hnRNPM protects against the dsRNA-mediated interferon response by repressing LINE-associated cryptic splicing.

RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites. hnRNPM preferentially binds at intronic LINEs to repress pseudo splice site usage for cryptic splicing. Remarkably, cryptic exons can generate long dsRNAs through base-pairing of inverted ALU transposable elements interspersed among LINEs and consequently trigger an interferon response, a well-known antiviral defense mechanism. Significantly, hnRNPM-deficient tumors show upregulated interferon-associated pathways and elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity by repressing cryptic splicing and suggest that targeting hnRNPM in tumors may be used to trigger an inflammatory immune response, thereby boosting cancer surveillance.

Silencing RNAs expressed from W-linked PxyMasc "retrocopies" target that gene during female sex determination in Plutella xylostella.

The Lepidoptera are an insect order of cultural, economic, and environmental importance, representing ∼10% of all described living species. Yet, for all but one of these species (silkmoth, Bombyx mori), the molecular genetics of how sexual fate is determined remains unknown. We investigated this in the diamondback moth (Plutella xylostella), a globally important, highly invasive, and economically damaging pest of cruciferous crops. Our previous work uncovered a regulator of male sex determination in P. xylostella-PxyMasc, a homolog of B. mori Masculinizer-which, although initially expressed in embryos of both sexes, is then reduced in female embryos, leading to female-specific splicing of doublesex. Here, through sequencing small RNA libraries generated from early embryos and sexed larval pools, we identified a variety of small silencing RNAs (predominantly Piwi-interacting RNAs [piRNAs]) complementary to PxyMasc, whose temporal expression correlated with the reduction in PxyMasc transcript observed previously in females. Analysis of these small RNAs showed that they are expressed from tandemly arranged, multicopy arrays found exclusively on the W (female-specific) chromosome, which we term "Pxyfem". Analysis of the Pxyfem sequences showed that they are partial complementary DNAs (cDNAs) of PxyMasc messenger RNA (mRNA) transcripts, likely integrated into transposable element graveyards by the noncanonical action of retrotransposons (retrocopies), and that their apparent similarity to B. mori feminizer more probably represents convergent evolution. Our study helps elucidate the sex determination cascade in this globally important pest and highlights the "shortcuts" that retrotransposition events can facilitate in the evolution of complex molecular cascades, including sex determination.

RNA G-quadruplex secondary structure promotes alternative splicing via the RNA-binding protein hnRNPF.

It is generally thought that splicing factors regulate alternative splicing through binding to RNA consensus sequences. In addition to these linear motifs, RNA secondary structure is emerging as an important layer in splicing regulation. Here we demonstrate that RNA elements with G-quadruplex-forming capacity promote exon inclusion. Destroying G-quadruplex-forming capacity while keeping G tracts intact abrogates exon inclusion. Analysis of RNA-binding protein footprints revealed that G quadruplexes are enriched in heterogeneous nuclear ribonucleoprotein F (hnRNPF)-binding sites and near hnRNPF-regulated alternatively spliced exons in the human transcriptome. Moreover, hnRNPF regulates an epithelial-mesenchymal transition (EMT)-associated CD44 isoform switch in a G-quadruplex-dependent manner, which results in inhibition of EMT. Mining breast cancer TCGA (The Cancer Genome Atlas) data sets, we demonstrate that hnRNPF negatively correlates with an EMT gene signature and positively correlates with patient survival. These data suggest a critical role for RNA G quadruplexes in regulating alternative splicing. Modulation of G-quadruplex structural integrity may control cellular processes important for tumor progression.

Mental health training for physicians supervising resident physicians: a cluster randomised controlled trial.

