Patients' and Clinicians' Perceptions of the Clinical Utility of Predictive Risk Models for Chemotherapy-Related Symptom Management: Qualitative Exploration Using Focus Groups and Interviews.

BACKGROUND: Interest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported. OBJECTIVE: We aim to explore patients' and clinicians' perspectives of the utility and real-world application of PRMs to improve the management of CRS. METHODS: Focus groups (N=10) and interviews (N=5) were conducted with patients (N=28) and clinicians (N=26) across 5 European countries. Interactions were audio-recorded, transcribed verbatim, and analyzed thematically. RESULTS: Both clinicians and patients recognized the value of having individualized risk predictions for CRS and appreciated how this type of information would facilitate the provision of tailored preventative treatments or supportive care interactions. However, cautious and skeptical attitudes toward the use of PRMs in clinical care were noted by both groups, particularly in relationship to the uncertainty regarding how the information would be generated. Visualization and presentation of PRM information in a usable and useful format for both patients and clinicians was identified as a challenge to their successful implementation in clinical care. CONCLUSIONS: Findings from this study provide information on clinicians' and patients' perspectives on the clinical use of PRMs for the management of CRS. These international perspectives are important because they provide insight into the risks and benefits of using PRMs to evaluate CRS. In addition, they highlight the need to find ways to more effectively present and use this information in clinical practice. Further research that explores the best ways to incorporate this type of information while maintaining the human side of care is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02356081; https://clinicaltrials.gov/study/NCT02356081.

Enhancer-promoter interactions become more instructive in the transition from cell-fate specification to tissue differentiation.

To regulate expression, enhancers must come in proximity to their target gene. However, the relationship between the timing of enhancer-promoter (E-P) proximity and activity remains unclear, with examples of uncoupled, anticorrelated and correlated interactions. To assess this, we selected 600 characterized enhancers or promoters with tissue-specific activity in Drosophila embryos and performed Capture-C in FACS-purified myogenic or neurogenic cells during specification and tissue differentiation. This enabled direct comparison between E-P proximity and activity transitioning from OFF-to-ON and ON-to-OFF states across developmental conditions. This showed remarkably similar E-P topologies between specified muscle and neuronal cells, which are uncoupled from activity. During tissue differentiation, many new distal interactions emerge where changes in E-P proximity reflect changes in activity. The mode of E-P regulation therefore appears to change as embryogenesis proceeds, from largely permissive topologies during cell-fate specification to more instructive regulation during terminal tissue differentiation, when E-P proximity is coupled to activation.

Relationship and Attachment to Digital Health Technology During Cancer Treatment.

OBJECTIVE: The aim of this study is to explore the relationship that people with cancer and their family caregivers develop with symptom management technology during chemotherapy. DATA SOURCES: A longitudinal and multi-perspective interpretative phenomenological approach was adopted. Data were collected using one-to-one in-depth interviews with people with colorectal cancer using supportive digital health symptom management technology (n=3) and their family caregivers (n=4) at two time points during chemotherapy treatment. Data were analyzed using interpretative phenomenological analysis and followed COREQ guidelines. CONCLUSION: People with cancer and their family caregivers can develop emotional bonds with supportive symptom management technology during cancer treatment. Digital health technology can be experienced as a person guiding them during their cancer treatment. Participants felt vulnerable after the technology was returned to the research team. Participants recognized that it was not the technology that successfully facilitated them through their initial chemotherapy cycles; rather, the technology helped them learn to manage their symptoms and promoted their self-efficacy, as well as how to emotionally respond. IMPLICATIONS FOR NURSING PRACTICE: The relationship and psychological bonds people with cancer and their family caregivers develop with technology during treatment may be critically important for oncology nurses to be aware of should digital health be prescribed within the outpatient model of cancer care. This study indicates that technology may not be needed for a full treatment experience, as digital health can promote confidence and self-efficacy regarding symptom management and prepare people with cancer to be independent after the digital health technology is returned to the research team. However, further research is needed regarding individual preferences for digital health provision.

Exploring heart failure nurse practitioner outcome measures: a scoping review.

