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Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.
Background: Meningiomas are the most common intracranial tumors. Radiotherapy (RT) serves as an adjunct following surgical resection; however, response varies. RTOG-0539 is a prospective, phase 2, trial that stratified patients risk groups based on clinical and pathological criteria, providing key benchmarks for RT outcomes. This is the first study that aims to characterize the molecular landscape of an RT clinical trial in meningiomas. Methods: Tissue from 100 patients was analyzed using DNA methylation, RNA sequencing, and whole-exome sequencing. Copy number variations and mutational profiles were assessed to determine associations with meningioma aggressiveness. Tumors were molecularly classified and pathway analyses were conducted to identify biological processes associated with RT response. Results: High-risk meningiomas exhibited cell cycle dysregulation and hypermetabolic pathway upregulation. 1p loss and 1q gain were more frequent in aggressive meningiomas, and NF2 and non-NF2 mutations co-occurred in some high-risk tumors. Molecular findings led to the reclassification of several cases, highlighting the limitations of histopathologic grading alone. Conclusions: This is the first study to comprehensively characterize the molecular landscape of any RT trial in meningioma, integrating multi-omic data to refine treatment stratification. Findings align with ongoing genomically driven meningioma clinical trials and underscore the need for prospective tissue banking to enhance biomarker-driven treatment strategies.
Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.
Background: We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation model compatible with newer methylation arrays. Methods: The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. A nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection. Results: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and a retrospective cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperformed 2021 WHO grade in predicting postoperative recurrence. Dichotomizing into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (log-rank p<0.05). Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Conclusions: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. This will help improve prognostication and inform patient selection for RT.
Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.
Background: The combination of PARP inhibitor and immune checkpoint inhibitors have been proposed as a potentially synergistic combinatorial treatment in IDH mutant glioma, targeting dysregulated homologous recombination repair pathways. This study analyzed the cell-free DNA methylome of patients in a phase 2 trial using the PARP inhibitor Olaparib and the PD-1 inhibitor Durvalumab. Methods: Patients with recurrent high-grade IDH-mutant gliomas were enrolled in a phase II open-label study (NCT03991832). Serum was collected at baseline and monthly and cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) was performed. Binomial GLMnet models were developed and model performance was assessed using validation set data. Results: 29 patients were enrolled between 2020–2023. Patients received olaparib 300mg twice daily and durvalumab 1500mg IV every 4 weeks. The overall response rate was 10% via RANO criteria. 144 plasma samples were profiled with cfMeDIP-seq along with 30 healthy controls. The enriched circulating tumour DNA methylome during response periods exhibited a highly specific signature, accurately discriminating response versus failure (AUC 0.98 ± 0.03). Additionally, samples that were taken while on treatment were able to be discriminated from samples off therapy (AUC 0.74 ± 0.11). Conclusions: The cell-free plasma DNA methylome exhibits highly specific signatures that enable accurate prediction of response to therapy.
We present the first results from a new backend on the Australian Square Kilometre Array Pathfinder, the Commensal Realtime ASKAP Fast Transient COherent (CRACO) upgrade. CRACO records millisecond time resolution visibility data, and searches for dispersed fast transient signals including fast radio bursts (FRB), pulsars, and ultra-long period objects (ULPO). With the visibility data, CRACO can localise the transient events to arcsecond-level precision after the detection. Here, we describe the CRACO system and report the result from a sky survey carried out by CRACO at 110-ms resolution during its commissioning phase. During the survey, CRACO detected two FRBs (including one discovered solely with CRACO, FRB 20231027A), reported more precise localisations for four pulsars, discovered two new RRATs, and detected one known ULPO, GPM J1839 $-$10, through its sub-pulse structure. We present a sensitivity calibration of CRACO, finding that it achieves the expected sensitivity of 11.6 Jy ms to bursts of 110 ms duration or less. CRACO is currently running at a 13.8 ms time resolution and aims at a 1.7 ms time resolution before the end of 2024. The planned CRACO has an expected sensitivity of 1.5 Jy ms to bursts of 1.7 ms duration or less and can detect $10\times$ more FRBs than the current CRAFT incoherent sum system (i.e. 0.5 $-$2 localised FRBs per day), enabling us to better constrain the models for FRBs and use them as cosmological probes.
