A hypercubic Mk model framework for capturing reversibility in disease, cancer, and evolutionary accumulation modelling.

Motivation: Accumulation models, where a system progressively acquires binary features over time, are common in the study of cancer progression, evolutionary biology, and other fields. Many approaches have been developed to infer the accumulation pathways by which features (e.g.

On Being Open in Closed Places: Vulnerability and Violence in Inpatient Psychiatric Settings.

High levels of violence and conflict occur in inpatient psychiatric settings, causing a range of psychological and physical harms to both patients and staff. Drawing on critiques of vulnerability from the philosophical literature, this paper contends that staff's understanding of their relationship with patients (including how they should respond to violence and conflict) rests on the dominant, reductive account of vulnerability. This account frames vulnerability as an increased susceptibility to harm and so regards 'invulnerable' staff's responsibility to be protecting and managing vulnerable patients.

HyperTraPS-CT: Inference and prediction for accumulation pathways with flexible data and model structures.

Accumulation processes, where many potentially coupled features are acquired over time, occur throughout the sciences from evolutionary biology to disease progression, and particularly in the study of cancer progression. Existing methods for learning the dynamics of such systems typically assume limited (often pairwise) relationships between feature subsets, cross-sectional or untimed observations, small feature sets, or discrete orderings of events. Here we introduce HyperTraPS-CT (Hypercubic Transition Path Sampling in Continuous Time) to compute posterior distributions on continuous-time dynamics of many, arbitrarily coupled, traits in unrestricted state spaces, accounting for uncertainty in observations and their timings.

De-escalating aggression in acute inpatient mental health settings: a behaviour change theory-informed, secondary qualitative analysis of staff and patient perspectives.

Background: De-escalation is often advocated to reduce harm associated with violence and use of restrictive interventions, but there is insufficient understanding of factors that influence de-escalation behaviour in practice. For the first time, using behaviour change and implementation science methodology, this paper aims to identify the drivers that will enhance de-escalation in acute inpatient and psychiatric intensive care mental health settings.

Methods: Secondary analysis of 46 qualitative interviews with ward staff (n = 20) and patients (n = 26) informed by the Theoretical Domains Framework.

Evolution and maintenance of mtDNA gene content across eukaryotes.

Across eukaryotes, most genes required for mitochondrial function have been transferred to, or otherwise acquired by, the nucleus. Encoding genes in the nucleus has many advantages. So why do mitochondria retain any genes at all? Why does the set of mtDNA genes vary so much across different species? And how do species maintain functionality in the mtDNA genes they do retain? In this review, we will discuss some possible answers to these questions, attempting a broad perspective across eukaryotes.

The cellular basis of feeding-dependent body size plasticity in sea anemones.

Many animals share a lifelong capacity to adapt their growth rates and body sizes to changing environmental food supplies. However, the cellular and molecular basis underlying this plasticity remains only poorly understood. We therefore studied how the sea anemones Nematostella vectensis and Aiptasia (Exaiptasia pallida) respond to feeding and starvation.

Evaluation of a novel co-designed and co-delivered training package to de-escalate violence and aggression in UK acute inpatient, PICU and forensic mental health settings.

Unlabelled: WHAT IS KNOWN ON THE SUBJECT?: Clinical guidelines and staff training recommend using de-escalation over restrictive practices, such as restraint and seclusion Evidence suggests that restrictive practices continue to be used frequently despite training This suggests a lack of impact of existing staff de-escalation training. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: The features of de-escalation training that are acceptable to staff and perceived to be impactful A co-designed and co-delivered training session on a trauma-informed approach to de-escalation on mental health wards was acceptable and perceived to be impactful Those attending training particularly valued how lived experience was incorporated into the training content and co-delivery The organizational and team context may need more consideration in adapting the training. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: De-escalation training that adopts a trauma-informed approach and considers the context of ward environments is acceptable to staff Co-delivery models of training to tackle restrictive practice can be acceptable and impactful Further research will show how clinically effective this training is in improving outcomes for service users in ward contexts.

The Nitroplast and Its Relatives Support a Universal Model of Features Predicting Gene Retention in Endosymbiont and Organelle Genomes.

Endosymbiotic relationships have shaped eukaryotic life. As endosymbionts coevolve with their host, toward full integration as organelles, their genomes tend to shrink, with genes being completely lost or transferred to the host nucleus. Modern endosymbionts and organelles show diverse patterns of gene retention, and why some genes and not others are retained in these genomes is not fully understood.

Understanding the Factors That Contribute to Creating a Collaborative Psychological Formulation: A Qualitative Systematic Review.

Objectives: Creating a formulation is one of the key competencies of a clinical psychologist and is understood to be important for guiding therapeutic input and understanding client distress. However, client experience of formulations can vary, with some reporting it is unhelpful and distressing. This novel review explores the experiences of clinicians and clients when creating a formulation, specifically the barriers and facilitators to collaborating on a formulation.

Connecting Species-Specific Extents of Genome Reduction in Mitochondria and Plastids.

Mitochondria and plastids have both dramatically reduced their genomes since the endosymbiotic events that created them. The similarities and differences in the evolution of the two organelle genome types have been the target of discussion and investigation for decades. Ongoing work has suggested that similar mechanisms may modulate the reductive evolution of the two organelles in a given species, but quantitative data and statistical analyses exploring this picture remain limited outside of some specific cases like parasitism.

