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Previous studies have emphasized culturally sensitive curricula in the context of enhancing minoritized students' education. We examined the relationship between second-year higher education students' perceptions of the cultural sensitivity of their curriculum and both majoritized and minoritized students' interest in their course. A total of 286 (228 F) students rated the cultural sensitivity of their curriculum on six scales using a revised version of the Culturally Sensitive Curricula Scales (CSCS-R), the perceived quality of their relationships with teachers, and their interest. The CSCS-R widened the construct with two new scales and showed better reliability. Ethnic minority students (n = 99) perceived their curriculum as less culturally sensitive than White students (n = 182), corroborating previous findings. Black students perceived their curriculum as less culturally sensitive than Asian students. There were no significant differences between ethnic minority and White students on interest or perceived quality of relationships with teachers. Five dimensions of cultural sensitivity "(Diversity Represented, Positive Depictions, Challenge Power, Inclusive Classroom Interactions, Culturally Sensitive Assessments)" and perceived quality of relationships with teachers predicted interest. Ethnicity did not. Ensuring curricula and assessments represent diversity positively, challenge power and are inclusive may support students' interest while reflecting an increasingly diverse society.

Abstract Metals have been used throughout history to manage disease. With the rising incidence of antibiotic-resistant bacterial strains, metal-based antimicrobials (MBAs) have re-emerged as an alternative to combat infections. Gallium nitrate has shown promising efficacy against several pathogens. Although its main toxicity mechanisms have focused on oxidative stress and its “trojan horse” iron mimetic strategy, there are still many knowledge gaps in the full-systems response elicited to counteract its toxic effects, especially in non-acute toxicity models that evaluate longer exposure times. In this study, we explore the transcriptomic response profile of Escherichia coli K12 BW25113 when challenged to grow planktonically for 10 h in the presence of a sublethal inhibitory concentration of gallium nitrate. 581 genes were significantly up-regulated, and 791 down-regulated. Some of the affected biological systems identified in our analysis include iron homeostasis, sulfate metabolism, oxidative and nitrosative stress response, cysteine biosynthesis, anaerobic respiration, toxin-antitoxin interactions, and DNA repair. Altogether, this work provides a valuable snapshot of how E. coli acclimates to this MBA and expands the current knowledge of mechanisms of sensitivity and tolerance. This is a significant step in understanding how bacteria can adjust their physiology to coexist with sublethal concentrations of toxic metals.

School-aged youth with behavioral health needs often struggle in the academic environment. When admitted to acute psychiatric hospital settings, the student's difficulties and needs increase upon discharge and return to the school setting. While the literature describes systemic issues in transitioning from an acute psychiatric hospital to the school setting, limited resources exist for practitioners to plan for and support the successful reintegration of affected students. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the purpose of the current systematic review was to collect and synthesize evidence from the literature (N = 20) in the areas of barriers, challenges, and significance of the need for a formal transition planning framework. Four major key factors emerged as important to assist in creating a transition planning framework for acute psychiatric hospitals to school-based settings: (a) Stakeholder Voice (Student, Caregiver, Hospital/Treatment Team, or School Team Voice); (b) Establishing a Point Person for Transition (Medical or School Point Person); (c) Recommendations/Accommodations (Formal or Informal Supports); and (d) Having a Transition Meeting. Other common factors are discussed, and recommendations are provided to aid practitioners in increasing the likelihood that school-age youth succeed in the school environment post-discharge from acute psychiatric settings. Finally, gaps in the literature are identified as areas for further research.

Abstract Van der Waals (vdW) magnetic materials are comprised of layers of atomically thin sheets, making them ideal platforms for studying magnetism at the two-dimensional (2D) limit. These materials are at the center of a host of novel types of experiments, however, there are notably few pathways to directly probe their magnetic structure. We confirm the magnetic order within a single crystal of NiPS3 and show it can be accessed with resonant elastic X-ray diffraction along the edge of the vdW planes in a carefully grown crystal by detecting structurally forbidden resonant magnetic X-ray scattering. We find the magnetic order parameter has a critical exponent of β ~ 0.36, indicating that the magnetism of these vdW crystals is more adequately characterized by the three-dimensional (3D) Heisenberg universality class. We verify these findings with first-principles density functional theory, Monte-Carlo simulations, and density matrix renormalization group calculations.

Abstract Neuroinflammation in the central nervous system (CNS), driven largely by resident phagocytes, has been proposed as a significant contributor to disability accumulation in multiple sclerosis (MS) but has not been addressed therapeutically. Bruton’s tyrosine kinase (BTK) is expressed in both B-lymphocytes and innate immune cells, including microglia, where its role is poorly understood. BTK inhibition may provide therapeutic benefit within the CNS by targeting adaptive and innate immunity-mediated disease progression in MS. Using a CNS-penetrant BTK inhibitor (BTKi), we demonstrate robust in vivo effects in mouse models of MS. We further identify a BTK-dependent transcriptional signature in vitro, using the BTKi tolebrutinib, in mouse microglia, human induced pluripotent stem cell (hiPSC)-derived microglia, and a complex hiPSC-derived tri-culture system composed of neurons, astrocytes, and microglia, revealing modulation of neuroinflammatory pathways relevant to MS. Finally, we demonstrate that in MS tissue BTK is expressed in B-cells and microglia, with increased levels in lesions. Our data provide rationale for targeting BTK in the CNS to diminish neuroinflammation and disability accumulation.

