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Juan Mundisugih,1,2 Caroline X Gao,1,3 Jillian F Ikin,1 Michael J Abramson,1 David Brown,1 Sinjini Biswas,1,2 Elizabeth M Dewar,2,4 Danny Liew,1 Dion Stub1,2,4 1School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 2Department of Cardiology, Alfred Health, Melbourne, VIC, Australia; 3Centre for Youth Mental Health (Orygen), University of Melbourne, Melbourne, VIC, Australia; 4Baker Heart and Diabetes Institute, Melbourne, VIC, AustraliaCorrespondence: Jillian F Ikin, Tel +61 3 9903 0308, Email jill.blackman@monash.eduBackground and Aims: Mega-wild fires are exposing large communities to weeks or months of high concentration smoke-related fine particulate air pollution (PM). However, little research has examined the long-term vascular responses from exposure to PM of this concentration and duration. We investigated whether level of exposure to 6 weeks of PM from the 2014 Hazelwood coal mine fire was associated with abnormal vascular responses approximately four years later.Methods: A cross-sectional analysis was undertaken of 387 participants (225 exposed, 162 unexposed) aged 55– 89 years, 3.5– 4 years after the mine fire. The primary outcome was flow-mediated dilatation (FMD), with time to reach peak diameter as the secondary outcome. Other secondary markers included high-sensitivity C-reactive protein (hsCRP) and ischaemic Electrocardiogram (ECG) changes.Results: There was no evidence of a difference in FMD between participants with high, medium, low or no mine-fire related PM2.5 exposure (4.09% vs 4.06% vs 4.02% vs 3.98%, respectively, p=0.99). Likewise, there was no difference in hsCRP or ischaemic ECG changes. In contrast, there was evidence of a difference in time to peak diameter (p=0.002) with more unexposed participants reaching peak diameter within 30 seconds (36%) compared to those who had high, medium, or low exposure (23%, 22%, 13%, respectively). Multivariate ordinal logistic regression analysis suggested that township, Morwell (exposed) vs Sale (unexposed), but not level of PM2.5 exposure, was associated with delayed time to peak diameter (OR 2.71; 95% CI 1.56, 4.69). Smokers also had delayed time to peak diameter.Conclusion: There was no association between level of exposure to PM2.5 from the 6-week Hazelwood coal mine fire smoke event and reduced FMD, elevated hsCRP or ischaemic ECG four years later. Evidence of delayed time to peak diameter observed in adults from the exposed town, compared to an unexposed town, requires further investigation.Keywords: vascular responses, flow mediated dilatation, time to peak diameter, particulate matter, epidemiology, air pollution

Hai-Sheng You,1,* Chun-Xia Gao,1,* Hai-Bin Wang,2 Sai-Sai Luo,1 Si-Ying Chen,1 Ya-Lin Dong,1 Jun Lyu,3 Tao Tian4 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Hangzhou Cognitive N&T. Co., Ltd, Hangzhou, Zhengjiang, People’s Republic of China; 3Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao TianDepartment of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86-13572206784Fax +86-29-85324086Email tiantao0607@163.comJun LyuClinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86 29 8532 3614Fax +86 29 8532 3473Email lujun2006@xjtu.edu.cnObjective: The disease complexity of metastatic non-small-cell lung cancer (mNSCLC) makes it difficult for physicians to make clinical decisions efficiently and accurately. The Watson for Oncology (WFO) system of artificial intelligence might help physicians by providing fast and precise treatment regimens. This study measured the concordance of the medical treatment regimens of the WFO system and actual clinical regimens, with the aim of determining the suitability of WFO recommendations for Chinese patients with mNSCLC.Methods: Retrospective data of mNSCLC patients were input to the WFO, which generated a treatment regimen (WFO regimen). The actual regimen was made by physicians in a medical team for patients (medical-team regimen). The factors influencing the consistency of the two treatment options were analyzed by univariate and multivariate analyses.Results: The concordance rate was 85.16% between the WFO and medical-team regimens for mNSCLC patients. Logistic regression showed that the concordance differed significantly for various pathological types and gene mutations in two treatment regimens. Patients with adenocarcinoma had a lower rate of “recommended” regimen than those with squamous cell carcinoma. There was a statistically significant difference in EGFR-mutant patients for “not recommended” regimens with inconsistency rate of 18.75%. In conclusion, the WFO regimen has 85.16% consistency rate with medical-team regimen in our treatment center. The different pathological type and different gene mutation markedly influenced the agreement rate of the two treatment regimens.Conclusion: WFO recommendations have high applicability to mNSCLC patients in our hospital. This study demonstrates that the valuable WFO system may assist the doctors better to determine the accurate and effective treatment regimens for mNSCLC patients in the Chinese medical setting.Keywords: metastatic non-small-cell lung cancer, Watson for Oncology, concordance, artificial intelligence, treatment recommendations

