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Global potent greenhouse gas nitrous oxide (N2O) emissions from soil are accelerating, with increases in the proportion of reactive nitrogen emitted as N2O, i.e., N2O emission factor (EF). Yet, the primary controls and underlying mechanisms of EFs remain unresolved. Based on two independent but complementary global syntheses, and three field studies determining effects of acidity on N2O EFs and soil denitrifying microorganisms, we show that soil pH predominantly controls N2O EFs and emissions by affecting the denitrifier community composition. Analysis of 5438 paired data points of N2O emission fluxes revealed a hump-shaped relationship between soil pH and EFs, with the highest EFs occurring in moderately acidic soils that favored N2O-producing over N2O-consuming microorganisms, and induced high N2O emissions. Our results illustrate that soil pH has a unimodal relationship with soil denitrifiers and EFs, and the net N2O emission depends on both the N2O/(N2O + N2) ratio and overall denitrification rate. These findings can inform strategies to predict and mitigate soil N2O emissions under future nitrogen input scenarios.

People form social evaluations of others following brief exposure to their voices, and these impressions are calibrated based on recent perceptual experience. Participants adapted to voices with fundamental frequency (f o; the acoustic correlate of perceptual pitch) manipulated to be gender-typical (i.e. masculine men and feminine women) or gender-atypical (i.e. feminine men and masculine women) before evaluating unaltered test voices within the same sex. Adaptation resulted in contrastive aftereffects. Listening to gender-atypical voices caused female voices to sound more feminine and attractive (Study 1) and male voices to sound more masculine and attractive (Study 2). Studies 3a and 3b tested whether adaptation occurred on a conceptual or perceptual level, respectively. In Study 3a, perceivers adapted to gender-typical or gender-atypical voices for both men and women (i.e. adaptors pitch manipulated in opposite directions for men and women) before evaluating unaltered test voices. Findings showed weak evidence that evaluations differed between conditions. In Study 3b, perceivers adapted to masculinized or feminized voices for both men and women (i.e. adaptors pitch manipulated in the same direction for men and women) before evaluating unaltered test voices. In the feminized condition, participants rated male targets as more masculine and attractive. Conversely, in the masculinized condition, participants rated female targets as more feminine and attractive. Voices appear to be evaluated according to gender norms that are updated based on perceptual experience as well as conceptual knowledge.

Cancer therapy, including immunotherapy, is inherently limited by chronic inflammation-induced tumorigenesis and toxicity within the tumor microenvironment. Thus, stimulating the resolution of inflammation may enhance immunotherapy and improve the toxicity of immune checkpoint inhibition (ICI). As epoxy-fatty acids (EpFAs) are degraded by the enzyme soluble epoxide hydrolase (sEH), the inhibition of sEH increases endogenous EpFA levels to promote the resolution of cancer-associated inflammation. Here, we demonstrate that systemic treatment with ICI induces sEH expression in multiple murine cancer models. Dietary omega-3 polyunsaturated fatty acid supplementation and pharmacologic sEH inhibition, both alone and in combination, significantly enhance anti-tumor activity of ICI in these models. Notably, pharmacological abrogation of the sEH pathway alone or in combination with ICI counter-regulates an ICI-induced pro-inflammatory and pro-tumorigenic cytokine storm. Thus, modulating endogenous EpFA levels through dietary supplementation or sEH inhibition may represent a unique strategy to enhance the anti-tumor activity of paradigm cancer therapies.

OBJECTIVES: The Salivary Gland Committee of the American Academy of Otolaryngology-Head and Neck Surgery seeks to standardize terminology and technique for ultrasonograpy used in the evaluation and treatment of salivary gland disorders. METHODS: Development of expert opinion obtained through interaction with international practitioners representing multiple specialties. This committee work includes a comprehensive literature review with presentation of case examples to propose a standardized protocol for the language used in ultrasound salivary gland assessment. RESULTS: A multiple segment proposal is initiated with this focus on the submandibular gland. We provide a concise rationale for recommended descriptive language highlighted by a more extensive supplement that includes an extensive literature review with additional case examples. CONCLUSION: Recommendations are provided to improve consistency both in performing and reporting submandibular gland ultrasound.