OBJECTIVE: To evaluate an online training program for physician supervisors with the aim of promoting a mentally healthy workplace by improving their use of both responsive and preventive mental health support strategies. STUDY DESIGN: Cluster randomised, waitlist-controlled trial. SETTING, PARTICIPANTS: Royal Australasian College of Physicians fellows who were supervising at least one resident physician in any of the 31 primary health networks in Australia and 20 district health boards in New Zealand (health network clusters). INTERVENTION: A brief online skills-based mental health training program, comprising twelve modules grouped into three topics: common mental illnesses; helping trainees you are concerned about (responsive strategies); and minimising mental health risks at work (preventive strategies). MAIN OUTCOME MEASURES: Change between baseline and the 3-month assessment in self-reported recommended supervisor behaviours; differences between intervention and control groups in recommended behaviour scores three weeks, three months, and six months after the program. RESULTS: Ninety physicians from 20 health network clusters were allocated to the intervention group, 88 physicians from 22 clusters to the control group. Intervention group participants reported greater positive change in behaviour across the study period than those in the control group (mixed model repeated measures analysis, group × time interaction: P < 0.001). The mean change in self-reported supervisory behaviour score was higher for the intervention than the control group at the 3-week (mean difference in score, 1.6; 95% confidence interval [CI], 0.8-2.4), 3-month (0.9; 95% CI, 0.2-1.6), and 6-month assessments (1.9; 95% CI, 1.1-2.7). The mean change in self-reported responsive behaviour score was also greater for the intervention group at the 3-week (mean difference, 2.3; 95% CI, 1.5-3.1), 3-month (1.0; 95% CI, 0.2-1.9), and 6-month assessments (2.0; 95% CI, 1.1-2.9); differences in the mean change in preventive behaviour scores were statistically significant at the 3-week (mean difference, 1.1; 95% CI, 0.1-2.2) and 6-month assessments (1.8; 95% CI, 0.8-2.8), but not the 3-month assessment (0.8; 95% CI, -0.1 to 1.7). CONCLUSIONS: Brief online mental health training for senior physicians can lead to changes in their self-reported behaviour for supporting the mental health needs of resident physicians. Whether this leads to better mental health for resident physicians should be investigated. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619001496101 (prospective).

Relationship between trauma, psychological distress and help-seeking among corrective service workers.

BACKGROUND: Corrective service workers (CSWs) are at high risk of post-traumatic stress disorder (PTSD) and other mental health problems. Prevalence rates and help-seeking behaviours are under-researched within this population. AIMS: To assess rates of PTSD and distress, and identify predictors of intention to seek help, among workers at an Australian corrective service agency. METHODS: A cross-sectional online survey was used to collect data on staff demographics, employment, PTSD symptoms and current distress. Participants received a tailored feedback report including referral to relevant mental health services (where applicable) and were asked to indicate their likelihood of seeking help. Prevalence data are reported. Binary logistic regression was used to examine relationships between participant characteristics and help-seeking for those with probable PTSD and/or high psychological distress. RESULTS: Participants (n=1001) were predominantly men (56.8%) with a mean age of 46.72 (SD=11.00). Over half (58.0%) were classified as probable PTSD cases, and one-third (33.0%) were experiencing high psychological distress. Around a third (34.3%) of participants with probable PTSD and/or elevated distress indicated they were likely to seek help. Older age and fewer years of service were associated with increased help-seeking intentions. CONCLUSIONS: CSWs were found to be experiencing probable PTSD at higher rates than reported in previous studies. Relatively few intended to seek help from mental health services, despite being provided with personalised screening and feedback along with access to specialised care. Future research should investigate the potential role of organisational support as a facilitator of help-seeking within this population.

Work-related factors and the risk of common mental disorder 1 year later: A prospective cohort study among junior doctors.