Objective: To compare the prevalence and trajectories of risky health behaviors in sexual minority (SM; lesbian/gay/bisexual/questioning/asexual) versus heterosexual undergraduates across their first year of post-secondary. Participants: First-year undergraduates (N = 704, M[subscript age] = 17.97 years, 24% SM) from a midsized Canadian university. Methods: Students completed monthly (September-April) online questionnaires assessing substance use (binge drinking, tobacco, cannabis, illicit drug use) and disordered eating (binge eating, fasting, purging). Results: At the outset of the academic year, SM students endorsed more frequent cannabis use, illicit drug use, fasting, and binge eating, but less frequent tobacco use, versus heterosexual students. Over the year, SM students' binge drinking frequency declined less than that of heterosexual students, but their illicit drug use decreased while that of their heterosexual peers increased, and all students reported declining disordered eating frequency. Conclusions: Campus wellness initiatives for SM students should offer prevention and harm-reduction strategies prior to or shortly after their arrival on campus.

This study evaluated the efficacy of (a) remote video-based behavioral skills training (BST) with added speech outlines on teaching public speaking behaviors and (b) remote video-based awareness training (AT) on speech-disfluency rates. A multiple-baseline design across speech behaviors was used to evaluate the training. Remote video-based BST and AT were effective at teaching public speaking behaviors and reducing speech disfluencies, respectively, for both participants. In addition, performance generalized to increased audience size. Although expert ratings of perceived public speaking effectiveness improved following BST, the ratings did not improve and some worsened following AT. Both participants reported satisfaction with video-based BST and AT. One participant reported greater comfort, confidence, overall ability, and less anxiety as a public speaker following BST. Both participants reported greater improvements in those categories following AT. Our results suggest that public speaking behaviors can be taught using remote video-based BST and speech disfluencies can be reduced using remote video-based AT.

Abstract Background and objectives Tolebrutinib is a covalent BTK inhibitor designed and selected for potency and CNS exposure to optimize impact on BTK-dependent signaling in CNS-resident cells. We applied a translational approach to evaluate three BTK inhibitors in Phase 3 clinical development in MS with respect to their relative potency to block BTK-dependent signaling and exposure in the CNS Methods We used in vitro kinase and cellular activation assays, alongside pharmacokinetic sampling of cerebrospinal fluid (CSF) in the non-human primate cynomolgus to estimate the ability of these candidates (evobrutinib, fenebrutinib, and tolebrutinib) to block BTK-dependent signaling inside the CNS. Results In vitro kinase assays demonstrated that tolebrutinib reacted with BTK 65-times faster than evobrutinib, while fenebrutinib, a classical reversible antagonist with a K i value of 4.7 nM and slow off-rate (1.54 x 10-5 s-1), also had an association rate 1760-fold slower (0.00245 μM-1 * s-1). Estimates of cellular potency were largely consistent with the in vitro kinase assays, with an estimated IC50 of 0.7 nM for tolebrutinib against 33.5 nM for evobrutinib and 2.9 nM for fenebrutinib. We then observed that evobrutinib, fenebrutinib, and tolebrutinib achieved similar levels of exposure in non-human primate CSF after oral doses of 10 mg/kg. However, tolebrutinib CSF exposure (4.8 ng/mL) (k p,uu CSF=0.40) exceeded the IC90 (the estimated concentration inhibiting 90% of kinase activity) value, while evobrutinib (3.2 ng/mL) (k p,uu CSF=0.13) and fenebrutinib (12.9 ng/mL) (kp,uu CSF=0.15) failed to reach the estimated IC90 values. Conclusions Tolebrutinib was the only candidate of the three that attained relevant CSF exposure in non-human primates. Graphical Abstract

Category: Ankle; Trauma Introduction/Purpose: Ankle fracture fixation can benefit from minimizing postoperative complications, particularly with wound healing and infection. Less invasive implant options necessitating smaller incisions have emerged, including the fibular intramedullary nail (i.e. Arthrex Fibulock) to minimize incisions and potentially allow earlier mobilization. The purpose of this study is to investigate the efficacy and clinical outcomes of a fibular intramedullary nail (Arthrex Fibulock) in ankle fracture treatment across a diverse patient cohort. Methods: A retrospective chart review from 2018 to 2022 was conducted in order to determine eligible patients. Inclusion criteria included adult patients treated for an ankle fracture with at least 3 months of follow-up and sufficient imaging available. Exclusion criteria included open fractures, other concomitant injuries, pilon and tibial shaft fractures, or previous ankle surgery. Results: A total of 132 patients were consecutively included, 44 in the conventional fixation group (33.33%) and 88 in the fibular nail group (66.67%). 4 out of 88 fibular nail patients (4.55%) and 3 out of 44 conventional patients (6.82%) had a postoperative infection (P = .43). 8 fibular nail (9.09%) and 6 conventional (13.64%) fixation patients underwent hardware removal postoperatively, which was not statistically significantly different (P = .55). Conclusion: This study shows no difference between the fibular nail device and a conventional plate and screw fixation approach in the treatment of ankle fractures when looking at postoperative infection and removal of hardware rates. The rate of postoperative infection and hardware removal trended higher in the conventional fixation patients but did not reach statistical significance. As such, the use of the fibular nail may offer a viable alternative for all patients undergoing ankle fracture operative treatment.

Abstract Nitrogen (N) dominates Earth's atmosphere (78% N2) but occurs in trace abundances in silicate minerals, making it a sensitive tracer of recycled surface materials into the mantle. The mechanisms controlling N transfer between terrestrial reservoirs remain uncertain because low N abundances in mineral‐hosted fluid inclusions (FIs) are difficult to measure. Using new techniques, we analyzed N and He isotope compositions and abundances in olivine‐ and pyroxene‐hosted FIs from arc volcanoes in Southern Chile, Cascadia, Central America, and the Southern Marianas. These measurements enable an estimate of the global flux of N outgassing from arcs (4.0 × 1010 mol/yr). This suggests that Earth is currently in a state of net N ingassing, with roughly half of subducted N returned to the mantle. Additionally, the N outgassing flux of individual arcs correlates with the thickness of subducting pelagic sediment, suggesting that N cycling in the modern solid Earth is largely controlled by sediment subduction.