BackgroundPlasma neurofilament light chain (NfL) is a promising biomarker of neurodegeneration with potential clinical utility in monitoring the progression of neurodegenerative diseases. However, the cross-sectional associations of plasma NfL with measures of cognition and brain have been inconsistent in community-dwelling populations.MethodsWe examined these associations in a large community-dwelling sample of early old age men (N = 969, mean age = 67.57 years, range = 61-73 years), who are either cognitively unimpaired (CU) or with mild cognitive impairment (MCI). Specifically, we investigated five cognitive domains (executive function, episodic memory, verbal fluency, processing speed, visual-spatial ability), as well as neuroimaging measures of gray and white matter.ResultsAfter adjusting for age, health status, and young adult general cognitive ability, plasma NfL level was only significantly associated with processing speed and white matter hyperintensity (WMH) volume, but not with other cognitive or neuroimaging measures. The association with processing speed was driven by individuals with MCI, as it was not detected in CU individuals.ConclusionsThese results suggest that in early old age men without dementia, plasma NfL does not appear to be sensitive to cross-sectional individual differences in most domains of cognition or neuroimaging measures of gray and white matter. The revealed plasma NfL associations were limited to WMH for all participants and processing speed only within the MCI cohort. Importantly, considering cognitive status in community-based samples will better inform the interpretation of the relationships of plasma NfL with cognition and brain and may help resolve mixed findings in the literature.

The cross-shell excited states of Si34 have been investigated via β decays of the 4- ground state and the 1+ isomeric state of Al34. Since the valence protons and valence neutrons occupy different major shells in the ground state as well as the intruder 1+ isomeric state of Al34, intruder levels of Si34 are populated via allowed β decays. Spin assignments to such intruder levels of Si34 were established through γ-γ angular correlation analysis for the negative-parity states with dominant configurations (νd3/2)-1⊗ - (νf7/2)1 as well as the positive-parity states with dominant configurations (νsd)-2⊗ - (νf7/2p3/2)2. The configurations of such intruder states play crucial roles in our understanding of the N=20 shell gap evolution. A configuration interaction model derived from the FSU Hamiltonian was utilized in order to interpret the intruder states in Si34. Shell model interaction derived from a more fundamental theory with the valence space in medium similarity renormalization group method was also employed to interpret the structure of Si34.

Abstract Background A dementia diagnosis can lead to a decline in cognitive, social, and physical health, but people with dementia can live meaningful lives and participate actively in society with psychosocial support. This single-arm, non-randomised feasibility study explored the feasibility and acceptability of a Comprehensive REsilience-building psychoSocial intervenTion (CREST) for people with dementia, their caregivers, General Practitioners (GPs), and the public. Methods Nine people with dementia and their primary caregivers living in the community (n = 9 dyads) completed the CREST intervention which had three components (cognitive stimulation therapy [CST], physical exercise, and dementia education). Quantitative secondary outcomes were assessed at baseline and following the 15-week intervention; qualitative interviews were conducted during and post-intervention. All study components were assessed against pre-defined criteria, to determine the feasibility of conducting a future definitive trial. Results Recruitment of people with dementia and their caregiver was a significant challenge and led to considerable delays to the onset and conduct of the intervention. Only 13% of eligible GP practices agreed to assist in recruitment and achieved a 6% enrolment rate; a community-based recruitment strategy proved more effective, yielding a 29% enrolment rate. However, once recruited, participants maintained high attendance and adherence to the content of each component with average adherence rates of 98% for CST, exercise sessions and caregiver education. Adherence to secondary exercise measures was lower, with home exercise diary completion at 37% and Fitbit wear adherence at 80% during the day and 67% at night. The people with dementia felt their concentration and fitness had improved over the 15-week intervention and particularly enjoyed the social aspects (e.g. group classes, exercising with partners from the community). Caregivers felt they had better knowledge and understanding following their education component and reported that the social aspects (interacting and sharing experiences with each other) were important. Overall, participants reported that the three components of the intervention were feasible and acceptable. In addition, the quantitative measures and health economic tools employed were feasible. However, the secondary elements of the exercise component (recording home exercise diaries and Fitbit use) were not considered feasible. Overall, pre-defined criteria for progression to a definitive intervention were fulfilled in terms of acceptability, retention and fidelity but not recruitment. Conclusion While overall, the CREST intervention was feasible and acceptable to participants, significant difficulties with recruitment of people with dementia and their caregiver through GP practices impacted the viability of delivering the intervention. Recruitment through community-based groups proved a more feasible option and further work is needed to overcome barriers to recruiting this cohort before a larger-scale trial can be conducted. Trial registration ISRCTN25294519.