OBJECTIVE: This study investigated the relationship between work-related factors at baseline and the risk of common mental disorder at 12 month follow-up among a cohort of junior doctors. METHOD: The data comprised the junior doctor respondents from two annual waves of the 'Medicine in Australia: Balancing Employment and Life' (MABEL) survey, a national longitudinal cohort of Australian doctors. Individual and work-related risk factors were assessed at baseline and the mental health outcome of caseness of common mental disorder (CMD) was assessed using the 6-item Kessler Psychological Distress Scale at 12-month follow-up. Unadjusted and adjusted logistic regressions were conducted to estimate the association between each baseline variable and the likelihood of CMD caseness at follow-up 1 year later. RESULTS: Among 383 junior doctors, 24 (6%) had CMD 1 year later. Five work-related baseline variables were significantly associated with a higher likelihood of CMD 1 year later in adjusted models; lack of social support in work location (odds ratios (OR) = 6.11; 95% confidence intervals (CI) = [2.52, 14.81]), work-life imbalance (OR = 4.50; 95% CI = [1.31, 15.46]), poor peer support network in the workplace (OR = 2.61; 95% CI = [1.08, 6.27]), perceptions of patient expectations (OR = 2.46; 95% CI = [1.06, 5.71]) and total weekly work hours (OR 1.04; 95% CI = [1.01, 1.07]; p = 0.002)in models adjusting for gender. CONCLUSION: These results identify key modifiable work-related factors that are associated with junior doctors' future mental health. Our findings suggest the need for a greater focus upon interpersonal factors and work-life balance in multi-level interventions while continuing to address workplace and system-level factors to prevent future mental disorder in junior doctors.

Work-related suicide: Evolving understandings of etiology & intervention.

Previously published analyses of suicide case investigations suggest that work or working conditions contribute to 10%-13% of suicide deaths. Yet, the way in which work may increase suicide risk is an underdeveloped area of epidemiologic research. In this Commentary, we propose a definition of work-related suicide from an occupational health and safety perspective, and review the case investigation-based and epidemiologic evidence on work-related causes of suicide. We identified six broad categories of potential work-related causes of suicide, which are: (1) workplace chemical, physical, and psychosocial exposures; (2) exposure to trauma on the job; (3) access to means of suicide through work; (4) exposure to high-stigma work environments; (5) exposure to normative environments promoting extreme orientation to work; and (6) adverse experiences arising from work-related injury or illness. We summarise current evidence in a schema of potential work-related causes that can also be applied in workplace risk assessment and suicide case investigations. There are numerous implications of these findings for policy and practice. Various principle- and evidence-based workplace intervention strategies for suicide prevention exist, some of which have been shown to improve suicide-prevention literacy, reduce stigma, enhance helping behaviours, and in some instances maybe even reduce suicide rates. Prevailing practice in workplace suicide prevention, however, overly emphasises individual- and illness-directed interventions, with little attention directed to addressing the working conditions that may increase suicide risk. We conclude that a stronger emphasis on improving working conditions will be required for workplace suicide prevention to reach its full preventive potential.

Client perspectives: Telehealth for mental health services.

OBJECTIVE: The COVID-19 pandemic required mental health clinicians globally to transition to the delivery of care via telehealth. This study aimed to gain an understanding of clients' satisfaction with and attitudes towards telehealth mental health services. METHOD: Seventy adults who had attended a clinic for mood and anxiety disorders, and participated in at least one telehealth consultation with a psychologist or psychiatrist, completed an anonymous online survey. RESULTS: The majority of participants (81.5%) reported satisfaction with telehealth mental health care provided during the COVID-19 pandemic. However, satisfaction overall was significantly higher amongst participants who had received both telehealth and face-to-face mental health care, compared to participants who received care via telehealth only. Advantages of telehealth care reported included convenience and increased access to mental health clinicians. However, disadvantages of telehealth care included greater difficulty developing a rapport with a clinician and expressing oneself via telehealth. CONCLUSIONS: Whilst client satisfaction with telehealth mental health care for mood and anxiety disorders is generally high, clinicians should consider the limitations of telehealth from clients' perspectives. In particular, strategies to enhance therapeutic connection during telehealth sessions may be needed, and client preferences for mode of delivery should be taken into consideration when possible.

Suicide among emergency service workers: a retrospective mortality study of national coronial data, 2001-2017.

