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Abstract This study aims to describe the ophthalmic characteristics of autosomal dominant (AD) WFS1-associated optic atrophy (AD WFS1-OA), and to explore phenotypic differences with dominant optic atrophy (DOA) caused by mutations in the OPA1-gene. WFS1-associated diseases, or ‘wolframinopathies’, exhibit a spectrum of ocular and systemic phenotypes, of which the autosomal recessive Wolfram syndrome has been the most extensively studied. AD mutations in WFS1 also cause various phenotypical changes including OA. The most common phenotype in AD WFS1-associated disease, the combination of OA and hearing loss (HL), clinically resembles the ‘plus’ phenotype of DOA. We performed a comprehensive medical record review across tertiary referral centers in the Netherlands and Belgium resulting in 22 patients with heterozygous WFS1 variants. Eighteen (82%) had HL in addition to OA. Diabetes mellitus was found in 7 (32%). Four patients had isolated OA. One patient had an unusual phenotype with anterior chamber abnormalities and malformations of the extremities. Compared to DOA, AD WFS1-OA patients had different color vision abnormalities (red-green vs blue-yellow in DOA), abnormal OPL lamination on macular OCT (absent in DOA), more generalized thinning of the retinal nerve fiber layer, and more reduced and delayed pattern reversal visual evoked potentials.

Abstract Background Patellar instability is a well-known pathology in which kinematics can be investigated using metrics such as tibial tuberosity tracheal groove (TTTG), the bisect offset (BO), and the lateral patellar tilt (LPT). We used dynamic computed tomography (CT) to investigate the patellar motion of healthy subjects in weight-bearing conditions to provide normative values for TTTG, BO, and LPT, as well as to define whether BO and LPT are affected by the morphology of the trochlear groove. Methods Dynamic scanning was used to acquire images during weight-bearing in 21 adult healthy volunteers. TTTG, BO, and LPT metrics were computed between 0° and 30° of knee flexion. Sulcus angle, sulcus depth, and lateral trochlear inclination were calculated and used with the TTTG for simple linear regression models. Results All metrics gradually decreased during eccentric movement (TTTG, -6.9 mm; BO, -12.6%; LPT, -4.3°). No significant differences were observed between eccentric and concentric phases at any flexion angle for all metrics. Linear regression between kinematic metrics towards full extension showed a moderate fit between BO and TTTG (R 2 0.60, β 1.75) and BO and LPT (R 2 0.59, β 1.49), and a low fit between TTTG and LPT (R 2 0.38, β 0.53). A high impact of the TTTG distance over BO was shown in male participants (R 2 0.71, β 1.89) and patella alta individuals (R 2 0.55, β 1.91). Conclusion We provided preliminary normative values of three common metrics during weight-bearing dynamic CT and showed the substantial impact of lateralisation of the patella tendon over patella displacement. Relevance statement These normative values can be used by clinicians when evaluating knee patients using TTTG, BO, and LPT metrics. The lateralisation of the patellar tendon in subjects with patella alta or in males significantly impacts the lateral displacement of the patella. Key Points Trochlear groove morphology had no substantial impact on motion prediction. The lateralisation of the patellar tendon seems a strong predictor of lateral displacement of the patella in male participants. Participants with patella alta displayed a strong fit between the patellar lateral displacement and tilt. TTTG, BO, and LPT decreased during concentric movement. Concentric and eccentric phases did not show differences for all metrics. Graphical Abstract

Abstract Background Patients diagnosed with radioiodine refractory (RAI-R) thyroid carcinoma (TC) have a significantly worse prognosis than patients with radiosensitive TC. These refractory malignancies are often dedifferentiated, hindering the effectiveness of iodine-based imaging. Additionally, the role of metabolic imaging using [18F]FDG PET/CT is also limited in these cases, making adequate staging of RAI-R TC challenging. Recent case series have shown promising results regarding the role of the prostate-specific membrane antigen (PSMA) in TC. In this study we explored the value of [18F]AlF-PSMA-11 PET/CT in RAI-R TC. Methods In this phase II study, lesions detected on [18F]AlF-PSMA-11 PET were compared to findings from [18F]FDG PET/CT. Additionally, the serologic soluble prostate-specific membrane antigen (sPSMA) was measured using ELISA. PSMA-expression on tumor tissue in any available resection specimens was analysed with an immunostainer. Results Eight patients were included, with a total of 39 identified lesions based on PET imaging. [18F]AlF-PSMA-11 PET identified 30 of 39 lesions, and [18F]FDG PET identified 33 lesions, leading to a detection rate of 76.9% and 84.6%, respectively. Interestingly, while nine lesions were solely visualized on [18F]FDG, six were uniquely seen on [18F]AlF-PSMA-11 PET. While sPSMA was immeasurable in all female patients, no correlation was found between sPSMA in male patients and disease-related factors. In five out of eight patients immunohistology showed PSMA expression on the primary tumor. Conclusions Although not all lesions could be visualized, [18F]PSMA-11 PET identified multiple lesions imperceptible on [18F]FDG PET. These results display the potential additional diagnostic role of PSMA-targeted imaging in patients with RAI-R TC. Trial registration number No. EudraCT 2021-000456-19.

