The World Health Organization’s (WHO) scalable psychological interventions, such as Problem Management Plus (PM+) and Step-by-Step (SbS) are designed to be cost-effective non-specialist delivered interventions to reduce symptoms of common mental disorders, such as anxiety, depression and post-traumatic stress disorder (PTSD). The STRENGTHS consortium aims to evaluate the effectiveness, cost-effectiveness and implementation of the individual format of PM+ and its group version (gPM+), as well as of the digital SbS intervention among Syrian refugees in seven countries in Europe and the Middle East. This is a study protocol for a prospective individual participant data (IPD) meta-analysis to evaluate (1) overall effectiveness and cost-effectiveness and (2) treatment moderators of PM+, gPM+ and SbS with Syrian refugees.Five pilot randomised controlled trials (RCTs) and seven fully powered RCTs conducted within STRENGTHS will be combined into one IPD meta-analytic dataset. The RCTs include Syrian refugees of 18 years and above with elevated psychological distress ) and impaired daily functioning (WHO Disability Assessment Schedule 2.0 (WHODAS 2.0>16)). Participants are randomised into the intervention or care as usual control group, and complete follow-up assessments at 1-week, 3-month and 12-month follow-up. Primary outcomes are symptoms of depression and anxiety (25-item Hopkins Symptom Checklist). Secondary outcomes include daily functioning (WHODAS 2.0), PTSD symptoms (PTSD Checklist for DSM-5) and self-identified problems (PSYCHLOPS). We will conduct a one-stage IPD meta-analysis using linear mixed models. Quality of evidence will be assessed using the GRADE approach, and the economic evaluation approach will be assessed using the CHEC-list.Local ethical approval has been obtained for each RCT. This IPD meta-analysis does not require ethical approval. The results of this study will be published in international peer-reviewed journals. An advantage of individual participant data meta-analysis concerns the acquired power to study overall treatment effect estimates, predictors and moderators.Selected randomised controlled trials are intentionally similar in study design, outcome measures and target population to allow for optimal pooling of data.The study sample will be large (estimated >1000 participants) and relatively homogeneous .The meta-analyses will have reduced power in case individual randomised controlled trials do not meet the required sample size.Since the outbreak of the civil war in Syria, over 13 million Syrians have been displaced. The leading destinations of Syrians displaced across borders include Turkey (3.6 million), Lebanon (910 600) and Jordan 654 700). One million fled to Europe by boat or overland.4 700. OnThe Syrian REfuGees MeNTal HealTH Care Systems (STRENGTHS) research consortium aims to evaluate the effectiveness, cost-effectiveness and implementation of scalable psychological interventions among Syrian refugees in Europe and the Middle-East.One of the interventions that is currently being tested by the STRENGTHS consortium is Problem Management Plus (PM+), which can be delivered by trained and supervised non-specialists to reduce psychological distress in communities affected by adversity.Pilot studies among Syrian refugees carried out by the STRENGTHS consortium indicated that PM+ delivered by peers is an acceptable and feasible intervention, and likely effective in reducing psychological distress.Initial results of PM+/gPM+ delivered by trained non-specialists are promising when looking at overall effects. However, individual differences in symptom severity, sociodemographic background, comorbidities, living circumstances and life events may result in individual differences in treatment response. Single trials do not have sufficient power to detect genuine interaction effects between participant characteristics and treatment outcome.This protocol outlines a planned IPD meta-analysis on combined datasets from the STRENGTHS project, aiming to examine (1) the overall effectiveness and cost-effectiveness of scalable psychological interventions  as compared with CAU alone on improving depression and anxiety (primary outcomes), PTSD symptoms, psychosocial functioning and self-identified problems (secondary outcomes) among Syrian refugees and (2) sociodemographic, migratory, and clinical predictors and moderators of treatment outcome .This protocol was pre-registered in Open Science Framework (DOI 10.17605/OSF.IO/WUHGF), and all individual RCTs were prospectively registered online see . The PreThe STRENGTHS project installed an independent external expert board (Project Advisory Board) including mental health professionals from Syria. The expert board is regularly consulted on the quality of the results and output of STRENGTHS, as well as on the dissemination and exploitation of the results. Prior to conducting the RCTs, qualitative studies among Syrian refugees in each participating country were conducted to inform intervention development, study design and recruitment strategies.We will include all STRENGTHS RCTs on the effectiveness of PM+ for individuals (Switzerland and the Netherlands), PM+ for groups (gPM+) (Jordan and Turkey), and SbS . These RCTs involve a relatively homogeneous population, and have similar study design and outcomes measures. The trials are presented in In the trials, Arabic-speaking Syrian refugees of 18 years and above are included if they report psychological distress )Across trials, participants are excluded if there are signs of imminent suicide risk .In line with the main aim of the STRENGTHS project, the IPD meta-analysis will include only Syrian refugees. The RCTs in Turkey, Switzerland and the Netherlands are conducted in a community setting, while the RCTs in Jordan are conducted in a refugee camp. At this moment, all pilot trials have been completed, with sample sizes ranging from 46 to 64 . Recruitment has been completed for the fully powered trials in Turkey (N=369), Jordan (N=410) and Egypt (N±538). All trials randomise individuals 1:1 to the intervention  or control group (CAU only). Assessments are conducted at baseline, 1 week after the intervention, 3 months after the intervention and 12 months after baseline. The 12-month assessment was not part of the pilot RCTs. The pilot RCT in Jordan only included a baseline and 1-week follow-up assessment. Treatment conditions are further explained below.The manuals for all interventions were adapted by the STRENGTHS consortium according to a framework for the cultural adaptation of psychological interventions,PM+ is a brief, transdiagnostic psychological intervention developed to reduce symptoms of common mental disorders such as depression, anxiety and PTSD.PM+ is delivered by Arabic-speaking peer-refugees who have completed high school, and have a background in education, social work, healthcare or another related field. In Jordan, group facilitators were members of the host community. Helpers/group facilitators in Switzerland, the Netherlands and Turkey also needed to be proficient in English or the local language . Helpers/group facilitators received an 8-day training of helpers (ToH) on common mental disorders, basic counselling skills, delivery of intervention strategies and self-care. The ToH was followed by practice cases. Helpers/group facilitators receive weekly supervision by trained PM+ trainers and supervisors throughout the trial. PM+ trainers/supervisors are mental healthcare professionals who received a 5-day training of trainers (ToT) on elements covered in the ToH, as well as on training and supervision skills. They receive monthly supervision by a PM+ master trainer.SbS is a five-session, digital self-help intervention for iOS, Android and Web platforms, aimed at reducing depressive symptoms. The strategies that are introduced in this 5-week intervention include psychoeducation and trying small and pleasant activities (session 1), behavioural activation (session 2), stress management (session 3), accessing social support (session 4) and positive self-verbalisation and relapse prevention (session 5). Homework practice is scheduled between sessions. WHO removed problem-solving from SbS, as it was found to be too complex to implement in a digital application with or without helper support.The identified studies compared PM+, gPM+ or SbS in addition to CAU, to CAU alone. CAU includes all  health services available to refugees across settings. In high-income countries, this includes referral to  mental health services through primary care practitioners . In Turkey, refugees have free access to mental health services in public hospitals and migrant health centres. Refugees residing in refugee camps in Jordan can access services inside the camp provided by national and international non-governmental organisations. However, across sites, access to mental health services is hampered by numerous barriers, such as the lack of Arabic-speaking health providers in European countries, and overburdened health systems of neighbouring countries hosting most refugees.Similar to the individual RCTs, the primary outcomes in this IPD meta-analysis will be symptoms of depression and anxiety at 3-month follow-up, measured by the subscales of the Hopkins Symptom Checklist (HSCL-25).To calculate cost-effectiveness, in addition to documented resources required for intervention delivery, we will examine the pooled changes in resource use associated with use of health-related services, and time out of usual activities that have been collected using an adapted version of the Client Service Receipt Inventory (CSRI).We will obtain study-level data for each trial including country and setting in which the study was conducted, and the type of intervention tested . We will thus test overall effectiveness for all interventions together as well as the differential effect of each type of intervention.We will extract individual-level data from each dataset to test a range of variables that may moderate the effects of the interventions on primary and secondary outcomes, to determine differential treatment effects based on participant characteristics. We will gather and synthesise all sociodemographic variables , clinical characteristics  and migration variables .All research teams have agreed to contribute RCT data to these IPD meta-analyses. De-identified primary datasets will be shared using secure password protected data links. Data will be stored in a secure cloud service (Surfdrive) developed for the Dutch education and research community, which can only be accessed by the IPD meta-analysis research team. Data transfer, storage and handling will follow the EU General Data Protection Regulations (GDPR).Data accuracy of the primary datasets will be examined to explore if it matches data reported in published reports. We will specifically check frequencies of sociodemographic variables  and descriptive statistics  of continuous scales. If discrepancies between the primary dataset and published report arise, clarification will be sought from authors. After the primary datasets are checked for accuracy, all eligible datasets will be merged into the IPD meta-analytical dataset.We will assess the quality of evidence by applying the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.All analyses will be conducted in R V.4.0.3The IPD meta-analysis will be conducted according to the intention-to-treat principle . Missing values for outcome data will be estimated under the missing-at-random assumption, using multiple imputation (100 imputations).