Li Cheng,1 Doris Yin-ping Leung,1 Janet Wing-hung Sit,1 Xiao-mei Li,2 Yu-ning Wu,3 Miao-yan Yang,4 Cui-xia Gao,5 Rong Hui6 1The Nethersole School of Nursing, Faculty of Medicine, The Chinese University of Hong Kong, Ma Liu Shui, Shatin, New Territories, Hong Kong; 2The Department of Nursing, Faculty of Medicine, The Xi’an Jiaotong University, 3The Department of Endocrinology, The Ninth Affiliated Hospital of Xi’an Jiaotong University, 4The Department of Endocrinology, The Second Affiliated Hospital of Xi’an Jiaotong University, 5The Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, 6The Department of Endocrinology, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China Background: The study was conducted to investigate the diet barriers perceived by patients with poorly controlled type 2 diabetes and examine the associations between diet barriers and sociodemographic characteristics, medical condition, and patient-centered variables. Methods: Secondary subgroup analyses were conducted based on the responses of 246 adults with poorly controlled type 2 diabetes from a multicenter, cross-sectional study. Diet barriers were captured by the Diet Barriers subscale of the Personal Diabetes Questionnaire. Participants also completed validated measures of diet knowledge, empowerment level, and appraisal of diabetes. Multiple regression techniques were used for model building, with a hierarchical block design to determine the separate contribution of sociodemographic characteristics, medical condition, and patient-centered variables to diet barriers. Results: Diet barriers were moderately evident (2.23±0.86) among Chinese patients with poorly controlled type 2 diabetes. The feeling of deprivation as a result of complying with a diet was the most recognized diet barrier (3.24±1.98), followed by “eating away from home” (2.79±1.82). Significantly higher levels of diet barriers were observed among those with lower levels of diet knowledge (β=-0.282, P

Background and Objectives: The Hazelwood Health Study was set up to study long-term health effects of a mine fire that blanketed residents of the Latrobe Valley with smoke for 45 days in 2014. The Respiratory Stream specifically assessed the impact of fine particulate matter <2.5 μm diameter (PM 2.5 ) exposure from mine fire smoke on lung health. The multiple breath nitrogen washout (MBW) test assesses ventilation heterogeneity, which may detect sub-clinical airways dysfunction not identified using standard tests such as spirometry. This analysis assessed the association of PM 2.5 exposure with measures of ventilation heterogeneity., Methods: Exposed (Morwell) and unexposed (Sale) participants were recruited 3.5-4 years after the fire from those who had participated in an Adult Survey. MBW was performed to measure lung clearance index (LCI), functional residual capacity (FRC), acinar (Sacin) and conductive (Scond) ventilation heterogeneity. PM 2.5 exposure was estimated with emission and chemical transport models. Multivariable linear regression models were fitted controlling for confounders., Results: We recruited 519 participants. MBW tests were conducted on 504 participants with 479 acceptable test results (40% male; 313 exposed, 166 unexposed). Exposure to mine fire-related PM 2.5 was associated with increasing Scond (β = 1.57/kL, 95%CI: 0.20-2.95, p = 0.025), which was comparable to the estimated effect on Scond of 4.7 years of aging. No other MBW outcomes were statistically different., Conclusion: Increasing exposure to PM 2.5 was associated with increased ventilation heterogeneity in the conductive region of the lungs 4 years after the event., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Objective: As highlighted in Australia's Productivity Commission Inquiry into mental health, subgroups of individuals are failing to have their needs met, or are 'falling through the cracks' in the current system - a phenomenon increasingly referred to as the 'missing middle'. A barrier to devising solutions is that the term 'missing middle' is not clearly defined. Using the Delphi method, we aimed to define the term and explore acceptability., Method: Three expert groups were recruited: carers and young people with a lived experience of mental ill-health; clinicians and service providers; researchers, policymakers and commissioners of mental health services. Using a three-stage Delphi process, we elicited definitions, refined and developed a consensus