation and mental health and well-being among adolescents. Results A strong emphasis on self-presentation was linked to increased levels of depression and anxiety in both males and females, and reduced well-being in females when compared to those with lower or intermediate self-presentation focus. The effect sizes ranged from small to medium. Furthermore, an escalation in self-presentation focus over time was associated with a slight increase in symptoms of anxiety and depression; however, the association with well-being did not reach statistical significance. Conclusion The results of the present study suggest that a heightened focus on self-presentation, which includes behaviours such as seeking feedback, employing strategic self-presentation tactics, and engaging in upward social comparisons, is associated with an elevated risk of reduced mental health.

Abstract Background A high burden of respiratory pathogens colonizing removable prosthesis surfaces suggests the potential of association between removable prosthesis-wearing and respiratory infections. Therefore, this systematic review and meta-analysis aimed to evaluate the evidence from clinical studies concerning the association between removable prosthesis-wearing and respiratory infections. Methods Clinical studies that reported respiratory infections associated with adult patients wearing removable prostheses in any centers (hospitals and nursing homes) or communities were included. Literature was searched across five electronic databases (MEDLINE, Cochrane Library, EMBASE, Web of Science, and Scopus) to 28 May 2024. An additional search was performed for unpublished trials and references cited in related studies. The Newcastle-Ottawa Scale was employed for the quality assessment. The certainty assessment was established using GRADE. The results were pooled using a frequentist random-effects meta-analysis and the odds ratios generated. Results A total of 1143 articles were identified. Thirteen articles had full-text articles screening and an additional two articles were added through reference linkage. Ultimately, six non-randomized clinical studies reporting various types of pneumonia contributed to this review. Overall odds of having pneumonia among prosthesis wearers were 1.43 (95% CI: 0.76 to 2.69) and 1.27 (95% CI: 1.11 to 1.46) using the random- and fixed-effects models, respectively. The heterogeneity in the meta-analysis was substantial. In subgroup analysis according to the study design, the heterogeneity within prospective studies was much reduced, I2 = 0% (p = 0.355). The certainty of the evidence evaluated using the GRADE approach was low to very low evidence for prosthesis wearers developing pneumonia based on studies. Conclusions There was no conclusive evidence from the non-randomized clinical studies supporting whether prosthesis-wearing is a risk factor for pneumonia based on outcomes from this review.

Abstract Background Examining support for substance use policies, including those for harm reduction, among the general public and policy influencers is a fundamental step to map the current policy landscape and leverage policy opportunities. Yet, this is a knowledge gap in Canada. Our paper identifies the level of support for substance use policies in two provinces in Canada and describes how the level of support is associated with intrusiveness and sociodemographic variables. Methods Data came from the 2019 Chronic Disease Prevention Survey. The representative sample included members of the general public (Alberta n = 1648, Manitoba n = 1770) as well as policy influencers (Alberta n = 204, Manitoba n = 98). We measured the level of support for 22 public policies concerning substance use through a 4-point Likert-scale. The Nuffield Council on Bioethics Intervention Ladder framework was applied to assess intrusiveness. We used cumulative link models to run ordinal regressions for identification of explanatory sociodemographic variables. Results Overall, there was generally strong support for the policies assessed. The general public in Manitoba was significantly more supportive of policies than its Alberta counterpart. Some differences were found between provinces and samples. For certain substance use policies, there was stronger support among women than men and among those with higher education than those with less education. Conclusions The results highlight areas where efforts are needed to increase support from both policy influencers and general public for adoption, implementation, and scaling of substance use policies. Socio-demographic variables related to support for substance use policies may be useful in informing strategies such as knowledge mobilization to advance the policy landscape in Western Canada.

Abstract Dual emission from thermally activated delayed fluorescence (TADF) emitters is often difficult to observe, especially in solution, limited by Kasha’s rule. Two TADF dendrimers containing N-doped polycyclic aromatic hydrocarbons as acceptors are designed and synthesized. Compound 2GCzBPN, having a strongly twisted geometry, exhibits TADF, while 2GCzBPPZ, possessing a less twisted geometry, shows dual emission associated with the monomer and aggregate that is TADF. The demonstration reveals that 2GCzBPPZ can serve as a temperature sensor with excellent temperature sensitivity and remarkably wide emission color response in solution. By embedding 2GCzBPPZ in paraffin we demonstrate a spatial-temperature sensor that shows a noticeable emission shift from yellow to green and ultimately to blue as the temperature increases from 20 to 200 °C. We finally demonstrate the utility of these TADF dendrimers in solution-processed organic light-emitting diodes.

Abstract The geosphere and the microbial biosphere have co-evolved for ~3.8 Ga, with many lines of evidence suggesting a hydrothermal habitat for life’s origin. However, the extent that contemporary thermophiles and their hydrothermal habitats reflect those that likely existed on early Earth remains unknown. To address this knowledge gap, 64 geochemical analytes were measured and 1022 metagenome-assembled-genomes (MAGs) were generated from 34 chemosynthetic high-temperature springs in Yellowstone National Park and analysed alongside 444 MAGs from 35 published metagenomes. We used these data to evaluate co-variation in MAG taxonomy, metabolism, and phylogeny as a function of hot spring geochemistry. We found that cohorts of MAGs and their functions are discretely distributed across pH gradients that reflect different geochemical provinces. Acidic or circumneutral/alkaline springs harbor MAGs that branched later and are enriched in sulfur- and arsenic-based O2-dependent metabolic pathways that are inconsistent with early Earth conditions. In contrast, moderately acidic springs sourced by volcanic gas harbor earlier-branching MAGs that are enriched in anaerobic, gas-dependent metabolisms (e.g. H2, CO2, CH4 metabolism) that have been hypothesized to support early microbial life. Our results provide insight into the influence of redox state in the eco-evolutionary feedbacks between thermophiles and their habitats and suggest moderately acidic springs as early Earth analogs.

Abstract Background Cognitive load impacts performance of debriefers and learners during simulations, but limited data exists examining debriefer cognitive load. The aim of this study is to compare the cognitive load of the debriefers during simulation-based team training (SbTT) with Rapid Cycle Deliberate Practice (RCDP) debriefing and Traditional Reflective Debriefing (TRD). We hypothesize that cognitive load will be reduced during RCDP compared to TRD. Methods This study was part of a large-scale, interdisciplinary team training program at Children’s Healthcare of Atlanta Egleston Pediatric Emergency Department, with 164 learners (physicians, nurses, medical technicians, paramedics, and respiratory therapists (RTs)). Eight debriefers (main facilitators and discipline-specific coaches) led 28 workshops, which were quasi-randomized to either RCDP or TRD. Each session began with a baseline medical resuscitation scenario and cognitive load measurement using the NASA Task Load Index (TLX), and the NASA TLX was repeated immediately following either TRD or RCDP debriefing. Raw scores of the NASA TLX before and after intervention were compared. ANOVA tests were used to compare differences in NASA TLX scores before and after intervention between the RCDP and TRD groups. Results For all debriefers, mean NASA TLX scores for physical demands and frustration significantly decreased (− 0.8, p = 0.004 and − 1.3, p = 0.002) in TRD and mean perceived performance success significantly increased (+ 2.4, p

Abstract Multiresonant thermally activated delayed fluorescence (MR‐TADF) emitters have been the focus of extensive design efforts as they are recognized to show bright, narrowband emission, which makes them very appealing for display applications. However, the planar geometry and relatively large singlet–triplet energy gap lead to, respectively, severe aggregation‐caused quenching (ACQ) and slow reverse intersystem crossing (RISC). Here, a design strategy is proposed to address both issues. Two MR‐TADF emitters triphenylphosphine oxide (TPPO)‐tBu‐DiKTa and triphenylamine (TPA)‐tBu‐DiKTa have been synthesized. Twisted ortho‐substituted groups help increase the intermolecular distance and largely suppress the ACQ. In addition, the contributions from intermolecular charge transfer states in the case of TPA‐tBu‐DiKTa help to accelerate RISC. The organic light‐emitting diodes (OLEDs) with TPPO‐tBu‐DiKTa and TPA‐tBu‐DiKTa exhibit high maximum external quantum efficiencies (EQEmax) of 24.4% and 31.0%, respectively. Notably, the device with 25 wt% TPA‐tBu‐DiKTa showed both high EQEmax of 28.0% and reduced efficiency roll‐off (19.9% EQE at 1000 cd m−2) compared to the device with 5 wt% emitter (31.0% EQEmax and 11.0% EQE at 1000 cd m−2). The new emitters were also introduced into single‐layer light‐emitting electrochemical cells (LECs), equipped with air‐stable electrodes. The LEC containing TPA‐tBu‐DiKTa dispersed at 0.5 wt% in a matrix comprising a mobility‐balanced blend‐host and an ionic liquid electrolyte delivered blue luminance with an EQEmax of 2.6% at 425 cd m−2. The high efficiencies of the OLEDs and LECs with TPA‐tBu‐DiKTa illustrate the potential for improving device performance when the DiKTa core is decorated with twisted bulky donors.