β coefficient indicates how many SD the dependent variables  change per SD increase in the independent variable. Thus, the larger the β coefficient, the greater the effect of the independent variable on the respective dependent variable, with no association among the variables if β is 0.To examine the effects of PM+, gPM+ and SbS on primary and secondary outcomes at 3-month follow-up, we will perform a mixed effect linear regression model with random intercepts with each trial having a random effect and a fixed effect for the intervention and the outcome measures. The severity of depressive and anxiety symptoms, PTSD symptoms, daily functioning, and self-identified problems, and costs of care at the 3-month follow-up will be used as dependent variables, and condition  will be the independent variable while adjusting for baseline scores. The standardised d will be calculated for all outcomes for every single trial separately (step 1), and will then be combined to calculate the pooled effect sizes using the random-effects model (step 2).To ensure robustness of our findings, the analysis of the primary outcomes will be repeated using the ‘two-stage IPD meta-analytic approach’. In a two-stage approach, Cohen’s For the economic analysis incremental cost-effectiveness ratios comparing changes in effect and costs between the intervention and control group on the primary outcome will also be estimated. Uncertainty in mean differences in intervention resource use as well as the use of health and other services between baseline and 3-month follow-up between the two groups will be accounted for using bias-corrected and accelerated bootstrapping. Purchasing power parity adjusted unit costs expressed in international dollars will be applied to resource use. Discounting will not be applied given the short duration of the study. Cost-effectiveness acceptability curves will be generated to showing the likelihood that intervention is cost-effective at different willingness-to-pay thresholds.We will test whether sociodemographic, clinical and migration variables moderate the effects of psychological interventions among Syrian refugees at 3-month follow-up. To examine the effects of potential moderators, we will add an interaction term between each moderator variable and condition on depressive and anxiety symptoms into the mixed-effects linear/logistic regression models. Each potential moderator variable will be added into separate bivariate models.I2 statistic to assess statistical heterogeneity indicated in percentages, with 0% indicating no heterogeneity, 25% low heterogeneity, 50% moderate heterogeneity, and 75% high heterogeneity.I2 using the non-central chi-squared-based approach to provide the full magnitude of heterogeneity.We will calculate the This study protocol describes a prospective IPD meta-analysis of RCTs conducted within the STRENGTHS project. We will examine small sample bias by inspecting the funnel plot in which sample size is plotted against the effect estimates of the primary outcome measures. Egger’s test of the intercept will be carried out to inspect the degree of asymmetry of the plot.www.STRENGTHS-project.eu).Local ethical approval has been obtained for each RCT. This IPD meta-analysis does not require ethical approval. The results of this study will be published in international peer-reviewed journals, and will be made publicly available through the STRENGTHS website , but this limits statistical power and accuracy due to a loss of degrees of freedom and variability in the moderator of interest.This study has important limitations that have to be taken into account when interpreting the results. First, overall statistical power may be reduced in case individual RCTs do not meet the required sample size based on a priori power calculation. Second, study participants reside in different settings, including refugee camps with limited access to mental healthcare, and community settings in high-income countries where specialist services are widely available although not always easily accessible to refugees. Although we will register the CAU delivered at each site using the CSRI measure, it cannot be precluded that differences in CAU may affect the results. Furthermore, migratory patterns as well as the ongoing stressors might differ considerably across settings.This IPD meta-analysis protocol will extend our current knowledge on the effectiveness of scalable psychological interventions for refugees and other populations affect by adversity. It will allow for more accurate estimations of treatment effects, cost-effectiveness, and the exploration of important predictors and treatment moderators of scalable interventions for subgroups of refugees in Europe and the Middle East. The results of this study will be disseminated through publication in peer-reviewed journals.


Self-disturbances constitute a hallmark of psychosis, but it remains unclear whether these alterations are present in at-risk populations, and therefore their role in the development of psychosis has yet to be confirmed. The present study addressed this question by measuring neural correlates of self-other processing in youth belonging to three developmental trajectories of psychotic experiences. Eighty-six youths were recruited from a longitudinal cohort of over 3800 adolescents based on their trajectories of Psychotic-Like Experiences from 12 to 16 years of age. Participants underwent neuroimaging at 17 years of age (mean). A functional neuroimaging task evaluating self- and other-related trait judgments was used to measure whole-brain activation and connectivity. Youth who showed an increasing trajectory displayed hypoactivation of the dorsomedial prefrontal cortex and hypoconnectivity with the cerebellum. By contrast, youth who showed a decreasing trajectory displayed decreased activation of the superior temporal gyrus, the inferior frontal gyrus, and the middle occipital gyrus. These findings suggest that the increasing trajectory is associated with alterations that might erode distinctions between self and other, influencing the emergence of symptoms such as hallucinations. The decreasing trajectory, in comparison, was associated with hypoactivations in areas influencing attention and basic information processing more generally. These alterations might affect the trajectories’ susceptibilities to positive vs. negative symptoms, respectively. PLEs are defined as subclinical positive psychotic symptoms that can be observed in the general population, including 17% of children aged 9–12 and over 7% of adolescents2. While most PLEs are transient in nature and do not extend into adulthood, persistent PLEs confer a four- to ten-fold increased risk for psychosis5.Psychosis risk is understood as existing on a continuum6. These trajectories have been replicated in multiple samples9, supporting their relevance in adolescent development. While the increasing trajectory is thought to be associated with increased risk of psychosis10, outcomes in the decreasing trajectory have been little investigated. Our own studies suggest that both trajectories can develop problems, with the increasing trajectory exhibiting progressively more positive psychotic symptoms while the decreasing trajectory displays more negative symptoms; and that both of these atypical trajectories are associated with altered neural profiles during facial emotion processing11. That these PLE trajectories can be dissociated from low risk youth and from each other on psychosis relevant clinical and neural measures supports their use in identifying and studying vulnerability to psychotic disorders before the onset of the disease, thereby limiting the confounding effect of antipsychotic medications and comorbidities. This research also suggests potentially two different psychosis profiles with distinct neurodevelopmental markers, but further research is needed to better characterise the neural and information processing differences between these two risk trajectories.Recent cohort studies provide evidence of heterogeneous PLE developmental trajectories during adolescence. In 2566 youths from the general population followed between the ages of 13 and 16, three trajectories were identified: 84% of adolescents (n = 2152) exhibited a typical trajectory of low PLE levels that decreased further over time, 8% (n = 203) exhibited high PLE levels that subsequently decreased, and another 8% (n = 211) reported moderate PLE levels that increased12. These self-disturbances include feelings of derealization, depersonalization, and alterations in the stream of thought14. They also encompass the alterations in the perception and understanding of the self, the perception and understanding of others (known as theory of mind), and impairments in self-other integration and distinction16. Furthermore, these alterations are present in the early stages of psychosis17 and predict transition to psychosis in at-risk individuals19. Based on these observations, self-disturbances might constitute a phenotypic marker of psychosis and should be further investigated in clinical and at-risk populations.Disturbances in self-reference processing, also called self-disturbances, have been recognized as a core feature of psychotic disorders21. A meta-analysis of functional magnetic resonance imaging studies (fMRI) on self- and other-related judgement tasks showed that self-other processing in healthy volunteers is associated with activations in the medial prefrontal cortex (MPFC), temporoparietal junction (TPJ), and posterior cingulate cortex (PCC)22. Similarly, false belief tasks, which aim to test the awareness of others (theory of mind), activate the MPFC, TPJ, precuneus, and middle temporal gyrus23. Other frontal areas are also recruited during self-processing, seemingly as part of a wider attentional network24.Strong evidence shows that information processing relevant to self and other is regulated by cortical midline structures25. While the Default-Mode-Network was first thought to be a task-negative network only, it is now documented as being also a task-positive network that contributes to different types of tasks26. It can be further divided into subsystems that are involved in different aspects of introspective processes27: (1) the midline core (comprising the anterior MPFC and PCC), which plays a role in mentalizing and social processing; (2) the dorsal medial prefrontal cortex system , which is involved in self-referential processes, such as autobiographical memory and self-other distinction; and (3) the medial temporal lobe memory system , which plays a role in episodic contextual memory.The self-other processing network overlaps with the Default-Mode-Network in the anterior MPFC, PCC, and TPJ28 identified hypoactivations in the dorsal anterior cingulate cortex (ACC) and the dorsomedial PFC, which are involved in cognitive control, salience attribution, decision-making and self-other differentiation. This suggests an impaired ability to direct attention towards the self in schizophrenia and/or self-other distinction deficits. Although less replicated, some evidence suggests that schizophrenia patients fail to activate the right TPJ, a region influencing self/other differentiations29. Furthermore, this study found hyperactivations in the lateral frontal cortex during both self- and other-reflection, suggesting a greater cognitive demand for this task in psychosis29. While less explored, it has been shown that schizophrenia patients exhibit reduced functional connectivity between the insula and precuneus/PCC during tasks of other-reflection30. This may indicate impaired integration of autobiographical memory and emotional awareness in relation to others.Neural alterations in self-processing have been seen with some consistency in people with schizophrenia. A recent meta-analysis of fMRI studies on self-other processing in schizophrenia31. Similarly, it has been shown that CHR individuals display decreased connectivity between the MPFC and the PCC compared to controls during a self-reference task, but increased connectivity between those two regions during resting-state32. Furthermore, positive schizotypal traits are associated with activation levels of the dorsomedial PFC, the dorsolateral PFC, the PCC and the lingual gyrus during self and other-processing33. To date, only one study has evaluated self-other processing in pre-clinical youths with high levels of PLEs. Youths with high psychosis-proneness displayed increased activation in the insula, the dorsomedial PFC, the ventromedial PFC for positive self-related traits, and in the insula, ACC cortex, and dorsomedial PFC for negative self-related traits34. It is worth noting that this study only looked at 36 individuals in total.Only a few studies have investigated neural correlates of self-other processing in at-risk individuals. Ultra-High-Risk (UHR) subjects showed less activation in the ventromedial PFC during