BACKGROUND: Emergency service workers (ESW) are known to be at increased risk of mental disorders but population-level and longitudinal data regarding their risk of suicide are lacking. METHOD: Suicide data for 2001-2017 were extracted from the Australian National Coronial Information Service (NCIS) for two occupational groups: ESW (ambulance personnel, fire-fighters and emergency workers, police officers) and individuals employed in all other occupations. Age-standardised suicide rates were calculated and risk of suicide compared using negative binomial regression modelling. RESULTS: 13 800 suicide cases were identified among employed adults (20-69 years) over the study period. The age-standardised suicide rate across all ESW was 14.3 per 100 000 (95% CI 11.0-17.7) compared to 9.8 per 100 000 (95% CI 9.6-9.9) for other occupations. Significant occupational differences in the method of suicide were identified (p < 0.001). There was no evidence for increased risk of suicide among ESW compared to other occupations once age, gender and year of death were accounted for (RR = 0.99, 95% CI 0.84-1.17; p = 0.95). In contrast, there was a trend for ambulance personnel to be at elevated risk of suicide (RR = 1.41, 95% CI 1.00-2.00, p = 0.053). CONCLUSION: Whilst age-standardised suicide rates among ESW are higher than other occupations, emergency service work was not independently associated with an increased risk of suicide, with the exception of an observed trend in ambulance personnel. Despite an increased focus on ESW mental health and wellbeing over the last two decades, there was no evidence that rates of suicide among ESW are changing over time.

Workplace mental health screening: a systematic review and meta-analysis.

Workplaces are an important location for population mental health interventions. Screening to detect employees at risk of or experiencing mental ill health is increasingly common. This systematic review and meta-analysis examined the efficacy of workplace mental health screening programmes on employee mental health, work outcomes, user satisfaction, positive mental health, quality of life, help-seeking and adverse effects. PubMed, PsycINFO, EMBASE, CENTRAL, Global Index Medicus, Global Health and SciELO were searched (database inception-10 November 2022) and results screened by two independent reviewers. Controlled trials evaluating screening of workers' mental health as related to their employment were included. Random effects meta-analysis was performed to calculate pooled effect sizes for each outcome of interest. Grading of Recommendations Assessment, Development and Evaluation was conducted to evaluate the certainty of findings. Of the 12 328 records screened, 11 were included. These reported 8 independent trials collectively assessing 2940 employees. Results indicated screening followed by advice or referral was ineffective in improving employee mental health symptoms (n=3; d=-0.07 (95% CI -0.29 to 0.15)). Screening followed by facilitated access to treatment interventions demonstrated a small improvement in mental health (n=4; d=-0.22 (95% CI -0.42 to -0.02)). Limited effects were observed for other outcomes. Certainty ranged from low to very low. The evidence supporting workplace mental health screening programmes is limited and available data suggest mental health screening alone does not improve worker mental health. Substantial variation in the implementation of screening was observed. Further research disentangling the independent effect of screening alongside the efficacy of other interventions to prevent mental ill health at work is required.

Substance use among vocational trainees in Australia: differences between medical specialties.

BACKGROUND: There have been few large-scale nationally representative studies on the prevalence of substance use among doctors. In addition, the association of different medical specialties with the use of different substances requires further research. AIMS: To investigate how the use of alcohol, tobacco and illicit drugs varied between junior doctors enrolled in different specialty training programmes. METHODS: A secondary analysis was conducted on a national survey of 12 252 Australian doctors. The population of interest was junior doctors currently enrolled in a specialty training programme, termed vocational trainees (VT; n = 1890; 15.4% of the overall sample). Self-report prevalence of current alcohol, tobacco and illicit drug use were assessed and hazardous alcohol use was assessed using the Alcohol Use Disorders Identification Test. Logistic regression was used to examine the association between specialty and substance use, adjusting for demographic characteristics when required. RESULTS: One in six VT reported hazardous levels of alcohol use (n = 268; 17.3%). After adjusting for confounders, the association between the prevalence of alcohol use and the specialties of emergency medicine/intensive care unit (odds ratio (OR) 2.15; 95% confidence interval (CI) 1.40-3.32; P < 0.001), anaesthetics (OR 2.53; 95% CI 1.35-4.76; P = 0.004) and obstetrics/gynaecology (OR 1.89; 95% CI 1.19-3.02; P = 0.007) remained significant. No significant associations were found between tobacco use/illicit drug use/hazardous alcohol use and medical specialty. CONCLUSIONS: While rates of substance use and hazardous alcohol use in VT are similar, if not lower, than the general population, it poses a concern that there are higher rates of alcohol use in certain medical specialties.