AIMS: Clinical guidelines recommend people with heart failure are managed within a multidisciplinary team to receive optimal evidence-based management of the syndrome. There is increasing evidence that Nurse Practitioners (NP) in heart failure demonstrate positive patient outcomes. However, their roles as key stakeholders in a multidisciplinary heart failure team are not clearly defined. The aim of the review was to explore the literature related to NP-sensitive outcomes in heart failure. METHODS AND RESULTS: A scoping review was conducted according to accepted guidelines using the Joanna Briggs Institute framework for conducting a scoping review, to identify the literature that related to NP-sensitive outcomes in heart failure management. Sixteen texts were selected for data extraction and analysis. The most common outcome measures reported were readmission rates, self-care measurement scales, functional status scores, quality of life measurements, and medication optimization outcomes. No two studies collected or reported on the same outcome measurements. CONCLUSION: This review highlights that the reporting of heart failure (HF) NP outcome indicators was inconsistent and disparate across the literature. The outcome measures reported were not exclusive to NP interventions. Nurse Practitioner roles are not clearly defined, and resulting outcomes from care are difficult to characterize. Standardized NP-specific outcome measures would serve to highlight the effectiveness of the role in a multidisciplinary HF team.

Unmet care needs of women who have undergone breast cancer surgery: A scoping review.

AIM: To summarize the evidence regarding the unmet care needs of women who have undergone breast cancer surgery and identify research gaps. DESIGN: A scoping review. DATA SOURCES: This review entailed a systematic search in EMBASE, Medline via PubMed, CINAHL Complete, APA PsycINFO, Cochrane Library, Web of Science and Scopus (up until 30 July 2023). REVIEW METHODS: This review was guided by Arksey and O'Malley's Framework (2005) and the Preferred Reporting Items for Systematic Reviews and Meta-analysis-Scoping Review extension (PRISMA-ScR). RESULTS: Twenty-five studies that included 4914 participants were retrieved. Fourteen studies employed quantitative designs, eight used qualitative methods, two were mixed-methods studies and one used a qualitative meta-synthesis. Women who have undergone breast cancer surgery experience a wide range of complex and multifaceted unmet care needs. The informational/educational and psychological/emotional domains were the most frequently reported among the identified domains. Meanwhile, the sexual and spiritual/religious beliefs domains remained relatively underexplored. Furthermore, none of the assessment tools used in these studies captured the entirety of the possible domains of unmet care needs. CONCLUSION: Needs assessment should be integrated into the routine care of women who have undergone breast cancer surgery. Interventions should be developed to address the unmet informational/educational and psychological/emotional needs of women. Future studies should employ high-quality mixed-methods approaches to explore women's sexual and spiritual/religious concerns. IMPACT: This review provides a comprehensive overview of the unmet care needs of women who have undergone the breast cancer surgery. These findings will contribute to the development of tailored interventions. This review also informs future studies to explore distinct domains of unmet care needs. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Targeted design of synthetic enhancers for selected tissues in the Drosophila embryo.

Enhancers control gene expression and have crucial roles in development and homeostasis1-3. However, the targeted de novo design of enhancers with tissue-specific activities has remained challenging. Here we combine deep learning and transfer learning to design tissue-specific enhancers for five tissues in the Drosophila melanogaster embryo: the central nervous system, epidermis, gut, muscle and brain. We first train convolutional neural networks using genome-wide single-cell assay for transposase-accessible chromatin with sequencing (ATAC-seq) datasets and then fine-tune the convolutional neural networks with smaller-scale data from in vivo enhancer activity assays, yielding models with 13% to 76% positive predictive value according to cross-validation. We designed and experimentally assessed 40 synthetic enhancers (8 per tissue) in vivo, of which 31 (78%) were active and 27 (68%) functioned in the target tissue (100% for central nervous system and muscle). The strategy of combining genome-wide and small-scale functional datasets by transfer learning is generally applicable and should enable the design of tissue-, cell type- and cell state-specific enhancers in any system.

Chromatin gene-gene loops support the cross-regulation of genes with related function.