self-reflection19, the current study measured neural correlates of self- and other-related processing in youths belonging to distinct developmental trajectories of PLEs. We hypothesized that the increasing PLE trajectory would display altered activation of brain regions involved in self-other differentiation (dmPFC and TPJ), while our analyses for the decreasing trajectory remained exploratory since its risk profile has not been characterized yet.The current study aimed to investigate the neural correlates of self- and other- related processing in youths belonging to distinct developmental trajectories of PLEs. Since self-disturbances may constitute a better predictor of transition to psychosis than even prodromal symptoms35. The Co-Venture cohort included 3966 Grade 7 students from 31 high schools of the greater Montreal area who completed annual clinical assessments from 13 to 17 years of age. A growth mixture model was used with the 4-year data (from ages 13 to 16) identified three developmental trajectories of PLEs: a low-decreasing trajectory , a high-decreasing trajectory , and a moderate-increasing trajectory 6. In brief, group-based trajectories were estimated using growth mixture models which were then fitted with different models ranging from one to four trajectories. The three-trajectory model was determined to be the best-fitting model using the Bayesian Information Criterion, the Akaike Information Criterion, the Lo-Mendell-Rubin Likelihood Ratio Test, and entropy. Missing data on the PLE score were handled through Full Information Maximum Likelihood.The ongoing Pro-Venture study is a 3-year longitudinal neuroimaging study that follows adolescents who were included in one of three different PLE trajectories over a previous 5-year period during early adolescence. It constitutes a neuroimaging add-on to the larger Co-Venture studyThe Pro-Venture sub-cohort consists of 86 adolescents  aged 16–20 at entry . Participants from the three trajectories who had consented to being contacted for future research were identified and were recruited randomly. The results presented here are based on data collected at the first neuroimaging assessment. Ethical approval was obtained from the CHU Sainte-Justine Research Ethics Committee in Montreal and the study and was conducted according to the declaration of Helsinki. All participants actively assented or gave informed consent to the study procedures, and parental informed consent was obtained for minors.Exclusion criteria for the Pro-Venture study included DSM-5 psychiatric disorders, family history of schizophrenia, taking antipsychotic medication, neurological disorders or IQ < 70 and a contraindication to undergo MRI examination. A urinary drug screening test was administered to assess recent substance use, with participants testing positive for alcohol, cannabis, MDMA, cocaine or opioids having to postpone their neuroimaging session. Since cannabis metabolites can be detected up to 7 days following use, individuals who tested positive but reported not having consumed cannabis within 24 h and showed no sign of intoxication prior to neuroimaging took part in testing.Adolescent Psychosis Screening Scale using nine items that have previously been described36. Three of the questionnaires’ items were shown to have significant positive predictive power for interview-verified PLEs that ranged between 80 and 100%37. Substance use during the past 12 months was measured using the DEP-ADO questionnaire38. Participants rated their consumption of alcohol, tobacco, cannabis and other substances on a 6-level scale ranging from “never” to “everyday”39.To develop the adolescent PLE trajectories, past year PLEs  were assessed with the 40. In this task, participants were presented with stories containing false beliefs  which served as a measure of second-order mentalizing. This task also contains items assessing non-social reasoning and first-order inference, and items controlling for inattention, memory lapses and false positives. Total scores and the percentage of correct answers were determined.We also administered a mentalizing (theory of mind) task adapted from Achim et al., which included 30 stories41. We selected a total of 75 positive and negative trait adjectives from Anderson’s list of personality traits42. The task design is shown in Fig. We used a self-other processing paradigm based on a block-design that has been successfully employed in several fMRI studies and has consistently shown robust activations in default-mode network brain regionsUnité de Neuroimagerie Fonctionnelle de l’Institut de Gériatrie de l’Université de Montréal) was used to acquire Blood Oxygenated Level Dependent (BOLD) signal. High-resolution structural images were collected with a T1-weighted anatomical images were acquired . In the same session, functional imaging data were acquired using a T2-weighed multiband echo planar imaging sequence . The functional slices were oriented in transverse plane and were angled to be parallel to the AC-PC line, with an inline retrospective motion correction algorithm during EPI image acquisition.A 3-Tesla Prisma Fit scanner (www.nitrc.org/projects/conn)43. The preprocessing involved realignment, correction for motion artifacts with the Artifact Detection Tools (ART), high pass filtering (> 0.008 Hz), and co-registration to the corresponding anatomical image. Outlier detection was conducted by scanning the global BOLD signal and removing volumes associated to signal changes above 4 standard deviations, or framewise displacements above 0.5 mm. After anatomical image segmentation, functional images were normalized to Montreal Neurological Institute stereotaxic space and were smoothed with an 8-mm 3D isotropic Gaussian kernel. The anatomical component-based noise correction method (CompCor)44 was used to remove confounding effects, such as the physiological noise caused by the white matter and cerebrospinal fluid, from the BOLD timeseries45.Data were preprocessed using the CONN-fMRI functional connectivity toolbox (https://www.fil.ion.ucl.ac.uk/spm/software/spm12/)46 in Matlab version 2020a. The experimental conditions of Self (adjectives relating to the participant), other (adjectives relating to another person) and Control (adjectives presented in uppercase or lowercase) were convolved to a canonical hemodynamic response function. Temporal correlations were accounted for by the “FAST” model47. Our primary contrast of interest was defined as (Other—Self) and isolates the differentiation between others and the self. We also implemented two other contrasts: the (Other—Control) and (Self—control) contrasts, which isolate other-related and self-related processing, respectively.For each participant, a general Linear Model (GLM) was mapped using SPM12 (48 was used to extract the estimated parameters of the regressors in the GLM model (beta weights). The statistical threshold was determined using a Monte Carlo simulation49, a widely used approach that takes into account spatial smoothing and allows for less Type II errors and increased sensitivity in studies with moderate sample sizes. For the full ANOVA, after 10,000 simulations, a cluster size of 41 resampled voxels was indicated to correct for multiple comparisons at p < 0.05.Between-group differences were evaluated using a full ANOVA F-test comparing the three groups for each of the three contrasts of interest (peak threshold: z > 3.1), using subject as a random effect, and pair-wise t-tests were subsequently performed. The Marsbar toolbox50. The model contained a psychological regressor for each condition, a physiological regressor, and an interaction term. The psychophysiological interaction term was then modelled against the time course for all brain voxels, testing for significant connectivity effects. The seed region was defined based on the results of the activation analyses. Between-group differences were evaluated using a full analysis of variance (ANOVA) for each of the contrasts of interest, and the same peak and cluster thresholds as those used for the brain activity analyses. Beta weights were extracted for all significant findings.Voxel-wise seed-based functional connectivity analyses were performed in CONN using generalized psycho-physiological interaction (gPPI) analyses. The gPPI model generated a regressor of each condition , as this approach has been shown to generate a more accurate model of the interaction between conditions and neural activity2-tests and pairwise comparisons were performed. Significance was set at p < 0.05. Analyses of covariance (ANCOVAs) assessed potential effects of clinical and behavioral variables on the between-group differences in brain activity. To test the relationship between behavioral variables (e.g. substance use and cognitive scores) and activation and connectivity strength estimates, bivariate Pearson correlation analyses were performed across and within groups .Between-group differences in continuous behavioral data  were examined with ANOVAs. Post-hoc analyses were performed using Tukey’s Honestly Significant Difference test. For dichotomous data (sex and handedness), χDemographic variables for each of the three trajectories are reported in Table For all contrasts, results are reported in Table In the (Other—Control) contrast Fig. , the PLEFor all activation estimates, post-hoc analyses of covariance were conducted to assess the effects of sex and age on group differences, and all the above-mentioned results remains significant.24. Comparatively, the other regions identified in the activation analyses are not assumed to play a direct role in self-other processing. Results are reported in Table Seed-based connectivity analyses were conducted using the dorsomedial PFC coordinates identified in the activation analyses. This seed was selected due to its significant role in self-other processing and its coordinates are consistent with the literature’s definition of the dorsomedial PFC, as determined by a recent meta-analysis of fMRI studiesPast year cannabis use level was found to be positively correlated  with the activation strength of the right middle occipital gyrus in the (Self—Other) contrast. No other behavioral variable was significantly correlated with fMRI results.This study showed that PLE trajectories that are associated with elevated positive vs. negative symptoms exhibit distinct neural alterations during self-other processing. The increasing PLE-2 trajectory (positive symptom risk) was associated with decreased activation of the right dorsomedial PFC during other-self distinction. The decreasing trajectory PLE-1 (negative symptom risk) was associated with decreased activation of the right middle occipital gyrus during self-other distinction and decreased activation of the left superior temporal gyrus and right IFG during other-processing.52. The self-other processing related hypoactivations seen here in the increasing trajectory have also been observed in people with schizophrenia54, which, interestingly, were also not shown to correlate with behavioural measures of self- and other- processing53. Despite heterogeneity in findings across studies54, one of the most consistent findings during self-other processing in schizophrenia is the reduced activity observed in a large cluster encompassing the dorsomedial PFC and the dorsal anterior cingulate cortex28. It will be important to develop more relevant behavioural tasks of self-other processing that better dissociate high risk individual, and which better capture what is being measured in fMRI tasks. For example, perhaps such tasks will be more sensitive when focusing on physiologic or subjective outcomes, rather than behavioural.As hypothesized, we found neural alterations during self-other differentiation in the increasing trajectory which we previously showed to be at greater risk for developing positive symptoms of psychosis. The dorsomedial PFC is activated in healthy volunteers during self-processing and is involved in the integration and separation of self- vs. other- related information55, and decreased prefrontal-cerebellar connectivity has been found to correlate with self-disturbances in psychosis and in ultra-high risk individuals56. It has been proposed that impairments in