definition., Results: Ten subthemes describing the 'missing middle' were identified, with four endorsed across all expert groups from the outset: service gap, inflexibility, inadequate service quality and duration, and social disadvantage. Additional subthemes were later endorsed. Feedback was sought on a consensus-driven definition that encompassed the original four endorsed subthemes. Findings supported a shift to a systemic focus - framing the 'missing middle' as a care gap., Conclusions: A consensus definition was developed, repositioning the term to a systems lens, describing a 'missing middle service gap'. The definition represents the 'missing middle' as a term to describe a gap in care where existing mental health services are not meeting the needs of individuals in a meaningful way. Research was carried out in relation to youth mental health in Australia and the definition may need to be adapted for other contexts., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In 2014, the Hazelwood coalmine fire in regional Victoria, Australia shrouded nearby communities in smoke for six weeks. Prior investigations identified substantial adverse effects, including increases in the use of health services. In this study, we examined the effects on hospital and ambulance use in the eight years following the fire., Methods: Using Victorian hospital (Jan 2009-Jun 2022) and ambulance (Jan 2013-Dec 2021) data, we conducted an interrupted time series of changes to the rate of hospital admissions, emergency presentations, and ambulance attendances. A categorical exposure model compared two locations, most-exposed Morwell and less-exposed Latrobe Valley, to the rest of regional Victoria. A continuous exposure model used spatial estimates of fire-related PM 2.5 . Analyses were stratified by sex, age group (<65/65+ years), and condition (cardiovascular, respiratory, mental health, injury)., Results: There were small but significant increases in overall hospital admissions and emergency presentations across all analyses, but little evidence of change in overall ambulance attendances. Effects varied considerably by condition, with the biggest relative increases observed among hospital admissions for mental health conditions and injuries. While cardiovascular-related hospital admissions and emergency presentations increased post-fire, ambulance attendances decreased., Conclusions: Our findings suggest the Hazelwood coalmine fire likely increased hospital usage. However, it is unclear whether this was due to the direct effects of smoke exposure on health, or the disruptive socioeconomic and behavioural impacts of an environmental disaster that affected how communities engaged with various health services., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Michael J Abramson reports financial support was provided by Pfizer Inc. Michael J Abramson reports financial support was provided by Boehringer Ingelheim Corp USA. Michael J Abramson reports financial support was provided by Sanofi. Michael J Abramson reports financial support was provided by GlaxoSmithKline Inc. Rongbin Xu reports financial support was provided by VicHealth. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In Australia, the first nationwide COVID-19 lockdown occurred in March 2020 bringing challenges for early intervention psychosis (EIP) services. Limited evidence exists on the impacts of the pandemic on treatment outcomes among EIP clients., Methods: This prospective cohort study analysed routine data from 15 headspace Early Psychosis centres in Australia. Participants were 12 to 25 years, meeting criteria for First Episode Psychosis (FEP) or Ultra High Risk of psychosis (UHR) comparing those who commenced treatment 'pre-COVID-19' (between 16th August 2018 and 15th August 2019), and 'during-COVID-19' (between 1st March 2020 and 15th September 2020). Clinical symptoms at treatment commencement were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Kessler Psychological Distress Scale (K10). with outcomes after 6 months compared between cohorts using linear mixed-effects regression, controlling for confounders., Results: Of 1246 young people analysed (653 FEP, 596 UHR), significant improvements were observed with treatment in both groups (5 to 13-point reduction in BPRS score per 6-months treatment). Treatment effectiveness reduced during-COVID-19 for psychosis symptoms, with the FEP BPRS treatment effect lower by 4.3 points (95%CI: 0.5, 8.1). UHR clients had lower BPRS negative symptoms during-COVID-19 (p = 0.020). Service contacts increased during-COVID-19, with increased telehealth services (p < 0.001)., Conclusions: Early intervention remained effective for FEP and UHR, despite the pandemic and transition of EIP services to virtual service delivery. Reduced treatment efficacy in FEP psychosis symptoms may indicate potential limitations of