Suicide among health professionals in Australia: A retrospective mortality study of trends over the last two decades.

OBJECTIVE: To examine the relative risk of suicide among healthcare professionals compared to other occupations and examine changes in suicide rates over time. METHODS: Suicide cases were identified using the National Coronial Information System and were included if they were recorded as a death by intentional self-harm between 2001 and 2017 and were by an employed adult aged 20-69 with a known occupation at the time of death. Suicide methods were reported descriptively. Workforce data at the population level was extracted from the Australian Bureau of Statistics 2011 Census. Age-standardised suicide rates per 100,000 person-years for each of the four occupational groups were calculated using direct standardisation and using the Australian Bureau of Statistics population-level data from the 2011 Census. Negative binomial regression was used to estimate suicide risk by healthcare employment status and profession, to investigate differences by sex and to examine trends in suicide rates over time, using rate ratios and 95% confidence intervals. RESULTS: Healthcare professionals were at increased risk of suicide compared to other occupations (rate ratio = 1.30, 95% confidence interval = [1.19, 1.42], p < 0.001), controlling for age, sex and year of death. Nurses and midwives were identified as being at significantly increased risk of suicide (rate ratio = 1.95, 95% confidence interval = [1.73, 2.19], p < 0.001). Suicide rates among female medical practitioners increased substantially over time (p = 0.01). CONCLUSION: Health professionals are at significantly increased risk of suicide, though the relative risk of different groups is changing over time. There has been a substantial increase in the risk of suicide among female medical practitioners with rates of suicide in this group more than doubling over the last two decades. Findings highlight the need for targeted suicide prevention initiatives for healthcare professionals.

Renewal of academic psychiatry without addressing gender equity will render it Jurassic rather than endangered.

While two editorials have raised concerns about the decline in Australian academic psychiatry, for a genuine rejuvenation to ever occur, we will need to re-examine how women can be better included in this important endeavour. While attainment of fellowship has reached gender parity, academic psychiatry has disappointingly lagged, with 80% of its senior leadership roles across Australia and New Zealand still held by men, with a similar situation in the United Kingdom and the United States as well as many other countries. Encouraging women into academic psychiatry is not only critical to progress as a profession but also will help address the current blindness to sex differences in biological psychiatry, as well the social impact of restrictive gender norms and the effects of gender-based violence on mental health. This potentially creates opportunities for significant gains and insights into mental disorders. However, addressing the barriers for women in academia requires tackling the entrenched disparities across salaries, grant funding, publications, teaching responsibilities, keynote invitations and academic promotions alongside the gender-based microaggressions, harassment and tokenism reported by many of our female academics. Many women must grapple with not just a 'second shift' but a 'third shift', making the burden of an academic career unreasonable and burnout more likely. Addressing this is no easy task. The varied research in academic medicine reveals no quick fixes, although promoting gender equity brings significant potential benefits. Areas such as academic psychiatry need to recognise our community's growing discomfort with workplaces that choose to maintain status quo. Gender equity must be a critical part of any quest to revive this important area of practice for our profession.

A blended face-to-face and smartphone intervention to improve suicide prevention literacy and help-seeking intentions among construction workers: a randomised controlled trial.