Background and objective: The tumor microenvironment (TME) in non–muscle-invasive bladder cancer (NMIBC) plays an important role in the anticancer response. We aimed to identify the prognostic biomarkers in the TME of patients with NMIBC for progression to ≥T2. Methods: From our institutional database, 40 patients with T1 high-risk NMIBC who progressed were pair matched for Club Urologico Español de Tratamiento Oncologico (CUETO) progression variables with 80 patients who never progressed despite longer follow-up. Progression was defined as ≥T2 or extravesical disease. Patients were treated at least with bacillus Calmette-Guérin (BCG) induction (five or more of six doses). Immunohistochemical (IHC) markers for the TME were used on tissue at first T1 diagnosis: CD8-PanCK, GZMB-CD8-FOXP3, CD163, PD-L1 SP142/SP263, fibroblast activation protein-α (FAP), and CK5-GATA3. Full tissue slides were annotated digitally. Relative marker area (IHC-positive area/total area) or density (IHC-positive cells per area; n/mm2) was calculated, differentiating between regions of interest (ROIs; T1, Ta, and carcinoma in situ) and between compartments (stromal, epithelial, and combined). Differences in IHC variables were assessed using the t test, for continuous variables using analysis of variance and comparisons of more than two groups using Tukey’s test. Conditional logistic regression for progression at 5-yr follow-up was performed with clusters based on pair matching. Key findings and limitations: Only FAP expression (increase per 50%) in T1 (odds ratio [OR]: 1.33; 95% confidence interval [CI]: 1.04–1.70) and all ROIs combined (OR: 1.62; 95% CI: 1.14–2.29) correlated significantly with progression. None of the other clinicopathological/IHC variables correlated with progression. Conclusions and clinical implications: FAP is a potential prognostic biomarker for progression in high-risk NMIBC. FAP is a marker for cancer-associated fibroblasts and is linked to immunosuppression and neoangiogenesis, which makes future investigation clinically relevant. Patient summary: We found that progression of high-risk non–muscle-invasive bladder cancer to muscle-invasive disease is less in patients with lower fibroblast activation protein-α (FAP) expression, which is a marker for cancer-associated fibroblasts.

Purpose: The purpose of this paper is to analyse data literacy in the new Digital Competence Framework for Citizens (DigComp 2.2). Mid-2022 the Joint Research Centre of the European Commission published a new version of the DigComp (EC, 2022). This new version focusses more on the datafication of society and emerging technologies, such as artificial intelligence. This paper analyses how DigComp 2.2 defines data literacy and how the framework looks at this from a societal lens. Design/methodology/approach: This study critically examines DigComp 2.2, using the data literacy competence model developed by the Knowledge Centre for Digital and Media Literacy Flanders-Belgium. The examples of knowledge, skills and attitudes focussing on data literacy (n = 84) are coded and mapped onto the data literacy competence model, which differentiates between using data and understanding data. Findings: Data literacy is well-covered in the framework, but there is a stronger emphasis on understanding data rather than using data, for example, collecting data is only coded once. Thematically, DigComp 2.2 primarily focusses on security and privacy (31 codes), with less attention given to the societal impact of data, such as environmental impact or data fairness. Originality/value: Given the datafication of society, data literacy has become increasingly important. DigComp is widely used across different disciplines and now integrates data literacy as a required competence for citizens. It is, thus, relevant to analyse its views on data literacy and emerging technologies, as it will have a strong impact on education in Europe.