telehealth. Further research to examine longer term clinical and functional outcomes due to the pandemic is required., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Using population-level cancer diagnosis data, we compared cancer incidence in locations affected by smoke from a six week-long open cut coal mine fire in regional Victoria, Australia, up to seven years following the event. There was no detectable effect on cancer incidence overall. While several subgroups exhibited changes, these were more likely due to statistical chance rather than real effects. These findings may be limited by low statistical power and short duration of follow up. To confirm the influence of open cut coal mine fires on cancer incidence, further research and an extended follow-up duration are necessary., Competing Interests: Declaration of Competing Interest MJA holds investigator-initiated grants from Pfizer, Boehringer-Ingelheim, GSK and Sanofi for unrelated research. He has undertaken an unrelated consultancy for Sanofi. He has also received a speaker’s fee from GSK. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: Young people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment., Methods: This is a naturalistic sample of young people aged 12-25 with FEP ( n = 1574) and UHR ( n = 1515), accessing treatment in the headspace Early Psychosis (hEP) programme. Engagement in education and employment was assessed at baseline and every 90 days in treatment. Mixed effects logistic regression were used to analyse changes over time., Results: On entering the hEP programme, approximately 49% of the young people with FEP and 28% of the young people at UHR status identified as Not in Education, Employment or Training (NEET). The odds of being NEET were reduced by 27% (95% confidence interval = [14, 39]) for every 6 months treatment for the FEP group, but no change in NEET status was observed in the UHR group. In both groups, absence from daily activities was significantly reduced during time in treatment., Conclusion: While there are methodological challenges analysing real-world non-control group cohort data, the findings indicate positive effects of the hEP programme on vocational and daily activity engagement for young people with FEP and at UHR status. A large proportion of the young people still identified as NEET after receiving treatment services, suggesting further refinement to ensure targeted and consistent vocational support throughout care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: Most lifetime mental health disorders begin by age 25 years, and the prevalence among young people has been increasing over recent years. We sought to understand what impact, if any, social determinants have had on this increase through the analysis of an Australian longitudinal dataset (with data from 2007 to 2021)., Methods: The analysis focused on five social determinants: loneliness and lack of social support, family relationships, participation in education and employment, receipt of government benefits and relative socio-economic status. We analysed cross-sectional changes in self-reported psychological distress between 2007 and 2021 (using the Kessler-10 item; K10 scores) and examined the effects of these five social determinants on psychological distress using weighted linear regression models., Results: We identified a significant increase in psychological distress among Australians from 2007 to 2021, with the sharpest rise among those aged 15 to 25 years, who saw more than doubling in the percentage of high and very high K10. This period also saw an increase in the prevalence of social determinants such as loneliness and lack of social support, as well as poor family relationships, particularly in 2021 post COVID-19 pandemic. Regression models suggest loneliness and lack of social support had the most pronounced and increasing impact on psychological distress, followed by poor family relationships., Discussion: The observed significant and steady increases in psychological distress and related social determinant factors, particularly loneliness and lack of social support among young people, highlight the urgent need for comprehensive actions. Coordinated research and community-based initiatives are needed to deliver intrapersonal, interpersonal and socially-focused interventions with a holistic approach to support psychosocial wellbeing. Policymakers must adopt a comprehensive shift in political commitment and a whole-of-government approach to address these challenges., Competing Interests: Conflict of interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: rygen is funded by the Australian Government Department of Health and Aged Care to provide technical advice and policy direction on a number of youth mental health topics, including social determinants. This is relevant for DB, RM and VB.