Abstract Background Hypertension, or high blood pressure, is a key modifiable risk factor for heart disease and stroke. International guidelines have highlighted ‘poor adherence to treatment’ and ‘physician inertia’ as major barriers to effective blood pressure management. The Maximising Adherence, Minimising Inertia (MIAMI) intervention, a theory-based complex intervention, supports General Practitioners (GPs) and people with hypertension in maximising medication use to manage blood pressure. This pilot cluster randomised control trial (RCT) aimed to collect and analyse feasibility data to refine the MIAMI intervention and assess the feasibility of a definitive RCT. Method A pilot cluster RCT with a MIAMI intervention arm and usual care control arm was conducted. Quantitative data collection consisting of clinical measures and a self-report questionnaire took place at baseline and twelve week follow up. Semi-structured interviews with GP and patient participants were conducted. Fidelity (as measured by a protocol checklist and through qualitative interviews) and health economics costings were assessed. Results Six GP practices (intervention arm n = 3, control arm n = 3) and 52 patients (intervention arm n = 25, control arm n = 27) took part. All six GP practices and 92% of patients were retained. Fidelity, as measured by a checklist and through qualitative interviews, was good but three deviations from protocol were identified. Outcomes and measures used were acceptable. The implementation cost of the MIAMI intervention was estimated at €490 per participant. The qualitative data demonstrated that the intervention was considered acceptable and feasible by both GP and patient participants, except for the urine test component, which GPs found difficult to incorporate into practice due to logistical challenges. Conclusions The MIAMI intervention was considered largely acceptable and feasible. Some changes to both intervention components and trial processes are required but with these in place a definitive RCT could be considered worthwhile. Trial registration ISRCTN registry, ISRCTN85009436, registered 17/1/23.

Abstract The global health crisis of antibacterial resistance (ABR) poses a particular threat in low-resource settings like East Africa. Interventions for ABR typically target antibiotic use, overlooking the wider set of factors which drive vulnerability and behaviours. In this cross-sectional study, we investigated the joint contribution of behavioural, environmental, socioeconomic, and demographic factors associated with higher risk of multi-drug resistant urinary tract infections (MDR UTIs) in Kenya, Tanzania, and Uganda. We sampled outpatients with UTI symptoms in healthcare facilities and linked their microbiology data with patient, household and community level data. Using bivariate statistics and Bayesian profile regression on a sample of 1610 individuals, we show that individuals with higher risk of MDR UTIs were more likely to have compound and interrelated social and environmental disadvantages: they were on average older, with lower education, had more chronic illness, lived in resource-deprived households, more likely to have contact with animals, and human or animal waste. This suggests that interventions to tackle ABR need to take account of intersectional socio-environmental disadvantage as a priority.

Abstract Background Vaping among 18-24-year-old Australians has increased from 5.8% in 2019 to 21% in 2023. This protocol describes a trial to investigate the dissemination and engagement achieved by three anti-vaping messages on Facebook. Methods This research employs a 3-arm randomised experimental design. Three distinct anti-vaping messages will be disseminated via Facebook using Meta Ads Manager. Each arm has a message that focuses on either health risks, environmental impact, or anti-vape industry sentiment. The campaign will run for three months. The primary outcome is the engagement rate as a measure of the effectiveness of anti-vaping message, and the secondary outcomes include network indicators: size, density, centralisation, and centrality to evaluate the extent to which the messages are disseminated. Participants will be randomly exposed to one of the three messages. Data on reach and engagement will be compared across the groups. Discussion This study will provide insights into the dissemination of social media-based anti-vaping campaigns. By evaluating engagement rates and network indicators, the research aims to identify which message themes engage most with young Australians. The findings will contribute to the development of more effective public health strategies for vaping cessation and prevention among youth. Trial Registration The study was registered on July 19th 2024 with the Australian New Zealand Clinical Trials Registry (ACTRN12624000885594).