Bioreactors are usually modelled as continuous stirred tank reactors (CSTRs) or CSTRs connected in series (Tanks-In-Series configuration). In large systems with non-ideal mixing, such approaches do not sufficiently capture the complex hydrodynamics, leading to model inaccuracies due to the lumping of spatial gradients. Highly detailed computational fluid dynamics (CFD) models provide insight into complex hydrodynamics but are computationally too expensive for flow-sheet models and digital twin applications. A compartmental model (CM) can be a middle-ground by providing a more realistic representation of the hydrodynamics and still being computationally affordable. However, the hydrodynamics of a plant can be very different under varying flow conditions. Dynamic CMs can capture these changes in an elegant way. So far, the application of CMs has been limited mostly to continuous flow systems. In this study, a dynamic CM of a sequencing batch reactor (SBR) is developed for a bio-P removal process. The SBR comes with challenges for CM development due to its distinct operational stages. The dynamic CM shows significant improvements over the CSTR model (using the same biokinetic parameters) for dissolved oxygen and phosphate predictions reducing the need for model recalibration that can lead to over-fitting and limited extrapolation capability of the model. HIGHLIGHTS CFD simulations showed incomplete mixing and stagnation zones in an SBR with an anaerobic/aerobic cycle.; A dynamic compartmental model was developed for an SBR with an anaerobic/aerobic cycle.; The impact of dynamic CM was investigated on biological phosphorus removal.; The dynamic CM showed significant improvement in the model prediction power.; CMs can reduce the calibration effort for the biokinetic models.;

Abstract Background The integration of mental health into primary care—i.e., the process by which a range of essential mental health care and services are made available in existing multipurpose health care settings that did not previously provide them—can be facilitated or hindered by several health system factors that are still poorly understood. This study aimed to identify health system facilitators and barriers to the integration of mental health services into primary care in the Democratic Republic of the Congo (DRC) to improve the success rate of integration programs. Methods We conducted a multimethod, cross-sectional exploratory study. Stakeholders (managers, health service providers, service users, etc.) from sixteen of the twenty-six provinces of the DRC participated. We collected qualitative data through 31 individual, semistructured, face-to-face key informant interviews. We then collected quantitative data through a population-based survey of 413 respondents. We analyzed the interviews via thematic analysis, assigning verbatims to predefined themes and subthemes. For the survey responses, we performed descriptive analysis followed by binomial logistic regression to explore the associations between the variables of interest. Results Strong leadership commitment, positive attitudes toward mental health care, the availability of care protocols, mental health task sharing (p

Abstract Background Only seven cases of ocular Spiroplasma infection have been reported to date, all presenting as congenital cataracts with concomitant intraocular inflammation. We describe the first case of Spiroplasma infection initially presenting as a corneal infiltrate. Case presentation A 1-month-old girl was referred for a corneal infiltrate in the left eye. She presented in our hospital with unilateral keratouveitis. Examination showed a stromal corneal infiltrate and dense white keratic precipitates in the left eye. Herpetic keratouveitis was suspected and intravenous acyclovir therapy was initiated. Two weeks later, the inflammation in the left eye persisted and was also noticed in the right eye. Acute angle-closure glaucoma and a cataract with dilated iris vessels extending onto the anterior lens capsule developed in the left eye. The inflammation resolved after treatment with azithromycin. Iridectomy, synechiolysis and lensectomy were performed. Bacterial metagenomic sequencing (16 S rRNA) and transmission electron microscopy revealed Spiroplasma ixodetis species in lens aspirates and biopsy. Consequently, a diagnosis of bilateral Spiroplasma uveitis was made. Conclusions In cases of congenital cataract with concomitant intraocular inflammation, Spiroplasma infection should be considered. The purpose of this case report is to raise awareness of congenital Spiroplasma infection as a cause of severe keratouveitis, cataract and angle-closure glaucoma in newborns. Performing molecular testing on lens aspirates is essential to confirm diagnosis. Systemic macrolides are suggested as the mainstay of treatment.

Social inequality in students' educational expectations, a strong predictor of educational attainment, differs substantially between countries. Although education system characteristics are translated into school composition effects, the school level is often forgotten in comparative research. Moreover, to explain school effects, we introduce the concept of student engagement into sociological research on expectations. Results of multilevel analyses (R) on data from 7566 students in 126 high schools in four cities--Barcelona (Spain), Ghent (Belgium), Bergen (Norway), and Reykjavík (Iceland)--demonstrated positive effects of (1) SES composition, but mainly in systems with substantial school segregation, (2) behavioral and emotional engagement on expectations.