Aims: The specific and multifaceted service needs of young people have driven the development of youth-specific integrated primary mental healthcare models, such as the internationally pioneering headspace services in Australia. Although these services were designed for early intervention, they often need to cater for young people with severe conditions and complex needs, creating challenges in service planning and resource allocation. There is, however, a lack of understanding and consensus on the definition of complexity in such clinical settings., Methods: This retrospective study involved analysis of headspace 's clinical minimum data set from young people accessing services in Australia between 1 July 2018 and 30 June 2019. Based on consultations with experts, complexity factors were mapped from a range of demographic information, symptom severity, diagnoses, illness stage, primary presenting issues and service engagement patterns. Consensus clustering was used to identify complexity subgroups based on identified factors. Multinomial logistic regression was then used to evaluate whether these complexity subgroups were associated with other risk factors., Results: A total of 81,622 episodes of care from 76,021 young people across 113 services were analysed. Around 20% of young people clustered into a 'high complexity' group, presenting with a variety of complexity factors, including severe disorders, a trauma history and psychosocial impairments. Two moderate complexity groups were identified representing 'distress complexity' and 'psychosocial complexity' (about 20% each). Compared with the 'distress complexity' group, young people in the 'psychosocial complexity' group presented with a higher proportion of education, employment and housing issues in addition to psychological distress, and had lower levels of service engagement. The distribution of complexity profiles also varied across different headspace services., Conclusions: The proposed data-driven complexity model offers valuable insights for clinical planning and resource allocation. The identified groups highlight the importance of adopting a holistic and multidisciplinary approach to address the diverse factors contributing to clinical complexity. The large number of young people presenting with moderate-to-high complexity to headspace early intervention services emphasises the need for systemic change in youth mental healthcare to ensure the availability of appropriate and timely support for all young people.

Arsenic contamination in environmental water sources poses a significant threat to human health, necessitating the development of sensitive and accessible detection methods. This study presents a multidimensional optimization of a bacterial biosensor for the susceptible and deoxyviolacein (DV)-based visual detection of arsenic. The research involved screening six different arsenic resistance (ars) operons and optimizing the genetic circuit to minimize background noise. Introducing an arsenic-specific transport channel enhanced the sensor's sensitivity to 1 nM with a quantitative range from 0.036 to 1.171 μM. The pigment-based biosensor offers a simple colorimetric approach for arsenic detection without complex instrumentation. The preferred biosensor demonstrated characteristics of anti-chelating agent interference, consistently quantified As(III) concentrations ranging from 0.036 to 1.171 μM covering the World Health Organization (WHO) drinking water limit. Innovatively, it effectively detects arsenic in seawater within a linear regression range of 0.071 to 1.125 μM. The biosensor's selectivity for arsenic was confirmed, with minimal cross-response to group 15 metals. Our naked-eye biosensor offers a novel approach for the rapid, on-site detection of arsenic in various water sources. Its simplicity, cost-effectiveness, and versatility make it a valuable tool for environmental monitoring and public health initiatives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Melatonin (MLT) is a circadian hormone that reportedly influences the development and cyclic growth of secondary hair follicles; however, the mechanism of regulation remains unknown. Here, we systematically investigated the role of MLT in hair regeneration using a hair depilation mouse model. We found that MLT supplementation significantly promoted hair regeneration in the hair depilation mouse model, whereas supplementation of MLT receptor antagonist luzindole significantly suppressed hair regeneration. By analysing gene expression dynamics between the MLT group and luzindole-treated groups, we revealed that MLT supplementation significantly up-regulated Wnt/β-catenin signalling pathway-related genes. In-depth analysis of the expression of key molecules in the Wnt/β-catenin signalling pathway revealed that MLT up-regulated the Wnt/β-catenin signalling pathway in dermal papillae (DP), whereas these effects were facilitated through mediating Wnt ligand expression levels in the hair follicle stem cells (HFSCs). Using a DP-HFSCs co-culture system, we verified that MLT activated Wnt/β-catenin signalling in DPs when co-cultured with HFSCs, whereas supplementation of DP cells with MLT alone failed to activate Wnt/β-catenin signalling. In summary, our work identified a critical role for MLT in promoting hair regeneration and will have potential implications for future hair loss treatment in humans., (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

During a survey of the diversity of lignicolous fungi in Yunnan Province, China, we collected and identified five microfungi species from dead woody litters of Castanopsis trees in terrestrial habitats. Through both morphological comparisons and phylogenetic analyses of multi-gene sequences, we identified two taxa as new species and three collections as new host records within Pleosporales. Pseudolophiostomalincangense sp. nov. is introduced as a sexual morph in Lophiostomataceae, Pleopunctumbaoshanense sp. nov. is introduced as a hyphomycetous fungi in Phaeoseptaceae, and Paraphomaaquatica as a first report of sexual morph in Paraphoma . In addition, Occultibambusakunmingensis and Pleopunctummegalosporum were isolated for the first time from the dead twigs of Castanopsisdelavayi and C.calathiformis , respectively. Comprehensive morphological descriptions, illustrations, and phylogenetic analysis results are provided for the above-mentioned species., Competing Interests: The authors have declared that no competing interests exist., (Guang-Cong Ren, Saowaluck Tibpromma, Kai-Xuan Dong, Chen-Xi Gao, Chao-Shan Zhang, Samantha C. Karunarathna, Abdallah M. Elgorban, Heng Gui.)