To meet the development needs of aeroengines for high thrust-to-weight ratios and fuel-air ratios, a high temperature rise triple-swirler main combustor was designed with a total fuel-air ratio of 0.037, utilising advanced technologies including staged combustion, multi-point injection and multi-inclined hole cooling. Fluent software was used to conduct numerical simulations under both takeoff and idle conditions, thereby obtaining the distribution characteristics of the velocity and temperature fields within the combustor, as well as the generation of pollutants. The simulation results indicate that under takeoff conditions, the high temperature rise triple-swirler combustor achieves a total pressure loss coefficient of less than 6% and a combustion efficiency exceeding 99%. Under takeoff conditions, the OTDF and RTDF values are 0.144 and 0.0738, respectively. The mole fraction of NOx emissions is 3,700ppm, while the mole fraction of soot emissions is 2.55×10−5ppm. Under idle conditions, the triple-swirler combustor maintains a total pressure loss coefficient of less than 6% and a combustion efficiency greater than 99.9%. The OTDF and RTDF values are 0.131 and 0.0624, respectively. The mole fractions of CO and UHC emissions are both 0×10−32ppm at the calculation limit of Fluent software.
In this paper, a brand-new adaptive fault-tolerant non-affine integrated guidance and control method based on reinforcement learning is proposed for a class of skid-to-turn (STT) missile. Firstly, considering the non-affine characteristics of the missile, a new non-affine integrated guidance and control (NAIGC) design model is constructed. For the NAIGC system, an adaptive expansion integral system is introduced to address the issue of challenging control brought on by the non-affine form of the control signal. Subsequently, the hyperbolic tangent function and adaptive boundary estimation are utilised to lessen the jitter due to disturbances in the control system and the deviation caused by actuator failures while taking into account the uncertainty in the NAIGC system. Importantly, actor-critic is introduced into the control framework, where the actor network aims to deal with the multiple uncertainties of the subsystem and generate the control input based on the critic results. Eventually, not only is the stability of the NAIGC closed-loop system demonstrated using Lyapunov theory, but also the validity and superiority of the method are verified by numerical simulations.
This study aimed to examine the efficacy of the automated mechanical repositioning chairs compared to canalith repositioning manoeuvres for elderly patients with benign paroxysmal positional vertigo (BPPV).
Methods:
A retrospective study included 969 patients with BPPV who were first diagnosed at Beijing Chaoyang Hospital, Capital Medical University between 1 January 2020 and 31 December 2020. Patients were followed up for one year. Demographics, disease status, treatment and various outcomes were collected through medical record reviews and follow-up interviews.
Results:
Based on the criteria for evaluating treatment efficacy using objective and subjective indicators, BPPV patients treated with automated mechanical repositioning chair therapy showed a significantly better prognosis and lower recurrence rates.
Conclusion:
Automated mechanical repositioning chair therapy is an effective approach for BPPV treatment, with advantages over conventional manual canalith repositioning procedures.
Major depressive disorder (MDD) is a prevalent and disabling condition. Approximately 30-50% of patients do not respond to first-line medication or psychotherapy. Therefore, several studies have investigated the predictive potential of pretreatment severity rating or neuroimaging features to guide clinical approaches that can speed optimal treatment selection.
Objectives
To evaluate the performance of 1) severity ratings (scores of Hamilton Depression/Anxiety Scale, illness duration, and sleep quality, etc.) and demographic characteristic and 2) brain magnetic resonance imaging (MRI) features in predicting treatment outcomes for MDD. Second, to assess performance variations among varied modalities and interventions in MRI studies.
Methods
We searched studies in PubMed, Embase, Web of Science, and Science Direct databases before March 22, 2023. We extracted a confusion matrix for prediction in each study. Separate meta-analyses were performed for clinical and MRI studies. The logarithm of diagnostic odds ratio [log(DOR)], sensitivity, and specificity were conducted using Reitsma’s random effect model. The area under curve (AUC) of summary receiver operating characteristic (SROC) curve was calculated.
