47 out of 54 genes (87%) contained at least one early frameshift-inducing DSB and 49 out of 54 (91%) did so when also considering Cas12a-mediated deletions. We suggest that the use of MENdel helps researchers use MMEJ at scale for reverse genetics screenings and with sufficient intra-gene density rates to be viable for nearly all loss-of-function based gene editing therapeutic applications.Intersectoral action is advocated as a social practice that can effectively address health inequalities and related social issues. Existing knowledge provides insight into factors that may facilitate or hinder successful intersectoral action, but not much is known about how intersectoral action evolves and becomes embedded in local health policies. This is where this study aims to make its contribution, by adopting the multilevel perspective on transitions, which is increasingly used to study social innovation in sustainability transitions but has not yet been applied to public health and health promotion. Through this perspective, it was unravelled how intersectoral action between youth-care organizations and community sports clubs became embedded in local health policies of Rotterdam, a large city in the Netherlands. A single explorative case study was conducted based on content analysis of policy documents and 15 in-depth interviews with policy officers, managers and field workers operating in the fields of youth and sports in Rotterdam. The findings showed that intersectoral action between community organizations and policymakers evolves through congruent processes at different levels that changed institutional logics. Moreover, it emerged that policymakers and other actors that advocate novel social practices and act as boundary spanners can adopt multiple strategies to embed these practices in local health policy. The multi-level perspective adds value to earlier approaches to research intersectoral collaboration for health promotion as it allows to better capture the politics involved in the social innovation processes. However, further sharpening and more comprehensive application of transition concepts to study transitions in public health and health promotion is needed.Single-cell RNA sequencing enables us to characterize the cellular heterogeneity in single cell resolution with the help of cell type identification algorithms. However, the noise inherent in single-cell RNA-sequencing data severely disturbs the accuracy of cell clustering, marker identification and visualization. We propose that clustering based on feature density profiles can distinguish informative features from noise. We named such strategy as 'entropy subspace’ separation and designed a cell clustering algorithm called ENtropy subspace separation-based Clustering for nOise REduction (ENCORE) by integrating the 'entropy subspace’ separation strategy with a consensus clustering method. We demonstrate that ENCORE performs superiorly on cell clustering and generates high-resolution visualization across 12 standard datasets. More importantly, ENCORE enables identification of group markers with biological significance from a hard-to-separate dataset. With the advantages of effective feature selection, improved clustering, accurate marker identification and high-resolution visualization, we present ENCORE to the community as an important tool for scRNA-seq data analysis to study cellular heterogeneity and discover group markers.Schizophrenia is a complex psychiatric disorder exhibiting alterations in spontaneous and task-related cerebral activity whose relation (termed „state dependence”) remains unclear. For unraveling their relationship, we review recent electroencephalographic (and a few functional magnetic resonance imaging) studies in schizophrenia that assess and compare both rest/prestimulus and task states, ie, rest/prestimulus-task modulation. Results report reduced neural differentiation of task-related activity from rest/prestimulus activity across different regions, neural measures, cognitive domains, and imaging modalities. Together, the findings show reduced rest/prestimulus-task modulation, which is mediated by abnormal temporospatial dynamics of the spontaneous activity. Abnormal temporospatial dynamics, in turn, may lead to abnormal prediction, ie, predictive coding, which mediates cognitive changes and psychopathological symptoms, including confusion of internally and externally oriented cognition. In conclusion, reduced rest/prestimulus-task modulation in schizophrenia provides novel insight into the neuronal mechanisms that connect task-related changes to cognitive abnormalities and psychopathological symptoms.This article reports an effective strategy for recruiting patients with asthma to a qualitative study using an animated comic advertised on social media. An ad spend of NZ$432 on Facebook resulted in 101 study enquiries, and 27 participants taking part in the focus groups, of which 16 (56%) were Māori, the Indigenous Peoples of New Zealand. Representation of Māori amongst participants was over five times higher than their proportion in the local population (9.7%), resulting in data fulfilling the principle of equal explanatory power, an approach to research which can help advance Māori health development and address inequity. The success of this campaign is of particular interest for health researchers in New Zealand where Māori continue to be disproportionately affected by poorer health outcomes compared with non-Māori, particularly those with asthma. Approaches that better engage and support participation of under-represented communities in clinical research are of wider global interest. We reflect on the recruitment strategy and outcomes within a Kaupapa Māori framework, explore how this can be applied more widely in healthcare, and suggest direction