Chromatin loops between gene pairs have been observed in diverse contexts in both flies and vertebrates. Combining high-resolution Capture-C, DNA fluorescence in situ hybridization, and genetic perturbations, we dissect the functional role of three loops between genes with related function during Drosophila embryogenesis. By mutating the loop anchor (but not the gene) or the gene (but not loop anchor), we disentangle loop formation and gene expression and show that the 3D proximity of paralogous gene loci supports their co-regulation. Breaking the loop leads to either an attenuation or enhancement of expression and perturbs their relative levels of expression and cross-regulation. Although many loops appear constitutive across embryogenesis, their function can change in different developmental contexts. Taken together, our results indicate that chromatin gene-gene loops act as architectural scaffolds that can be used in different ways in different contexts to fine-tune the coordinated expression of genes with related functions and sustain their cross-regulation.

CTCF, BEAF-32, and CP190 are not required for the establishment of TADs in early Drosophila embryos but have locus-specific roles.

The boundaries of topologically associating domains (TADs) are delimited by insulators and/or active promoters; however, how they are initially established during embryogenesis remains unclear. Here, we examined this during the first hours of Drosophila embryogenesis. DNA-FISH confirms that intra-TAD pairwise proximity is established during zygotic genome activation (ZGA) but with extensive cell-to-cell heterogeneity. Most newly formed boundaries are occupied by combinations of CTCF, BEAF-32, and/or CP190. Depleting each insulator individually from chromatin revealed that TADs can still establish, although with lower insulation, with a subset of boundaries (~10%) being more dependent on specific insulators. Some weakened boundaries have aberrant gene expression due to unconstrained enhancer activity. However, the majority of misexpressed genes have no obvious direct relationship to changes in domain-boundary insulation. Deletion of an active promoter (thereby blocking transcription) at one boundary had a greater impact than deleting the insulator-bound region itself. This suggests that cross-talk between insulators and active promoters and/or transcription might reinforce domain boundary insulation during embryogenesis.

Evaluation of a nurse practitioner clinical practicum module using a capability education framework: A case study design.

AIMS AND OBJECTIVES: The aim of this research was to evaluate a nurse practitioner's clinical practicum module designed with a capability education framework. The objectives were to determine if the module prepared students adequately for their role and to determine if the Mini-CEX assessment tool was suitable for use with nurse practitioners. BACKGROUND: Capability is a necessary part of expertise, where a capable person takes responsibility to develop their own education, knowledge and skills. The capability learning framework offers nurse practitioners flexible learning pathways between the student, the university and clinical practice. This capability learning framework focuses on the wider complexities of nurse practitioner practice as opposed to a point-in-time assessment. DESIGN: A case study design was used. METHODS: Mixed methods including, document review, focus group and field notes were used in the case study evaluation adhering to the standards for the reporting of organisational case studies. RESULTS: A layered incremental approach to learning and assessments were applied. Students and assessors were satisfied with using the Mini-CEX assessment tool in the module. The Mini-CEX tool was familiar to clinical mentors, who compared students demonstrating competency in a similar manner to medicine. The feedback component of the tool provided deep and meaningful engagement for students. The module provided mentors with insight and understanding of the nurse practitioner role. Students identified the transitioning process from competent to capable practitioners. The module learning and assessments were mapped to regulatory nurse practitioner standards and requirements. CONCLUSIONS: The module provided comprehensive preparation for students to develop their nurse practitioner role. The Mini-CEX assessment tool is a fitting assessment for nurse practitioner students, particularly when supplemented with a corresponding reflective exercise. The assessments and feedback provided the students with opportunities to focus on agreed learning outcomes in their specialist area of practice. RELEVANCE TO CLINICAL PRACTICE: Nurse practitioners are required to practice autonomously and independently at a level of capability in clinical practice. The education preparation of nurse practitioner students must be directed appropriately.

A bridge from uncertainty to understanding: The meaning of symptom management digital health technology during cancer treatment.