Subgroup analyses were conducted in MRI studies based on modalities: resting-state functional MRI (rsfMRI), task-based fMRI (tbfMRI), and structural MRI (sMRI), and interventions: antidepressant (including selective serotonin reuptake inhibitors [SSRI]) and electroconvulsive therapy (ECT). Meta-regression was conducted 1) between clinical and MRI studies and 2) among modality or intervention subgroups in MRI studies.
Results
We included ten studies used clinical features covering 6494 patients, yielded a log(DOR) of 1.42, AUC of 0.71, sensitivity of 0.61, and specificity of 0.74. In terms of MRI, 44 studies with 2623 patients were included, revealing an overall log(DOR) of 2.53. The AUC, sensitivity, and specificity were 0.89, 0.78, and 0.75.
Studies using MRI features had a higher sensitivity (0.89 vs. 0.61) in predicting treatment outcomes than clinical features (P < 0.001). RsfMRI had higher specificity (0.79 vs. 0.69) than tbfMRI subgroup (P = 0.01). No significant differences were found between sMRI and other modalities, nor between antidepressants (SSRIs and others) and ECT. Antidepressant studies primarily identified predictive imaging features in limbic and default mode networks, while ECT mainly focused on limbic network.
Conclusions
Our findings suggest a robust promise for pretreatment brain MRI features in predicting treatment outcomes in MDD, offering higher accuracy than clinical studies. While tasks in tbfMRI studies differed, those studies overall had less predictive utility than rsfMRI data. For MRI studies, overlapping but distinct network level measures predicted outcomes for antidepressants and ECT.
Obsessive-compulsive disorder (OCD) is a common psychiatric disorder. It is considered that dysregulation of cytokine levels is related to the pathophysiological mechanism of OCD. However, the results of previous studies on cytokine levels in OCD are inconsistent.
Objectives
To perform a meta-analysis assessing cytokine levels in peripheral blood of OCD patients.
Methods
We searched in PubMed, Web of Science, and Embase from inception to March 31, 2023 for eligible studies. We conducted multivariate meta-analysis in combined proinflammatory cytokines (interleukin-6 [IL-6], IL-1β, IL-2, tumor necrosis factor-α [TNF-α], and interferon-γ [IFN-γ]) and combined anti-inflammatory cytokines (IL-10 and IL-4) respectively, and calculated the same meta-analysis in each cytokine. We also performed sensitivity analysis and publication bias tests, as well as subgroup analysis (i.e. different age groups, varied cytokine measurement methods, medication treated or naïve, and presence of psychiatric comorbidities) and meta-regression analysis (variables including patients’ sex ratio, age, age at symptom onset, illness duration, scores of Y-BOCS, family history of psychiatric disorders, and BMI).
Results
17 original studies (13, 13, 10, 5, 4, 3, 2 studies for IL-6, TNF-α, IL-1β, IL-10, IL-2, IL-4, and IFN-γ, respectively), 573 patients (mean age, 25.2; 50.3% female) and 498 healthy controls (HC; mean age, 25.3; 51.4% female) were included. The results showed that the levels of combined pro- or anti-inflammatory cytokines and each signle cytokine were not significantly different between OCD patients and HC (all P>0.05), with significant heterogeneities in all analyses (I2 from 79.1% to 91.7%). We did not find between-group differences in cytokine levels in all subgroup analyses. Meta-regression analysis suggested that age at onset (P=0.0003) and family history (P=0.0062) might be the source of heterogeneity in TNF-α level. Sensitivity analysis confirmed that all results were stable, except for IL-4 where different cytokine measurement methods may be the contributing factor. Egger test did not find publication bias.
Conclusions
Our study showed no difference in cytokine levels between OCD patients and HC, but age at onset and family history may affect TNF-α level. Confounding factors such as age at onset, family history, and cytokine measurement methods should be controlled in future studies to further explore the immune mechanism of OCD.
Adolescence is a period marked by highest vulnerability to the onset of depression, with profound implications for adult health. Neuroimaging studies have revealed considerable atrophy in brain structure in these patients with depression. Of particular importance are regions responsible for cognitive control, reward, and self-referential processing. However, the causal structural networks underpinning brain region atrophies in adolescents with depression remain unclear.
