Job Loss Due to COVID-19: A Longitudinal Study of Mental Health, Protective and Risk Factors.

The COVID-19 pandemic had a devastating impact on unemployment, which-compounded by the additional stressors associated with the pandemic-had considerable mental health impact. The current study examined the trajectory of mental health amongst those experiencing pandemic-related job loss, alongside the impact of risk and protective factors. Data were obtained from 374 Australian participants who were allocated to a waitlist control arm of a randomised control trial. The outcome variables assessed at baseline and six-month follow-up consisted of depression, anxiety, and suicidality. The assessed risk and protective factors were age, gender, relationship status, education, exercise frequency, COVID-related stress, dispositional resilience, and coping self-efficacy. Re-employment by follow-up was used as a covariate. Overall, there were decreases in depression and anxiety symptoms, and partial evidence of decreased suicidality, demonstrating an apparent capacity for individuals to better cope with their circumstances over time. Demographics and exercise had no effect on changes in mental health. Those with high COVID-related stress, low resilience, and low coping self-efficacy had worse mental health at baseline, although exhibited significantly greater improvements in mental health over time. Obtaining re-employment by follow-up did not predict changes in mental health. The present results offer an optimistic picture of recovery for those experiencing pandemic-related job loss, even for those with the most substantial risk and severity. The likely protective role played by Australian social welfare policies over the course of the study is explored. Stress around one's broader sociocultural or economic circumstances, perceived resilience, and coping self-efficacy are valuable targets for intervention.

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.

Extra-appendiceal mucinous neoplasms: A tumour with clinicopathologic similarities to low- and high-grade appendiceal counterpart.

AIMS: Appendiceal mucinous neoplasms feature neoplastic mucinous epithelium with pushing borders and densely fibrotic walls. We have identified five examples of analogous colorectal tumours. METHODS AND RESULTS: Slides, pathology reports, and clinical data were reviewed. Whole genome sequencing was performed in two cases. Three were women and the mean age was 70. Associated GI conditions included Crohn's disease [1], diverticulosis [2], and sarcoma of the terminal ileum [1]. Signs/symptoms included obstruction [2], nausea, vomiting, abdominal pain [1], and positive faecal immunohistochemical test [1]. Colonoscopic findings included narrowing [1], "fullness" [1], and caecal lesion concerning for GIST [1]. Tumours involved the rectosigmoid [2], sigmoid [1], transverse colon [1], and cecum [1] and ranged from 1.5 cm to 8.5 cm. All but one tumour arose in the setting of faecal stream abnormalities related to obstruction, diverticulosis, or bowel diversion. All cases showed columnar, variably mucinous epithelium associated with little-to-no lamina propria. All but one case showed fibrosis of the submucosa. Three cases had high-grade areas. Neoplastic glands and/or mucin dissected through the muscularis propria or subserosa in 3 examples. No extracolonic neoplastic cells/mucin, infiltrative invasion, or desmoplastic response were identified. Three patients with available follow-up [5.5-28 months] are alive. Whole genome sequencing identified pathogenic TP53 and ERBB2 variants, as well as ERBB2 copy number amplification in one high-grade example. CONCLUSIONS: Though these tumours share clinicopathologic characteristics with their appendiceal counterparts, our cohort is too small to draw solid conclusions. We propose the term "extra-appendiceal mucinous neoplasm [EAMN]" for these rare lesions.

Yoga resilience training to prevent the development of posttraumatic stress disorder in active-duty first responders: A cluster randomized controlled trial.

OBJECTIVE: Evidence on effective prevention of posttraumatic stress disorder (PTSD) is sparse, particularly among first responders. This study evaluated the effectiveness of a Tactical Mind-Body Resilience Training program on PTSD symptoms in first responders. METHOD: Active-duty first responders (n = 80; Mage = 41.8 years, 82.5% men) were randomized to the intervention group or the waitlist control condition. PTSD symptoms as measured by the PTSD-8 were the primary outcome assessed at postintervention and at 3-month follow-up. Secondary outcomes were cognitive and emotional coping strategies, resilience, somatic symptoms, work performance, and sickness absence. RESULTS: At postintervention, the intervention group had significantly reduced PTSD symptoms compared to the control group (d = -0.26, difference = -2.52, 95% confidence interval [CI] [-4.93, -0.11], p = .040); however, this difference was attenuated at 3-month follow-up (d = -0.07, difference = -1.41, 95% CI [-3.83, 1.01], p = .248). The intervention group had significant improvements in cognitive reappraisal and resilience at postintervention compared to the control group, which were sustained at 3 months. The remaining secondary outcomes had statistically nonsignificant improvements. CONCLUSIONS: This workplace-delivered intervention shows potential in preventing the development of PTSD in first responders. Further research is needed on maintaining long-term benefits of this training. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Transgenic expression of cif genes from Wolbachia strain wAlbB recapitulates cytoplasmic incompatibility in Aedes aegypti.