Objective: Digital health technology is valued as a tool to provide person-centred care and improve health outcomes amongst people with cancer and their family caregivers. Although the evidence to date shows encouraging effectiveness, there is limited knowledge regarding the lived experience and personal meaning of using supportive technology during cancer treatment. The aim of this study was to explore the lived experiences of people with colorectal cancer receiving chemotherapy using digital health symptom management technology and their family caregivers. Methods: A longitudinal and multi-perspective interpretative phenomenological analytical approach was adopted including three people with newly diagnosed colorectal cancer and four family caregivers. Findings: Three superordinate themes and related subthemes were identified. The first theme (The 3 Cs of symptom management technology) centred on the continuity of care that participants felt while using the technology. The second theme (Digital health technology as a psychosocial support) offered insights into the psychological benefits using technology incurred as they navigated their cancer diagnosis including sense of control and psychological safety. The final theme (Impact of digital health technology on family caregivers) details the supportive effect the technology had on family caregivers' role, responsibilities and well-being during the cancer experience. Conclusion: Digital health technology can act as a bridge from uncertainty to an understanding regarding a cancer diagnosis and its treatment. Digital health technology can support peoples' understanding of cancer and enhance self-management practices, while being a psychological support in navigating the uncertain and often worrying period of receiving cancer treatment.

The psychosocial implication of childhood constipation on the children and family: A scoping review protocol.

Background: Constipation is a common problem in childhood that can have psychological, emotional, social, and health-related quality-of-life (HRQOL) consequences on children and their families. Primary or functional constipation (FC) has no known underlying pathology but is associated with lifestyle, psychological, and behavioural factors. Misdiagnosis and inadequate management of constipation can result in chronicity that can continue to adulthood, reducing quality of life for the child and their parents/family. It also causes emotional, psychological and emotional distress and concern for children and their families. This scoping review aims to answer the research question, "What has been reported about the psychosocial implication of childhood constipation among children and their families?" Methods: The methodology for this scoping review will draw on the six stages of Arksey and O'Malley Framework and the updated and refined version by Peters et al. (2022). The process and reporting will follow the PRISMA-ScR guidelines. The Population, Concept and Context (PCC) framework will guide the development of inclusion criteria and the search strategy for this scoping review. Systematic literature searches of PUBMED, CINAHL, ASSIA, PsycInfo and Cochrane Library will be conducted from inception to present. The critical appraisal will be performed on selected articles to promote trustworthiness and methodological rigour. Plans for consultation exercise and dissemination of findings will also be presented. Conclusion: This scoping review aims to present a comprehensive synthesis of the characteristics and extent of available literature to develop an understanding of and identify gaps in current knowledge regarding the psychosocial implication of childhood constipation on children and their families.

Enhancers have more cofactor specificity than we think: A potential new way to classify enhancers based on their functional cofactor requirements.

By systematically assessing the effects of depleting eight cofactors on enhancer activity, Neumayr et al. (2022) found that different enhancers have different requirements for some perceived universal cofactors. While some cofactors influence enhancer strength, others affect enhancer-promoter specificity.

The continuum of Drosophila embryonic development at single-cell resolution.

Drosophila melanogaster is a powerful, long-standing model for metazoan development and gene regulation. We profiled chromatin accessibility in almost 1 million and gene expression in half a million nuclei from overlapping windows spanning the entirety of embryogenesis. Leveraging developmental asynchronicity within embryo collections, we applied deep neural networks to infer the age of each nucleus, resulting in continuous, multimodal views of molecular and cellular transitions in absolute time. We identify cell lineages; infer their developmental relationships; and link dynamic changes in enhancer usage, transcription factor (TF) expression, and the accessibility of TFs' cognate motifs. With these data, the dynamics of enhancer usage and gene expression can be explored within and across lineages at the scale of minutes, including for precise transitions like zygotic genome activation.

Regulating specificity in enhancer-promoter communication.

Enhancers are cis-regulatory elements that can activate transcription remotely to regulate a specific pattern of a gene's expression. Genes typically have many enhancers that are often intermingled in the loci of other genes. To regulate expression, enhancers must therefore activate their correct promoter while ignoring others that may be in closer linear proximity. In this review, we discuss mechanisms by which enhancers engage with promoters, including recent findings on the role of cohesin and the Mediator complex, and how this specificity in enhancer-promoter communication is encoded. Genetic dissection of model loci, in addition to more recent findings using genome-wide approaches, highlight the core promoter sequence, its accessibility, cofactor-promoter preference, in addition to the surrounding genomic context, as key components.