Abstract Background Chitinase-like proteins (CLPs) play a key role in immunosuppression under inflammatory conditions such as cancer. CLPs are enzymatically inactive and become neutralized upon binding of their natural ligand chitin, potentially reducing CLP-driven immunosuppression. We investigated the efficacy of chitin treatment in the context of triple-negative breast cancer (TNBC) using complementary mouse models. We also evaluated the immunomodulatory influence of chitin on immune checkpoint blockade (ICB) and compared its efficacy as general CLP blocker with blockade of a single CLP, i.e. chitinase 3-like 1 (CHI3L1). Methods Female BALB/c mice were intraductally injected with luciferase-expressing 4T1 or 66cl4 cells and systemically treated with chitin in combination with or without anti-programmed death (PD)-1 ICB. For single CLP blockade, tumor-bearing mice were treated with anti-CHI3L1 antibodies. Metastatic progression was monitored through bioluminescence imaging. Immune cell changes in primary tumors and lymphoid organs (i.e. axillary lymph nodes and spleen) were investigated through flow cytometry, immunohistochemistry, cytokine profiling and RNA-sequencing. CHI3L1-stimulated RAW264.7 macrophages were subjected to 2D lymphatic endothelial cell adhesion and 3D lymphatic integration in vitro assays for studying macrophage-mediated lymphatic remodeling. Results Chitin significantly reduced primary tumor progression in the 4T1-based model by decreasing the high production of CLPs that originate from tumor-associated neutrophils (TANs) and Stat3 signaling, prominently affecting the CHI3L1 and CHI3L3 primary tumor levels. It reduced immunosuppressive cell types and increased anti-tumorigenic T-cells in primary tumors as well as axillary lymph nodes. Chitin also significantly reduced CHI3L3 primary tumor levels and immunosuppression in the 66cl4-based model. Compared to anti-CHI3L1, chitin enhanced primary tumor growth reduction and anti-tumorigenicity. Both treatments equally inhibited lymphatic adhesion and integration of macrophages, thereby hampering lymphatic tumor cell spreading. Upon ICB combination therapy, chitin alleviated anti-PD-1 resistance in both TNBC models, providing a significant add-on reduction in primary tumor and lung metastatic growth compared to chitin monotherapy. These add-on effects occurred through additional increase in CD8α+ T-cell infiltration and activation in primary tumor and lymphoid organs. Conclusions Chitin, as a general CLP blocker, reduces CLP production, enhances anti-tumor immunity as well as ICB responses, supporting its potential clinical relevance in immunosuppressed TNBC patients.

Abstract Trypanosoma cruzi causes Chagas disease and has a unique extranuclear genome enclosed in a structure called the kinetoplast, which contains circular genomes known as maxi- and minicircles. While the structure and function of maxicircles are well-understood, many aspects of minicircles remain to be discovered. Here, we performed a high-throughput analysis of the minicirculome (mcDNA) in 50 clones isolated from Colombia’s diverse T. cruzi I populations. Results indicate that mcDNA comprises four diverse subpopulations with different structures, lengths, and numbers of interspersed semi-conserved (previously termed ultra-conserved regions mHCV) and hypervariable (mHVPs) regions. Analysis of mcDNA ancestry and inter-clone differentiation indicates the interbreeding of minicircle sequence classes is placed along diverse strains and hosts. These results support evidence of the multiclonal dynamics and random bi-parental segregation. Finally, we disclosed the guide RNA repertoire encoded by mcDNA at a clonal scale, and several attributes of its abundance and function are discussed.

Increasing natural resistance and resilience in plants is key for ensuring food security within a changing climate. Breeders improve these traits by crossing cultivars with their wild relatives and introgressing specific alleles through meiotic recombination. However, some genomic regions are devoid of recombination especially in crosses between divergent genomes, limiting the combinations of desirable alleles. Here, we used pooled-pollen sequencing to build a map of recombinant and non-recombinant regions between tomato and five wild relatives commonly used for introgressive tomato breeding. We detected hybrid-specific recombination coldspots that underscore the role of structural variations in modifying recombination patterns and maintaining genetic linkage in interspecific crosses. Crossover regions and coldspots show strong association with specific TE superfamilies exhibiting differentially accessible chromatin between somatic and meiotic cells. About two-thirds of the genome are conserved coldspots, located mostly in the pericentromeres and enriched with retrotransposons. The coldspots also harbor genes associated with agronomic traits and stress resistance, revealing undesired consequences of linkage drag and possible barriers to breeding. We presented examples of linkage drag that can potentially be resolved by pairing tomato with other wild species. Overall, this catalogue will help breeders better understand crossover localization and make informed decisions on generating new tomato varieties.