Background Worldwide, more immigrants experience vitamin D (vitD) deficiency than non-immigrants. Recommendations in current clinical practice guidelines (CPGs) concerning vitD are inadequate to address vitD deficiency among immigrants, and there are concerns regarding the quality of guidance in these CPGs.Objectives This study aimed to identify and evaluate the quality of published CPGs addressing vitD and immigrants’ health using the Appraisal of Guidelines for Research and Evaluation-II (AGREE II) tool and clarify the recommendations pertaining to vitD and immigrant populations in these CPGs.Methods We performed a systematic search to identify the most recent CPGs across various databases (Ovid MEDLINE ALL, Embase and Turning Research Into Practice), guideline repositories and grey literature. Two reviewers independently conducted study selection and data abstraction and evaluated the quality of the included guidelines using the AGREE II tool.Results We identified 25 relevant CPGs; 21 focused on vitD and 4 covered immigrants’ health. Around one-quarter of the included CPGs were high quality (≥60% in at least four of the six domains, including ‘rigour of development’). The highest mean scores among the six AGREE II domains were for ‘clarity of presentation’ and ‘scope and purpose’. About 4.8% (1/21) of the CPGs on vitD had immigrant-related recommendations. VitD recommendations were emphasised in one out of the four immigrant health CPGs (25%). CPGs covering immigrants’ health and vitD were inadequately systematically appraised. Moreover, recommendations regarding vitD were insufficient to address the growing epidemic of vitD deficiency among immigrant populations.Conclusion The insufficient recommendations for vitD fail to address the rising vitD deficiency among immigrants, highlighting a critical gap in healthcare provisions. Urgent national and international efforts are needed to develop comprehensive CPGs, bridging research, policy and practice disparities. Future guidelines must prioritise routine vitD screening, supplementation protocols for vulnerable immigrant groups, and culturally appropriate interventions to improve health outcomes for immigrants globally.PROSPERO registration number CRD42021240562.

Introduction: The neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) are markers of inflammation and prognosis in systemic diseases. This study determined the association between hematological indices, and disease activity in patients with systemic lupus erythematosus (SLE). Methods: This prospective, observational and analytical cross-sectional study included 87 Paraguayan patients diagnosed with SLE, according to the ACR/EULAR 2019 criteria. We investigate four hematological indices: neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), eosinophil/lymphocyte ratio (ELR), and monocytes/lymphocyte ratio (MLR). Results: Eighty-seven percent were female, with a median age of 34.9 ±12.3 years. SLEDAI mean of 3.68 ± 4.76 was found. SLEDAI mean was 3.68 ± 4.76. Positivity of anti-DNAds was found in 52% of the patients. CRP mean was 3.5 ± 4.6. Regarding values of hematological indices, we found: NLR mean of 2.4 ± 1.6 was obtained, ELR 0.07 ± 0.09, MRL 0.07 ± 0.07 and PLR 155.89 ± 80.69. A significant positive correlation was found with SLEDAI and NLR (r=0.34, p=0.001). Based on the ROC curve, the best cut-off value for our patient cohort capable of predicting patients with high activity is for NLR values ? 2.283 (AUC: 0.66). Conclusion: NLR could be a valuable and accessible biomarker to identify elevated activity in patients with SLE.

Background Calcium intake is below recommendations in several parts of the world. Improving calcium intake has benefits not only for bone health but also helps to prevent pregnancy hypertension disorders. Calcium concentration of tap water is usually low The aim of the present study was to determine the maximum amount of calcium that can be added to tap water while complying with drinking water Argentine regulations. Methods Tap water samples were collected from the Province of Buenos Aires (Argentina). Physicochemical properties and saturation index were measured. Different incremental concentrations of calcium chloride were added to the experimental aliquots. Results Baseline water had a mean calcium concentration of 22.00 ± 2.54 mg/L, water hardness of 89.9 ± 6.4 mg/L CaCO3, and a saturation index of -1.50 ± 0.11. After the addition of 0.4554 ± 0.0071 g of salt, water hard-ness reached 355.0 ± 7.1 mg/L CaCO3, a calcium concentration of 140.50 ± 2.12 mg/L, and a saturation index -0.53 ± 0.02. Conclusions This study shows that at laboratory level it is feasible to increase calcium concentration of drinking water by adding calcium chloride while complying with national standards. Calcium concentration of drinking tap water could be evaluated and minimum calcium concentration of tap water regulated so as to improve calcium intake in populations with low calcium intake.

The fossil-diagenetic characteristics, such as mineralogical aspects present in the ribs of Catonyx cuvieri (Lund, 1839) (Mammalia, Xenarthra), were analyzed in this work. These analyzed remains come from the Risso Cave, San Lazaro's District, Concepción Department, Paraguay. The vibrational response was studied using Raman and Fourier transform infrared (FTIR) and the mineralogy and elemental compositions were examined using multiple characterizations techniques. The main functional groups belong to the mineral part of the bone, and specific functional groups were associated with organic components. The characterization indicated that material was composed of apatites and the original mineral structure was affected by partial ionic substitutions, probably due to the interaction of the fossil with the environment. A Gaussian deconvolution model (GM) was used to identify the individual overlapping bands in the regions of interest in the spectra. A diagenesis pathway for the fossil involved the inclusion of calcium carbonate on the surface of the bone due to the accumulation of moisture, which allowed the recrystallization of hydroxyapatite and the precipitation of calcite in the pores and silicates of the bone. It’s worth mentioning that this work is the first in the ground sloths C. cuvieri in South America. In addition, the material here constitutes the most complete fossil record of a member of the Pleistocene megafaunal of Paraguay.

Silicic caldera volcanoes present major volcanic and seismic hazards but also host dynamic hydrothermal and groundwater systems and a rich but largely unexplored subsurface biosphere. Many of these volcanoes are hosted in rift settings. The intricate connections and feedbacks among magmatism, rifting, hydrothermal processes, and the biosphere in these complex systems remain poorly understood, necessitating subsurface joint observations that are only enabled by scientific drilling. The CALDERA (Connections Among Life, geo-Dynamics and Eruptions in a Rifting Arc caldera) project workshop funded by the International Continental Scientific Drilling Program (ICDP) gathered multi-disciplinary international experts in January 2023 to advance planning of a scientific drilling project within one of these dynamic, rift-hosted calderas, the Okataina Volcanic Centre (OVC), Aotearoa New Zealand. The OVC's high eruption rate, frequent unrest events and earthquake swarms, location in a densely faulted rapidly extending rift, abundant groundwater–geothermal fluid circulations, and diverse surface hot spring microbiota make it an ideal location for exploring a connected geo-hydro-biosphere via scientific drilling and developing a test bed for novel volcano monitoring approaches. Drilling configurations with at least two boreholes (∼ 200 and ∼ 1000–1500 m deep) were favoured to achieve the multi-disciplinary objectives of the CALDERA project. Decadal monitoring including biosphere activity and composition has the potential to evaluate the response of the hydro-bio system to volcano-tectonic activity. In addition to the OVC caldera-scale datasets already available, site surveys will be conducted to select the best drilling locations. The CALDERA project at the OVC would provide, for the first time, an understanding of volcanic–tectonic–hydrological–biological connections in a caldera–rift system and a baseline for global comparisons with other volcanoes, rifts, and hydrothermal systems. CALDERA would serve as an unprecedented model system to understand how and how quickly the subsurface biosphere responds to geologic activities. Discoveries will improve assessment of volcanic and seismic hazards, guide the sustainable management and/or conservation of groundwater and geothermal resources and microbial ecosystems, and provide a forum for interweaving mātauranga Māori and Western knowledge systems.