ABSTRACT Genome-wide association studies (GWAS) with binary or single phenotype data have successfully identified disease-associated genotypes and determinants of antimicrobial resistance. We describe a novel phenotype-to-genotype approach for a major bacterial pathogen that involves simultaneously testing for associations among multiple disease-related phenotypes and linkages between phenotypic variation and genetic determinants. High-throughput assays quantified variation among 163 Neisseria meningitidis serogroup W ST-11 clonal complex isolates for 11 phenotypic traits. A comparison of carriage and two disease subgroups detected significant differences between groups for eight phenotypic traits. Candidate genotypic testing indicated that indels in csw, a capsular biosynthesis gene, were associated with reduced survival in antibody-depleted heat-inactivated serum. GWAS testing detected 341 significant genetic variants (3 single-nucleotide polymorphisms and 338 unitigs) across all traits except serum bactericidal antibody-depleted assays. Growth traits were associated with variants of capsular biosynthesis genes, carbonic anhydrase, and an iron-uptake system while adhesion-linked variation was in pilC2, marR, and mutS. Multiple phase variation states or combinatorial phasotypes were associated with significant differences in multiple phenotypes. Controlling for group effects through regression and recursive random forest approaches detected group-independent effects for nalP with biofilm formation and fetA with a growth trait. Through random forest testing, nine phenotypes were weakly predictive of MenW:cc11 sub-lineage, original or 2013, for disease isolates while three characteristics separated carriage and disease isolates with >80% accuracy. This study demonstrates the power of combining high-throughput phenotypic testing of pathogenically relevant isolate collections with genomics for identifying genetic determinants of specific disease-relevant phenotypes and the pathobiology of microbial pathogens.IMPORTANCENext-generation sequencing technologies have led to the creation of extensive microbial genome sequence databases for several bacterial pathogens. Mining of these databases is now imperative for unlocking the maximum benefits of these resources. We describe a high-throughput methodology for detecting associations between phenotypic variation in multiple disease-relevant traits and a range of genetic determinants for Neisseria meningitidis, a major causative agent of meningitis and septicemia. Phenotypic variation in 11 disease-related traits was determined for 163 isolates of the hypervirulent ST-11 lineage and linked to specific single-nucleotide polymorphisms, short sequence variants, and phase variation states. Application of machine learning algorithms to our data outputs identified combinatorial phenotypic traits and genetic variants predictive of a disease association. This approach overcomes the limitations of generic meta-data, such as disease versus carriage, and provides an avenue to explore the multi-faceted nature of bacterial disease, carriage, and transmissibility traits.

With the introduction of x-ray free electron laser sources around the world, new scientific approaches for visualizing matter at fundamental length and time-scales have become possible. As it relates to magnetism and ‘magnetic-type’ systems, advanced scattering methods are being developed for studying ultrafast magnetic responses on the time-scales at which they occur. We describe three capabilities which have the potential to seed new directions in this area and presentoriginal results from each: pump-probe x-ray scattering with low energy excitation, x-ray photon fluctuation spectroscopy, and ultrafast diffuse x-ray scattering. By combining these experimental techniques with advanced modeling together with machine learning, we describe how the combination of these domains allows for a new understanding in the field of magnetism. Finally, we give an outlook for future areas of investigation and the newly developed instruments which will take us there.

This study explores the synthesis and characterization of gold nanoparticles (AuNPs) using green and chemical methods, employing ginger extract and curcumin as reducing agents, in comparison to sodium citrate reduction. The biosynthesized AuNPs synthesized with ginger extract exhibited an average hydrodynamic diameter of 15 and 10 nm for curcumin-conjugated AuNPs, while chemically synthesized AuNPs with sodium citrate displayed an average size of 10 nm. Assessments via Zeta potential measurements revealed negative surface charges across all samples, with the curcumin-conjugated AuNPs showing −36.3 mV, ginger extract-synthesized AuNPs showing −31.7 mV, and chemically produced gold nanoparticles having a surface charge of −40.4 mV. Transmission Electron Microscopy (TEM) confirmed spherical morphologies for the synthesized nanoparticles,and it revealed the presence of biomolecules embedded within the nanoparticles synthesized using biological materials, whereas chemically synthesized AuNPs lacked such features. The FTIR spectra of the biosynthesized AuNPs highlighted the presence of phenolic and aromatic compounds from the ginger extract and curcumin, indicating their role in coating the nanoparticles. Gas chromatography-mass spectrometry (GC-MS) analysis identified gingerol as a key component in the ginger extract, contributing to nanoparticle capping. The antimicrobial efficacy of the AuNPs was evaluated against P. aeruginosa, E. coli, and S. aureus, revealing superior activity for curcumin-AuNPs, with ginger-AuNPs also outperforming chemically synthesized counterparts. These findings confirm the advantages of biological approaches, using a plant extract like ginger and pure curcumin suspension, for better size distribution when used as reducing agents, along with improved antimicrobial efficacy compared to chemically produced gold nanoparticles synthesized with sodium citrate. This study also highlight the potential of green-synthesized AuNPs in biomedical applications, due to their enhanced stability from higher surface charge and the repeatability of biological methods.