Oudere volwassenen lopen meer risico op bijwerkingen van medicatie. Voornamelijk anticholinerge bijwerkingen kunnen leiden tot centrale en perifere bijwerkingen op somatisch en cognitief vlak. In dit pilootonderzoek hebben we de anticholinerge lading van de medicatieschema’s van 75 bewoners van een woonzorgcentrum bepaald aan de hand van twee gevalideerde meetschalen, nl. de Anticholinergic Cognitive Burden Scale (ACB) en de Drug Burden Index (DBI) Tevens bekeken we in welke mate de verschillende klasse(n) van medicijnen deze anticholinerge lading beïnvloeden. Tenslotte hebben we de samenhang van een hoge anticholinerge lading met incidenten (urineweginfecties, vallen, delier) geanalyseerd. We zien een hoge mate van polymedicatie en gebruik van psychofarmaca met een anticholinerge werking; de gemiddelde score bedraagt 1,67 op de ACB en 0,87 op de DBI. De anticholinerge lading wordt in de ACB voornamelijk bepaald door antipsychotica (t = 6,110, p < 0,001), bij de DBI zien we een invloed van alle medicatie met anticholinerge eigenschappen (F = 6,764, p < 0.001). Een risicoscore op de DBI heeft een statistisch significante samenhang met het doormaken van een urineweginfectie (F = 5,877, p = 0,018). Deze invloed blijft significant na het corrigeren voor covariaten. De anticholinerge lading van medicatieschema’s bij residenten is hoog. Tevens hangt een verhoogde anticholinerge lading samen met het doormaken van urineweginfectie. Het verlagen van de anticholinerge lading binnen woonzorgcentra vormt dan ook een belangrijke uitdaging naar de toekomst toe.

Homelessness in psychiatric patients in Flanders, Belgium, has never been investigated. Advocacy groups from patients with lived experience of psychiatric disorders have sounded the alarm on the scarcity of suitable housing options, the strain on psychiatric institutions, and the challenges faced by social service workers. To investigate the extent of the problem a survey on the topic was initiated. A “homelessness-in-mental-health-questionnaire” was designed by experts in the field. The social services of all Flemish psychiatric hospitals and all psychiatric wards in general hospitals were contacted and invited to complete this survey. 24 of 70 contacted services responded. The total number of homeless patients in the inpatient setting on an annual basis are estimated to an average 19.5%. 18% of homeless patients remain longer in admission due to the lack of housing options. 13.7% of homeless psychiatric patients are referred to a community care facility such as an assisted living facility. Social service respondents reported spending an average of 27.4% of their work time on housing issues. The main focus points according to the respondents are the lack of priority measures for homeless psychiatric patients, psychiatric problems as a barrier to housing options and the shortage of adapted housing capacity. The conclusion of this study is the need for comprehensive policy interventions to ensure an adequate supply of suitable social housing for psychiatric patients, accessible mental health care, alternative housing options and crisis accommodation facilities. We propose a 10-point action plan on housing for psychiatric patients for policymakers and politicians.

IntroductionIntegrated nature-based interventions in healthcare facilities are gaining importance as promising health and biodiversity promotion strategies. This type of interventions combines the restoration of biodiversity in the vicinity of the healthcare facility with guiding patients in that natural environment for health outcomes. However, quality appraisal of these interventions is still poorly developed. Based on a recent scoping review, the authors developed a preliminary quality framework in support of healthcare facilities designing, implementing and evaluating integrated nature-based interventions. This present study aims to fine-tune the practical relevance of the quality framework within the emerging practice.MethodsA qualitative interview study was conducted in seven healthcare facilities in Belgium. Using a combination of snowball and purposive sampling, 22 professionals, involved in the integrated nature-based intervention in their facility, participated in the study. The semi-structured interviews were transcribed and imported into NVivo. A deductive and inductive thematic analysis was used to explore the practical relevance of the quality framework. A stakeholders’ assembly review and a member checking of the findings were also part of the study.FindingsTwenty-two interviews with nature management coordinators, healthcare professionals, and healthcare managers were conducted by three principal investigators in seven healthcare facilities implementing integrated nature-based interventions. The contextualization and complexity of integrated nature-based interventions in the participating healthcare facilities demonstrated the need for an evidence-based quality framework describing nature-based interventions. The study led to nine quality criteria, confirming the eight quality criteria derived from a previous scoping review, and the identification of a new quality criterion ‘Capacity building, leverage and continuity’. These quality criteria have been refined. Finally, a proposal for a quality framework was developed and operationalized in a checklist. Deployment of the quality framework should be embedded in a continuous cyclical, adaptive process of monitoring and adjusting based on evaluations at each phase of an integrated nature-based intervention.DiscussionBridging the domains of healthcare and nature management in the context of an integrated nature-based intervention in a healthcare facility requires a transdisciplinary approach. Scientific frameworks such as “complex interventions,” Planetary Health and One Health can support the co-design, implementation and evaluation of integrated nature-based interventions within a cyclical, adaptive process. In addition, the importance of the quality of the interactions with nature could gain from more sophisticated attention. Finally, the implications for healthcare facilities, policymakers and education are discussed, as well as the strengths and limitations of the study.