Abstract Background There is a need to improve mental health policy in Canada to address the growing population burden of mental illness. Understanding support for policy options is critical for advocacy efforts to improve mental health policy. Our purpose was to describe support for population-level healthy public policies to improve mental health among policy influencers and the general public in Alberta and Manitoba; and, identify associations between levels of support and sociodemographic variables and relative to the Nuffield Bioethics Intervention Ladder framework. Methods We used data from the 2019 Chronic Disease Prevention Survey, which recruited a representative sample of the general public in Alberta (n = 1792) and Manitoba (n = 1909) and policy influencers in each province (Alberta n = 291, Manitoba n = 129). Level of support was described for 16 policy options using a Likert-style scale for mental health policy options by province, sample type, and sociodemographic variables using ordinal regression modelling. Policy options were coded using the Nuffield Council on Bioethics Intervention Ladder to classify support for policy options by level of intrusiveness. Results Policy options were categorized as ‘Provide Information’ and ‘Enable Choice’ according to the Nuffield Intervention Ladder. There was high support for all policy options, and few differences between samples or provinces. Strong support was more common among women and among those who were more politically left (versus center). Immigrants were more likely to strongly support most of the policies. Those who were politically right leaning (versus center) were less likely to support any of the mental health policies. Mental health status, education, and Indigenous identity were also associated with support for some policy options. Conclusions There is strong support for mental health policy in Western Canada. Results demonstrate a gap between support and implementation of mental health policy and provide evidence for advocates and policy makers looking to improve the policy landscape in Canada.

Abstract Simulating future land use changes can be an important tool to support decision-making, especially in areas that are experiencing rapid anthropogenic pressure, such as the Cerrado–Brazilian savanna. Here we used a spatially-explicit model to identify the main drivers of native vegetation loss in the Cerrado and then extrapolate this loss for 2050 and 2070. We also analyzed the role of property size in complex Brazilian environmental laws in determining different outcomes of these projections. Our results show that distance to rivers, roads, and cities, agricultural potential, permanent and annual crop agriculture, and cattle led to observed/historical loss of vegetation, while protected areas prevented such loss. Assuming full adoption of the current Forest Code, the Cerrado may lose 26.5 million ha (± 11.8 95% C.I.) of native vegetation by 2050 and 30.6 million ha (± 12.8 95% C.I.) by 2070, and this loss shall occur mainly within large properties. In terms of reconciling conservation and agricultural production, we recommend that public policies focus primarily on large farms, such as protecting 30% of the area of properties larger than 2500 ha, which would avoid a loss of more than 4.1 million hectares of native vegetation, corresponding to 13% of the predicted loss by 2070.

Abstract Background In simulation-based education, debriefing is necessary to promote knowledge acquisition and skill application. Rapid Cycle Deliberate Practice (RCDP) and Traditional Reflective Debriefing (TRD) are based in learning theories of deliberate practice and reflective learning, respectively. In this study, we compared the effectiveness of TRD versus RCDP on acquisition of conceptual knowledge and teamwork skills among interdisciplinary learners in the pediatric emergency department. Methods One hundred sixty-four learners including emergency department attending physicians, fellows, nurses, medical technicians, paramedics, and respiratory therapists, participated in 28 in-situ simulation workshops over 2 months. Groups were quasi-randomized to receive RCDP or TRD debriefing. Learners completed a multiple-choice test to assess teamwork knowledge. The TEAM Assessment Tool assessed team performance before and after debriefing. Primary outcomes were teamwork knowledge and team performance. Results Average pre-intervention baseline knowledge assessment scores were high in both groups (TRD mean 90.5 (SD 12.7), RCDP mean 88.7 (SD 15.5). Post-test scores showed small improvements in both groups (TRD mean 93.2 (SD 12.2), RCDP mean 89.9 (SD 13.8), as indicated by effect sizes (ES = 0.21 and 0.09, for TRD and RCDP, respectively). Assessment of team performance demonstrated a significant improvement in mean scores from pre-assessment to post-assessment for all TEAM Assessment skills in both TRD and RCDP arms, based on p-values (all p 0.8). While pre-post improvements in TEAM scores were generally higher in the RCDP group based on effect sizes, analysis did not indicate either debriefing approach as meaningfully improved over the other. Conclusions Our study did not demonstrate that either TRD versus RCDP was meaningfully better in teamwork knowledge acquisition or improving skill application and performance. As such, we propose Reflective Deliberate Practice as a framework for future study to allow learners to reflect on learning and practice in action.

Abstract In contemporary drug discovery, enhancing the sp3-hybridized character of molecular structures is paramount, necessitating innovative synthetic methods. Herein, we introduce a deoxygenative cross-electrophile coupling technique that pairs easily accessible carboxylic acid-derived redox-active esters with aldehyde sulfonyl hydrazones, employing Eosin Y as an organophotocatalyst under visible light irradiation. This approach serves as a versatile, metal-free C(sp3)−C(sp3) cross-coupling platform. We demonstrate its synthetic value as a safer, broadly applicable C1 homologation of carboxylic acids, offering an alternative to the traditional Arndt-Eistert reaction. Additionally, our method provides direct access to cyclic and acyclic β-arylethylamines using diverse aldehyde-derived sulfonyl hydrazones. Notably, the methodology proves to be compatible with the late-stage functionalization of peptides on solid-phase, streamlining the modification of intricate peptides without the need for exhaustive de-novo synthesis.

Abstract Nucleobase editors represent an emerging technology that enables precise single-base edits to the genomes of eukaryotic cells. Most nucleobase editors use deaminase domains that act upon single-stranded DNA and require RNA-guided proteins such as Cas9 to unwind the DNA prior to editing. However, the most recent class of base editors utilizes a deaminase domain, DddAtox, that can act upon double-stranded DNA. Here, we target DddAtox fragments and a FokI-based nickase to the human CIITA gene by fusing these domains to arrays of engineered zinc fingers (ZFs). We also identify a broad variety of Toxin-Derived Deaminases (TDDs) orthologous to DddAtox that allow us to fine-tune properties such as targeting density and specificity. TDD-derived ZF base editors enable up to 73% base editing in T cells with good cell viability and favorable specificity.

Abstract Background Vancomycin is a commonly prescribed antibiotic to treat gram-positive infections. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. However, in most countries, steady-state plasma concentrations are used as a surrogate parameter of target AUC/MIC, but this practice has some drawbacks. Hence, direct AUC-guided monitoring of vancomycin using model-informed precision dosing (MIPD) tools has been proposed for earlier attainment of target concentrations and reducing vancomycin-related nephrotoxicity. However, solid scientific evidence for these benefits in clinical practice is still lacking. This randomized controlled trial (RCT) aims to investigate the clinical utility of MIPD dosing of vancomycin administered via continuous infusion in hospitalized adults. Methods Participants from 11 wards at two Belgian hospitals are randomly allocated to the intervention group or the standard-of-care comparator group. In the intervention group, clinical pharmacists perform dose calculations using CE-labeled MIPD software and target an AUC24h of 400 to 600 mg × h/L, whereas patients in the comparator group receive standard-of-care dosing and monitoring according to the institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400–600 between 48 and 72 h after start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury (AKI) during and until 48 h after stop of vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400–600 between 72 and 96 h after start of vancomycin treatment, and the proportion of time within the target AUC24h/MIC of 400–600. Discussion This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment. Trial registration EudraCT number: 2021-003670-31. Registered June 28, 2021. ClinicalTrials.gov identifier: NCT05535075. Registered September 10, 2022. Protocol version 3, protocol date: April 21, 2023.