Background and Aims: Since the onset of the COVID-19 pandemic, a significant rise in mental ill health has been observed globally in young people, particularly those in their final years of secondary school. Students' negative experiences coincide with a critical transitional period which can disrupt milestones in social and educational development. This study aimed to use innovative population-level data to map the impact of the pandemic on students entering higher education., Methods: Pre-pandemic (2019/2020) and pandemic (2020/2021) tertiary education application data were obtained from the Victorian Tertiary Admissions Centre. Prevalence of applications for special consideration related to mental ill health were compared between cohorts across various geographical areas and applicant demographic subgroups. Relative risk regression models were used to understand the role of different risk factors., Results: Rates of mental health-related special consideration applications increased by 38% among all applications (pre-pandemic: 7.8%, n = 56 916; pandemic: 10.8%, n = 58 260). Highest increases were observed among students in areas with both extended and close-quarter lockdown experiences, and areas impacted by 2019/2020 black summer bushfires. The increases were higher among Year 12 students and students with other special consideration needs (e.g., physical condition, learning disability). Slightly higher increases were observed in areas with higher socio-economic status, which may potentially be related to inequality in mental health service access., Conclusion: As consequences of mental health difficulties and academic disruption in youth can be long lasting, it is critical to establish a mental health support framework both in and outside of higher education to facilitate young people's recovery from the pandemic., (© 2024 The Author(s). Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Fermentative production of natural colorants using microbial strains has emerged as a cost-effective and sustainable alternative to chemical synthesis. Visual pigments are used as signal outputs in colorimetric bacterial biosensors, a promising method for monitoring environmental pollutants. In this study, we engineered four self-sufficient indigo-forming enzymes, including HbpAv, bFMO, cFMO, and rFPMO, in a model bacterium E. coli . TrxA-bFMO was chosen for its strong ability to produce indigo under T7 lac and mer promoters' regulation. The choice of bacterial hosts, the supplementation of substrate l-tryptophan, and ventilation were crucial factors affecting indigo production. The indigo reporter validated the biosensors for Hg(II), Pb(II), As(III), and Cd(II). The biosensors reported Hg(II) as low as 14.1 nM, Pb(II) as low as 1.5 nM, and As(III) as low as 4.5 nM but increased to 25 μM for Cd(II). The detection ranges for Hg(II), Pb(II), As(III), and Cd(II) were quantified from 14.1 to 225 nM, 1.5 to 24.4 nM, 4.5 to 73.2 nM, and 25 to 200 μM, respectively. The sensitivity, responsive concentration range, and selectivity are comparable to β-galactosidase and luciferase reporter enzymes. This study suggests that engineered enzymes for indigo production have great potential for green chemical synthesis. Additionally, heterologous biosynthesis of indigo production can lead to the development of novel, low-cost, and mini-equipment bacterial biosensors with zero background noise for visual monitoring of pollutant heavy metals., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: In randomized clinical trials, treatment effects may vary, and this possibility is referred to as heterogeneity of treatment effect (HTE). One way to quantify HTE is to partition participants into subgroups based on individual's risk of experiencing an outcome, then measuring treatment effect by subgroup. Given the limited availability of externally validated outcome risk prediction models, internal models (created using the same dataset in which heterogeneity of treatment analyses also will be performed) are commonly developed for subgroup identification. We aim to compare different methods for generating internally developed outcome risk prediction models for subject partitioning in HTE analysis., Methods: Three approaches were selected for generating subgroups for the 2,441 participants from the United States enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial. An extant proportional hazards-based outcomes predictive risk model developed on the overall ASPREE cohort of 19,114 participants was identified and was used to partition United States' participants by risk of experiencing a composite outcome of death, dementia, or persistent physical disability. Next, two supervised non-parametric machine learning outcome classifiers, decision trees and random forests, were used to develop multivariable