integrating or differentiating self- and other-related information may underlie the emergence of other symptoms of psychosis such as hallucinations57. According to this model, hallucinations would arise from a blurred distinction between the self and other, such that internal speech can be wrongfully attributed to external sources. Our findings bolster this view, suggesting further that deficits in self-other differentiation and integration affect the early development of psychosis, specifically within the increasing trajectory.The increasing trajectory also displayed hypoconnectivity between the dorsomedial PFC and the Crus II region of the cerebellum during other-related processing. This area of the cerebellum is thought to be involved in mentalizing11, the current study showed that this group exhibited a more generalized profile of neural alterations during other-related processing, including hypoactivation of the right IFG, left superior temporal cortex and middle occipital gyrus. None of these regions are thought to play a critical role in self-other processing. The right IFG is usually recruited in cognitive tasks requiring the detection of novel or task-relevant cues, indicating its role in attentional control and/or attentional salience58. The IFG can also be activated during tasks requiring semantic encoding during in trait judgements regardless of the condition (self or other)59, yet not in control judgements 60. However, these results have not been consistently replicated. Taken together, these results suggest that the decreasing PLE trajectory displays alterations in regions more implicated in attentional and cognitive control than during self-other processing.With respect to the decreasing PLE trajectory, which we previously showed to predict risk for negative symptoms61. While the anterior part of the left superior temporal gyrus is involved socio-emotion processing62, its precise role in self-other processing remains uncertain. In the (Other—Self) contrast, the decreasing trajectory displayed decreased activation of the right middle occipital gyrus, which is known to be involved prominently in visual information processing63. The middle occipital gyrus was found to exhibit structural changes associated with poor insight in psychosis64, however the meaning of this association remains elusive. In our sample, the activation level of the middle occipital gyrus was positively correlated with past year cannabis use across groups, which is consistent with a meta-analysis that found that cannabis use was associated with altered activation of this region65. These findings suggest that the decreasing trajectory is associated with a range of alterations in areas that are not specific to self-other processing, but are more generally involved in attention, basic information processing, and potentially a pattern of substance use that is highly comorbid with psychosis, which may explain the increased non-specific negative-like symptoms  in this group.The decreasing trajectory also displayed a hypoactivation of the left superior temporal gyrus, which has been shown to exhibit altered connectivity during other-processing in individuals with schizophrenia66, the number of participants in this study was limited and unbalanced due to the low prevalence of the atypical trajectories in the general population cohort, with only 8% of youths on either decreasing and increasing trajectories, and the difficulty in recruiting these participants. Future studies would benefit from increased participants as the smaller sample size could account for the absence of significant differences on the behavioural measures. It is worth noting that while the decreasing and increasing trajectories displayed group differences at the level of positive and negative symptoms11, no correlations between symptoms and activation and connectivity measures were found at the individual level. This may be due to the subclinical nature of symptoms. Similarly, no behavioral differences were found in the Theory of Mind task between groups. This may be because this task isolates different constructs than the fMRI task, whereby it not only requires the participant to think about others, but it also involves the integration of various social cues . The inclusion of a scale on self-disturbances, such as the Examination of Anomalous Self-Experience (EASE) scale67, may have produced better results. It is also possible that the Theory of Mind task—which has been validated in adult patients—is not adapted to discern differences in this at-risk population. Finally, this study did not include additional measures related to self-other processing, and future studies should implement multimodal testing that evaluates different aspects of social cognition to evaluate whether these neural alterations translate into impairments in social functioning. These features noted, our findings highlight the relevance of assessing developmental trajectories of PLEs when studying the early neural markers of psychosis.While the present study offers novel information on a key pre-clinical population, it presents some limitations. Although studies of self-other processing have used similar sample sizes in schizophreniaIn conclusion, the current study showed that youths with atypical PLE trajectories display different neural alterations during self-other processing. The main finding of impaired dorsomedial PFC activations in the increasing trajectory is similar to results reported in schizophrenia. Considering that the dorsomedial PFC plays a crucial role in self-other differentiation and that this trajectory predicts susceptibility to more positive psychotic-like symptoms in young adulthood, the altered dorsomedial PFC activation during self-other processing should be further investigated as a biomarker of psychosis risk. In comparison, the decreasing trajectory (at risk of more negative symptoms) displayed hypoactivations in different areas that are involved in various functions, indicating a less specific profile of neural changes. Confirmatory studies using predefined regions of interest should be conducted on these trajectories to further validate these findings. Future longitudinal studies following atypical trajectories of psychotic experiences should assess the evolution of these alterations and their capacity to predict clinical symptom emergence in at-risk youth.Supplementary Information.


Over the last several years, two-photon polymerization has been a popular fabrication approach for photonic crystals due to its high spatial resolution. One-dimensional photonic crystals with photonic bandgap reflectivities over 90% have been demonstrated for the infrared spectral range. With the success of these structures, methods which can provide tunability of the photonic bandgap are being explored. In this study, we demonstrate the use of mechanical flexures in the design of one-dimensional photonic crystals fabricated by two-photon polymerization for the first time. Experimental results show that these photonic crystals provide active mechanically induced spectral control of the photonic bandgap. An analysis of the mechanical behavior of the photonic crystal is presented and elastic behavior is observed. These results suggest that one-dimensional photonic crystals with mechanical flexures can successfully function as opto-mechanical structures. Photonic crystals have been explored for photonic bandgap filtering applications over the last several decades ,3,4,5,6.There are several effective fabrication approaches for one-dimensional photonic crystals such as spin coating, self-assembly, chemical/physical vapor deposition, top-down etching, and molecular beam epitaxy ,14. WhilWhile the highly reflective photonic bandgaps are in themselves extremely useful spectral features, many researchers have looked to provide even further spectral control by mechanical means ,12,20,21In this study, we present a one-dimensional photonic crystal design which allows mechanically induced spectral tuning of the photonic bandgap in the infrared spectral range for the first time. To accomplish this, a bow tie flexure design adapted from reference  is scaleThe one-dimensional photonic crystals under study were designed using a stratified-layer optical model  in combination with a mechanical finite-element model . A single photo-sensitive polymer (IP-Dip) was used to fabricate the one-dimensional photonic crystal. The mechanical properties for IP-Dip vary widely depending on fabrication parameters, the properties which were employed during finite-element modeling were obtained from references ,27. To iTo demonstrate the ability of the designed photonic crystals to produce spectral bandgap shifts upon compression, the layer thickness and dielectric composition of the low-density layers were designed such that several bandgaps were induced within the measurement window  was employed in the fabrication of these one-dimensional photonic crystals from a single photosensitive monomer (IP-Dip). The selection of appropriate print parameters is essential in order to produce a sample which is true to design. The designed bow tie flexures push the resolution limits of this system, limiting the range of print parameters which can successfully produce a given geometry. Many print parameters such as the choice of objective, monomer, laser power, scan speed, and hatching and slicing distance will affect the voxel size of the system ,32,33,34The scanning electron microscope images for the two best scan speed and laser power combinations can be seen in A 4 × 4 array of one-dimensional photonic crystals with 3 mm square lattice periodicity were fabricated on a fused silica substrate. This arrangement was chosen based on finite-element model calculations of the elastic properties of the bow tie flexure design. Compressive force was applied to the photonic crystals in increments. In order to provide an even distribution of pressure while maintaining transparency for measurement, a fused silica window with thickness 0.7 mm was placed on the array. This window was measured to have a mass of 1.37 g. Subsequent slides were placed on top of the initial window in log-cabin style to provide incremental increases in compressive force without interfering with the central measurement aperture. These subsequent increases in loading were done in steps of 2.83 g.Infrared reflection measurements were taken of the photonic crystal for the spectral range from 1000 cmIn order to determine which photonic bandgaps were appropriate to observe upon compression, two Fourier-transform infrared reflection measurements were taken of the photonic crystal both with and without the presence of the fused silica window. Here kapton tape spacers are placed around around the edges of the fused silica window in order to prevent compression, allowing the effects of the fused silica window on the photonic bandgaps to be isolated. These measurements are given in The experimental reflection data for two compressive cycles are given in One-dimensional photonic crystals with mechanical flexures fabricated by two-photon polymerization have demonstrated spectral shifting as a function of compressive force. The photonic crystal consists of 13 alternating layers of high- and low-density. The ability of such a device to induce high-contrast photonic bandgaps in the infrared spectral range has been demonstrated previously ,17. In tIn conclusion, a mechanically tunable one-dimensional photonic crystal designed for the infrared spectral range was fabricated using two-photon polymerization. The elastic capabilities of this device were tested by conducting loading and unloading cycles. During cycles, Fourier-transform infrared reflection measurements were taken to observe the effect of compressive force on the photonic bandgap’s spectral location and amplitude. The results of this study suggest one-dimensional photonic crystals with mechanical flexures allow dynamic control of spectral features by way of mechanical stimuli. While static one-dimensional photonic crystals have clear applications in sensing and bandgap filtering, the addition of mechanical tunability opens doors for uses in fields such as micro-robotics and micro-optomechanical systems (MOEMS) .