ABSTRACTBackground The microbiomes on the surface of unclean removable prostheses are complex and yet largely underexplored using metagenomic sequencing technology.Objectives To characterize the microbiome of removable prostheses with different levels of cleanliness using Type IIB Restriction-site Associated DNA for Microbiome (2bRAD-M) sequencing and compare the Microbial Index of Pathogenic Bacteria (MIP) between clean and unclean prostheses.Materials and Methods Ninety-seven removable prostheses were classified into ‘clean’ and ‘unclean’ groups. All prosthesis plaque samples underwent 2bRAD metagenomic sequencing to characterize the species-resolved microbial composition. MIPs for clean and unclean prostheses were calculated based on the sum of the relative abundance of pathogenic bacteria in a microbiome using a reference database that contains opportunistic pathogenic bacteria and disease-associated information.Results Beta diversity analyses based on Jaccard qualitative and Bray-Curtis quantitative distance matrices identified significant differences between the two groups (p

With the spread of resistance to long-established insecticides targeting Anopheles malaria vectors, understanding the actions of compounds newly identified for vector control is essential. With new commercial vector-control products containing neonicotinoids under development, we investigate the actions of 6 neonicotinoids (imidacloprid, thiacloprid, clothianidin, dinotefuran, nitenpyram and acetamiprid) on 13 Anopheles gambiae nicotinic acetylcholine receptor (nAChR) subtypes produced by expression of combinations of the Agα1, Agα2, Agα3, Agα8 and Agβ1 subunits in Xenopus laevis oocytes, the Drosophila melanogaster orthologues of which we have previously shown to be important in neonicotinoid actions. The presence of the Agα2 subunit reduces neonicotinoid affinity for the mosquito nAChRs, whereas the Agα3 subunit increases it. Crystal structures of the acetylcholine binding protein (AChBP), an established surrogate for the ligand-binding domain, with dinotefuran bound, shows a unique target site interaction through hydrogen bond formation and CH-N interaction at the tetrahydrofuran ring. This is of interest as dinotefuran is also under trial as the toxic element in baited traps. Multiple regression analyses show a correlation between the efficacy of neonicotinoids for the Agα1/Agα2/Agα8/Agβ1 nAChR, their hydrophobicity and their rate of knockdown of adult female An. gambiae, providing new insights into neonicotinoid features important for malaria vector control.

Introduction The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an ongoing Australian prospective cohort study investigating how modifiable prenatal and early-life exposures drive the development of islet autoimmunity and type 1 diabetes (T1D) in children. In this profile, we describe the cohort’s parental demographics, maternal and neonatal outcomes and human leukocyte antigen (HLA) genotypes.Research design and methods Inclusion criteria were an unborn child, or infant aged less than 6 months, with a first-degree relative (FDR) with T1D. The primary outcome was persistent islet autoimmunity, with children followed until a T1D diagnosis or 10 years of age. Demographic data were collected at enrollment. Lifestyle, clinical and anthropometric data were collected at each visit during pregnancy and clinical pregnancy and birth data were verified against medical case notes. Data were compared between mothers with and without T1D. HLA genotyping was performed on the ENDIA child and all available FDRs.Results The final cohort comprised 1473 infants born to 1214 gestational mothers across 1453 pregnancies, with 80% enrolled during pregnancy. The distribution of familial T1D probands was 62% maternal, 28% paternal and 11% sibling. The frequency of high-risk HLA genotypes was highest in T1D probands, followed by ENDIA infants, and lowest among unaffected family members. Mothers with T1D had higher rates of pregnancy complications and perinatal intervention, and larger babies of shorter gestation. Parent demographics were comparable to the Australian population for age, parity and obesity. A greater percentage of ENDIA parents were Australian born, lived in a major city and had higher socioeconomic advantage and education.Conclusions This comprehensive profile provides the context for understanding ENDIA’s scope, methodology, unique strengths and limitations. Now fully recruited, ENDIA will provide unique insights into the roles of early-life factors in the development of islet autoimmunity and T1D in the Australian environment.Trial registration number ACTRN12613000794707.

BackgroundEvidence suggests that having a chronic physical illness (CPI; eg, asthma, diabetes, and epilepsy) is an independent risk factor for suicidality (ie, suicidal ideation or attempts) among youth. Less is known about the mechanisms linking CPI and suicidality. Some evidence suggests that mental illness (eg, depression and anxiety) or neurodevelopmental disorder (eg, attention-deficit/hyperactivity disorder) mediates or moderates the CPI-suicidality association. Missing from the knowledge base is information on the association between having co-occurring CPI and mental illness or neurodevelopmental disorder (MIND) on youth suicidality. ObjectiveThis study uses epidemiological data from the 2019 Canadian Health Survey of Children and Youth (CHSCY) to study the intersection of CPI, MIND, and suicidality in youth. We will estimate prevalence, identify predictors, and investigate psychosocial and service use outcomes for youth with CPI-MIND comorbidity versus other morbidity groups (ie, healthy, CPI only, and MIND only). MethodsConducted by Statistics Canada, the CHSCY collected data from 47,850 children (aged 1-17 years) and their primary caregiving parent. Measures of youth CPI, MIND, family environment, and sociodemographics are available using youth and parent informants. Information on psychiatric services use is available via parent report and linkage to national administrative health data found in the National Ambulatory Care Reporting System and the Discharge Abstract Database, which allow the investigation of hospital-based mental health services (eg, emergency department visits, hospitalizations, and length of stay in hospital). Questions about suicidality were restricted to youths aged 15-17 years (n=6950), which form our analytic sample. Weighted regression-based analyses will account for the complex survey design. ResultsOur study began in November 2023, funded by the American Foundation for Suicide Prevention (SRG-0-008-22). Access to the linked CHSCY microdata file was granted in May 2024. Initial examination of CHSCY data shows that approximately 20% (1390/6950) of youth have CPI, 7% (490/6950) have MIND, 7% (490/6950) seriously considered suicide in the past year, and 3% (210/6950) had attempted suicide anytime during their life. ConclusionsFindings will provide estimates of suicidality among youth with CPI-MIND comorbidity, which will inform intervention planning to prevent loss of life in this vulnerable population. Modeling correlates of suicidality will advance understanding of the relative and joint effects of factors at multiple levels—information needed to target prevention efforts and services. Understanding patterns of psychiatric service use is vital to understanding access and barriers to services. This will inform whether use matches need, identifying opportunities to advise policy makers about upstream resources to prevent suicidality. Importantly, findings will provide robust baseline of information on the link between CPI-MIND comorbidity and suicidality in youth, which can be used by future studies to address questions related to the impact of the COVID-19 pandemic and associated countermeasures in this vulnerable population of youth. International Registered Report Identifier (IRRID)DERR1-10.2196/57103

In recent years, the field of coordination chemistry has experienced a surge in interest regarding the synthesis and characterization of coordination complexes for diverse applications. This study is dedicated to investigating coordination compounds resulting from the interaction of nonsteroidal anti-inflammatory drugs (NSAIDs) with metal ions. The study research places significant emphasis on understanding the stability and thermal behavior of these coordination compounds. The utilization of thermoanalytical techniques is crucial in achieving this goal. Thermal analysis and thermokinetics provide valuable insights into the underlying mechanisms, kinetics, and energetics of these reactions, thereby facilitating the optimization of synthesis procedures. The research employs concurrent techniques, namely thermogravimetric analysis (TG) and differential scanning calorimetry (DSC), to explore the thermal stability and decomposition pathways of these coordination compounds. Thermokinetic models and optimization methodologies are subsequently applied to identify key reaction parameters. The primary aim of this research is to unveil the thermal behavior, stability, and reaction kinetics of aceclofenac coordination compounds, thus contributing significantly to the understanding of thermokinetics and thermal analysis in the domain of coordination chemistry. Specifically, this study is focused on aceclofenac coordination complexes involving lanthanum and gadolinium, with the ultimate goal of advancing the field of coordination chemistry.