ABSTRACT Multi-target antimicrobial agents are considered a viable alternative to target-specific antibiotics, resistance to which emerged as a global threat. Used centuries before the discovery of conventional antibiotics, metal(loid)-based antimicrobials (MBAs), which target multiple biomolecules within the bacterial cell, are regaining research interest. However, there is a significant limiting factor—the balance between cost and efficiency. In this article, we utilize a checkerboard assay approach to explore antimicrobial combinations of MBAs with commonly used quaternary ammonium compound (QAC) antiseptics in order to discover novel combinations with more pronounced antimicrobial properties than would be expected from a simple sum of antimicrobial effects of initial components. This phenomenon, called synergy, was herein demonstrated for several mixtures of Al3+with cetyltrimethylammonium bromide (CTAB) and TeO32- with benzalkonium chloride (BAC) and didecyldimethylammonium bromide (DDAB) against planktonic and biofilm growth of Pseudomonas aeruginosa ATCC27853. Biofilm growth of Escherichia coli ATCC25922 was synergistically inhibited by the Cu2 +and benzalkonium chloride (BAC) mixture. Multiple additive mixtures were identified for both organisms. The current study observed unexpected species and growth state specificities for the synergistic combinations. The benefit of synergistic mixtures will be captured in economy/efficiency optimization for antimicrobial applications in which MBAs and QACs are presently used.IMPORTANCEWe are entering the antimicrobial resistance era (AMR), where resistance to antibiotics is becoming more and more prevalent. In order to address this issue, various approaches are being explored. In this article, we explore for synergy between two very different antimicrobials, the antiseptic class of quaternary ammonium compounds and antimicrobial metals. These two antimicrobials have very different actions. Considering a OneHealth approach to the problem, finding synergistic mixtures allows for greater efficacy at lower concentrations, which would also address antimicrobial pollution issues.

Joint analyses of the large-scale distribution of galaxies, and their motions under the gravitational influence of this density field, allow powerful tests of the cosmological model, including measurement of the growth rate of cosmic structure. In this paper we perform a statistical comparison between two important classes of method for performing these tests. In the first method, which we refer to as the "power-spectrum method", we measure the 2-point power spectra between the velocity and density tracers, and jointly fit these statistics using theoretical models. In the second method, which we refer to as the "reconstruction-and-scaling method", we use the density tracers to reconstruct a model velocity field through space, which we compare with the measured galaxy velocities on a point-by-point basis. By generating an ensemble of numerical simulations in a simplified test scenario, we show that the error in the growth rate inferred by the reconstruction-and-scaling method may be under-estimated, unless the full covariances of the underlying and reconstructed velocity fields are included in the analysis. In this case the inferred growth rate errors agree with both the power-spectrum method and a Fisher matrix forecast. We provide a roadmap for evaluating these covariances, considering reconstruction performed using both a Fourier basis within a cuboid, and a Spherical Fourier-Bessel basis within a curved-sky observational volume.

Background: Precautionary Allergen (“may contain”) Labelling (PAL) is used by industry to communicate potential risk to food-allergic individuals posed by unintended allergen presence (UAP). In 2014, the World Allergy Organization (WAO) highlighted that PAL use was increasing, but often applied inconsistently and without regulation — which reduces its usefulness to consumers with food allergy and those purchasing food for them. WAO proposed the need for a regulated, international framework to underpin application of PAL. In 2019, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations convened an expert consultation to address the issue of PAL, the outputs of which are now being considered by the Codex Committee on Food Labelling (CCFL). Objectives: To summarise the latest data to inform the application of PAL in a more systematic way, for implementation into global food standards. Methods: A non-systematic review of issues surrounding precautionary labelling and food allergens in pre-packaged products. Results: Approximately, 100 countries around the world have legislation on the declaration of allergenic ingredients. Just a few have legislation on UAP. Given the risks that UAP entails, non-regulated PAL creates inconvenience in real life due to its unequal, difficult interpretation by patients. The attempts made so far to rationalize PAL present lights and shadows. Conclusions: At a time when CCFL is considering the results of the FAO/WHO Expert Consultation 2020–2023, we summarise the prospects to develop an effective and homogeneous legislation at a global level, and the areas of uncertainty that might hinder international agreement on a regulated framework for PAL of food allergens.

Abstract In this research, biogenic selenium nanoparticles were produced by the fungi Yarrowia lipolytica, and the biological activity of its nanoparticles was studied for the first time. The electron microscopy analyses showed the production of nanoparticles were intracellular and the resulting particles were extracted and characterized by XRD, zeta potential, FESEM, EDX, FTIR spectroscopy and DLS. These analyses showed amorphous spherical nanoparticles with an average size of 110 nm and a Zeta potential of −34.51 ± 2.41 mV. Signatures of lipids and proteins were present in the capping layer of biogenic selenium nanoparticles based on FTIR spectra. The antimicrobial properties of test strains showed that Serratia marcescens, Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis were inhibited at concentrations between 160 and 640 μg/mL, while the growth of Candida albicans was hindered by 80 μg/mL of biogenic selenium nanoparticles. At concentrations between 0.5 and 1.5 mg/mL of biogenic selenium nanoparticles inhibited up to 50% of biofilm formation of Klebsiella pneumonia, Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa. Additionally, the concentration of 20–640 μg/mL of these bioSeNPs showed antioxidant activity. Evaluating the cytotoxicity of these nanoparticles on the HUVEC and HepG2 cell lines did not show any significant toxicity within MIC concentrations of SeNPs. This defines that Y. lipolytica synthesized SeNPs have strong potential to be exploited as antimicrobial agents against pathogens of WHO concern.

Abstract NASA's Orbiting Carbon Observatories (OCO‐2 and OCO‐3) provide measurements of column‐averaged carbon dioxide concentrations (XCO2) with sufficient spatial resolution and precision to constrain bottom‐up estimates of CO2 fluxes at regional scales. We use Bayesian inversion methods assimilating satellite retrievals to improve estimates of CO2 fluxes in the South Coast Air Basin (SoCAB) which surrounds Los Angeles, and in the San Francisco Bay Area Air Basin (SFBA). We study 2020 to understand the impact of the COVID‐19 lockdowns and an active wildfire season. Our results indicated that a 50% (30%) reduction in CO2 emissions relative to 2015 during the COVID‐19 lockdown period was consistent with OCO measurements for SFBA (SoCAB). We find that posterior wildfire emissions differed significantly from the prior at the scale of individual wildfires, though with large uncertainties, and that wildfire emissions in SFBA are significant, attributing 72% of the region's CO2 emissions during August 2020 to wildfires.

