Histology independent drug development - Is this the future for cancer drugs?

The Cancer Drug Development Forum (CDDF)'s 'Histology independent drug development - is this the future for cancer drugs?' workshop was set up to explore the current landscape of histology independent drug development, review the current regulatory landscape and propose recommendations for improving the conduct of future trials. The first session considered lessons learnt from previous trials, including innovative solutions for reimbursement. The session explored why overall survival represents the most valuable endpoint, and the importance of duration of response, which can be captured with swimmer and spider plots. The second session on biomarker development and treatment optimisation considered current regulations for companion diagnostics, FDA guidance on histology independent drug development in oncology, and the need to establish cut-offs for the biomarker of tumour mutational burden to identify the patients most likely to benefit from PDL1 treatment. The third session reviewed novel trial designs, including basket, umbrella and platform trials, and statistical approaches of hierarchical modelling where homogeneity between study cohorts enables information to be borrowed between cohorts. The discussion highlighted the need to agree 'common assessment standards' to facilitate pooling of data across studies. In the fourth session, the sharing of data sets was recognised as a key step for improving equity of access to precision medicines across Europe. The session considered how the European Health Data Space (EHDS) could streamline access to medical records, emphasizing the importance of introducing greater accountability into the digital space. In conclusion the workshop proposed 11 recommendations to facilitate histology agnostic drug development.

SMRT-AgRenSeq-d in potato (Solanum tuberosum) as a method to identify candidates for the nematode resistance Gpa5.

Potato is the third most important food crop in the world. Diverse pathogens threaten sustainable crop production but can be controlled, in many cases, through the deployment of disease resistance genes belonging to the family of nucleotide-binding, leucine-rich-repeat (NLR) genes. To identify effective disease resistance genes in established varieties, we have successfully established SMRT-AgRenSeq in tetraploid potatoes and have further enhanced the methodology by including dRenSeq in an approach that we term SMR-AgRenSeq-d. The inclusion of dRenSeq enables the filtering of candidates after the association analysis by establishing a presence/absence matrix across resistant and susceptible varieties that is translated into an F1 score. Using a SMRT-RenSeq-based sequence representation of the NLRome from the cultivar Innovator, SMRT-AgRenSeq-d analyses reliably identified the late blight resistance benchmark genes Rpi-R1, Rpi-R2-like, Rpi-R3a, and Rpi-R3b in a panel of 117 varieties with variable phenotype penetrations. All benchmark genes were identified with an F1 score of 1, which indicates absolute linkage in the panel. This method also identified nine strong candidates for Gpa5 that controls the potato cyst nematode (PCN) species Globodera pallida (pathotypes Pa2/3). Assuming that NLRs are involved in controlling many types of resistances, SMRT-AgRenSeq-d can readily be applied to diverse crops and pathogen systems.

HISS: Snakemake-based workflows for performing SMRT-RenSeq assembly, AgRenSeq and dRenSeq for the discovery of novel plant disease resistance genes.

BACKGROUND: In the ten years since the initial publication of the RenSeq protocol, the method has proved to be a powerful tool for studying disease resistance in plants and providing target genes for breeding programmes. Since the initial publication of the methodology, it has continued to be developed as new technologies have become available and the increased availability of computing power has made new bioinformatic approaches possible. Most recently, this has included the development of a k-mer based association genetics approach, the use of PacBio HiFi data, and graphical genotyping with diagnostic RenSeq. However, there is not yet a unified workflow available and researchers must instead configure approaches from various sources themselves. This makes reproducibility and version control a challenge and limits the ability to perform these analyses to those with bioinformatics expertise. RESULTS: Here we present HISS, consisting of three workflows which take a user from raw RenSeq reads to the identification of candidates for disease resistance genes. These workflows conduct the assembly of enriched HiFi reads from an accession with the resistance phenotype of interest. A panel of accessions both possessing and lacking the resistance are then used in an association genetics approach (AgRenSeq) to identify contigs positively associated with the resistance phenotype. Candidate genes are then identified on these contigs and assessed for their presence or absence in the panel with a graphical genotyping approach that uses dRenSeq. These workflows are implemented via Snakemake, a python-based workflow manager. Software dependencies are either shipped with the release or handled with conda. All code is freely available and is distributed under the GNU GPL-3.0 license. CONCLUSIONS: HISS provides a user-friendly, portable, and easily customised approach for identifying novel disease resistance genes in plants. It is easily installed with all dependencies handled internally or shipped with the release and represents a significant improvement in the ease of use of these bioinformatics analyses.

Asynchronous Peer Review Feedback in an Undergraduate Nursing Course: What Students Can Teach Each Other About Writing.

BACKGROUND: Because patient care depends on nurses' ability to effectively communicate, nursing students need opportunities to develop written and oral communication skills through low-stakes activities. However, content-intensive classes and clinical schedules are obstacles to explicit writing support. Online asynchronous peer review can be an effective solution. PURPOSE: Students participated in an online asynchronous peer review intervention. Students reported their perceptions of the peer review and subsequent revisions. METHODS: The authors developed a peer review activity, designed to guide students to give online asynchronous feedback. Students evaluated its effectiveness and value through pre- and posttest surveys. RESULTS: Ninety-four percent (n = 68) of participants reported peer review as beneficial to the writing process, with 74% reporting they revised their writing in meaningful ways. Students felt peer feedback was useful, positive, valid, and reliable. CONCLUSION: Findings suggest that even when delivered asynchronously online, peer review can support nursing students' writing process and scaffold content learning.