We examined the effect of sugar-sweetened beverages (SSB) and common drink intake on pubertal development in both sexes.Data were retrieved from Taiwan Children Health Study, which involved detailed pubertal stage assessments of 2,819 schoolchildren aged 11 years in 2011–2012. Drawings of secondary sexual characteristics and self-reported age at menarche or voice breaking were used to assess pubertal stages. Dietary intake was assessed using a detailed semi-quantitative food frequency questionnaire. Generalized estimating equation modeling was applied to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to represent the effects of each drink on early pubertal development outcomes.In boys, an one cup/day increment of a SSB was associated with earlier voice breaking , whereas consuming yogurt (≥2 cups/day) was a protective factor against early puberty . In girls, SSB consumption was associated with increased risk of early puberty in a dose–response manner, and a similar protective effect of yogurt consumption and fermented probiotic drink (≥2 cups/day) against early puberty was observed . Furthermore, the intake of both total sugar and added sugar within SSBs increased risk of early puberty in girls but not in boys.Sugar-sweetened beverages were associated with early puberty, and probiotic drinks appeared to mitigate this link. These findings indicate that the gut–brain axis could play a crucial role in sexual maturation. Puberty refers to the process of physical changes under the cascade of endocrine actions. It is generally regarded as a hallmark of sexual maturation . The pubvia weight status, SSB consumption is independently associated with earlier age at menarche in a large prospective US study  has been associated with pro-glycemic traits, such as higher fasting glucose and fasting insulin levels , and a hUS study , even af ovaries . Specifi ovaries . Despitevia SHBG and bioavailable sex steroids on pubertal onset has also been observed for other macronutrients , a prospective, nationwide cohort study focusing on obesity, pubertal development, and atopic diseases in adolescents. The TCHS had an open-cohort study design and comprised 3,229 children at age 11. The cross-sectional analysis herein mainly involved 2,819 schoolchildren aged 11–12 years in 2011–2012 with FFQ assessment and pubertal outcomes available . The detPuberty oucomes were assessed at age 11, 12, and 18. We used two types of children self-filled questionnaire to define pubertal outcomes: the Chinese version of the puberty development scale (PDS)  and the Lactobacillus spp. The common probiotics contents within the yogurt include Streptococcus thermophiles, Bifidobacterium lactis, Lactobacillus bulgaricus, and Lactobacillus acidophilus. Detailed contents of fermented probiotic drinks and yogurt are listed in We assessed diet using a self-administered, semi-quantitative 71-food-item FFQ in 2011 . It was a priori confounders based on previous research . Participants with missing covariate information were included in the model by using missing indicators  and analysis of variance (mean with standard deviation). To evaluate the repeated measurements of pubertal outcomes at age 11 and 12, we used generalized estimating equations (GEEs) -Time lagAmong 2,819 children analyzed in this study , 472  in male participants . HoweverIn girls, SSB consumption was associated with an increased risk of early puberty in a dose–response manner . Girls cTo investigate which component of the selected drinks might contribute to the aforementioned association with early puberty, we examined the effects of total sugar and added sugar from selected drinks on early puberty risk after adjustment for BMI, parental educational level, family income, and household smoking , 3. NotaIn this study, we identified SSB-related risk and protective factors of pubertal timing among Taiwanese adolescents. To our knowledge, this is the first study to reveal that SSB consumption is significantly associated with early puberty in both sexes; probiotic drinks to a higher amount may mitigate this risk. Our findings indicate that health care providers should increase awareness of the effects of SSBs on adolescent health and pubertal development. The novel finding that fermented probiotic drinks or yogurt have a protective effect against early puberty suggests that early puberty might be a gut–brain disease. Further experimental studies are warranted to prove the aforementioned associations.per se is associated with an increase in the production of insulin and IGF-1, which could enhance cell proliferation and growth , it is difficult to ascertain whether the exposure truly precedes the pubertal outcome. There could be instances where children in this study had attained puberty before 11 years; this could affect the interpretation of the study findings, which may be biased by reverse causality. Moreover, we tested several regression models in Our study identified an independent association between SSBs and early pubertal timing after adjustments were made for BMI. Probiotic use to a certain amount appeared to mitigate the risk of early puberty. These findings not only highlight the importance of nutritional screening when consulting adolescents going through puberty but also elucidate the gut–brain connection. From the perspective of public health nutrition, a potential way to reduce adverse effects brought by early sexual maturation is to restrict sugar consumption in growing children. More research may be required to identify the specific probiotic species and molecular pathways linking food consumption and pubertal timing.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by National Taiwan University Ethics Committees. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.M-CT contributed to data interpretation and writing the manuscript. YCC and YLL contributed to data analysis, cohort data collection, hypothesis generation, data interpretation, and writing the manuscript. All authors approved the final manuscript as submitted and published and agreed to be accountable for all aspects of the work.This study was supported by grants 103-2314-B-002-043-MY3 and 106-2314-B-001-007-MY3 from YLL. The study was also supported by grants 104-2314-B-532-002-MY3, 107-2314-B-038-113-MY3, 109-2314-B-038-057, MOST 110-2314-B-038-156, and MOST 111-2314-B-038-004 (PI. YCC) from the Ministry of Science and Technology of Taiwan.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer YCC a shared affiliation with one of the authors' YCC to the handling editor at the time of review.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To systematically review the literature for studies investigating the biomechanical properties of constructs used to repair isolated subscapularis tears in time zero human cadaveric studies.A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three electronic databases were searched for studies that reported on the construct technique and biomechanical outcomes for the repair of isolated subscapularis tears in human cadaveric specimens. Ultimate load, gap formation, stiffness, and failure mode were documented. Methodological quality was assessed using the Quality Appraisal for Cadaveric Studies (QUACS) scale.Six articles qualified  and were analyzed. Studies varied in the number and type of anchors and construct technique  and suture(s) used (no. 2 FiberWire or FiberTape), subscapularis tear type , and whether a knotless or knotted fixation was used. In studies that created full-thickness, upper subscapularis tears (Fox-Romeo II/III or Lafosse II), no significant differences were seen in ultimate load, gap formation, and stiffness for knotted versus knotless single-row repair (2 studies) and single-row versus double-row repair (1 study). Double-row repair of complete subscapularis tears demonstrated higher ultimate load, stiffness, and lower gap formation in 1 study. Ultimate load differed between the studies and constructs . Suture cutout was the most common mode of failure (59%).Because of the limited number of studies and varying study designs in examining the biomechanical properties of repair constructs used for subscapularis tears, there is inconclusive evidence to determine which construct type is superior for repairing subscapularis tears.Results from biomechanical studies of clinically relevant subscapularis repair constructs are important to guide decision-making for choosing the optimal construct for patients with subscapularis tears. It primarily functions as an internal rotator of the humerus but also plays an important role in balancing glenohumeral joint forces and in maintaining anterior shoulder stability.Adequate fixation of subscapularis tears is important for restoring normal joint function.20,Clinical studies have demonstrated that arthroscopic single- and double-row repair of subscapularis tears results in significant improvements in clinical outcomes.20Given that there is limited tendon-to-bone healing in the early postoperative window, the initial success of the repair depends largely on the strength of the construct and its ability to transfer load from tendon to bone.This systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Eligible studies consisted of biomechanical studies published in the English language that reported on the construct technique and biomechanical outcomes for the repair of simulated isolated subscapularis tears in human cadaveric specimen. Exclusion criteria were (1) review articles, animal studies, clinical studies, book chapters, technique articles, and case reports; (2) studies pertaining to subscapularis repair during shoulder arthroplasty; and (3) studies examining tendon transfers. In the event of different studies with duplicate (or overlapping) subject populations, the study with the greatest number of subjects or greatest clarity of methods and results was included if the subjects could not be separated. After removal of duplicates, titles or abstracts were screened, and full text articles were further assessed based on inclusion and exclusion criteria by 2 independent reviewers . The search results were reviewed for duplicates and the inclusion criteria to determine the articles that were included in the final analysis .Fig 1FloArticles were reviewed and data were extracted from the included studies by the 2 independent reviewers using the methodology recommended by Harris et al.The risk of study bias and methodological quality was assessed using the Quality Appraisal for Cadaveric Studies (QUACS) scale, a 13-item checklist that assesses the design, conduct, and report of cadaveric dissection studies for inclusion into systematic reviews.Due to the heterogeneity between studies, pooling of data and meta-analysis was not performed. Thus, a qualitative synthesis with descriptive summaries of the studies is presented.,,,,,2 to 631.5 mm2 (The initial search yielded 1188 articles. After removing duplicates, 916 records were screened for eligibility. Of these, 12 articles underwent full text review, resulting in six articles that were included and analyzed .28, 29, 31.5 mm2 .Table 1C,,,,,,,Three studiesDouble-row repairs used three,,All 6 studies recorded ultimate load and mode of failure. The load to failure protocol for the studies was either 0.5 mm/s or 1 mm/s. The mean ultimate load for single-row constructs ranged from 244 N to 678 N. No significant differences in ultimate load were seen in the 2 studies comparing knotted and knotless single-row constructs.,The number of cycles of loading ranged from 50 to 300 . All artThe present systematic review included 6 studies that investigated the biomechanical properties of repair constructs used for isolated subscapularis tears in cadaveric specimens. Despite the variation in the number of anchors, anchor type, suture type, and tear pattern between the studies, all 6 articles investigated single-row repair constructs. Other repair types that were studied included double-row and transosseous repair. Although tendon healing is affected by a variety of parameters such as patient demographics, tear characterization, biological factors, and tissue quality, biomechanical properties of the repair construct are strong predictors of successful repair.Single-row repair in the current review used either 1 or 2 double-loaded suture anchors and were knotless or tied with variations of mattress or modified Mason-Allen stitches. Sgroi et al.There were 2 studies that directly compared single-row to double-row suture anchor repair, although the double-row constructs varied between studies. Dyrna et al.,,,Prior systematic reviews of biomechanical evidence for rotator cuff constructs have focused on the posterosuperior rotator cuff, concluding that double-row constructs are biomechanically stronger to single-row fixation.,,,,Isolated tears make up about 10% to 25%This analysis has several limitations. The study design resulted in analysis of relatively few studies. The studies included in this review varied with respect to subscapularis tear size, anchor placement, and testing parameters. Given the varying parameters, head-to-head comparisons of knotted and knotless constructs or single- and double-row constructs yielded few studies, which may affect final conclusions. Because of the study heterogeneity, pooling of results could not be performed. The double-row constructs included in this review were either all-knotlessBecause of the limited number of studies and varying study designs in examining the biomechanical properties of repair constructs used for subscapularis tears, there is inconclusive evidence to determine which construct type is superior for repairing subscapularis tears.