PURPOSE: In Australia and elsewhere, suicide rates among construction workers remain high. Construction workplaces are thus an important setting for targeted suicide prevention programs. This study aimed to compare suicide prevention literacy and help-seeking intentions among participants receiving face-to-face suicide prevention training, with those receiving face-to-face training augmented by a smartphone application. METHODS: A two-arm randomised controlled trial of a smartphone suicide prevention intervention was conducted among construction workers in four Australian states (trial registration number: ACTRN12619000625178). All participants received face-to-face training and were randomised to the control condition (face-to-face only, n = 575), or MATESmobile condition (face-to-face + smartphone application, n = 509). Surveys administered at baseline and 3-month follow-up measured suicide prevention literacy and help-seeking intentions for personal/emotional problems and suicidal thoughts. A mixed-model repeated measures (MMRM) analysis included all 1084 randomised participants. RESULTS: Outcomes did not differ significantly for suicide prevention literacy, nor help-seeking intentions from formal sources, informal sources outside the workplace, or no one (did not intend to seek help from anyone). However, relative to those in the control condition, those in the MATESmobile group showed greater increase in help-seeking intentions for emotional problems from a MATES worker/Connector (mean difference 0.54, 95% CI 0.22-0.87) and help-seeking intentions for suicidal thoughts from a workmate (mean difference 0.47, 95% CI 0.10-0.83) or MATES worker/Connector (mean difference 0.47, 95% CI 0.09-0.85). CONCLUSION: Results indicate that the MATESmobile application, together with face-to-face training, is beneficial in enhancing help-seeking intentions from MATES workers/Connectors and workmates to a greater extent than face-to-face training only. While this research provides some evidence that smartphone applications may support suicide prevention training, further research is needed.

Correction: Preliminary Investigation of Shift, a Novel Smartphone App to Support Junior Doctors' Mental Health and Well-being: Examination of Symptom Progression, Usability, and Acceptability After 1 Month of Use.

[This corrects the article DOI: 10.2196/38497.].

Selective Prevention of Depression in Workers Using a Smartphone App: Randomized Controlled Trial.

BACKGROUND: There is increasing evidence that depression can be prevented; however, universal approaches have had limited success. Appropriate targeting of interventions to at-risk populations has been shown to have potential, but how to selectively determine at-risk individuals remains unclear. Workplace stress is a risk factor for depression and a target for intervention, but few interventions exist to prevent depression among workers at risk due to heightened stress. OBJECTIVE: This trial aimed to evaluate the efficacy of a smartphone-based intervention in reducing the onset of depression and improving related outcomes in workers experiencing at least moderate levels of stress. METHODS: A randomized controlled trial was conducted with participants who were currently employed and reported no clinically significant depression and at least moderate stress. The intervention group (n=1053) were assigned Anchored, a 30-day self-directed smartphone app-based cognitive behavioral- and mindfulness-based intervention. The attention-control group (n=1031) were assigned a psychoeducation website. Assessment was performed via web-based self-report questionnaires at baseline and at 1-, 3-, and 6-month postbaseline time points. The primary outcome was new depression caseness aggregated over the follow-up period. The secondary outcomes included depressive and anxiety symptoms, stress, well-being, resilience, work performance, work-related burnout, and quality of life. Analyses were conducted within an intention-to-treat framework using mixed modeling. RESULTS: There was no significant between-group difference in new depression caseness (z score=0.69; P=.49); however, those in the Anchored arm had significantly greater depressive symptom reduction at 1 month (Cohen d=0.02; P=.049) and 6 months (Cohen d=0.08; P=.03). Anchored participants also showed significantly greater reduction in anxiety symptoms at 1 month (Cohen d=0.07; P=.04) and increased work performance at 1 month (Cohen d=0.07; P=.008) and 6 months (Cohen d=0.13; P=.01), compared with controls. Notably, for Anchored participants completing at least two-thirds of the intervention, there was a significantly lower rate of depression onset (1.1%, 95% CI 0.0%-3.7%) compared with controls (9.0%, 95% CI 6.8%-12.3%) at 1 month (z score=4.50; P<.001). Significant small to medium effect sizes for most secondary outcomes were seen in the highly engaged Anchored users compared with controls, with effects maintained at the 6-month follow-up for depressive symptoms, well-being, stress, and quality of life. CONCLUSIONS: Anchored was associated with a small comparative reduction in depressive symptoms compared with controls, although selective prevention of case-level depression was not observed in the intention-to-treat analysis. When users adequately engaged with the app, significant findings pertaining to depression prevention, overall symptom reduction, and functional improvement were found, compared with controls. There is a need for a greater focus on engagement techniques in future research. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000178943; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378592.

How to use the Bristol Stool Chart in childhood constipation.