IntroductionParkinson’s disease (PD) is an incurable, progressive, neurodegenerative disorder. As PD advances and symptoms progress, patients become increasingly dependent on family and carers. Traditional cost-effectiveness analyses (CEA) only consider patient and payer-related outcomes, failing to acknowledge impacts on families, carers, and broader society. This novel Social Return on Investment (SROI) analysis aimed to evaluate the broader impact created by improving access to levodopa (LD) device-aided therapies (DATs) for people living with advanced PD (aPD) in Australia.MethodsA forecast SROI analysis over a three-year time horizon was conducted. People living with aPD and their families were recruited for qualitative interviews or a quantitative survey. Secondary research and clinical trial data was used to supplement the primary research. Outcomes were valued and assessed in a SROI value map in Microsoft Excel™. Financial proxies were assigned to each final outcome based on willingness-to-pay, economic valuation, and replacement value. Treatment cost inputs were sourced from Pharmaceutical Benefits Schedule (PBS) and Medicare Benefits Scheme (MBS) published prices.ResultsTwenty-four interviews were conducted, and 55 survey responses were received. For every $1 invested in access to LD-based DATs in Australia, an estimated $1.79 of social value is created. Over 3 years, it was estimated $277.16 million will be invested and $406.77 million of social return will be created. This value is shared between people living with aPD (27%), their partners (22%), children (36%), and the Australian Government (15%). Most of the value created is social and emotional in nature, including reduced worry, increased connection to family and friends, and increased hope for the future.DiscussionInvestment in LD-based DATs is expected to generate a positive social return. Over 50% of the value is created for the partners and children of people living with aPD. This value would not be captured in traditional CEA. The SROI methodology highlights the importance of investing in aPD treatment, capturing the social value created by improved access to LD-based DATs.

Gene silencing without gene editing holds great potential for the development of safe therapeutic applications. Here, we describe a novel strategy to concomitantly repress multiple genes using zinc finger proteins fused to Krüppel-Associated Box repression domains (ZF-Rs). This was achieved via the optimization of a lentiviral system tailored for the delivery of ZF-Rs in hematopoietic cells. We showed that an optimal design of the lentiviral backbone is crucial to multiplex up to three ZF-Rs or two ZF-Rs and a chimeric antigen receptor. ZF-R expression had no impact on the integrity and functionality of transduced cells. Furthermore, gene repression in ZF-R-expressing T cells was highly efficient in vitro and in vivo during the entire monitoring period (up to 10 weeks), and it was accompanied by epigenetic remodeling events. Finally, we described an approach to improve ZF-R specificity to illustrate the path toward the generation of ZF-Rs with a safe clinical profile. In conclusion, we successfully developed an epigenetic-based cell engineering approach for concomitant modulation of multiple gene expressions that bypass the risks associated with DNA editing.

IntroductionThis study aimed to investigate the relationship between adverse childhood experiences (ACEs) and dental anxiety among Chinese adults in Hong Kong.MethodsA cross-sectional survey was conducted at a university in Hong Kong. The recruiting period and data collection started in January 2023 and ended in June 2023. Participants completed an online questionnaire that assessed ACEs (using the Adverse Childhood Experiences International Questionnaire – ACE-IQ) and dental anxiety (using the Modified Dental Anxiety Scale – MDAS and Dental Fear Survey – DFS). The study examined the impacts of both cumulative (i.e., total number) and independent ACE components on dental anxiety. To explore the relationships between cumulative ACEs, individual ACE components and dental anxiety (MDAS and DFS score), Pearson correlations, linear regression and logistic regression were conducted.ResultsSignificant associations were observed between ACEs and dental anxiety among 171 subjects. Cumulative ACEs were positively correlated with MDAS scores (r = 0.169, p = 0.027) and DFS scores (r = 0.253, p

Social media plays a significant role in adolescents’ lives, with both positive and negative effects. Implementing interventions to mitigate the negative aspects and enhance the positive ones could improve adolescents’ well-being. Unfortunately, there is a scarcity of evidence-based interventions available. To fill this gap, we have developed a school-based program based on combining evidence-based and consensus-based approaches, incorporating input from adolescents, school personnel, researchers, and municipal advisers. This paper describes the program’s content and principles, and presents the results from a pilot evaluation, which assesses feedback from pupils and teachers, thereby informing potential enhancements and the program’s overall significance. The intervention description encompasses theoretical perspectives, behavior change techniques, and procedural details. Pupils ( n = 266; 16+ years) evaluated the program concerning satisfaction, relevance, importance, and usefulness through a questionnaire. Additionally, exploratory focus group interviews were conducted with seven teachers and eleven pupils to gather their perspectives on the program’s relevance, impact, and potential changes to the theme-based teaching. Results from the pilot showed an average score of 7.3/10 for overall satisfaction with the program. Sub-questions assessing perceived relevance, engagement, and usefulness averaged between 6.7 and 7.5. Gender differences were observed, with boys tending to rate the program lower than girls. In focus group interviews, the pupils expressed increasing awareness of their own and others’ social media use, that the topic was important and exciting, and that the program generally worked well. The pupils’ evaluation indicates the need for this kind of program described in this study.

Introdução: O aumento da carga de trabalho dos profissionais de saúde e o grau de complexidade dos pacientes, atribuem maior risco para o estresse psicossocial. Objetivo: Avaliar as associações entre o estresse ocupacional, a qualidade de vida no trabalho e as estratégias de enfrentamento pela equipe de enfermagem hospitalar na pandemia de COVID-19. Métodos: Estudo transversal, quantitativo com amostragem por conveniência, coleta de dados de agosto a dezembro de 2020; em duas unidades da rede hospitalar privada, com questionário sociodemográfico, ocupacional e de saúde; escala visual analógica de avaliação da qualidade de vida no trabalho; Escala de Demanda-Controle-Apoio Social (DCS); Escala de Coping ocupacional. Resultados: A amostra total foi de 196 profissionais de Enfermagem. Houve correlação significativa negativa, porém fraca, entre a dimensão “Demanda” da DCS e QVT (p

Abstract Allopatric speciation has been difficult to examine among microorganisms, with prior reports of endemism restricted to sub-genus level taxa. Previous microbial community analysis via 16S rRNA gene sequencing of 925 geothermal springs from the Taupō Volcanic Zone (TVZ), Aotearoa-New Zealand, revealed widespread distribution and abundance of a single bacterial genus across 686 of these ecosystems (pH 1.2-9.6 and 17.4-99.8 °C). Here, we present evidence to suggest that this genus, Venenivibrio (phylum Aquificota), is endemic to Aotearoa-New Zealand. A specific environmental niche that increases habitat isolation was identified, with maximal read abundance of Venenivibrio occurring at pH 4-6, 50-70 °C, and low oxidation-reduction potentials. This was further highlighted by genomic and culture-based analyses of the only characterised species for the genus, Venenivibrio stagnispumantis CP.B2T, which confirmed a chemolithoautotrophic metabolism dependent on hydrogen oxidation. While similarity between Venenivibrio populations illustrated that dispersal is not limited across the TVZ, extensive amplicon, metagenomic, and phylogenomic analyses of global microbial communities from DNA sequence databases indicates Venenivibrio is geographically restricted to the Aotearoa-New Zealand archipelago. We conclude that geographic isolation, complemented by physicochemical constraints, has resulted in the establishment of an endemic bacterial genus.

This study reports the successful synthesis and characterization of a uranyl nicotinate compound, UO2(C6H4NO2)2·0.25H2O. The compound was synthesized using a metal 1:2 ligand ratio and water as the solvent. The average yield of the compound was 67 %. Thermogravimetric analysis revealed multiple stages of mass loss, including dehydration, nitrogen decomposition and UO2 2+ reduction. Fourier-transform infrared spectroscopy confirmed the coordination of the carboxylate group in the compound. Field emission gun scanning electron microscope analysis showed the particles with a regular oval shape. Energy-dispersive X-ray spectroscopy provided semi-quantitative data on the elemental composition of the compound. The major elements identified were uranium, carbon, oxygen and nitrogen. These results contribute to understanding the compound’s synthesis, thermal behaviour, molecular composition, particle morphology and elemental composition. Further research can build upon these findings to explore potential applications and develop new compounds with tailored properties.