Abstract Background Among the crises engulfing the world is the symbiotic rise of ultra-processed foods (UPFs) and plastics. Together, this co-dependent duo generates substantial profits for agri-food and petrochemical industries at high costs for people and planet. Cheap, lightweight and highly functional, plastics have ideal properties that enable business models to create demand for low-cost, mass-produced and hyper-palatable UPFs among populations worldwide, hungry, or not. Evidence linking UPF consumption to deterioration in diet quality and higher risk of chronic diseases is well-established and growing rapidly. At the same time, the issue of plastic food contact chemicals (FCCs) is receiving increasing attention among the human health community, as is the generation and dispersion of micro- and nanoplastics. Main body In this commentary, we explore how the lifecycles and shared economic benefits of UPFs and plastics interact to co-produce a range of direct and indirect harms. We caution that the chemical dimension of these harms is underappreciated, with thousands of plastic FCCs known to migrate into foodstuffs. Some of these are hazardous and have been detected in humans and the broader environment, while many are yet to be adequately tested. We question whether policies on both UPF and plastic chemicals are fit for purpose when production and consumption of these products is adding to the chronic chemical exposures that plausibly contribute to the increasing global burden of non-communicable diseases. Conclusions In the context of ongoing negotiations for a legally binding global treaty to end plastics pollution, and rapidly growing concern about the burgeoning share of UPFs in diets worldwide, we ask: What steps are needed to call time on this toxic relationship?

Abstract Background Walking impairment after stroke is associated with substantial limitations in functional independence, quality of life, and long-term survival. People in the subacute phase after stroke who are unable to walk are most likely to benefit the greatest from use of overground robotic gait training (RGT). This study will provide preliminary evidence regarding the clinical use and efficacy of RGT during the subacute phase of stroke recovery as well as observational findings associated with the safety, tolerability, feasibility, and cost of delivering RGT during inpatient stroke rehabilitation. Methods This prospectively registered randomized controlled trial will enroll 54 patients admitted to inpatient rehabilitation within six months of stroke. Admitted patients will be screened at admission to inpatient rehabilitation for eligibility. Consented patients will be randomized based on stroke severity to receive either RGT or usual care for 90 minutes per week of gait training intervention during inpatient rehabilitation length of stay. Patients will complete assessments on walking and health outcomes at admission and discharge from inpatient rehabilitation and at 1- and 3-month follow-up. Intent-to-treat and per protocol analysis will be performed to evaluate safety [rate of adverse events, visual analog scale, and treatment completion rate], walking function [gait speed via 10-Meter Walk Test, Functional Ambulation Category, gait endurance via 6-Minute Walk Test] and health outcomes [Modified Rankin Scale, Stroke Rehabilitation Assessment of Movement, Continuity Assessment Record and Evaluation Tool, 5 Times Sit-to-Stand Test, Berg Balance Scale, and Stroke Impact Scale–16], and cost-analysis. Discussion This study will provide foundational evidence regarding the clinical use and efficacy of a RGT program during the subacute phase of stroke recovery with specific findings associated with the safety, tolerability, feasibility, and cost-analysis of delivering RGT during inpatient stroke rehabilitation. Trial registration NCT06430632.

Abstract Objective Eating disorders (EDs) comprise a range of illnesses characterised by disordered eating, distressing thoughts, and changes in weight. EDs in the perinatal period are a growing concern. Maternity staff receive little training in this area and often report feeling ill-equipped to recognise or respond to presentations of ED during this time. The study aimed to develop and evaluate an online educational module for clinicians and support workers to improve knowledge of EDs in the perinatal period. Method Education modules were developed using a co-design process with consumer advocates, peer support workers, clinicians, and experts. Consumer perspectives, evidence-based videos, activities, and text relating to screening, management, monitoring and referral of perinatal individuals with EDs were included in the module. Quantitative and qualitative data from pre- and post- surveys were used to evaluate changes in knowledge and confidence before and after completing the module, and to assess staff satisfaction, usability, and obtain feedback for improvement. Results Use of the online education module significantly increased staff knowledge of EDs in the perinatal period. Participants also felt more confident in discussing the topic with patients, screening, supporting, and referring a person with ED in the perinatal period. Participants also reported the module was engaging and easy-to-use. Conclusions Findings indicate that the ED online education module is an engaging and easy-to-use tool for improving the knowledge and skills of the healthcare workforce, thereby improving patient care and health outcomes. The development of additional online resources for clinicians would be beneficial for increasing staff capability and improving patient services.