Objectives
This study aimed to investigate the temporal course and causal relationships of gray matter atrophy within the brains of adolescents with depression.
Methods
We analyzed T1-weighted structural images using voxel-based morphometry in first-episode adolescent patients with depression (n=80, 22 males; age = 15.57±1.78) and age, gender matched healthy controls (n=82, 25 males; age = 16.11±2.76) to identify the disease stage-specific gray matter abnormalities. Then, with granger causality analysis, we arranged the patients’ illness duration chronologically to construct the causal structural covariance networks that investigated the causal relationships of those atypical structures.
Results
Compared to controls, smaller volumes in ventral medial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), middle cingulate cortex (MCC) and insula areas were identified in patients with less than 1 year illness duration, and further progressed to the subgenual ACC, regions of default, frontoparietal networks in longer duration. Causal network results revealed that dACC, vmPFC, MCC and insula were prominent nodes projecting exerted positive causal effects to regions of the default mode and frontoparietal networks. The dACC, vmPFC and insula also had positive projections to the reward network, which included mainly the thalamus, caudate and putamen, while MCC also exerted a positive causal effect on the insula and thalamus.
Conclusions
These findings revealed the progression of structural atrophy in adolescent patients with depression and demonstrated the causal relationships between regions involving cognitive control, reward and self-referential processes.
The occurrence of depression in adolescence, a critical period of brain development, linked with neuroanatomical and cognitive abnormalities. Neuroimaging studies have identified hippocampal abnormalities in those of adolescent patients. However, few studies have investigated the atypically developmental trends in hippocampal subfields in adolescents with depression and their relationships with cognitive dysfunctions.
Objectives
To explore the structural abnormalities of hippocampal subfields in patients with youth depression and examine how these abnormalities associated with cognitive deficits.
Methods
We included a sample of 79 first-episode depressive patients (17 males, age = 15.54±1.83) and 71 healthy controls (23 males, age = 16.18±2.85). The severity of these adolescent patients was assessed by depression scale, suicidal risk and self-harm behavior. Nine cognitive tasks were used to evaluate memory, cognitive control and attention abilities for all participants. Bilateral hippocampus were segmented into 12 subfields with T1 and T2 weighted images using Freesurfer v6.0. A mixed analysis of variance was performed to assess the differences in subfields volumes between all patients and controls, and between patients with mild and severe depression. Finally, LASSO regression was conducted to explore the associations between hippocampal subfields and cognitive abnormalities in patients.
Results
We found significant subfields atrophy in the CA1, CA2/3, CA4, dentate gyrus, hippocampal fissure, hippocampal tail and molecular layer subfields in patients. For those patients with severe depression, hippocampal subfields showed greater extensive atrophy than those in mild, particularly in CA1-4 subfields extending towards the subiculum. These results were similar across various severity assessments. Regression indicated that hippocampal subfields abnormalities had the strongest associations with memory dysfunction, and relatively week associations with cognitive control and attention. Notably, CA4 and dentate gyrus had the highest weights in the regression model.
Conclusions
As depressive severity increases, hippocampal subfield atrophy tends to spread from CA regions to surrounding areas, and primarily affects memory function in patients with youth depression. These results suggest hippocampus might be markers in progression of adolescent depression, offering new directions for early clinical intervention.
There’s large heterogeneity present in major depressive disorder (MDD) and controversial evidence on alterations of brain functional connectivity (FC), making it hard to elucidate the neurobiological basis of MDD. Subtyping is one promising solution to characterize this heterogeneity.
Objectives
To identify neurophysiological subtypes of MDD based on FC derived from resting-state functional magnetic resonance imaging using large multisite data and investigate the differences in genetic mechanisms and neurotransmitter basis of FC alterations, and the differences of FC-related cognition between each subtype.
Methods
Consensus clustering of FC patterns was applied to a population of 829 MDD patients from REST-Meta-MDD database after data cleaning and image quality control. Gene transcriptomic data derived from Allen Human Brain Atlas and neurotransmitter receptor/transporter density data acquired by using neuromap toolbox were used to characterize the molecular mechanism underlying each FC-based subtype by identifying the gene set and neurotransmitters/transporters showing high spatial similarity with the profiles of FC alterations between each subtype and 770 healthy controls. The FC-related cognition in each subtype was also selected by lasso regression.