The endosymbiotic bacteria Wolbachia can invade insect populations by modifying host reproduction through cytoplasmic incompatibility (CI), an effect that results in embryonic lethality when Wolbachia-carrying males mate with Wolbachia-free females. Here we describe a transgenic system for recreating CI in the major arbovirus vector Aedes aegypti using CI factor (cif) genes from wAlbB, a Wolbachia strain currently being deployed to reduce dengue transmission. CI-like sterility is induced when cifA and cifB are co-expressed in testes; this sterility is rescued by maternal cifA expression, thereby reproducing the pattern of Wolbachia-induced CI. Expression of cifB alone is associated with extensive DNA damage and disrupted spermatogenesis. The strength of rescue by maternal cifA expression is dependent on the comparative levels of cifA/cifB expression in males. These findings are consistent with CifB acting as a toxin and CifA as an antitoxin, with CifA attenuating CifB toxicity in both the male germline and in developing embryos. These findings provide important insights into the interactions between cif genes and their mechanism of activity and provide a foundation for the building of a cif gene-based drive system in Ae. aegypti.

A multiplexed, confinable CRISPR/Cas9 gene drive can propagate in caged Aedes aegypti populations.

Aedes aegypti is the main vector of several major pathogens including dengue, Zika and chikungunya viruses. Classical mosquito control strategies utilizing insecticides are threatened by rising resistance. This has stimulated interest in new genetic systems such as gene drivesHere, we test the regulatory sequences from the Ae. aegypti benign gonial cell neoplasm (bgcn) homolog to express Cas9 and a separate multiplexing sgRNA-expressing cassette inserted into the Ae. aegypti kynurenine 3-monooxygenase (kmo) gene. When combined, these two elements provide highly effective germline cutting at the kmo locus and act as a gene drive. Our target genetic element drives through a cage trial population such that carrier frequency of the element increases from 50% to up to 89% of the population despite significant fitness costs to kmo insertions. Deep sequencing suggests that the multiplexing design could mitigate resistance allele formation in our gene drive system.

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.

CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus.

Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging in Culex. Here we test a CRISPR-based homing gene drive for Culex quinquefasciatus, and show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to include Culex alongside Anopheles and Aedes, and pave the way for future development of these technologies to control Culex mosquitoes.

Generalized Mantel-Haenszel Estimators for Simultaneous Differential Item Functioning Tests.

The Mantel-Haenszel estimator is one of the most popular techniques for measuring differential item functioning (DIF). A generalization of this estimator is applied to the context of DIF to compare items by taking the covariance of odds ratio estimators between dependent items into account. Unlike the Item Response Theory, the method does not rely on the local item independence assumption which is likely to be violated when one item provides clues about the answer of another item. Furthermore, we use these (co)variance estimators to construct a hypothesis test to assess DIF for multiple items simultaneously. A simulation study is presented to assess the performance of several tests. Finally, the use of these DIF tests is illustrated via application to two real data sets.

The prevalence of anxiety in adult endocrinology outpatients: A systematic review and meta-analysis.