Automated manufacture of ΔNPM1 TCR-engineered T cells for AML therapy.

Acute myeloid leukemia (AML) is a heterogeneous malignancy that requires further therapeutic improvement, especially for the elderly and for subgroups with poor prognosis. A recently discovered T cell receptor (TCR) targeting mutant nucleophosmin 1 (ΔNPM1) presents an attractive option for the development of a cancer antigen-targeted cellular therapy. Manufacturing of TCR-modified T cells, however, is still limited by a complex, time-consuming, and laborious procedure.

Ecological Predictors of Organelle Genome Evolution: Phylogenetic Correlations with Taxonomically Broad, Sparse, Unsystematized Data.

Comparative analysis of variables across phylogenetically linked observations can reveal mechanisms and insights in evolutionary biology. As the taxonomic breadth of the sample of interest increases, challenges of data sparsity, poor phylogenetic resolution, and complicated evolutionary dynamics emerge. Here, we investigate a cross-eukaryotic question where all these problems exist: which organismal ecology features are correlated with gene retention in mitochondrial and chloroplast DNA (organelle DNA or oDNA).

Development and evaluation of a de-escalation training intervention in adult acute and forensic units: the EDITION systematic review and feasibility trial.

Background: Containment (e.g. physical restraint and seclusion) is used frequently in mental health inpatient settings.

Applied Methods to Assess the Antimicrobial Activity of Metallic-Based Nanoparticles.

With the rise of antibiotic resistance, the drive to discover novel antimicrobial substances and standard testing methods with the aim of controlling transmissive diseases are substantially high. In healthcare sectors and industries, although methods for testing antibiotics and other aqueous-based reagents are well established, methods for testing nanomaterials, non-polar and other particle-based suspensions are still debatable. Hence, utilities of ISO standard validations of such substances have been recalled where corrective actions had to be taken.

Stochastic organelle genome segregation through Arabidopsis development and reproduction.

Organelle DNA (oDNA) in mitochondria and plastids is vital for plant (and eukaryotic) life. Selection against damaged oDNA is mediated in part by segregation - sorting different oDNA types into different cells in the germline. Plants segregate oDNA very rapidly, with oDNA recombination protein MSH1 a key driver of this segregation, but we have limited knowledge of the dynamics of this segregation within plants and between generations.

Generation of Antibodies Selectively Recognizing Epitopes in a Formaldehyde-Fixed Cell-Surface Antigen Using Virus-like Particle Display and Hybridoma Technology.

Efficient induction of target-specific antibodies can be elicited upon immunization with highly immunogenic virus-like particles (VLPs) decorated with desired membrane-anchored target antigens (Ags). However, for example, for diagnostic purposes, monoclonal antibodies (mAbs) are required to enable the histological examination of formaldehyde-fixed paraffin-embedded (FFPE) biopsy tissue samples. Aiming at the generation of FFPE-antigen-specific mAbs and as a proof of concept (POC), we first established a simplified protocol using only formaldehyde and 90 °C heat fixation (FF90) of cells expressing the target Ag nerve growth factor receptor (NGFR).

Stromule Geometry Allows Optimal Spatial Regulation of Organelle Interactions in the Quasi-2D Cytoplasm.

In plant cells, plastids form elongated extensions called stromules, the regulation and purposes of which remain unclear. Here, we quantitatively explore how different stromule structures serve to enhance the ability of a plastid to interact with other organelles: increasing the effective space for interaction and biomolecular exchange between organelles. Interestingly, electron microscopy and confocal imaging showed that the cytoplasm in Arabidopsis thaliana and Nicotiana benthamiana epidermal cells is extremely thin (around 100 nm in regions without organelles), meaning that inter-organelle interactions effectively take place in 2D.

Targeting Stage-Specific Embryonic Antigen 4 (SSEA-4) in Triple Negative Breast Cancer by CAR T Cells Results in Unexpected on Target/off Tumor Toxicities in Mice.

Due to the paucity of targetable antigens, triple-negative breast cancer (TNBC) remains a challenging subtype of breast cancer to treat. In this study, we developed and evaluated a chimeric antigen receptor (CAR) T cell-based treatment modality for TNBC by targeting stage-specific embryonic antigen 4 (SSEA-4), a glycolipid whose overexpression in TNBC has been correlated with metastasis and chemoresistance. To delineate the optimal CAR configuration, a panel of SSEA-4-specific CARs containing alternative extracellular spacer domains was constructed.

Evaluation of low-density SNP panels and imputation for cost-effective genomic selection in four aquaculture species.

Genomic selection can accelerate genetic progress in aquaculture breeding programmes, particularly for traits measured on siblings of selection candidates. However, it is not widely implemented in most aquaculture species, and remains expensive due to high genotyping costs. Genotype imputation is a promising strategy that can reduce genotyping costs and facilitate the broader uptake of genomic selection in aquaculture breeding programmes.

Exchange on dynamic encounter networks allows plant mitochondria to collect complete sets of mitochondrial DNA products despite their incomplete genomes.

Mitochondria in plant cells usually contain less than a full copy of the mitochondrial DNA (mtDNA) genome. Here, we asked whether mitochondrial dynamics may allow individual mitochondria to 'collect' a full set of mtDNA-encoded gene products over time, by facilitating exchange between individuals akin to trade on a social network. We characterise the collective dynamics of mitochondria in hypocotyl cells using a recent approach combining single-cell time-lapse microscopy, video analysis and network science.