The coronavirus disease (COVID-19) pandemic has had a significant worldwide impact since its emergence in 2019. End-stage kidney disease patients have been among the most vulnerable population affected and have a higher risk of acquiring infection and developing more severe disease. We have encountered three major COVID-19 waves in Qatar and they have required different strategies to overcome. The most recent wave was due to the Omicron variant characterized by higher transmissibility. The monthly incidence of COVID-19 infection during the Omicron wave in patients with end-stage renal disease peaked at 256 patients compared to 35 and 39 patients during the first and second waves, respectively. In addition, more than one-third of our dialysis staff became infected during this wave. Unlike the previous two waves, COVID-19 due to the Omicron variant was less severe with only 5% of hemodialysis patients requiring admission to the intensive care unit compared to 25% during the previous waves. The Omicron variant wave resulted in a crisis in our country due to the high number of non-hospitalized COVID-19 hemodialysis patients and the severe staff shortage. Several measures were taken to overcome the crisis, such as designating one facility to dialyze all COVID-19 ambulatory patients, reducing dialysis sessions to 3 hours, and introducing a fourth dialysis shift.This article describes the challenges we faced in the ambulatory hemodialysis service during the Omicron wave and the measures taken in the COVID-19 and non-COVID-19 designated facilities to combat the crisis. End-stage kidney disease (ESKD) patients receiving dialysis have been among the most vulnerable population affected by the COVID-19 pandemic and have had a higher risk of acquiring the infection and having a more severe disease course. Mortality from COVID-19 infection has been among the highest in ESKD patients, with reported death rates of 15%–35%. In response to this rising concern, recommendations have emerged to guide nephrologists and caregivers of ESKD patients to prevent COVID-19 infection. Although these guidelines have paved the way for COVID-19 prevention and management, recent studies continue to report uncontrolled infection rates and high mortality.Coronavirus disease (COVID-19) due to the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and its different variants has had a significant impact worldwide. More than 500 million cases of COVID-19 have been reported and more than 6 million deaths have been recorded worldwide as of June 2022. Furthermore, the Omicron variant has many genetic mutations in the spike proteins leading to concerns regarding the ability of the virus to evade immunity and the effectiveness of the currently available vaccines. Unlike the original virus, Omicron has spread to 86 countries within 3 weeks of its emergence. Qatar reported the first four cases due to the Omicron variant on December 17, 2021. Since then, daily COVID-19 cases in the general population continued to rise and peaked at 4,169 cases per day in less than 4 weeks, with Omicron being the dominant variant in the country.With the emergence of the SARS-CoV-2 B.1.1.529 (Omicron) variant in South Africa, the World Health Organization designated the virus as a variant of concern (VOC) due to its high contagiousness and transmissibilityThere was high transmissibility in dialysis patients . The observation that the Omicron variant results in less disease severity led to a crisis in the ambulatory hemodialysis (HD) service, particularly since a significant number of dialysis patients and staff became infected within a short time but the majority did not require hospitalization. Different countries managed dialysis patients differently during the Omicron epidemic. In this study, we summarize the effect of the Omicron variant on HD patients and staff and how it resulted in a crisis in the ambulatory HD service in Qatar. We also report the national response and protocols developed by the nephrology crisis committee to combat the crisis. and a population of approximately 2.79 million. The high prevalence of diabetes mellitus, hypertension, heart disease, and obesity among the citizens and migrants has translated into an increased ESKD burden. Analysis of annual renal data from Qatar in 2021 revealed that the prevalence of ESKD patients treated with renal replacement therapy was 737 per million population; 44.5% on HD, 12% on peritoneal dialysis, and 43.5% with a functioning kidney allograft.Qatar rests on the western coast of the Arabian Gulf. It has an area of nearly 11,600 kmThe ambulatory HD facilities conform to the population density distribution in the country, as shown in Compared to the original COVID-19 virus and the Delta variant, the Omicron variant resulted in less disease severity and a higher peak during a shorter period (weeks vs. months) . COVID-1. The Omicron variant led to a crisis in the ambulatory HD service, as most COVID-19 patients did not require hospitalization, and infected HD nurses and technicians were not permitted to rejoin work for at least 7 days. Thus, during this crisis, we had to dialyze many non-hospitalized COVID-19 HD patients, isolate COVID-19 patients from other non-COVID-19 HD patients, and manage the severe workforce shortage in our HD units.In the previous COVID-19 waves, all dialysis patients were hospitalized for close monitoring given their higher risk of severe disease compared to the general population. Among the dialysis patients, 72% developed pneumonia, 25% required admission to the intensive care unit, and 15% died during the first wave of COVID-19 in QatarSoon after announcing the first four cases of the Omicron variant in the State of Qatar in December 2021, a nephrology crisis committee was formed under the leadership of the chief of nephrology at Hamad Medical Corporation, responding promptly to the challenge. The committee consisted of medical directors of the dialysis units, the director of dialysis nurses , the dialysis head nurses, and chief dialysis technicians, representing all hospitals and ambulatory dialysis units. The committee met weekly, more often if needed, to get updates from different facilities and take timely actions. Having such a committee enabled designating of one unit to dialyze all COVID-19 ambulatory HD patients. It also allowed redistributing the staff and resources, as needed, to cover different facilities during the crisis. Additionally, there were daily updates from all facilities regarding the number of available dialysis slots and the number of patients and staff who tested positive for COVID-19 to determine workforce needs at each site and provide immediate support.The committee made several important decisions during the Omicron crisis, such as canceling annual leave of the staff and asking all staff on leave to return to work (unless they had an emergency or sick leave). We also mobilized nurses from quality, research, and specialty programs, such as anemia and mineral bone disease, to join the HD nursing workforce. In addition, we increased the nursing: patient ratio from a baseline ratio of 1:2 to 1:3, and we increased working hours from 8 to 12. Moreover, we reduced the duration of the dialysis sessions to 3 hours, if a patient's condition allowed, and increased the number of dialysis shifts in COVID-19 designated units to four shifts to meet the increasing number of infected, non-hospitalized HD patients. Although we temporarily suspended routine monthly patient reviews, we maintained monthly laboratory investigations, monitored critical values, and addressed all of the HD patients’ needs throughout the Omicron crisis to ensure that the standard of care was maintained. These measures helped overcome the severe staff shortage and allowed us to mobilize staff across different facilities without affecting the patient standard of care or safety with proper monitoring and observation. A new ten-station dialysis unit was prepared as a backup plan, anticipating a rise in infected dialysis patients. Thankfully, due to the brief duration of the crisis, the measures taken were sufficient and we did not need to use the new unit. The crisis committee decisions are summarized in The Ministry of Health had designated Hazm Mebaireek General Hospital (HMGH) as the main COVID-19 facility for every COVID-19 wave in Qatar. Therefore, we positioned a six-station mobile dialysis unit there and dedicated it to COVID-19 patients since the first wave started. We also had another 12-station dialysis unit at HMGH that was only used for non-COVID-19 ESKD patients.The Omicron wave caused a surge in the number of infected home-quarantined HD patients, and the six-station mobile unit reached its maximum capacity of 36 patients within 10 days. Then, we converted the 12-station dialysis unit into a COVID-19 designated unit and transferred all non-COVID HD patients (n = 45) to other dialysis units. Moreover, we converted one of the HMGH rooms into a temporary three-station dialysis room to accommodate the rising number of COVID-19 ambulatory HD patients. We also shortened the time (by updating treatment and the discharge pathway) to transfer patients from HMGH back to their non-COVID dialysis units using time-based criteria (10 days from the first positive test) instead of waiting 21 days for a negative PCR test result. Despite all efforts, we reached the maximum capacity of 126 dialysis patients , so we temporarily reduced dialysis time from 4 to 3 hours and started a fourth shift of dialysis. The steps taken at the HMGH facility to accommodate the Omicron wave against time and the number of positive cases on dialysis are summarized in During the Omicron crisis, we implemented several measures in the non-COVID-19 ambulatory dialysis units to capture HD patients with COVID-19 before spreading the infection among other dialysis patients. For example, temperature and Ehteraz, a local smartphone application that shows if a patient should be in quarantine due to a COVID-19 infection, was checked by security at the entrance of the dialysis units. We also limited the number of companions, enforced social distancing, and transferred all meetings to virtual instead of physical to limit gatherings.We used a screening questionnaire for patients before initiating dialysis. A rapid antigen COVID-19 test was performed in suspected cases and positive patients were directed to HMGH for dialysis, as shown in Once patients returned from the COVID-19 facility, we used extra precautions .COVID-19 due to the Omicron variant has resulted in a crisis in the ambulatory dialysis service in the state of Qatar. This VOC led to a surge in the number of infected, non-hospitalized HD patients and a severe shortage in the HD workforce. Here we report a unique experience of combating the Omicron wave from a Middle East country. Several preemptive steps were taken to provide optimal care for COVID-19 patients while retaining non-COVID-19 patient safety and well-being. Leadership efforts to redistribute resources and the workforce averted a bad outcome during this wave.We profusely thank Dham T, Joseph J, Aly S, Singh P, Yasin F, Akl T, Ibrahim R, and all the Hamad Medical Corporation staff for their devotion to patient care during the COVID-19 pandemic. We also thank Hamza Asim for the computer graphics.