Building research capacity and culture: Exploring nurses' experience of implementing a nurse-led clinical trial.

AIM: To explore the experiences of a nursing team who implemented an international nurse-led clinical trial in practice and understand the facilitators to their involvement. BACKGROUND: The role and responsibilities of the clinical nurse are advancing to encompass research activity to help inform evidence-based practice. However, several personal and organisational challenges can inhibit nurses' capacity to implement and undertake research within clinical practice. METHODS: Three focus groups were conducted with members of a nursing team (N = 18). Thematic analysis was employed, and themes were identified and agreed upon by the research team. RESULTS: Five themes were identified: 'Previous experience of and attitudes to participation in clinical research', 'Decision-making regarding participation in the clinical trial', 'Facilitators of participation in the clinical trial', 'Challenges of research in nursing practice' and 'Future orientation towards research'. CONCLUSION: Through their experiences of implementing a nurse-led clinical trial within practice, nurses recognized a number of facilitators and challenges to their participation. The perceived relevance of the clinical trial to the nurses' practice, potential to improve patient care and appreciation of the nurse leader's expertise and understanding of their context were key motivators. Reciprocal trust with the nurse leader who was encouraging, motivating, supportive and accessible resulted in the engagement and commitment of the nursing team. IMPLICATIONS FOR NURSING MANAGEMENT: This paper offers a perspective that can inform senior nursing management teams when implementing and conducting evidence-based research amongst nursing teams and in doing so meet the needs of developing research capacity amongst clinical nurses.

Simultaneous cellular and molecular phenotyping of embryonic mutants using single-cell regulatory trajectories.

Developmental progression and cellular diversity are largely driven by transcription factors (TFs); yet, characterizing their loss-of-function phenotypes remains challenging and often disconnected from their underlying molecular mechanisms. Here, we combine single-cell regulatory genomics with loss-of-function mutants to jointly assess both cellular and molecular phenotypes. Performing sci-ATAC-seq at eight overlapping time points during Drosophila mesoderm development could reconstruct the developmental trajectories of all major muscle types and reveal the TFs and enhancers involved. To systematically assess mutant phenotypes, we developed a single-nucleus genotyping strategy to process embryo pools of mixed genotypes. Applying this to four TF mutants could identify and quantify their characterized phenotypes de novo and discover new ones, while simultaneously revealing their regulatory input and mode of action. Our approach is a general framework to dissect the functional input of TFs in a systematic, unbiased manner, identifying both cellular and molecular phenotypes at a scale and resolution that has not been feasible before.

scDALI: modeling allelic heterogeneity in single cells reveals context-specific genetic regulation.

While it is established that the functional impact of genetic variation can vary across cell types and states, capturing this diversity remains challenging. Current studies using bulk sequencing either ignore this heterogeneity or use sorted cell populations, reducing discovery and explanatory power. Here, we develop scDALI, a versatile computational framework that integrates information on cellular states with allelic quantifications of single-cell sequencing data to characterize cell-state-specific genetic effects. We apply scDALI to scATAC-seq profiles from developing F1 Drosophila embryos and scRNA-seq from differentiating human iPSCs, uncovering heterogeneous genetic effects in specific lineages, developmental stages, or cell types.

The management of delirium in the older adult in advanced nursing practice.

Delirium is a term used to describe an array of symptoms that indicate a disruption in cerebral metabolism, a condition that is often under-recognised, leading to delayed interventions. The condition is a common cause of older adults presenting in hospital, with significant morbidity and mortality associated with increased length of stay. A case study is used to illustrate the use of a diagnostic algorithm for older adults presenting with delirium to an advanced nurse practitioner (ANP)-led service. The clinical decision pathway provides four differential diagnoses, using the case study to put the decision-making process in context. The article demonstrates the ability of the ANP to practise at a high level of expertise as an autonomous practitioner and shows how the pathway supports the nurse to reach an accurate diagnosis. It shows that prompt and accurate diagnosis of delirium in older adults is crucial to avoiding the complications and cognitive decline associated with the condition.