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Integrating behavioral and neurophysiological measures has created new and advanced ways to understand the development of self-regulation. Electroencephalography (EEG) has been used to examine how self-regulatory processes are related to frontal alpha power during infancy and early childhood. However, findings across previous studies have been inconsistent. To address this issue, the current meta-analysis synthesized all prior literature examining associations between individual differences in self-regulation and frontal EEG alpha power (baseline and/or task). In total, 23 studies consisting of 1275 participants between 1 month and 6 years of age were included, which yielded 149 effect sizes. Findings of the three-level meta-analytic model demonstrated a non-significant overall association between self-regulation and frontal alpha power. Yet, significant moderating effects were found for self-regulation construct (emotion regulation, effortful control, executive function), self-regulation measurement (behavioral task, computer assessment, lab observation, questionnaire), and children's mean age. Self-regulation was only significantly correlated with frontal alpha power when studies focused on the executive functioning construct. Moreover, the use of behavioral tasks or questionnaires and a higher mean age of the children resulted in small but significant effect size estimates. Higher frontal alpha power values were related to higher order top-down mechanisms of self-regulation, indicating that these mechanisms might become stronger when the frontal cortex is sufficiently developed. The findings of the current meta-analysis highlight the importance of longitudinal analyses and multimethod approaches in future work to reach a more comprehensive understanding of the role of frontal EEG alpha activity in the etiology of individual differences in early self-regulation.

Abstract Software that employs screening prioritization through active learning (AL) has accelerated the screening process significantly by ranking an unordered set of records by their predicted relevance. However, failing to find a relevant paper might alter the findings of a systematic review, highlighting the importance of identifying elusive papers. The time to discovery (TD) measures how many records are needed to be screened to find a relevant paper, making it a helpful tool for detecting such papers. The main aim of this project was to investigate how the choice of the model and prior knowledge influence the TD values of the hard-to-find relevant papers and their rank orders. A simulation study was conducted, mimicking the screening process on a dataset containing titles, abstracts, and labels used for an already published systematic review. The results demonstrated that AL model choice, and mostly the choice of the feature extractor but not the choice of prior knowledge, significantly influenced the TD values and the rank order of the elusive relevant papers. Future research should examine the characteristics of elusive relevant papers to discover why they might take a long time to be found.

Abstract Cytomegalovirus (CMV) is known to alter circulating effector memory or re-expressing CD45RA+ (TemRA) T-cell numbers, but whether Epstein–Barr virus (EBV) does the same or this is amplified during a CMV and EBV co-infection is unclear. Immune cell numbers in blood of children and young, middle-aged, and senior adults (n = 336) were determined with flow cytometry, and additional multivariate linear regression, intra-group correlation, and cluster analyses were performed. Compared to non-infected controls, CMV-seropositive individuals from all age groups had more immune cell variance, and CMV+ EBV− senior adults had more late-differentiated CD4+ and CD8+ TemRA and CD4+ effector memory T-cells. EBV-seropositive children and young adults had a more equal immune cell composition than non-infected controls, and CMV− EBV+ senior adults had more intermediate/late-differentiated CD4+ TemRA and effector memory T-cells than non-infected controls. CMV and EBV co-infected young and middle-aged adults with an elevated BMI and anti-CMV antibody levels had a similar immune cell composition as senior adults, and CMV+ EBV+ middle-aged adults had more late-differentiated CD8+ TemRA, effector memory, and HLA-DR+ CD38− T-cells than CMV+ EBV− controls. This study identified changes in T-cell numbers in CMV- or EBV-seropositive individuals and that some CMV and EBV co-infected young and middle-aged adults had an aging-related T-cell phenotype.

Background An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns. Methods In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11–18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately. Results In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13–0.25), maintenance OCS use (OR 0.75, 95% CI 0.61–0.92) and dose (mean −3.93 mg·day−1, 95% CI −5.24–2.62 mg·day−1) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns. Conclusions By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.