INTRODUCTION: Anxiety disorders and anxiety symptoms are common mental disorders in the medically unwell and have significant impacts on patients' quality of life and engagement with psychiatric and medical services. Several systematic reviews have examined the prevalence of anxiety in specific endocrinology settings with estimates varying significantly from study to study. No meta-analysis has examined anxiety rates across the endocrinology outpatient setting. The aim of this meta-analysis is to provide endocrinologists with a precise estimate of the prevalence of anxiety - and impacting factors - in their outpatient clinics. METHOD: PubMed, Embase, Cochrane and PsycINFO databases and Google Scholar were searched to identify studies that assessed anxiety prevalence in endocrinology outpatients published up to 23 January 2023. This was part of a larger systematic review search of anxiety prevalence in common medical outpatient clinics. Data characteristics were extracted independently by two investigators. Studies of patients 16 years and older and representative of the clinic were included. The point prevalence of anxiety or anxiety symptoms was measured using validated self-report questionnaires or structured interviews. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Pooled estimates were analysed under the random-effects model and subgroup analyses on relevant variables were conducted under a mixed-effects model. Heterogeneity was assessed using the I2 statistic. RESULTS: Fifty-nine studies with a total of 25,176 participants across 37 countries were included in this study. The overall pooled prevalence of anxiety or anxiety symptoms was 25·1% (95%CI 21·4-29·2; 6372/25,176; n = 59). Subgroup analyses revealed no difference in prevalence between outpatients with diabetes mellitus compared to other grouped endocrine disorders. Generalized Anxiety Disorder (GAD) was the most frequent clinical diagnosis 11·7% (95%CI 8·1-16·7; I2=87·93%; 443/4604; n = 17), while panic disorder was significantly higher in the non-diabetes group 9·5% (95%CI 5·9-14·9; I2=57·28%; 56/588; n = 8), compared to the diabetes group 5·2% (95%CI 3·7-7·3; I2=32·18%; 184/3669; n = 6). Estimates of prevalence were higher when assessed with a self-report scale 32·4% (95%CI 25·6-40·0; I2=96·06%; 1565/4675; n = 21) compared to diagnostic interview 17·6% (95%CI 12·2-24·7; I2=94·39%; 636/5168; n = 21). Outpatients in developing countries had higher rates of anxiety than those in developed countries. Female diabetes patients reported higher rates of anxiety compared to males. CONCLUSION: Our study provides evidence that anxiety occurs frequently amongst endocrinology outpatients and at a higher rate than is estimated in the general population. Given the impact anxiety has on patient outcomes, it is important that effective management strategies be developed to support endocrinologists in identifying and treating these conditions in their outpatient clinics.

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.

CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus.

Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging in Culex. Here we test the first CRISPR-based homing gene drive for Culex quinquefasciatus, demonstrating the possibility of using this technology to control Culex mosquitoes. Our results show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to include Culex alongside Anopheles and Aedes, and pave the way for future development of these technologies to control Culex mosquitoes.

Mind-body exercise interventions for prevention of post-traumatic stress disorder in trauma-exposed populations: a systematic review and meta-analysis.

OBJECTIVE: Mind-body exercise (MBE) interventions, such as yoga, are increasingly recognised as an adjunct treatment for trauma-related mental disorders but less is known about their efficacy as a preventative intervention. We aimed to systematically review if, and what type of, MBE interventions are effective at preventing the development of post-traumatic stress disorder (PTSD) or acute stress disorder (ASD) in trauma-exposed populations. DESIGN: Systematic review and meta-analysis. METHODS: A systematic search of MEDLINE, PsycINFO, EMBASE and CENTRAL databases was conducted to identify controlled trials of MBE interventions aimed at preventing the development of PTSD or ASD in high-risk populations. Risk of bias was assessed using the revised Cochrane risk-of-bias and ROBINS-I tools. Pooled effect sizes using Hedges' g and 95% CIs were calculated using random effects modelling for the main meta-analysis and planned subgroup and sensitivity analyses. RESULTS: Six studies (N analysed=399) were included in the final meta-analysis. Overall, there was a small effect for MBE interventions in preventing the development of PTSD (g=-0.25, 95% CI -0.56 to 0.06) among those with previous or ongoing exposure to trauma. Although a prespecified subgroup analyses comparing the different types of MBE intervention were conducted, meaningful conclusions could not be drawn due to the small number of studies. None of the included studies assessed ASD symptoms. CONCLUSION: Limited evidence was found for MBE interventions in reducing PTSD symptomology in the short term. Findings must be interpreted with caution due to the small number of studies and possible publication bias. PROSPERO REGISTRATION NUMBER: CRD42020180375.

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.

Global Prevalence of Anxiety in Adult Cardiology Outpatients: A Systematic Review and Meta-analysis.

Anxiety and anxiety disorders are associated with adverse cardiovascular outcomes, and reduced quality of life. Despite this, no comprehensive study on the global prevalence of anxiety symptoms and disorders among adult cardiology outpatients exists. This systematic review and meta-analysis aims to provide cardiologists with a precise estimate of the prevalence of anxiety in their outpatient clinics. PubMed, Embase, Cochrane and PsycINFO databases and Google Scholar were searched from database inception to January 23, 2023. Data characteristics were extracted independently by 2 investigators. Ninety-three studies, n = 36,687 participants across 31 countries, were included. Global prevalence of anxiety symptoms/disorders was 28.9% (95%CI 25.7-32.4; 8927/36, 687; I2 = 97.33; n = 93). The highest rates were found in patients presenting with hypertension, 43.6%. Subgroup analyses revealed higher prevalence estimates when using self-report screening compared to gold-standard diagnostic interview. When using diagnostic interview, the highest rates were reported in outpatients with undifferentiated chest pain/palpitations, 19·0%. Panic disorder was the most frequent diagnosis 15.3%, and rates were significantly higher in patients with undifferentiated chest pain/palpitations compared to ischemic heart disease. Higher rates of anxiety were found in studies of outpatients from developing countries, and female outpatients tended to have higher rates compared to males. Anxiety occurred frequently among cardiology outpatients and at a higher rate than estimated in the general population. Given the impact anxiety has on patient outcomes, it is important that effective identification and management strategies be developed to support cardiologists in identifying and treating these conditions in their clinics.