Constipation in children is common and is a frequent cause for healthcare attendances in both primary and secondary care. The Bristol Stool Chart has become ubiquitous as an aid in the diagnosis and treatment of constipation, but many clinicians may not be aware of its origins or strengths and weaknesses. In this article, we outline the history and rationale behind the development of the Bristol Stool Chart and how it should be used in childhood constipation.

Mental illness and suicide among physicians.

The COVID-19 pandemic has heightened interest in how physician mental health can be protected and optimised, but uncertainty and misinformation remain about some key issues. In this Review, we discuss the current literature, which shows that despite what might be inferred during training, physicians are not immune to mental illness, with between a quarter and a third reporting increased symptoms of mental ill health. Physicians, particularly female physicians, are at an increased risk of suicide. An emerging consensus exists that some aspects of physician training, working conditions, and organisational support are unacceptable. Changes in medical training and health systems, and the additional strain of working through a pandemic, might have amplified these problems. A new evidence-informed framework for how individual and organisational interventions can be used in an integrated manner in medical schools, in health-care settings, and by professional colleagues is proposed. New initiatives are required at each of these levels, with an urgent need for organisational-level interventions, to better protect the mental health and wellbeing of physicians.

A combinatorially regulated RNA splicing signature predicts breast cancer EMT states and patient survival.

During breast cancer metastasis, the developmental process epithelial-mesenchymal transition (EMT) is abnormally activated. Transcriptional regulatory networks controlling EMT are well-studied; however, alternative RNA splicing also plays a critical regulatory role during this process. A comprehensive understanding of alternative splicing (AS) and the RNA binding proteins (RBPs) that regulate it during EMT and their impact on breast cancer remains largely unknown. In this study, we annotated AS in the breast cancer TCGA data set and identified an AS signature that is capable of distinguishing epithelial and mesenchymal states of the tumors. This AS signature contains 25 AS events, among which nine showed increased exon inclusion and 16 showed exon skipping during EMT. This AS signature accurately assigns the EMT status of cells in the CCLE data set and robustly predicts patient survival. We further developed an effective computational method using bipartite networks to identify RBP-AS networks during EMT. This network analysis revealed the complexity of RBP regulation and nominated previously unknown RBPs that regulate EMT-associated AS events. This study highlights the importance of global AS regulation during EMT in cancer progression and paves the way for further investigation into RNA regulation in EMT and metastasis.

Preventing depression using a smartphone app: a randomized controlled trial.

BACKGROUND: There is evidence that depression can be prevented; however, traditional approaches face significant scalability issues. Digital technologies provide a potential solution, although this has not been adequately tested. The aim of this study was to evaluate the effectiveness of a new smartphone app designed to reduce depression symptoms and subsequent incident depression amongst a large group of Australian workers. METHODS: A randomized controlled trial was conducted with follow-up assessments at 5 weeks and 3 and 12 months post-baseline. Participants were employed Australians reporting no clinically significant depression. The intervention group (N = 1128) was allocated to use HeadGear, a smartphone app which included a 30-day behavioural activation and mindfulness intervention. The attention-control group (N = 1143) used an app which included a 30-day mood monitoring component. The primary outcome was the level of depressive symptomatology (PHQ-9) at 3-month follow-up. Analyses were conducted within an intention-to-treat framework using mixed modelling. RESULTS: Those assigned to the HeadGear arm had fewer depressive symptoms over the course of the trial compared to those assigned to the control (F3,734.7 = 2.98, p = 0.031). Prevalence of depression over the 12-month period was 8.0% and 3.5% for controls and HeadGear recipients, respectively, with odds of depression caseness amongst the intervention group of 0.43 (p = 0.001, 95% CI 0.26-0.70). CONCLUSIONS: This trial demonstrates that a smartphone app can reduce depression symptoms and potentially prevent incident depression caseness and such interventions may have a role in improving working population mental health. Some caution in interpretation is needed regarding the clinical significance due to small effect size and trial attrition.Trial Registration Australian and New Zealand Clinical Trials Registry (www.anzctr.org.au/) ACTRN12617000548336.