risk prediction models and partition participants into subgroups with varied risks of experiencing the composite outcome. Then, we assessed how the partitioning from the proportional hazard model compared to those generated by the machine learning models in an HTE analysis of the 5-year absolute risk reduction (ARR) and hazard ratio for aspirin vs. placebo in each subgroup. Cochran's Q test was used to detect if ARR varied significantly by subgroup., Results: The proportional hazard model was used to generate 5 subgroups using the quintiles of the estimated risk scores; the decision tree model was used to generate 6 subgroups (6 automatically determined tree leaves); and the random forest model was used to generate 5 subgroups using the quintiles of the prediction probability as risk scores. Using the semi-parametric proportional hazards model, the ARR at 5 years was 15.1% (95% CI 4.0-26.3%) for participants with the highest 20% of predicted risk. Using the random forest model, the ARR at 5 years was 13.7% (95% CI 3.1-24.4%) for participants with the highest 20% of predicted risk. The highest outcome risk group in the decision tree model also exhibited a risk reduction, but the confidence interval was wider (5-year ARR = 17.0%, 95% CI= -5.4-39.4%). Cochran's Q test indicated ARR varied significantly only by subgroups created using the proportional hazards model. The hazard ratio for aspirin vs. placebo therapy did not significantly vary by subgroup in any of the models. The highest risk groups for the proportional hazards model and random forest model contained 230 participants each, while the highest risk group in the decision tree model contained 41 participants., Conclusions: The choice of technique for internally developed models for outcome risk subgroups influences HTE analyses. The rationale for the use of a particular subgroup determination model in HTE analyses needs to be explicitly defined based on desired levels of explainability (with features importance), uncertainty of prediction, chances of overfitting, and assumptions regarding the underlying data structure. Replication of these analyses using data from other mid-size clinical trials may help to establish guidance for selecting an outcomes risk prediction modelling technique for HTE analyses., (© 2024. The Author(s).)

In 2014, a fire at an open cut coalmine in regional Victoria, Australia burned for 6 weeks. Residents of the nearby town of Morwell were exposed to smoke, which included high levels of fine particulate matter (PM 2.5 ). We investigated whether the long-term effects of PM 2.5 on respiratory health were moderated by diet quality. A cross-sectional analysis was conducted of data collected 8.5 years after the mine fire from 282 residents of Morwell and 166 residents from the nearby unexposed town of Sale. Primary outcomes were respiratory symptoms. Exposure was coalmine fire-related PM 2.5 and diet quality was assessed as Australian Recommended Food Score (ARFS) derived using the Australian Eating Survey (AES). The moderating effect of diet quality on respiratory outcomes associated with PM 2.5 was assessed using logistic regression models, adjusting for potential confounders. Diet quality was poor in this sample, with 60% in the lowest category of overall diet quality. Overall diet quality and fruit and vegetable quality significantly attenuated the association between PM 2.5 and prevalence of chronic cough and phlegm. Sauce/condiment intake was associated with a greater effect of PM 2.5 on COPD prevalence. No other moderating effects were significant. The moderating effects of overall diet quality and vegetable and fruit intake aligned with a priori hypotheses, suggesting potential protective benefits. While more evidence is needed to confirm these findings, improving diets, especially fruit and vegetable intake, may provide some protection against the effects of smoke exposure from fire events., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Thara Govindaraju, Matthew Carroll, Brigitte M. Borg, Catherine L. Smith, Caroline X. Gao, David Brown, David Poland, Shantelle Allgood, Jillian F. Skin, Michael J. Abrasion, Tyler J. Lane reports financial support was provided by Victoria Department of Health. Michael J. Abramson reports a relationship with Pfizer, Boehringer-Ingelheim, Sanofi, GSK that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: There are few long-term studies of respiratory health effects of landscape fires, despite increasing frequency and intensity due to climate change. We investigated the association between exposure to coal mine fire PM 2.5 and fractional exhaled nitric oxide (FeNO) concentration 7.5 years later., Methods: Adult residents of Morwell, who were exposed to the 2014 Hazelwood mine fire over 6 weeks, and unexposed residents of Sale, participated