Mental health and unemployment: A systematic review and meta-analysis of interventions to improve depression and anxiety outcomes.

BACKGROUND: Unemployment is associated with substantially greater depression and anxiety, constituting a considerable public health concern. The current review provides the most comprehensive synthesis to date, and first meta-analysis, of controlled intervention trials aimed at improving depression and anxiety outcomes during unemployment. METHODS: Searches were conducted within PsycInfo, Cochrane Central, PubMed and Embase from their inception to September 2022. Included studies conducted controlled trials of interventions focused on improving mental health within unemployed samples, and reported on validated measures of depression, anxiety, or distress (mixed depression and anxiety). Narrative syntheses and random effects meta-analyses were conducted among prevention- and treatment-level interventions for each outcome. RESULTS: A total of 39 articles reporting on 33 studies were included for review (sample sizes ranging from 21 to 1801). Both prevention and treatment interventions tended to be effective overall, with treatment interventions producing larger effect sizes than prevention interventions. The clearest evidence for particular intervention approaches emerged for prevention-level Cognitive Therapy/CBT, followed by prevention-level work-related interventions, although neither produced entirely consistent effects. LIMITATIONS: Risk of bias was generally high across studies. Low numbers of studies within subgroups precluded any comparisons between long-term and short-term unemployment, limited comparisons among treatment studies, and reduced the power of meta-analyses. CONCLUSIONS: Both prevention- and treatment-level mental health-focused interventions have merit for reducing symptoms of anxiety and depression among those experiencing unemployment. Cognitive Therapy/CBT and work-related interventions hold the most robust evidence base, which can inform both prevention and treatment strategies implemented by clinicians, employment services providers, and governments.

Restoration of normal blood flow in atherosclerotic arteries promotes plaque stabilization.

Blood flow is a key regulator of atherosclerosis. Disturbed blood flow promotes atherosclerotic plaque development, whereas normal blood flow protects against plaque development. We hypothesized that normal blood flow is also therapeutic, if it were able to be restored within atherosclerotic arteries. Apolipoprotein E-deficient (ApoE-/-) mice were initially instrumented with a blood flow-modifying cuff to induce plaque development and then five weeks later the cuff was removed to allow restoration of normal blood flow. Plaques in decuffed mice exhibited compositional changes that indicated increased stability compared to plaques in mice with the cuff maintained. The therapeutic benefit of decuffing was comparable to atorvastatin and the combination had an additive effect. In addition, decuffing allowed restoration of lumen area, blood velocity, and wall shear stress to near baseline values, indicating restoration of normal blood flow. Our findings demonstrate that the mechanical effects of normal blood flow on atherosclerotic plaques promote stabilization.

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.].

LINE-associated cryptic splicing induces dsRNA-mediated interferon response and tumor immunity.

RNA splicing plays a critical role in post-transcriptional gene regulation. Exponential expansion of intron length poses a challenge for accurate splicing. Little is known about how cells prevent inadvertent and often deleterious expression of intronic elements due to cryptic splicing. In this study, we identify hnRNPM as an essential RNA binding protein that suppresses cryptic splicing through binding to deep introns, preserving transcriptome integrity. Long interspersed nuclear elements (LINEs) harbor large amounts of pseudo splice sites in introns. hnRNPM preferentially binds at intronic LINEs and represses LINE-containing pseudo splice site usage for cryptic splicing. Remarkably, a subgroup of the cryptic exons can form long dsRNAs through base-pairing of inverted Alu transposable elements scattered in between LINEs and trigger interferon immune response, a well-known antiviral defense mechanism. Notably, these interferon-associated pathways are found to be upregulated in hnRNPM-deficient tumors, which also exhibit elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity. Targeting hnRNPM in tumors may be used to trigger an inflammatory immune response thereby boosting cancer surveillance.