Abstract Background The transition from childhood to adolescence is associated with an increase in rates of some psychiatric disorders, including major depressive disorder, a debilitating mood disorder. The aim of this systematic review is to update the evidence on the benefits and harms of screening for depression in primary care and non-mental health clinic settings among children and adolescents. Methods This review is an update of a previous systematic review, for which the last search was conducted in 2017. We searched Ovid MEDLINE® ALL, Embase Classic+Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and CINAHL on November 4, 2019, and updated on February 19, 2021. If no randomized controlled trials were found, we planned to conduct an additional search for non-randomized trials with a comparator group. For non-randomized trials, we applied a non-randomized controlled trial filter and searched the same databases except for Cochrane Central Register of Controlled Trials from January 2015 to February 2021. We also conducted a targeted search of the gray literature for unpublished documents. Title and abstract, and full-text screening were completed independently by pairs of reviewers. Results In this review update, we were unable to find any randomized controlled studies that satisfied our eligibility criteria and evaluated the potential benefits and harms of screening for depression in children and adolescents. Additionally, a search for non-randomized trials yielded no studies that met the inclusion criteria. Conclusions The findings of this review indicate a lack of available evidence regarding the potential benefits and harms of screening for depression in children and adolescents. This absence of evidence emphasizes the necessity for well-conducted clinical trials to evaluate the effectiveness of depression screening among children and adolescents in primary care and non-mental health clinic settings. Systematic review registration PROSPERO CRD42020150373 .

Dyspnea, the subjective sensation of breathlessness, is a common source of distress for patients living with advanced cancer. Effective assessment and management of dyspnea among patients living with advanced cancer represents core competencies for front-line clinicians and professional caregivers. However, there is still a lack of standardized procedures for handling dyspnea in China. Based on evidence-based medicine, the American Society of Clinical Oncology practice guidelines for management of dyspnea in advanced cancer was released, which outlines assessment and management of dyspnea among patients living with advanced cancer. This article aims to provide detailed interpretation of key clinical content to guide China's clinical practice.

Objectives: The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, reduces human prostate cancer incidence, and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro. Cancer evolves with stage, and whether advanced-stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove that human metastatic castrate-resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo. We hypothesised that mCRPC would thus be detectable by positron emission tomography/computed tomography (PET/CT) using a radiotracer bound to a GLP-1R ligand, as in exendin PET/CT. Materials and methods: Men with mCRPC, with more than one prostate-specific membrane antigen (PSMA)-avid lesion on PET/CT scanning (pathognomic in that setting for prostate cancer lesions), were approached to undergo PET/CT with gallium68-Dota-exendin-4. We documented PET/CT PSMA-avid lesions, which were also PET/CT exendin avid, as evidence of in vivo GLP-1R expression. Results: Out of the 24 men referred, three did not meet the inclusion criteria. Seventeen declined, largely because the study offered them no therapeutic benefit. Among the four men imaged, three had no exendin-avid lesions, while one had six osseous PSMA-avid lesions, three of which were also exendin avid. Conclusions: We demonstrated in vivo GLP-1R expression by human mCPRC, detecting PET/CT lesions avid for both PSMA and exendin, in one of four participants. GLP-1R expression may thus occur even in advanced-stage prostate cancer. Our data contribute to growing evidence supporting the testing of GLP-1 receptor agonists for therapeutic benefit in prostate cancer.

Introducción: La Enfermedad por el virus del Chikungunya (CHIKV) es una virosis que se caracteriza por fiebre acompañada de dolores articulares. La epidemia de esta enfermedad en los últimos dos años causó más de cien mil casos confirmados y sospechosos, incluido personas con Lupus Eritematoso Sistémico (LES). Objetivo: Los objetivos del siguiente trabajo consistieron en determinar la evolución de la Enfermedad por el CHIKV en pacientes con LES, caracterizar a la población incluida en el estudio, determinar la frecuencia de la Enfermedad por el CHIKV en pacientes con LES, describir las manifestaciones clínicas de la Enfermedad por el CHIKV en pacientes con LES y registrar la impresión de los pacientes en relación con la actividad de la enfermedad y las manifestaciones clínicas que aparecieron posterior a la Enfermedad por el CHIKV. Metodología: El estudio realizado fue de tipo descriptivo de corte transversal. Se incluyeron 101 pacientes con Lupus Eritematoso Sistémico, a quienes se les encuestó mediante un formulario virtual. Los investigadores establecieron contacto con los pacientes a través de llamadas telefónicas o mensajería, y si los pacientes aceptaban participar en el estudio, se les enviaba el formulario o, en algunos casos, se completaba durante la llamada telefónica, si el paciente lo solicitaba. Resultados: El valor de la media de edad es de 38,2 ± 11,8 años. El 85,1% (86/101) de los pacientes corresponden al sexo femenino, mientras que el 14,9% (15/101) corresponde al sexo masculino. El 37,6% (38/101) presentó la enfermedad por el CHIKV, la cual se caracterizó en la fase aguda por la presencia de artralgias en un 84,2% (32/38), fiebre en un 71,1% (27/38), debilidad en un 57,9% (22/38) y cefalea en un 55,3% (21/38). En la fase subaguda, las artralgias se manifestaron mayoritariamente en un 73,7% (28/38) de los pacientes. La fase crónica estuvo presente en el 71,1% (27/38) con la persistencia de artralgias en un 81,48% (22/27) de los pacientes acompañada de otros síntomas como la artritis en un 40,74% (11/27). A causa de la enfermedad por el CHIKV, el 21,1% (8/38) recibió la indicación en la fase subaguda o crónica de realizar cambios en su medicación para el LES. El 62,5% (5/8) recibió la indicación de aumentar la dosis del corticoesteroide, mientras que el 50% (4/8) de aumentar la dosis del inmunosupresor. Según la impresión de los pacientes, en cuanto a la actividad de la enfermedad de base, posterior a la enfermedad por el CHIKV, presentaron una exacerbación del LES en un 10,5% (4/38) de los pacientes, de los cuales un 50% (2/4) refirieron exacerbación de síntomas ya existentes antes de la infección y la aparición de nuevos síntomas en un 50% (2/4). El 5,2% (2/38) tuvo requerimiento de hospitalización debido a la enfermedad por el CHIKV en la fase aguda. Conclusión: Las artralgias fueron frecuentes en las fases aguda, subaguda y crónica. En términos de tratamiento, algunos pacientes ajustaron sus medicaciones para el LES, aumentando la dosis de inmunosupresores o corticoides. En cuanto a la evolución, la mayoría de los pacientes no experimentaron una exacerbación de la enfermedad de base debido a la enfermedad por el CHIKV, al igual que solo un par de pacientes requirió hospitalización.

Abstract Objective Differentiating status epilepticus (SE) from prolonged psychogenic nonepileptic seizures (pPNES) can be difficult clinically. We aimed to define the utility of peripheral cell counts, cell ratios, and lactate levels in distinguishing SE from pPNES. Methods Retrospective two‐center study investigating the sensitivity and specificity of acute (≤12 h of event offset) peripheral cell counts, cell ratios (neutrophil–lymphocyte ratio, neutrophil–monocyte ratio, monocyte–lymphocyte ratio, platelet–lymphocyte ratio, systemic immune‐inflammatory index [SII], systemic inflammatory response index [SIRI]), and lactate levels in differentiating SE from pPNES. Patients were identified from two tertiary hospitals, with one forming the development cohort and the other the validation cohort. Using generalized additive models to generate biomarker vs time curves, optimal blood collection times were defined for set parameters. Three diagnostic scores combining neutrophil count, SII, or SIRI with lactate levels were developed and validated in separate cohorts. Results For the development cohort, 1262 seizure‐like events were reviewed and 79 SE and 44 pPNES events were included. For the validation cohort, 241 events were reviewed and 20 SE and 11 pPNES events were included. Individually, the biomarkers generally had low sensitivity and reasonable specificity for differentiating SE from pPNES, with the neutrophil count, SIRI, and SII performing best with sensitivities of 0.65–0.84, specificities of 0.64–0.89, and ROC AUCs of 0.78–0.79. Lactate levels peaked at 60 min, while cell counts and ratios peaked after 240 min. Combining early peaking lactate levels and later peaking neutrophil count, SIRI or SII resulted in three scores that improved predictive potential with sensitivities of between 0.75 and 0.79, specificities between 0.93 and 1.00, and ROC AUCs of 0.89–0.91. Significance Lactate levels peak early post‐SE, whereas cell counts and ratios do so later. The differing post‐event time profiles of lactate levels vs neutrophil count, SIRI, and SII allow incorporation into three separate scores which can assist in differentiating SE from pPNES.