Abstract While ethnobiology is a discipline that focuses on the local, it has an outstanding, but not yet fully realized potential to address global issues. Part of this unrealized potential is that universalistic approaches often do not fully recognize culturally grounded perspectives and there are multiple challenges with scaling up place-based research. However, scalability is paramount to ensure that the intimate and context-specific diversity of human–environmental relationships and understandings are recognized in global-scale planning and policy development. Here, we identify four pathways to enable the scalability of place-based ethnobiological research from the ground up: local-to-global dialogues, aggregation of published data, multi-sited studies, and geospatial analyses. We also discuss some major challenges and consideration to encourage continuous reflexivity in these endeavours and to ensure that scalability does not contribute to unnecessarily decontextualizing, co-opting, or overwriting the epistemologies of Indigenous Peoples and local communities. As ethnobiology navigates multiple scales of time and space and seeks to increase its breadth, this study shows that the use of deliberately global approaches, when carefully nested within rich field-based and ecological and ethnographically grounded data, can contribute to: (1) upscaling case-specific insights to unveil global patterns and dynamics in the biocultural contexts of Indigenous Peoples and local communities; (2) bringing ethnobiological knowledge into resolutions that can influence global environmental research and policy agendas; and (3) enriching ethnobiology’s field-based ethos with a deliberate global analytical focus.

Abstract Background Care for injured patients in England is provided by inclusive regional trauma networks. Ambulance services use triage tools to identify patients with major trauma who would benefit from expedited Major Trauma Centre (MTC) care. However, there has been no investigation of triage performance, despite its role in ensuring effective and efficient MTC care. This study aimed to investigate the accuracy of prehospital major trauma triage in representative English trauma networks. Methods A diagnostic case-cohort study was performed between November 2019 and February 2020 in 4 English regional trauma networks as part of the Major Trauma Triage Study (MATTS). Consecutive patients with acute injury presenting to participating ambulance services were included, together with all reference standard positive cases, and matched to data from the English national major trauma database. The index test was prehospital provider triage decision making, with a positive result defined as patient transport with a pre-alert call to the MTC. The primary reference standard was a consensus definition of serious injury that would benefit from expedited major trauma centre care. Secondary analyses explored different reference standards and compared theoretical triage tool accuracy to real-life triage decisions. Results The complete-case case-cohort sample consisted of 2,757 patients, including 959 primary reference standard positive patients. The prevalence of major trauma meeting the primary reference standard definition was 3.1% (n=54/1,722, 95% CI 2.3 – 4.0). Observed prehospital provider triage decisions demonstrated overall sensitivity of 46.7% (n=446/959, 95% CI 43.5-49.9) and specificity of 94.5% (n=1,703/1,798, 95% CI 93.4-95.6) for the primary reference standard. There was a clear trend of decreasing sensitivity and increasing specificity from younger to older age groups. Prehospital provider triage decisions commonly differed from the theoretical triage tool result, with ambulance service clinician judgement resulting in higher specificity. Conclusions Prehospital decision making for injured patients in English trauma networks demonstrated high specificity and low sensitivity, consistent with the targets for cost-effective triage defined in previous economic evaluations. Actual triage decisions differed from theoretical triage tool results, with a decreasing sensitivity and increasing specificity from younger to older ages.

Abstract How RNA-binding proteins (RBPs) convey regulatory instructions to the core effectors of RNA processing is unclear. Here, we document the existence and functions of a multivalent RBP–effector interface. We show that the effector interface of a conserved RBP with an essential role in metazoan development, Unkempt, is mediated by a novel type of ‘dual-purpose’ peptide motifs that can contact two different surfaces of interacting proteins. Unexpectedly, we find that the multivalent contacts do not merely serve effector recruitment but are required for the accuracy of RNA recognition by Unkempt. Systems analyses reveal that multivalent RBP–effector contacts can repurpose the principal activity of an effector for a different function, as we demonstrate for the reuse of the central eukaryotic mRNA decay factor CCR4-NOT in translational control. Our study establishes the molecular assembly and functional principles of an RBP–effector interface.

Cryoseismology is a powerful toolset for progressing the understanding of the structure and dynamics of glaciers and ice sheets. It can enable the detection of hidden processes such as brittle fracture, basal sliding, transient hydrological processes, and calving. Addressing the challenge of detecting signals from many different processes, we present a novel approach for the semi-automated detection of events and event-like noise, which is well-suited for use as Part 1 of a workflow where unsupervised machine learning will be used as Part 2 (Latto et al., 2024) to facilitate the main reconnaissance of diverse detected event types. Implemented in the open-source and widely used ObsPy Python package, the multi-STA/LTA algorithm constructs a hybrid characteristic function from a set of short-term average (sta)–long-term average (lta) pairs (refer to Sect. 2 in the main text for an explanation of how uppercase and lowercase STA/sta and LTA/lta abbreviations are differentiated). We apply the algorithm to data from a seismic array deployed on the Whillans Ice Stream (WIS) in West Antarctica (austral summer 2010–2011) to form a “catch-all” catalogue of events and event-like noise. The new algorithm compares favorably with standard approaches, yielding a diversity of seismic events, including all previously identified stick-slip events (Pratt et al., 2014), teleseisms, and other noise-type signals. In terms of a catalogue overview, we investigate a partial association of seismicity with the tidal cycle and a slight association with ice temperature changes of the Antarctic summer. The new algorithm and workflow will assist in the comparison of different glacier environments using seismology, the identification of process change over time, and the targeting of possible subsequent high-resolution studies.