When sparsely sampled data are used to accelerate magnetic resonance imaging (MRI), conventional reconstruction approaches produce significant artifacts that obscure the content of the image. To remove aliasing artifacts, we propose an advanced convolutional neural network (CNN) called fully dense attention CNN (FDA-CNN). We updated the Unet model with the fully dense connectivity and attention mechanism for MRI reconstruction. The main benefit of FDA-CNN is that an attention gate in each decoder layer increases the learning process by focusing on the relevant image features and provides a better generalization of the network by reducing irrelevant activations. Moreover, densely interconnected convolutional layers reuse the feature maps and prevent the vanishing gradient problem. Additionally, we also implement a new, proficient under-sampling pattern in the phase direction that takes low and high frequencies from the k-space both randomly and non-randomly. The performance of FDA-CNN was evaluated quantitatively and qualitatively with three different sub-sampling masks and datasets. Compared with five current deep learning-based and two compressed sensing MRI reconstruction techniques, the proposed method performed better as it reconstructed smoother and brighter images. Furthermore, FDA-CNN improved the mean PSNR by 2 dB, SSIM by 0.35, and VIFP by 0.37 compared with Unet for the acceleration factor of 5. Magnetic resonance imaging (MRI) is a sophisticated and noninvasive medical imaging technique that has full control over data capture to visualize the anatomy and functions of the human brain and body . It playDeep learning (DL) has been successfully adopted in medical image processing ,10,11,12The first multilayer perceptron  is appliHere, we adopt a post-processing strategy and propose an efficient fully dense attention convolutional neural network (FDA-CNN) architecture to remove aliasing and ghost artifacts from sparsely reconstructed 2D MRI images. The FDA-CNN method generates aliasing-free images instead of prediction artifacts, which is a key difference from previous MRI de-aliasing techniques. Guan et al.  proposedThe data obtained from an MRI scanner are known as the Fourier space or k-space and can be represented as follows:The reconstruction of an image with n pixels requires at least n frequencies. However, it takes more scan time to capture n frequencies, because the number of frequencies acquired is linearly related to the length of the MRI scan. Acquiring only 1/5 of the frequencies can reduce both the scan time and cost by a factor of 5, but aliasing artifacts are introduced. Under-sampled k-space Conventional CS methods recover images by solving the following optimization problem:A DL-based method is applied to adjust the under-sampled image and reconstruct an artifact-free image that is close to the actual image. This is called a supervised learning strategy, which aims to find an appropriate reconstruction function that matches the given image with the expected output. This can be expressed with the following equation:As shown in The proposed MRI de-aliasing network architecture is presented in this section. We designed an improved CNN model based on the Unet  architecThe network structure shown in The decoding or up-sampling section restores the size of the feature maps and maintains a form symmetric to the encoding section. This symmetry enables the reuse of features by concatenating feature maps at the same level and reduces the loss of information caused by the encoding/decoding process. Before concatenation, the features of encoding and decoding layers go through the AG to focus on target features from different spatial information. Every layer of the decoding section executes a 1 × 1 convolution with padding 1 and ReLU before going into a DB. A 1-channel 1 × 1 convolution is executed before generating the final output.Moreover, dense connectivity generates deeper networks. For comparison, Unet has 23 layers, while FDA-CNN has 97 convolutional and deconvolutional levels. The vanishing gradient problem arises because the gradient information must flow through different layers and may disappear before it arrives at the succeeding layers. Dense connectivity adds more links to enable the effective backpropagation of gradient information. This lessens the vanishing gradient issue and makes it easier to train the network.Densely connected networks  maximizeAs shown in Models trained with AGs  intuitivWe incorporate an AG with every decoding part in our fully dense Unet framework. As shown in We used fully sampled brain k-space data from BraTs-2020 , fastMRIDuring training, the sub-sampled zero-filled (ZF) noisy and artifact images were used as the network input along with the fully sampled images as target images. Our new MCP-US pattern was used for training and compared with 2D Gaussian under-sampling (2DG-US) and 1D Gaussian under-sampling (1DG-US) distributions. Mostly, 2D-US and 1DG-US focus on the central low frequencies of the k-space. However, low-spatial-frequency data, which determine the overall contrast, brightness, and form of the image, are located in the center of the k-space. On the other hand, high-spatial-frequency data determining the image edges and details are located in the periphery of the k-space. As the k-space has a symmetric nature, our MCP-US takes both the low and high frequencies. Among the total sampled data In both training and testing, we took only 20% of data of each k-space for all three sub-sampling patterns, where white spaces were replaced with zero, as shown in Among the sampled data The disparity between the sub-sampled aliasing image and the fully sampled aliasing-free image was evaluated using the loss function. The optimum objective of FDA-CNN is to minimize the value of the loss function. Smaller values between the under-sampled and fully sampled images ensure better reconstruction. We used the mean square error (MSE) as the loss function to calculate pixel-wise disparity and update the network parameters, which can be expressed as follows:To evaluate the network performance, we summarized the findings using four parameters: structural similarity index measure (SSIM) , peak siThe PSNR calculates the ratio of the signal’s highest potential power (image intensity throughout a volume) to its fidelity-affecting distorting noise power. This can be expressed asThe ground truth and the pixel differences in network output images are compared by the NRMSE, which can be expressed asThe human viewer’s perceptual evaluation approach, VIFP, measures image information by computing two mutual information quantities from the reference and distorted images. This can be defined asThese criteria were chosen as they are typically used to evaluate image reconstruction. Higher values of SSIM, PSNR, and VIFP indicate better results, while smaller values of the NRMSE define better reconstructions. Moreover, the reconstruction time for each image indicates the transformation of MRI raw data into pictures. The reconstruction time of each method was calculated using the MCP-US pattern.The training and testing of FDA-CNN were executed on an Intel Core i7-9800X 3.80 GHz processor and 128 GB memory with NVIDIA GeForce RTX 2080 Ti GPU running on Windows 10 Pro 64 bit. This model was implemented in Python 3.8 with the DL open-source libraries TensorFlow v2.4 and Keras v2.4 in the PyCharm environment. We used the Adam optimizer with momentum values of β1 = 0.9 and β2 = 0.999 to reduce the loss function. The starting learning rate was The performance of our network was compared to classical CS total variation (TV) , waveletThe T1-weighted axial brain Brats-2020 dataset was used for both the training and testing of all the networks. In an ideal dataset, the training and test data are very well correlated, providing an opportunity to acquire, from the training data, most of the features that are required to perform effectively during testing. The efficiency of CNNs can be compared in this ideal situation without being affected by the data. This BraTS-2020 dataset was obtained using a clinical 3T multimodal MR scanner. Among 150 k-spaces, 100 k-spaces were used for training; 30 k-spaces were used for validation; and 20 k-spaces were used for testing. Each k-space contained 155 axial cross-sectional T1-weighted (256 × 256) images. In the training, validation, and test sets, there was no duplication of the same k-space.In this experiment, the same MRI sequence was used for both training and testing, with 25% of the training data being used for validation to increase the reliability of the results. The learning potential of FDA-CNN to eliminate artifacts was measured by adjusting the hyperparameters (feature maps and growth rate) of the dense block. Comparative DL methods were trained using the MCP-US pattern and evaluated on the associated datasets with each under-sampling mask. The efficiencies of all CNNs in terms of eliminating artifacts were compared using various sub-sampling masks for an acceleration factor of 5. In general, the CNN produced a better image with minimal artifacts. As seen in The classical CS methods required almost 0.5 s and 0.97 s in reconstruction time for each slice, and the dual-domain network required approximately 0.4 s. In contrast, the single-domain post-processing methods required approximately 0.30 s to 0.33 s. Our proposed method generated better images than Unet within the same reconstruction time of 0.30 s for each slice.As shown in The second experiment used the fastMRI and IXI datasets to test the CNNs after they had been trained on the BraTs dataset. This represents a scenario using different training and test datasets that are not perfectly matched. For testing, fastMRI comprised 2560 T1-weighted axial brain images from 160 k-spaces, while IXI comprised the same number of T2-weighed coronal brain images from 10 k-spaces. BraTs and fastMRI have many similarities, such as features and MR sequences. On the other hand, BraTs and IXI have distinctly dissimilar features and are not compatible due to their MR sequences. This experiment was performed to assess how well the CNN performs and generalizes when the training and testing datasets are different. The results of FDA-CNN and other methods without fine-tuning the fastMRI dataset are shown in With the 2DG-US mask, the CS methods slightly improved image quality, but under the other two Cartesian samplings, these methods did not perform well. The CNNs removed the artifacts and improved the image quality using all three sub-sampling patterns. Instead of VIFP, our method produced better average PSNR, SSIM, and NRMSE than the multidomain (Wnet) network in two cases. As shown in The test results of FDA-CNN and other methods on the IXI dataset are shown in As shown in The average NRMSEs of the BraTs test dataset slices are displayed in FDA-CNN performed better in artifact removal and image restoration than the regular Unet-based CNN and CS techniques according to the described test results. The two 3 × 3 convolutions in Unet are replaced by a dense block in FD-CNN. The input and output of all of the convolutional layers are comparatively small, although the dense block has eight distinct convolutional layers (four 1 × 1 and four 3 × 3). Therefore, the computational cost of the dense block-based convolutional layer is less expensive than that of Unet. Additionally, the regularizing impact of extensive connectivity lessens the possibility of overfitting the training data. The effectiveness of the CNN is heavily reliant on the accuracy of the MRI spatial frequencies, which is a drawback of post-processing techniques such as FDA-CNN. CNN reconstruction is likely to restore image features inaccurately if they are heavily obscured. Some of the lower frequencies may be recoverable if the CNN is directly employed to restore the sensor data. Furthermore, FD-CNN is more generalized than other state-of-the-art methods, as it generated higher average SSIM and PSNR, and lower average NRMSE on both the fastMRI and IXI datasets.This article presents an efficient and effective deep learning-based method for MRI reconstruction from a sparsely sampled k-space using a fully dense attention convolutional neural network. In the proposed approach, edge information and geometry structure are restored more effectively from zero-filled MRI images. This network has the competency to extract realistic features and reconstruct 2D images that are virtually similar to the original. Dense connectivity remarkably promotes feature reuse and improves information flow within the network. Furthermore, AGs combine lower and higher spatial information to pick up more useful features, so the model needs a smaller number of parameters than the more complex Unet. This makes the network more generalized. Although network training requires many hours, reconstruction can be performed fast after training. Compared with CS-based iterative existing approaches, the proposed network needs less reconstruction time.Compared with existing DL-based denoising and de-aliasing methods, the proposed network shows outstanding performance with regard to quantitative and qualitative human vision indexes, and reconstruction time. Furthermore, the correlations between the acquired image quality and several under-sampling patterns were evaluated. Future research will focus on recovering unmeasured frequencies in the k-domain. Moreover, we will implement our approach for real-time interactive temperature-based MRI.