Turi Reiten Finserås,1 Gunnhild Johnsen Hjetland,1,2 Børge Sivertsen,1,3 Ian Colman,4,5 Randi Træland Hella,6 Amanda Iselin Olesen Andersen,1 Jens Christoffer Skogen1,2,7 1Department of Health Promotion, Norwegian Institute of Public Health, Bergen, Norway; 2Centre for Evaluation of Public Health Measures, Norwegian Institute of Public Health, Oslo, Norway; 3Department of Research and Innovation, Helse Fonna HF, Haugesund, Norway; 4School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada; 5Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; 6Regional Centre for Child and Youth Mental Health and Child Welfare, NORCE, Bergen, Norway; 7Alcohol and Drug Research Western Norway, Stavanger University Hospital, Stavanger, NorwayCorrespondence: Turi Reiten Finserås, Norwegian Institute of Public Health, PO Box 973 Sentrum, Bergen, 5808, Norway, Tel +47 980 79 303, Email Turireiten.Finseras@fhi.noPurpose: Previous approaches used to assess problematic social media use risk inflating prevalence numbers and classifying unproblematic social media use as problematic. The main aim of this study was to take an exploratory view as to how different types of activities, experiences, and motivations on social media are associated with problematic mental health outcomes in adolescents.Patients and Methods: This study is based on a cross-sectional survey of 2023 adolescents (mean age 17.4 years (SD 0.9), 44.4% males) from the year 2020. Exploratory graph analysis and exploratory factor analysis were performed on 28 pre-selected items assessing adolescents’ use of social media, to identify underlying potentially problematic factors associated with social media use. Sets of gender-adjusted multiple linear regression analyses were performed to assess the degree to which social media factors predicted depression, anxiety, well-being, and time spent on social media.Results: Three factors were identified: 1) “subjective overuse”, 2) “social obligations”, and 3) “source of concern”. All three factors showed significant positive associations with mental health problems. The factor “source of concern”, which identifies feelings of being overwhelmed and concerned over social media use, had the strongest association to mental health problems and simultaneously the weakest association to time spent on social media.Conclusion: Three identified factors measuring problematic social media use showed positive associations with mental health problems. This lends support to the notion that problematic social media use is a multidimensional phenomenon and demonstrates the need to move beyond addiction criteria when assessing problematic social media use.Keywords: social networking, youth, depression, anxiety, well-being

Abstract Introduction Although youth‐friendly service characteristics have been previously identified, consensus among a representative group of stakeholders about which of these characteristics are truly relevant to the youth‐friendliness of services is currently lacking. In our study, young adults, parents and professionals were consulted on this topic to reveal existing (dis)agreement. In addition, (dis)agreement on feasibility for implementation in clinical practice was also assessed. Methods A mixed‐method Delphi approach was used with three online questionnaire rounds and a physical meeting. Young adults (18–26 years) and parents were part of a public panel and professionals were allocated to the professional panel. In the rounds, participants were asked to rate the importance and feasibility of each item. Subsequently, the percentage agreement (% of participants giving a score of 7 or above on a 9‐point Likert scale) within and across panels was calculated. Consensus was assumed to have been reached when at least 70% agreement was achieved. A thematic analysis of the qualitative data, obtained in the rounds and the physical meeting, was performed to identify overarching themes and characteristics of relevance to the youth‐friendliness of services. Results For 65% of the items included in the Delphi questionnaire, consensus on importance was reached within both panels. Participants showed more insecurity about the feasibility of these items, however. Our thematic analysis revealed reasons for disagreement between and within the panels. Conclusions Our study revealed substantial between‐ and within‐panel agreement on youth‐friendly service characteristics. We recommend that the items for which consensus was reached should be used as a checklist in terms of youth mental health service development, design and delivery. The characteristics for which there was disagreement between and within the panels should inspire an ongoing trialogue between young adults, parents and professionals both on the individual level and the service level. Patient or Public Contribution In this study, (parents of) young adults with lived experience were included as experts, including one of the coauthors. This coauthor contributed to the manuscript by having a final say about the included quotes.

Background: The Belt and Road Initiative (BRI) aims to strengthen China's connectivity with the world and, in doing so, improve health and well-being. There is a dearth of information relating to schoolchildren's oral health to inform oral health–related BRI initiatives. The aim of this research was to report on the oral health status of 12-year-old children across BRI countries and determine variations in oral health regarding geographic regions (BRI routes) and country-income levels. Method: Dental caries experience of 12-year-old children was obtained from the World Health Organization's (WHO) database. BRI countries were classified into BRI routes and country income level. Data were assessed for completeness and contemporariness. Variations in dental caries experiences were examined across BRI routes and with respect to country income levels. Results: Dental caries experience data were available in the WHO database for most BRI countries (95.7%, 135/141). Most dental caries data were collected pre-2010 (74.1%, 74/135). The mean number of decayed, missing, and filled teeth (DMFT) was approximately 2 (weighted mean, 1.7; SD, 1.2). Variations in DMFT existed with respect to BRI routes—WHO regions (P < .001) and World Bank regions (P < .001)—and with respect to country income levels (P < .01). Conclusions: Dental caries data for 12-year-old schoolchildren are readily available (in the WHO database) for most BRI countries, although the data are not very current. In addition, dental caries experience varies with respect to BRI routes (geographic locations) and country income levels. These findings have implications by way of situation analyses to inform oral health–related BRI initiatives.

Abstract Objective To report trends in Australian hospitalisations coded for sepsis and their associated costs. Design Retrospective analysis of Australian national hospitalisation data from 2002 to 2021. Methods Sepsis-coded hospitalisations were identified using the Global Burden of Disease study sepsis-specific ICD-10 codes modified for Australia. Costs were calculated using Australian-Refined Diagnosis Related Group codes and National Hospital Cost Data Collection. Results Sepsis-coded hospitalisations increased from 36,628 in 2002-03 to 131,826 in 2020-21, an annual rate of 7.8%. Principal admission diagnosis codes contributed 13,843 (37.8%) in 2002-03 and 44,186 (33.5%) in 2020-21; secondary diagnosis codes contributed 22,785 (62.2%) in 2002-03 and 87,640 (66.5%) in 2020-21. Unspecified sepsis was the most common sepsis code, increasing from 15,178 hospitalisations in 2002-03 to 68,910 in 2020-21. The population-based incidence of sepsis-coded hospitalisations increased from 18.6 to 10,000 population (2002-03) to 51.3 per 10,000 (2021-21); representing an increase from 55.1 to 10,000 hospitalisations in 2002-03 to 111.4 in 2020-21. Sepsis-coded hospitalisations occurred more commonly in the elderly; those aged 65 years or above accounting for 20,573 (55.6%) sepsis-coded hospitalisations in 2002-03 and 86,135 (65.3%) in 2020-21. The cost of sepsis-coded hospitalisations increased at an annual rate of 20.6%, from AUD199M (€127 M) in financial year 2012 to AUD711M (€455 M) in 2019. Conclusion Hospitalisations coded for sepsis and associated costs increased significantly from 2002 to 2021 and from 2012 to 2019, respectively.