This article examines inclusivity in digital youth work initiatives which use and discuss media and technology. The research focusses on initiatives aimed at socially vulnerable youth. Socially vulnerable and digitally excluded youth face educational inequalities due to limited resources, such as inadequate hardware or lack of academic support at home (Correa et al., 2020; Faure et al., 2022; Garmendia & Karrera, 2019). Youth work as non-formal learning plays a crucial role here, possessing certain advantages that formal education does not have—for instance, the freedom to set needs-specific learning goals that are more responsive to societal signals. Through a two-fold comparative case study analysis, we delve deeper into the successful approaches to organising digitally inclusive digital youth work. The case studies (N = 14), located in Flanders, Belgium, were conducted through an in-depth analysis consisting of a QuickScan of practices and in-depth interviews with practice representatives. Our findings identify four success factors for the setup of digitally inclusive practices: (a) providing young people with the means to actively participate during the activity, (b) informing youth workers about digital inclusion factors, (c) providing youth workers with the means to seek help from other actors working on digital inclusion, and (c) including the target group in the creation process of the activity. Based on these four success factors, this study emphasises the importance of a signal-based approach that starts from the needs and talents of youth.

BackgroundUnemployment affects millions of people worldwide and, beyond its economic impact, has severe implications for people’s well-being and mental health. Different programs have been developed in response to this phenomenon, but to date, job-search interventions have proved to be most effective, especially the JOBS II program. The JOBS II program proved not only to be effective for re-employment but also has a positive impact on beneficiaries’ mental health (ie, reduces anxiety or depression). However, by now, this evidence-based program has been delivered only on site in the various countries where it was implemented. In the digital era, web-based alternatives to such programs are highly needed because they have the advantages of scalability and cost-effectiveness. ObjectiveIn this context, we aim to investigate the efficacy of iJobs, the web-based adaptation of the JOBS II program, on job-search intensity and effort, the quality of job-search behaviors, and job-search self-efficacy. Further, 1 month after the intervention, we will also assess the employment status and the satisfaction with the job (if applicable). This study will also investigate the effect of iJobs on well-being and mental health (ie, anxiety and depression). MethodsThis study is a 2-arm randomized controlled trial. The 2 independent groups (intervention vs waiting list control group) will be crossed with 3 measurement times (ie, baseline, the postintervention time point, and 1-month follow-up). The design will be a 2 (intervention vs control) × 3 (baseline, the postintervention time point, and 1-month follow-up) factorial design. iJobs is a 2-week intervention consisting of 6 modules: an introductive module and 5 modules adapted from the original JOBS II program to the web-based setting and Romanian population. The web-based intervention also has a human component, as beneficiaries receive personalized written feedback after each module on the platform from a team of psychologists involved in the project. ResultsThe enrollment of study participants started in June 2023 and is expected to end in May 2024. The data collection is expected to be completed by July 2024. The results are expected to be submitted for publication in the summer of 2024. ConclusionsThis study is the first large-scale randomized controlled trial aiming to test the efficacy of a web-based adaptation of the JOBS II program. If our results support the efficacy of iJobs, they will offer the premise for it to become an evidence-based, accessible alternative for unemployed people in Romania and might be implemented in other countries. Trial RegistrationClinicalTrials.gov NCT05962554; https://clinicaltrials.gov/study/NCT05962554 International Registered Report Identifier (IRRID)PRR1-10.2196/55374