Results
Two stable neurophysiological MDD subtypes were found and labeled as hypoconnectivity (n=527) and hyperconnectivity (n=299) characterized by the FC differences in each subtype relative to controls, respectively. The two subtypes did not differ in age, sex, and scores of Hamilton Depression/Anxiety Scale.
The genes related to FC alterations were enriched in ion transmembrane transport, synaptic transmission/organization, axon development, and regulation of neurotransmitter level for both subtypes, but specifically enriched in glial cell differentiation for hypoconnectivity subtype, while enriched in regulation of presynaptic membrane and regulation of neuron differentiation for hyperconnectivity subtype.
FC alterations were associated with the density of 5-HT2a receptor in both subtypes. For hyperconnectivity subtype, FC alterations were also correlated with the density of norepinephrine transporter, glutamate receptor, GABA receptor, 5-HT1b receptor, and cannabinoid receptor.
Both subtypes showed correlations between FC and categorization, motor inhibition, and localization. The FC in hypoconnectivity subtype correlated with response inhibition, selective attention, face recognition, sleep, empathy, expertise, uncertainty, and anticipation, while that was related to inference, speech perception, and reward anticipation in hyperconnectivity subtype.
Conclusions
Our findings suggested the presence of two neuroimaging subtypes of MDD characterized by hypo or hyper-connectivity. The two subtypes had both shared and distinct genetic mechanisms, neurotransmitter receptor/transporter profiles, and cognition types.
Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of subsequent stroke is uncertain. Methods: Electronic databases were searched for observational studies reporting subsequent stroke during a minimum follow-up of 1 year in patients with TIA or minor stroke. Unpublished data on number of stroke events and exact person-time at risk contributed by all patients during discrete time intervals of follow-up were requested from the authors of included studies. This information was used to calculate the incidence of stroke in individual studies, and results across studies were pooled using random-effects meta-analysis. Results: Fifteen independent cohorts involving 129794 patients were included in the analysis. The pooled incidence rate of subsequent stroke per 100 person-years was 6.4 events in the first year and 2.0 events in the second through tenth years, with cumulative incidences of 14% at 5 years and 21% at 10 years. Based on 10 studies with information available on fatal stroke, the pooled case fatality rate of subsequent stroke was 9.5% (95% CI, 5.9 – 13.8). Conclusions: One in five patients is expected to experience a subsequent stroke within 10 years after a TIA or minor stroke, with every tenth patient expected to die from their subsequent stroke.
Background: Liquid biopsy represents a major development in cancer research, with significant translational potential. Similarly, the integration of multiple molecular platforms has yielded novel insights into disease biology and heterogeneity. We hypothesise that applying contemporary multi-omic approaches to liquid biopsies will improve the power of current models. Methods: We have compiled a cohort of 51 patients with glioblastoma, brain metastasis, and primary CNS lymphoma who underwent CSF sampling as part of clinical care. Cell free methylated DNA and shotgun proteomic profiling was obtained from the CSF of each patient and used to build tumour-specific classifiers. Integrated classifiers were compared with single platform classifiers using multiple approaches. Results: In this study, we show that the DNA methylation and protein profiles of cerebrospinal fluid can be combined to fully discriminate lymphomas from their major diagnostic counterparts with perfect AUCs of 1 (95% confidence interval 1-1) and 100% specificity. Each integrated lymphoma classifier significantly outperforms single-platform classifiers, suggesting synergistic biology is obtained using multiple molecular platforms. Conclusions: We present the most specific and accurate CNS lymphoma classifier to date by integrating the methylome and proteome of CSF. This has important implications for the future of cancer diagnostics and generates immediate utility for patients with CNS lymphoma.
TDuring COVID-19 pandemic, it was noticed that it was students who were mostly affected by the changes that aroused because of the pandemic. The interesting part is whether students’ well-being could be associated with their fields of study as well as coping strategies.
Objectives
In this study, we aimed to assess 1) the mental health of students from nine countries with a particular focus on depression, anxiety, and stress levels and their fields of study, 2) the major coping strategies of students after one year of the COVID-19 pandemic.