Abstract We generated synthetic equiaxed grain structures using computer graphics software to explore the relationship between various grain size determination methods and true three-dimensional (3D) grain diameters. Mirroring grain measurement techniques, the synthetic 3D grain structures are imaged as 2D micrographs which are measured to yield 1D grain size parameters. Synthetic grain structures provide data at a mass scale and permit exploration of both polished and fractured surface micrographs, revealing one-to-one correspondence between exposed 2D grain cross-sections and individual 3D grains. Analysis of this correspondence yielded a procedure to approximate 3D equiaxed grain size and volume distributions based on the mode of the 2D fractograph grain size distribution. The 3D approximation procedure is shown to be less susceptible to different imaging conditions that affect small, undiscernible grains compared to the standard planimetric and linear intercept methods, which by design also tend to underestimate the 3D grain diameter. The procedure requires larger sample sizes to lower variance and a deeper analysis which could become more practical with machine learning (ML) models for grain boundary segmentation, which synthetic grain structures can help train. This work lays the foundation for analyzing other grain distributions such as columnar and composite grains in similar depth.

Abstract Cisplatin and oxaliplatin cause the secretion of high mobility group box 1 (HMGB1) protein from cancer cells, which is necessary for initiation of immunogenic cell death (ICD). Calreticulin (CRT) translocation from the endoplasmic reticulum to the plasma membrane is also required; oxaliplatin induces this translocation but cisplatin does not. We have discovered that oxaliplatin causes the secretion of both HMGB1 and HMGB2 from the cell nucleus into the extracellular milieu. We previously showed that cisplatin-mediated secretion of HMGB1 is controlled by the nuclear exporter XPO1 (chromosomal maintenance 1; CRM1). We now find that XPO1 regulates oxaliplatin-mediated secretion of both HMGB1 and HMGB2. XPO1 inhibition causes nuclear accumulation of both proteins, inhibition of oxaliplatin-mediated ferroptosis of colon cancer cells, and inhibition of CRT translocation to the plasma membrane of lung and colon cancer cells. Incubation of cancer cells with cell targeted (CT)-HMGB2 confirmed that HMGB2 is required for the CRT translocation. Furthermore, CT-HMGB2 is three orders of magnitude more potent at inducing CRT translocation than oxaliplatin.

Inclusion of autistic pupils into mainstream schools is common practice and staff should have adequate knowledge on teaching and managing classroom behaviour. However, autism knowledge among teaching staff may be inconsistent. A mixed-methods design examined differences between school staff in autism knowledge, perceived barriers to inclusion and required support. 138 early years staff, school teachers and pupil support assistants took part. Knowledge and experience were assessed using Knowledge about Childhood Autism among Health Workers questionnaire (KCAHW; [Bakare, M. O., P. O. Ebigbo, A. O. Agomoh, and N. C. Menkiti. 2008. Knowledge about childhood autism among health workers (KCAHW) questionnaire: description, reliability and internal consistency. Clinical Practice and Epidemiology in Mental Health 4 (1): 17]). Qualitative measures addressed perceived barriers to inclusion and recommended supports. Significant differences in the knowledge of autism scores were shown.. Similar themes were identified across all staff, with five themes reflecting barriers to inclusion (Knowledge, Support, Training, Management of ASC features and Parent involvement) and four themes relating to required support (Individualising educational experience, Changes to learning spaces, Opportunities to learn about ASC and Communication). Government inclusion policy should take a whole school approach and consider staffs' actual and perceived barriers to inclusion of autistic children.