in the Hazelwood Health Study Respiratory Stream in 2021, including measurements of FeNO concentration, a marker of eosinophilic airway inflammation. Individual exposure to coal mine fire PM 2.5 was modelled and mapped to time-location diaries. The effect of exposure to PM 2.5 on log-transformed FeNO in exhaled breath was investigated using multivariate linear regression models in the entire sample and stratified by potentially vulnerable subgroups., Results: A total of 326 adults (mean age: 57 years) had FeNO measured. The median FeNO level (interquartile range [IQR]) was 17.5 [15.0] ppb, and individual daily exposure to coal mine fire PM 2.5 was 7.2 [13.8] µg/m 3 . We did not identify evidence of association between coal mine fire PM 2.5 exposure and FeNO in the general adult sample, nor in various potentially vulnerable subgroups. The point estimates were consistently close to zero in the total sample and subgroups., Conclusion: Despite previous short-term impacts on FeNO and respiratory health outcomes in the medium term, we found no evidence that PM 2.5 from the Hazelwood coal mine fire was associated with any long-term impact on eosinophilic airway inflammation measured by FeNO levels., (© 2024. The Author(s).)

Randomized controlled trials can be used to generate evidence on the efficacy and safety of new treatments in eating disorders research. Many of the trials previously conducted in this area have been deemed to be of low quality, in part due to a number of practical constraints. This article provides an overview of established and more innovative clinical trial designs, accompanied by pertinent examples, to highlight how design choices can enhance flexibility and improve efficiency of both resource allocation and participant involvement. Trial designs include individually randomized, cluster randomized, and designs with randomizations at multiple time points and/or addressing several research questions (master protocol studies). Design features include the use of adaptations and considerations for pragmatic or registry-based trials. The appropriate choice of trial design, together with rigorous trial conduct, reporting and analysis, can establish high-quality evidence to advance knowledge in the field. It is anticipated that this article will provide a broad and contemporary introduction to trial designs and will help researchers make informed trial design choices for improved testing of new interventions in eating disorders. PUBLIC SIGNIFICANCE: There is a paucity of high quality randomized controlled trials that have been conducted in eating disorders, highlighting the need to identify where efficiency gains in trial design may be possible to advance the eating disorder research field. We provide an overview of some key trial designs and features which may offer solutions to practical constraints and increase trial efficiency., (© 2024 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Bacteria and fungi are ubiquitous throughout built environments and are suspended in the air, potentially affecting human health. However, the impacts of climate zones on the diversity, structure, and stochastic assembly of indoor airborne microbes remain unknown. This study comprehensively analyzed indoor airborne microbes across five climate zones in China during the summer and winter using high-throughput sequencing. The diversity and structure of indoor airborne communities vary across climatic zones. A random forest model was used to identify biomarkers in different climate zones. The results showed no relationship between the biomarkers and their rankings in mean relative abundance. The Sloan neutral model fitting results indicated that the impact of climate zones on the stochastic process in the assembly of indoor airborne microbes was considerably more important than that of seasons. Additionally, the influence of seasons on the diversity, structure, and stochastic assembly process of indoor airborne microbes differed among different climate zones. The diversity, structure, and stochastic assembly processes of bacteria present distinctive outcomes in climate zones and seasons compared with those of fungi. Overall, these findings indicate that customized strategies are necessary to manage indoor airborne microbial communities in each climate zone, season, and for specific microbial species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus . The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus ., Results: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC 50 ) of 2 μM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 μg/mL. Time-kill assays showed that myricetin was a bactericidal agent against S. aureus . In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner., Conclusions: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.