IntroductionFirst responders and other public safety personnel (PSP; e.g. correctional workers, firefighters, paramedics, police, public safety communicators) are often exposed to events that have the potential to be psychologically traumatizing. Such exposures may contribute to poor mental health outcomes and a greater need to seek mental health care. However, a theoretically driven, structured qualitative study of barriers and facilitators of help-seeking behaviours has not yet been undertaken in this population. This study used the Theoretical Domains Framework (TDF) to identify and better understand critical barriers and facilitators of help-seeking and accessing mental health care for a planned First Responder Operational Stress Injury (OSI) clinic. MethodsWe conducted face-to-face, one-on-one semistructured interviews with 24 first responders (11 firefighters, five paramedics, and eight police officers), recruited using purposive and snowball sampling. Interviews were analyzed using deductive content analysis. The TDF guided study design, interview content, data collection, and analysis. ResultsThe most reported barriers included concerns regarding confidentiality, lack of trust, cultural competency of clinicians, lack of clarity about the availability and accessibility of services, and stigma within first responder organizations. Key themes influencing help-seeking were classified into six of the TDF’s 14 theoretical domains: environmental context and resources; knowledge; social influences; social/professional role and identity; emotion; and beliefs about consequences. ConclusionThe results identified key actions that can be utilized to tailor interventions to encourage attendance at a First Responder OSI Clinic. Such approaches include providing transparency around confidentiality, policies to ensure greater cultural competency in all clinic staff, and clear descriptions of how to access care; routinely involving families; and addressing stigma.

IntroductionLes premiers répondants comme les autres membres du personnel de sécurité publique (travailleurs correctionnels, pompiers, ambulanciers paramédicaux, policiers, agents des communications en sécurité publique, etc.) sont souvent exposés à des événements potentiellement traumatisants sur le plan psychologique. Ces expositions sont susceptibles de contribuer à des problèmes de santé mentale et à un besoin accru en soins de santé mentale. Pourtant, aucune étude qualitative structurée et fondée théoriquement sur les obstacles aux comportements de recherche d’aide et sur les facteurs facilitant ces comportements n’a encore été entreprise auprès de cette population. Cette étude repose sur le cadre Theoretical Domains Framework (TDF) pour cerner et mieux comprendre les principaux obstacles et facteurs facilitants relatifs à la recherche d’aide et à l’accès aux soins de santé mentale dans le cadre d’une clinique de traitement des blessures de stress opérationnel pour premiers répondants. MéthodologieNous avons mené des entretiens semi-structurés en personne avec 24 premiers répondants (11 pompiers, 5 ambulanciers paramédicaux et 8 policiers), recrutés à l’aide d’un échantillonnage raisonné et par boule de neige. Les entretiens ont été analysés à l’aide d’une analyse de contenu déductive. Le cadre TDF a guidé la conception de l’étude, le contenu des entretiens, la collecte et l’analyse des données. RésultatsLes obstacles les plus signalés ont été des préoccupations concernant la confidentialité, le manque de confiance, le manque de connaissances des cliniciens sur la culture professionnelle, le manque de transparence quant à l’accès aux services et la stigmatisation au sein des organismes de premiers répondants. Les principaux thèmes influençant la recherche d’aide ont pu être classés au sein de 6 des 14 domaines du cadre TDF : le contexte environnemental et les ressources; les connaissances; les influences sociales; le rôle social/professionnel et l’identité; les émotions et enfin les croyances à l’égard des conséquences. ConclusionNous avons pu cerner les principales mesures utilisables pour adapter les interventions afin d’encourager la participation à une clinique de traitement des blessures de stress opérationnel pour les premiers répondants : la transparence en matière de confidentialité, la présence de politiques visant à accroître les connaissances sur la culture professionnelle par l’ensemble du personnel de la clinique, des descriptions claires des modalités d’accès aux soins, la participation systématique des familles et la lutte contre la stigmatisation.

In recent decades, the field of statistical linguistics has made significant strides, which have been fueled by the availability of data. Leveraging Twitter data, this paper explores the English and Spanish languages, investigating their rank diversity across different scales: temporal intervals (ranging from 3 to 96 h), spatial radii (spanning 3 km to over 3000 km), and grammatical word ngrams (ranging from 1-grams to 5-grams). The analysis focuses on word ngrams, examining a time period of 1 year (2014) and eight different countries. Our findings highlight the relevance of all three scales with the most substantial changes observed at the grammatical level. Specifically, at the monogram level, rank diversity curves exhibit remarkable similarity across languages, countries, and temporal or spatial scales. However, as the grammatical scale expands, variations in rank diversity become more pronounced and influenced by temporal, spatial, linguistic, and national factors. Additionally, we investigate the statistical characteristics of Twitter-specific tokens, including emojis, hashtags, and user mentions, revealing a sigmoid pattern in their rank diversity function. These insights contribute to quantifying universal language statistics while also identifying potential sources of variation.

Introduction The only biologic therapy currently approved to treat moderate to severe Crohn’s disease in children (8 weeks and endoscopic remission (simple endoscopic severity-Crohn’s disease≤2).Ethics and dissemination ). The study protocol has been approved by the Cincinnati Children’s Hospital Medical Centre Institutional Review Board. Study results will be disseminated in peer-reviewed journals and presented at scientific meetings.Trial registration number NCT05660746.

Hydrogen (H2) is among the most common and widely utilized electron donors in microbial metabolism. This is particularly true for microorganisms that inhabit subsurface environments where H2 concentrations can be high due to H2 generation via one or more abiotic and biotic processes, such as serpentinization, radiolysis, cataclasis, and microbial fermentation. A surge in interest in the exploration for and exploitation of geologic (i.e., white and orange) H2 as a clean low carbon fuel therefore necessitates an evaluation of the influence of microorganisms on its flux and potential recovery from subsurface systems. The widespread application of high throughput metagenomic sequencing approaches to rock-hosted ecosystems now makes it possible to readily identify microorganisms that harbor the potential to metabolize H2 and to predict their mode of coupling H2 oxidation with available oxidants using comparative genomic data from natural samples alone. When combined with several recent reports of measured rates of net microbial H2 consumption in rock-hosted ecosystems, such information provides new perspective on the potential for microorganisms to impact the economics of H2 recovery from geologic systems. In this perspective, the different classes of enzymes that microorganisms use to reversibly oxidize H2 to fuel their energy metabolism are introduced and their distribution in several rock-hosted ecosystems is discussed. A compilation of net microbial H2 oxidation activities in rock-hosted ecosystems is also presented to enable estimates of potential H2 loss from natural or stimulated geologic reservoirs during mining activities, with an example provided from the Samail Ophiolite that indicates >90% of geologic H2 produced could be lost to microbial consumption. Finally, avenues to guide future microbial research in environments where geologic H2 mining is planned are discussed.

Para evaluar la capacidad supresiva sobre una comunidad espontánea del sistema lino en intercultivo con distintas leguminosas forrajeras, en diferentes arreglos espaciales, se hicieron dos años de ensayo a campo en La Plata, Argentina. Los tratamientos fueron: el monocultivo de lino con y sin uso de herbicida y lino en intercultivo con trébol rojo, trébol blanco o lotus, sembrados en el surco o al voleo. Se evaluó el rendimiento del lino, la biomasa total del residuo de cosecha y sus componentes al momento de la siembra, la cobertura total del suelo, la cobertura de malezas y el rendimiento relativo de las malezas. Además, en el segundo año de ensayo se evaluó el residuo a los 3 meses de la cosecha. En ambos años el monocultivo con herbicida logró el mayor rendimiento a expensas de usar dicho agroquímico lo que implica mayor demanda de insumos externos y riesgo ambiental. Los intercultivos tuvieron rendimientos aceptables no diferenciándose entre sí. Los intercultivos tuvieron mayor capacidad para suprimir cuando se sembró la leguminosa al voleo que en el surco. Además, permiten lograr un residuo de mejor cantidad y calidad aportando a la conservación de las propiedades del suelo y a la diversidad. El intercultivo con trébol rojo fue el que tuvo mayor capacidad supresiva en el mediano plazo. El intercultivo de lino con leguminosas forrajeras puede considerarse una estrategia para el manejo agroecológico de malezas en el largo plazo. Estas consociaciones, podrían adaptarse como alternativa productiva en la región pampeana argentina, mejorando la diversidad funcional y la sustentabilidad, con menor uso de insumos externos.