Given the high number and diversity of events in a typical cryoseismic dataset, in particular those recorded on ice sheet margins, it is desirable to use a semi-automated method of grouping similar events for reconnaissance and ongoing analysis. We present a workflow for employing semi-unsupervised cluster analysis to inform investigations of the processes occurring in glaciers and ice sheets. In this demonstration study, we make use of a seismic event catalogue previously compiled for the Whillans Ice Stream, for the 2010–2011 austral summer (outlined in Part 1, Latto et al., 2024). We address the challenges of seismic event analysis for a complex wave field by clustering similar seismic events into groups using characteristic temporal, spectral, and polarization attributes of seismic time series with the k-means++ algorithm. This provides the basis for a reconnaissance analysis of a seismic wave field that contains local events (from the ice stream) set in an ambient wave field that itself contains a diversity of signals (mostly from the Ross Ice Shelf). As one result, we find that two clusters include stick-slip events that diverge in terms of length and initiation locality (i.e., central sticky spot and/or the grounding line). We also identify a swarm of high-frequency signals on 16–17 January 2011 that are potentially associated with a surface melt event from the Ross Ice Shelf. Used together with the event detection presented in Part 1, the semi-automated workflow could readily be generalized to other locations and, as a possible benchmark procedure, could enable the monitoring of remote glaciers over time and comparisons between locations.

Summary: Inspired by advancements in natural language processing, we utilize self-supervised learning and an equivariant graph neural network to develop a unified platform for training generative models capable of generating inorganic crystal structures, as well as efficiently adapting to downstream tasks in material property prediction. To mitigate the challenge of evaluating the reliability of generated structures during training, we employ a generative adversarial network (GAN) with its discriminator being a cost-effective reliability evaluator, significantly enhancing model performance. We demonstrate the utility of our model in optimizing crystal structures under predefined conditions. Without external properties acquired experimentally or numerically, our model further displays its capability to help understand inorganic crystal formation by grouping chemically similar elements. This paper extends an invitation to further explore the scientific understanding of material structures through generative models, offering a fresh perspective on the scope and efficacy of machine learning in material science.

Abstract Many pathological conditions lead to defects in intestinal epithelial integrity and loss of barrier function; Sphingosine‐1‐phosphate (S1P) has been shown to augment intestinal barrier integrity, though the exact mechanisms are not completely understood. We have previously shown that overexpression of Sphingosine Kinase 1 (SphK1), the rate limiting enzyme for S1P synthesis, significantly increased S1P production and cell proliferation. Here we show that microRNA 495 (miR‐495) upregulation led to decreased levels of SphK1 resultant from a direct effect at the SphK1 mRNA. Increasing expression of miR‐495 in intestinal epithelial cells resulted in decreased proliferation and increased susceptibility to apoptosis. Transgenic expression of miR‐495 inhibited mucosal growth, as well as decreased proliferation in the crypts. The intestinal villi also expressed decreased levels of barrier proteins and exaggerated damage upon exposure to cecal ligation‐puncture. These results implicate miR‐495 as a critical negative regulator of intestinal epithelial protection and proliferation through direct regulation of SphK1, the rate limiting enzyme critical for production of S1P.

Abstract Nanoscience, a pivotal field spanning multiple industries, including healthcare, focuses on nanomaterials characterized by their dimensions. These materials are synthesized through conventional chemical and physical methods, often involving costly and energy‐intensive processes. Alternatively, biogenic synthesis using bacteria, fungi, or plant extracts offers a potentially sustainable and non‐toxic approach for producing metal‐based nanoparticles (NP). This eco‐friendly synthesis approach not only reduces environmental impact but also enhances features of NP production due to the unique biochemistry of the biological systems. Recent advancements have shown that along with chemically synthesized NPs, biogenic NPs possess significant antimicrobial properties. The inherent biochemistry of bacteria enables the efficient conversion of metal salts into NPs through reduction processes, which are further stabilized by biomolecular capping layers that improve biocompatibility and functional properties. This mini review explores the use of bacteria to produce NPs with antimicrobial activities. Microbial technologies to produce NP antimicrobials have considerable potential to help address the antimicrobial resistance crisis, thus addressing critical health issues aligned with the United Nations Sustainability Goal #3 of good health and well‐being.

Combining zinc nitrate with 3- and/or 4- aminocinnamic acid (3-ACA and 4-ACA, respectively) leads to the formation of the 0D complex [Zn(4-AC)2(H2O)2], the 1D coordination polymer [Zn(3-AC)(4-AC)], and the 2D and 3D MOFs [Zn(3-AC)2]∙2H2O and [Zn(4-AC)2]∙H2O, respectively. These compounds result from the deprotonation of the acid molecules, with the resulting 3- and 4-aminocinnamate anions serving as bidentate terminal or bridging ligands. All solids were fully characterized via single crystal and powder X-ray diffraction and thermal techniques. Given the mild antimicrobial properties of cinnamic acid derivatives and the antibacterial nature of the metal cation, these compounds were assessed and demonstrated very good planktonic cell killing as well as inhibition of biofilm growth against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus.

Abstract Soils are a major source of nitrogen oxides, which in the atmosphere help govern its oxidative capacity. Thus the response of soil nitric oxide (NO) emissions to forcings such as warming or forest loss has a meaningful impact on global atmospheric chemistry. We find that the soil emission rate of NO in Amazonia from a common inventory is biased low by at least an order of magnitude in comparison to tower‐based observations. Accounting for this regional bias decreases the modeled global methane lifetime by 1.4%–2.6%. In comparison, a fully deforested Amazonia, representing a 37% decrease in global emissions of isoprene, decreases methane lifetime by at most 4.6%, highlighting the sensitive response of oxidation rates to changes in emissions of NO compared to those of terpenes. Our results demonstrate that improving our understanding of soil NO emissions will yield a more accurate representation of atmospheric oxidative capacity.

Abstract Introduction This article provides an overview of presentations and discussions from the inaugural Healthcare Delivery Science: Innovation and Partnerships for Health Equity Research (DESCIPHER) Symposium. Methods The symposium brought together esteemed experts from various disciplines to explore models for translating evidence‐based interventions into practice. Results The symposium highlighted the importance of disruptive innovation in healthcare, the need for multi‐stakeholder engagement, and the significance of family and community involvement in healthcare interventions. Conclusions The article concluded with a call to action for advancing healthcare delivery science to achieve health equity.