The objective of this paper is to design a protocol for a systematic review and meta-analysis on the effectiveness of self-management interventions in patients with chronic heart failure.The protocol is developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol has been registered in PROSPERO (CRD42021246973). Base on the population, intervention, comparator, and outcome (PICO) framework, our research questions are: 1) What are the effects of eHealth self-management interventions on patients with chronic heart failure? 2) What factors of interventions might affect outcomes? The process includes: 1) search strategy and inclusion criteria; 2) data extraction; 3) risk of bias assessment and 4) data analysis. Searching process and data extraction will be guided by Cochrane Handbook for Systematic Reviews of Interventions. We will use Cochrane Risk of Bias tool to assess the risk of bias. The data analysis will be performed using Metafor package in R.This systemic review will synthesize the current evidence and identify gaps. Findings in the meta-analysis will provide guidance for designing a more effective self-management intervention for patients with chronic heart failure in future. Chronic heart failure (CHF) is a severe long-term disease . EspeciaSelf-management intervention is an individuals’ ability to manage personal symptoms conditions, psychological health and lifestyles by utilizing resources , 9. eHeaCompared with traditional self-management intervention such as medication adherence, exercise training and smoking cessation, eHealth self-management intervention may improve self-management in chronic disease settings more efficiently . eHealthCurrent evidence could suggest that eHealth self-management intervention in patients with heart diseases is effective, but there are some limitations in previous research . First, Overall, a systematic review and meta-analysis on eHealth self-management interventions in patients with CHF, including the effectiveness and affecting factors, is lacking. Therefore, we will conduct a systematic review and meta-analysis to identify eHealth self-management interventions for patients with chronic heart failure and assess their effectiveness and potential harm to patients, patient satisfaction, economic costs, and supporting evidence of their validity. This systemic review will identify the gaps and intend to design a more effective method for patients.The systematic review and meta-analysis was registered in PROSPERO network (CRD42021246973). The protocol of systematic review was accomplished according Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . The whoTo identify randomized controlled trials that provide self-management interventions to patients with chronic heart failure, we developed the search strategy with a librarian through an iterative process. Search terms consist of three parts using Medical Subject Headings terms and keywords: 1) chronic heart failure; 2) self-management interventions; 3) eHealth and 4) randomized controlled trials. The whole search strings are in Inclusion and Exclusion Criteria are followed the Participants-Intervention-Comparison-Outcome (PICO) framework see  27]. We. We27]. For each selected study, we will collect the author(s), publication year, country, study design, number of participants, outcomes, descriptions of the control and the intervention, and the theoretical model. We will calculate Cohen’s d as the effect size. For cluster RCTs, we will use the adjusted value reported in the study. If it is not reported, we will extract the intraclass correlation (ICC) value, mean and standard deviation (for continuous outcomes), or odds ratio (for dichotomous outcomes) to calculate the correct effect size. As a reference, Cohen’s d <0.2 means a small effect, 0.2< = Cohen’s d <0.8 means a medium effect, Cohen’s d >0.8 means a large effect .To assess the risk of bias in each study, we will use the Cochrane Collaboration Risk of Bias Tool . This vaI2) will be assessed with the omnibus homogeneity test (Q) with the following metrics: 0%-40% (not important heterogeneity); 30%-60% (moderate heterogeneity); 50%-90% ; and 75%-100% (considerable heterogeneity) [Outcomes will be reported in two groups: patient outcomes and process outcomes. We will conduct a meta-analysis to summarize the evidence in previous RCTs. We will apply the random-effects model to control the heterogeneity that existed in different studies. The heterogeneity  , and theDespite the above mentioning advantages in our research, pivotal challenges still remain in the preparation and implementation of this review protocol and the following meta-analysis. First, there are challenges existing in developing the inclusion and exclusion criteria. Generally speaking, considering the complexity of the pathogenesis of chronic heart failure and the diversity of noun expressions, there exist difficulties screening patients with chronic heart failure. Therefore, careful consideration is taken to ensure the accuracy and representativeness of the evidence to support our research. Second, preliminary search results in the databases revealed more than 1000 clinical trials and research studies, with considerable overlap in the four databases. Therefore, patience and caution are required to ensure the preciseness of the selected research data during the data extraction process. Third, on account of the lack of research on the affecting factors of eHealth self-management interventions in patients with chronic heart failure, the integration and analysis of data is considered to be a challenge. As the literature of clinical trials in this field continues to grow, we will constantly update the retrieval results to ensure the reliability of the results of our meta-analysis.This systemic review will synthesize the current evidence and identify gaps. Findings in the meta-analysis will provide guidance for designing a more effective self-management intervention for patients with chronic heart failure in the future.S1 Checklist(DOC)Click here for additional data file.S1 File(DOCX)Click here for additional data file.


Muscles are capable of modulating the body and adapting to environmental changes with a highly integrated sensing and actuation. Inspired by biological muscles, coiled/twisted fibers are adopted that can convert volume expansion into axial contraction and offer the advantages of flexibility and light weight. However, the sensing-actuation integrated fish line/yarn-based artificial muscles are still barely reported due to the poor actuation-sensing interface with off-the-shelf fibers. We report herein artificial coiled yarn muscles with self-sensing and actuation functions using the commercially available yarns. Via a two-step process, the artificial coiled yarn muscles are proved to obtain enhanced electrical conductivity and durability, which facilitates the long-term application in human-robot interfaces. The resistivity is successfully reduced from 172.39 Ω·cm (first step) to 1.27 Ω·cm (second step). The multimode sense of stretch strain, pressure, and actuation-sensing are analyzed and proved to have good linearity, stability and durability. The muscles could achieve a sensitivity  of the contraction strain perception up to 1.5. We further demonstrate this self-aware artificial coiled yarn muscles could empower non-active objects with actuation and real-time monitoring capabilities without causing damage to the objects. Overall, this work provides a facile and versatile tool in improving the actuation-sensing performances of the artificial coiled yarn muscles and has the potential in building smart and interactive soft actuation systems. Twisting is a genius invention of nature that imparts enhanced mechanical properties to non-functional fibers by increasing their compactness, which could be found in widespread molecules  ,2, plantWith the developing trend of miniaturization, light weight and intelligence of soft robots and artificial muscles, actuation-sensing integration is increasingly emerging as a focus of the artificial muscles ,18,19. CFor fiber-based artificial muscles, the primary approach is to adopt core-shell structure ,26, coatHere, we propose a two-step method for fabricating self-aware artificial coiled yarn muscles. By leveraging the difference in morphology between the planar structure of carbon black and the fibrous form of carbon nanotubes, we achieve superior penetration into the surface and interior to improve the electrical conductivity and durability of the yarn. The artificial coiled yarn muscles can perceive multi-somatosensory tactile signals including stretching strains and pressure and can monitor the electrothermal actuation process in real time. We provide a facile and versatile method in fabricating self-aware artificial coiled yarn muscles, and intrinsic actuation-sensing properties from the active materials can reduce the complexity of intelligent structures and systems, thereby facilitating the development of the field of flexible wearable devices, soft robotics, etc.The fabrication process of the self-aware artificial coiled yarn muscles is shown in In The controlling system including three power supplies, a current transducer and a PLC control board is developed to detect the signals during the actuation process . The curp < 0.05 were considered statistically significant, and all data are presented at a p < 0.05 significance level unless otherwise stated.Each test of lifting experiments was repeated 10 valid times under same conditions for further analysis and comparison. The results are showed as mean ± standard deviation. Statistical significance was tested using ANOVA (single factor) by SPSS 25.0 software . Probability values of 0 is initial resistance, and ε is the strain ratio of the artificial coiled yarn muscles. The resistance increases linearly with the increase of pressure in both the low strain region (0 to 10%) and the high-pressure region (10% to 30%) but with different slopes  to 1.27 Ω·cm (second step). This artificial coiled yarn muscles can perceive multimode excitation signals  and then execute contractile commands in response to electrothermal stimulation, accompanied by a real-time monitoring of the actuation state. They can achieve a sensitivity  of the contraction strain perception up to 1.5. Finally, two applications including smart textiles and entangled soft tube were conducted to demonstrate the ability to monitor and empower inactive objects with execution capabilities. The introduction of the two-step method alleviates the particle detachment problem caused by mismatched interfaces. This integrated design endows lightweight and good interface to the artificial coiled yarn muscles without compromising their flexibility, and provide promising alternatives towards the fields of wearable devices, soft robots, etc.