Staphylococcus aureus is the main causative pathogen of subcutaneous, bone, and implant-related infections, forming structures known as staphylococcal abscess communities (SACs) within tissues that also contain immunosuppressive myeloid-derived suppressor cells (MDSCs). Although both SACs and MDSCs are present in chronic S. aureus infections, it remains unknown whether SACs directly trigger MDSC expansion. To investigate this, a previously developed 3D in vitro SAC model was co-cultured with murine and human bone marrow cells. Subsequently, it was shown that SAC-exposed human CD11blow/− myeloid cells or SAC-exposed murine CD11b+ Gr-1+ cells were immunosuppressive mainly by reducing absolute CD4+ and CD8α+ T cell numbers, as shown in T cell proliferation assays and with flow cytometry. Monocytic MDSCs from mice with an S. aureus bone infection also strongly reduced CD4+ and CD8α+ T cell numbers. Using protein biomarker analysis and an immunoassay, we detected in SAC–bone marrow co-cultures high levels of GM-CSF, IL-6, VEGF, IL-1β, TNFα, IL-10, and TGF-β. Furthermore, SAC-exposed neutrophils expressed Arg-1 and SAC-exposed monocytes expressed Arg-1 and iNOS, as shown via immunofluorescent stains. Overall, this study showed that SACs cause MDSC expansion from bone marrow cells and identified possible mediators to target as an additional strategy for treating chronic S. aureus infections.

In the context of REDD+, Measurement, Reporting and Verification (MRV) is one way to manage forest change information. A national carbon and non-carbon database will be used in REDD+ to negotiate compensation schemes with the international community. Much of this data will be collected at the local level, thus a reporting system that can integrate these locally collected data into the national database is crucial. In this paper we compare and draw lessons from three existing local to national reporting systems that include the participation of local communities: 1) the government extension services, 2) the government owned forestry company, and 3) a private logging company in Indonesia, and provide recommendations for REDD+ reporting systems. The results suggest that the main desired conditions for effective data flow are: benefits to motivate local participation, based on contributions to reporting activities; simple data format and reporting procedures to allow local participation in the reporting process, and to support data aggregation at the national level; a facilitator to mediate data aggregation at the village level to ensure data consistency, completeness and accuracy; and a transparent and clear data flow. Under these conditions, continuous, accountable and consistent data flow from the local level will reach the national level where it can be fully utilized.

Participatory Measurement, Reporting and Verification (PMRV), in the context of reducing emissions from deforestation and forest degradation with its co-benefits (REDD+) requires sustained monitoring and reporting by community members. This requirement appears challenging and has yet to be achieved. Other successful, long established, community self-monitoring and reporting systems may provide valuable lessons. The Indonesian integrated village healthcare program (Posyandu) was initiated in the 1980s and still provides effective and successful participatory measurement and reporting of child health status across the diverse, and often remote, communities of Indonesia. Posyandu activities focus on the growth and development of children under the age of five by recording their height and weight and reporting these monthly to the Ministry of Health. Here we focus on the local Posyandu personnel (kaders) and their motivations and incentives for contributing. While Posyandu and REDD+ measurement and reporting activities differ, there are sufficient commonalities to draw useful lessons. We find that the Posyandu kaders are motivated by their interests in health care, by their belief that it benefits the community, and by encouragement by local leaders. Recognition from the community, status within the system, training opportunities, competition among communities, and small payments provide incentives to sustain participation. We examine these lessons in the context of REDD+.

BACKGROUND: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-β signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-β and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-β and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-β were found especially in MFS patients with aortic root dilatation (124 pg/ml), when compared to MFS patients with normal aorta (10 pg/ml; p = 8×10(-6), 95% CI: 70-159 pg/ml). Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR) = 0%), ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC) = 1.8; 1.4; 1.5, FDR = 0%) and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%). Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF) in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02) and increased number of CD8+ T-cells (p = 0.003) in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients.

We describe an infant presenting with contractures of the fingers, a large ventricular septal defect (VSD), and severe pulmonary artery dilatation. He had clinical and echocardiographic features of both neonatal or infantile Marfan syndrome (MFS) and congenital contractural arachnodactyly. After surgical VSD closure, the aortic root developed progressive dilatation while the size of pulmonary artery returned to normal limits. Eventually the diagnosis of MFS was confirmed by DNA analysis.