Following successful oral immunotherapy (OIT) for peanut allergy using boiled peanuts (BOPI trial), this study investigated the potential of wet-thermal-processing-induced allergen modification, specifically soaking and boiling (1–4 h) to reduce the allergenicity of cashew and pistachio allergens. In addition, this study provides a foundation of understanding for developing safer forms of cashew/pistachio administration for application in OIT by gradual exposure to increasing doses of modified allergens with reduced potency as an “allergen ladder”. An SDS-PAGE analysis and an intrinsic-fluorescence spectroscopy revealed altered tertiary structures of the allergens, leading to their denaturation and even degradation. Notably, the reduction in both allergen-specific polyclonal IgG and human-specific IgE (sIgE) binding correlated with the treatment time, with the most significant decrease observed after 4 h of boiling. In contrast, shorter soaking treatments showed negligible effects on the IgE-binding capacity of these nuts, therefore indicating a further need for optimization. These findings indicate that extended boiling effectively reduced the amounts of the highly potent allergenic component Ana o 3 in cashew and Pis v 1 in pistachio, as confirmed by ELISA using polyclonal anti-Ana o 3 antibodies, and an immunoblot showed decreased IgE epitope binding in cashew and pistachio allergens, which further modified their allergenic profiles. This approach shows promise as a viable method for offering a safer therapeutic option for cashew/pistachio allergy.

Abstract Background Point mutations in histone variant H3.3 (H3.3K27M, H3.3G34R) and the H3.3-specific ATRX/DAXX chaperone complex are frequent events in pediatric gliomas. These H3.3 point mutations affect many chromatin modifications but the exact oncogenic mechanisms are currently unclear. Histone H3.3 is known to localize to nuclear compartments known as promyelocytic leukemia (PML) nuclear bodies, which are frequently mutated and confirmed as oncogenic drivers in acute promyelocytic leukemia. Results We find that the pediatric glioma-associated H3.3 point mutations disrupt the formation of PML nuclear bodies and this prevents differentiation down glial lineages. Similar to leukemias driven by PML mutations, H3.3-mutated glioma cells are sensitive to drugs that target PML bodies. We also find that point mutations in IDH1/2—which are common events in adult gliomas and myeloid leukemias—also disrupt the formation of PML bodies. Conclusions We identify PML as a contributor to oncogenesis in a subset of gliomas and show that targeting PML bodies is effective in treating these H3.3-mutated pediatric gliomas.

Abstract CAR (CARSKNKDC) is a wound-homing peptide that recognises angiogenic neovessels. Here we discover that systemically administered CAR peptide has inherent ability to promote wound healing: wounds close and re-epithelialise faster in CAR-treated male mice. CAR promotes keratinocyte migration in vitro. The heparan sulfate proteoglycan syndecan-4 regulates cell migration and is crucial for wound healing. We report that syndecan-4 expression is restricted to epidermis and blood vessels in mice skin wounds. Syndecan-4 regulates binding and internalisation of CAR peptide and CAR-mediated cytoskeletal remodelling. CAR induces syndecan-4-dependent activation of the small GTPase ARF6, via the guanine nucleotide exchange factor cytohesin-2, and promotes syndecan-4-, ARF6- and Cytohesin-2-mediated keratinocyte migration. Finally, we show that genetic ablation of syndecan-4 in male mice eliminates CAR-induced wound re-epithelialisation following systemic administration. We propose that CAR peptide activates syndecan-4 functions to selectively promote re-epithelialisation. Thus, CAR peptide provides a therapeutic approach to enhance wound healing in mice; systemic, yet target organ- and cell-specific.

Background: Taking inspiration from the classical 1974, “moving room experiment” by Lee and Aronson, a “virtual moving room paradigm (Vroom)” was designed using virtual reality (VR) to assess postural control behavior. Methods: Thirty healthy adults (age: 21 ± 1 years; height: 166.5 ± 7.3 cm; mass: 71.7 ± 16.2 kg) were tested for postural stability in a virtual moving room paradigm (Vroom). The Vroom consisted of randomized virtual and visual perturbations of the virtual room moving toward and away from the individual, during both unexpected and expected trials. Objective postural sway variables and subjective experiences to VR using the simulator sickness questionnaire as well as balance confidence scale were also assessed and analyzed using a two way (2 × 2 [2 moving room direction (Toward vs. Away) and 2 knowledge of moving room (unexpected vs. expected)] repeated measures analysis of variance (ANOVA), and a one-way repeated measures ANOVA and paired sample t-test, respectively at an alpha level of 0.05. Results: Significantly greater postural sway was observed when the virtual room moved toward the participant than when moving away, and when it moved unexpectedly, compared with the expected moving room. Significantly improved balance confidence with realistic immersion and without simulator sickness was also observed. Conclusions: Our findings provide evidence indicating that the virtual moving room induces postural perturbations that challenge the postural control system, especially when the moving room is unexpected and moves toward the individual. Additionally, increased balance confidence and realistic immersion in the virtual environment with no adverse effects of simulator sickness were observed, providing evidence for the beneficial effects of the Vroom. Thus, the Vroom can be an easy and cost-effective method to expose individuals to realistic, virtual, and visual perturbations that challenge the postural control system and increase balance confidence, with realistic immersion and without adverse effects.