Methods
We conducted an anonymous online cross-sectional survey on 12th April – 1st June 2021 that was distributed among the students from Poland, Mexico, Egypt, India, Pakistan, China, Vietnam, Philippines, and Bangladesh. To measure the emotional distress, we used the Depression, Anxiety, and Stress Scale-21 (DASS-21), and to identify the major coping strategies of students - the Brief-COPE.
Results
We gathered 7219 responses from students studying five major studies: medical studies (N=2821), social sciences (N=1471), technical sciences (N=891), artistic/humanistic studies (N=1094), sciences (N=942). The greatest intensity of depression (M=18.29±13.83; moderate intensity), anxiety (M=13.13±11.37; moderate intensity ), and stress (M=17.86±12.94; mild intensity) was observed among sciences students. Medical students presented the lowest intensity of all three components - depression (M=13.31±12.45; mild intensity), anxiety (M=10.37±10.57; moderate intensity), and stress (M=13.65±11.94; mild intensity). Students of all fields primarily used acceptance and self-distraction as their coping mechanisms, while the least commonly used were self-blame, denial, and substance use. The group of coping mechanisms the most frequently used was ‘emotional focus’. Medical students statistically less often used avoidant coping strategies compared to other fields of study. Substance use was only one coping mechanism that did not statistically differ between students of different fields of study. Behavioral disengagement presented the highest correlation with depression (r=0.54), anxiety (r=0.48), and stress (r=0.47) while religion presented the lowest positive correlation with depression (r=0.07), anxiety (r=0.14), and stress (r=0.11).
Conclusions
1) The greatest intensity of depression, anxiety, and stress was observed among sciences students, while the lowest intensity of those components was found among students studying medicine.
2) Not using avoidant coping strategies might be associated with lower intensity of all DASS components among students.
3) Behavioral disengagement might be strongly associated with greater intensity of depression, anxiety, and stress among students.
4) There was no coping mechanism that provided the alleviation of emotional distress in all the fields of studies of students.
Major depressive disorder (MDD) is characterized by both clinical symptoms and cognitive deficits. Prior studies have typically examined either symptoms or cognition correlated with brain measures, thus causing a notable paucity of stable brain markers that capture the full characteristics of MDD. Brain controllability derived from newly proposed brain model integrating both metabolism (energy cost) and dynamics from a control perspective has been considered as a sensitive biomarker for characterizing brain function. Thus, identifying such a biomarker of controllability related to both symptoms and cognition may provide a promising state monitor of MDD.
Objectives
To assess the associations between two multi-dimensional clinical (symptoms and cognition) and brain controllability data of MDD in an integrative model.
Methods
Sparse canonical correlation analysis (sCCA) was used to investigate the association between brain controllability at a network level and both clinical symptoms and cognition in 99 first-episode medication-naïve patients with MDD. The potential mediation effect of cognition on relationship between controllability and symptoms was also tested.
Results
Average controllability was significantly correlated with both symptoms and cognition (rmean=0.54, PBonferroni=0.03). Average controllability of dorsal attention network (DAN) (r=0.46) and visual network (r=0.29) had the highest correlation with both symptoms and cognition. Among clinical variables, depressed mood (r=-0.23) , suicide(r=-0.25), work and activities(r=-0.27), gastrointestinal symptoms (r=-0.25) were significantly negatively associated with average controllability, while cognitive flexibility (r=0.29) was most strongly positively correlated with average controllability. Additionally, cognitive flexibility fully mediated the association between average controllability of DAN and depressed mood (indirect effect=-0.11, 95% CI [-0.18, -0.04], P=0.001) in MDD.
Conclusions
Brain average controllability was correlated with both clinical symptoms and cognition in first-episode medication-naïve patients with MDD. The results suggest that average controllability of DAN and visual network reached high associations with clinical variates in MDD, thus these brain features may serve as stable biomarkers to control the brain functional states transitions to be relevant to cognitions deficits and clinical symptoms of MDD. Additionally, altered average controllability of DAN in patients could induce impairment of cognitive flexibility, and thus cause severe depressed mood, indicating that controllability of DAN may be a potential intervention target for alleviating depressed mood through improving cognitive flexibility in MDD.