for future study and implementation. Lay summary We designed an animated comic to advertise a study for patients with asthma. This was shared locally with a Facebook ad. The approach was highly engaging with the public, and resulted in rapid recruitment. Interestingly, participation of Māori (the Indigenous People of New Zealand) was over five times higher than their proportion in the local population. Māori have poorer health outcomes and increased barriers to healthcare access compared with non-Māori, particularly those with asthma. Approaches which can engage and support under-represented communities to participate in clinical research are of wider global interest. In this article, we reflect on the recruitment strategy and outcomes, and suggest direction for future study and implementation.Racism is a public health crisis. Black communities (including Africans, the African diaspora and people of African descent) experience worse health outcomes as demonstrated by almost any measure of health and wellbeing-e.g. life expectancy; disease prevalence; maternal mortality rates. While health promotion has its foundation in promoting equity and social justice, it is clear that however well-intended, we are not affecting meaningful change for Black communities quickly enough. Through this article, we outline the intersection of social determinants of health and anti-Black racism. We describe how in the first 8 months of 2020 Black communities around the globe have been disproportionately affected by COVID-19, while also having to respond to new instances of police brutality. We assert that the time has come for health promotion to stop neutralizing the specific needs of Black communities into unspoken 'good intentions’. Instead, we offer some concrete ways for the field to become outspoken, intentional and honest in acknowledging what it will take to radically shift how we promote health and wellbeing for Black people.Cryptococcal meningitis (CM) is a common opportunistic infection in HIV-negative patients, with mortality rates as high as those in the HIV-negative population. This requires accurate initial clinical decision-making, warranting the development of a prognostic score. Two groups of patients were investigated separately to develop a novel prognostic model (AAIT) for HIV-negative patients with CM. A retrospective analysis of 201 HIV-negative patients with CM was conducted to develop the CM prognostic score. In addition, the CM cohort (n = 21) was recruited longitudinally to verify the new prognostic score. Meanwhile, the association between the prognostic score and 1-year mortality of CM was expounded. AAIT (age, albumin, combined bacterial infection, and total triiodothyronine) is a novel prognostic score based on age, albumin level, combined bacterial infection, and total triiodothyronine (TT3) level, which were significantly higher in nonsurvivors than in survivors (0.68 [-0.70 to 1.55] vs – 1.72 [-3.75 to -0.73], P

AAIT (age, albumin, combined bacterial infection, and total triiodothyronine) is a straightforward and clear prognostic score that can add value to predict the outcomes HIV-negative patients with CM.

AAIT (age, albumin, combined bacterial infection, and total triiodothyronine) is a straightforward and clear prognostic score that can add value to predict the outcomes HIV-negative patients with CM.To examine whether a public health project to reduce problem behavior in schools and improve the classroom climate, undertaken among eight secondary schools in a municipality in Sweden, was accompanied by favorable changes in the school environment over time. Data were collected from ninth grade students (aged 15-16 years) at three different time points the year before the project began (2005), during the project (2008) and when the project finished (2011). Changes in the school environment, measured as damage, littering, noise and classroom disorder, were compared between the project municipality and a comparison group of other municipalities in the same county, using multinomial logistic regression analysis. Descriptive comparisons were made between the schools within the project municipality. The school environment improved significantly from 2005 to 2011 in the project municipality compared with the other municipalities. The school environment was improved in all schools within the project municipality. The biggest improvements took place in two schools which systematically worked with one program incorporated into the school schedule. This study demonstrates that it may be possible to improve the school environment by implementing health programs. Further studies based on experimental designs are required in order to confirm the potential and efficiency of school health programs.MicroRNAs are regulators of gene expression. A wide-spread, yet not validated, assumption is that the targetome of miRNAs is non-randomly distributed across the transcriptome and that targets share functional pathways. We developed a computational and experimental strategy termed high-throughput miRNA interaction reporter assay (HiTmIR) to facilitate the validation of target pathways. First, targets and target pathways are predicted and prioritized by computational means to increase the specificity and positive predictive value. Second, the novel webtool miRTaH facilitates guided designs of reporter assay constructs at scale. Third, automated and standardized reporter assays are performed. We evaluated HiTmIR using miR-34a-5p, for which TNF- and TGFB-signaling, and Parkinson’s Disease (PD)-related categories were identified and repeated the pipeline for miR-7-5p. HiTmIR validated 58.9% of the target genes for miR-34a-5p and 46.7% for miR-7-5p. We confirmed the targeting by measuring the endogenous protein levels of targets in a neuronal cell model.