Abstract A search is presented for single production of a vector-like B quark decaying into a Standard Model b-quark and a Standard Model Higgs boson, which decays into a b b ¯ $$ b\overline{b} $$ pair. The search is carried out in 139 fb −1 of s $$ \sqrt{s} $$ = 13 TeV proton-proton collision data collected by the ATLAS detector at the LHC between 2015 and 2018. No significant deviation from the Standard Model background prediction is observed, and mass-dependent exclusion limits at the 95% confidence level are set on the resonance production cross-section in several theoretical scenarios determined by the couplings c W , c Z and c H between the B quark and the Standard Model W, Z and Higgs bosons, respectively. For a vector-like B occurring as an isospin singlet, the search excludes values of c W greater than 0.45 for a B resonance mass (m B ) between 1.0 and 1.2 TeV. For 1.2 TeV < m B < 2.0 TeV, c W values larger than 0.50–0.65 are excluded. If the B occurs as part of a (B, Y) doublet, the smallest excluded c Z coupling values range between 0.3 and 0.5 across the investigated resonance mass range 1.0 TeV < m B < 2.0 TeV.

ABSTRACT Novel antimicrobial agents are needed to combat antimicrobial resistance. This study tested novel pentafluorosulfanyl-containing triclocarban analogs for their potential antibacterial efficacy. Standard procedures were used to produce pentafluorosulfanyl-containing triclocarban analogs. Twenty new compounds were tested against seven Gram-positive and Gram-negative indicator strains as well as 10 clinical isolates for their antibacterial and antibiofilm activity. Mechanistic investigations focused on damage to cell membrane, oxidizing reduced thiols, iron-sulfur clusters, and oxidative stress to explain the compounds’ activity. Safety profiles were assessed using cytotoxicity experiments in eukaryotic cell lines. Following screening, selected components had significantly better antibacterial and antibiofilm activity against Gram-positive bacteria in lower concentrations in comparison to ciprofloxacin and gentamycin. For instance, one compound had a minimum inhibitory concentration of

Background. Diabetic foot syndrome is defined as the presence of a diabetic foot ulcer (DFU) associated with neuropathy, peripheral artery disease and infection. While the use of antimicrobials in the treatment of DFU infection remains a mainstay, the choice of antimicrobial remains problematic owing to the presence of multidrug-resistant polymicrobial infections. In the South African public healthcare sector, the treatment of DFUs is based on the Standard Treatment Guidelines (STGs) and the Essential Drug List. These guidelines are developed using evidence-based medicine and are based on global susceptibility patterns rather than local susceptibility data, and may not provide the most appropriate treatment options. Objectives. To determine the antimicrobial susceptibility patterns of DFUs isolated from patients visiting selected Gauteng provincial public hospitals in order to determine a clinically effective treatment protocol for the management of these infections. Methods. Sample swabs were taken from 51 DFUs using the Levine method. Each sample swab was spread onto blood agar plates, and thereafter individual pathogens were isolated. The antimicrobial susceptibility patterns of all isolated pathogens were determined using zone of inhibition measurements. Pathogens were grouped according to macromorphological characteristics as well as susceptibility patterns, and a representative isolate from each group was then identified. Results. A total of 51 DFU ulcer swabs from 45 patients were included in the study. From the sample swabs, a total of 445 pathogens were isolated. The most effective antimicrobial was found to be gentamicin, followed by ciprofloxacin. Amoxicillin/clavulanic acid, the first-line treatment according to the STGs, was found to be ineffective for many of the isolated pathogens. The most commonly isolated pathogens were Proteus mirabilis, Enterococcus faecalis and Pseudomonas aeruginosa. Conclusion. These findings demonstrate the urgent need to reassess the STGs and base treatment plans on local epidemiological data. This study provides valuable data on common causative pathogens in DFU infections, as well as the resistance patterns of these pathogens, forming a baseline on which to base future DFU treatment plans.

Background: Occupational workers at altitudes are more prone to falls, leading to catastrophic outcomes. Acrophobia, height-related anxiety, and affected executive functions lead to postural instabilities, causing falls. This study investigated the effects of repeated virtual height exposure and training on cognitive processing and height-related anxiety. Methods: Twenty-eight healthy volunteers (age 20.48 ± 1.26 years; mass 69.52 ± 13.78 kg) were recruited and tested in seven virtual environments (VE) [ground (G), 2-story altitude (A1), 2-story edge (E1), 4-story altitude (A2), 4-story edge (E2), 6-story altitude (A3), and 6-story edge (E3)] over three days. At each VE, participants identified occupational hazards present in the VE and completed an Attitude Towards Heights Questionnaire (ATHQ) and a modified State-Trait Anxiety Inventory Questionnaire (mSTAIQ). The number of hazards identified and the ATHQ and mSTAIQ scores were analyzed using a 7 (VE; G, A1, A2, A3, E1, E2, E3) x 3 (DAY; DAY 1, DAY 2, DAY 3) factorial repeated measures analysis of variance. Results: The participants identified the lowest number of hazards at A3 and E3 VEs and on DAY 1 compared to other VEs and DAYs. ATHQ scores were lowest at G, A1, and E1 VEs. Conclusion: Cognitive processing is negatively affected by virtual altitudes, while it improves with short-term training. The features of virtual reality, such as higher involvement, engagement, and reliability, make it a better training tool to be considered in ergonomic settings. The findings of this study will provide insights into cognitive dual-tasking at altitude and its challenges, which will aid in minimizing occupational falls.

Abstract Understanding the nature and origin of collective excitations in materials is of fundamental importance for unraveling the underlying physics of a many-body system. Excitation spectra are usually obtained by measuring the dynamical structure factor, S(Q, ω), using inelastic neutron or x-ray scattering techniques and are analyzed by comparing the experimental results against calculated predictions. We introduce a data-driven analysis tool which leverages ‘neural implicit representations’ that are specifically tailored for handling spectrographic measurements and are able to efficiently obtain unknown parameters from experimental data via automatic differentiation. In this work, we employ linear spin wave theory simulations to train a machine learning platform, enabling precise exchange parameter extraction from inelastic neutron scattering data on the square-lattice spin-1 antiferromagnet La2NiO4, showcasing a viable pathway towards automatic refinement of advanced models for ordered magnetic systems.