Genome-Annotated Bacterial Collection of the Barley Rhizosphere Microbiota.

A culture collection of 41 bacteria isolated from the rhizosphere of cultivated barley (Hordeum vulgare subsp. vulgare) is available at the Division of Plant Sciences, University of Dundee (UK). The data include information on genes putatively implicated in nitrogen fixation, HCN channels, phosphate solubilization, and linked whole-genome sequences.

The Influence of Journaling on Nursing Students: A Systematic Review.

BACKGROUND: Nursing students often experience anxiety and stress from the expectations to develop clinical reasoning skills, internalize new knowledge, and learn to care for patients. Previous research has proposed reflective thinking as a tool to lessen anxiety and promote metacognition. This article examines the role of journaling in promoting reflection among undergraduate nursing students. METHOD: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were used to conduct the review. Concepts for journaling and nursing students were searched in four databases. Data were extracted from 19 sources to identify study type, participants, descriptions of journaling, and findings. RESULTS: Studies took place in a variety of clinical and classroom settings; the majority used a guided format. Various frameworks and tools were used to provide conceptual support. CONCLUSION: Most studies found journaling to be effective in promoting reflection and the development of clinical judgment and emotional competency. However, more studies are needed to develop appropriate rubrics for assessment. [J Nurs Educ. 2022;61(1):29-35.].

Resisting Potato Cyst Nematodes With Resistance.

Potato cyst nematodes (PCN) are economically important pests with a worldwide distribution in all temperate regions where potatoes are grown. Because above ground symptoms are non-specific, and detection of cysts in the soil is determined by the intensity of sampling, infestations are frequently spread before they are recognised. PCN cysts are resilient and persistent; their cargo of eggs can remain viable for over two decades, and thus once introduced PCN are very difficult to eradicate. Various control methods have been proposed, with resistant varieties being a key environmentally friendly and effective component of an integrated management programme. Wild and landrace relatives of cultivated potato have provided a source of PCN resistance genes that have been used in breeding programmes with varying levels of success. Producing a PCN resistant variety requires concerted effort over many years before it reaches what can be the biggest hurdle-commercial acceptance. Recent advances in potato genomics have provided tools to rapidly map resistance genes and to develop molecular markers to aid selection during breeding. This review will focus on the translation of these opportunities into durably PCN resistant varieties.

At the X-Roads of Sex and Genetics in Pulmonary Arterial Hypertension.

Group 1 pulmonary hypertension (pulmonary arterial hypertension; PAH) is a rare disease characterized by remodeling of the small pulmonary arteries leading to progressive elevation of pulmonary vascular resistance, ultimately leading to right ventricular failure and death. Deleterious mutations in the serine-threonine receptor bone morphogenetic protein receptor 2 (BMPR2; a central mediator of bone morphogenetic protein (BMP) signaling) and female sex are known risk factors for the development of PAH in humans. In this narrative review, we explore the complex interplay between the BMP and estrogen signaling pathways, and the potentially synergistic mechanisms by which these signaling cascades increase the risk of developing PAH. A comprehensive understanding of these tangled pathways may reveal therapeutic targets to prevent or slow the progression of PAH.

Resilient agri-food systems for nutrition amidst COVID-19: evidence and lessons from food-based approaches to overcome micronutrient deficiency and rebuild livelihoods after crises.

COVID-19 has had an instant effect on food systems in developing countries. Restrictions to the movement of people and goods have impaired access to markets, services and food. Unlike other concurrent crises, rather than threatening the material hardware of food systems, COVID-19 has so far affected the 'software' of food systems, highlighting again that connectivity is at the heart of these systems. Drops in demand, the loss of markets and employment and growing concerns about international cooperation are indications of possible deeper disruptions to come. Amidst this uncertainty, strategies to safeguard food and nutrition security of the world's poor need to prioritize diversification of production and markets. Nutritious, biofortified crops such as potato, sweetpotato, but also wheat, maize and beans among others, can play a more significant role to provide key micronutrients (vitamin A, iron, zinc) at large scale. Strong local market chains, robust smallholder production systems and increasing commercial utilization make these crops powerful vehicles for securing nutrition when markets and mobility look uncertain. We posit that the evolving impacts of COVID-19 provide an opportunity to focus agricultural innovations, including the development and delivery of biofortified crops, on new and more specifically defined 'jobs to be done' throughout the food system. This will help bridge some of the current disruptions in supply and demand and will help prepare food systems for future crises.

A Diabetes Screening and Educational Event in Rural Alabama.

Type 2 diabetes mellitus is an increasingly urgent public health issue in the United States. Prevention through early detection and education can help decrease the prevalence and complications of the disease. A nursing faculty member and a postgraduate year one pharmacy resident collaborated to provide diabetes screening and education at a local festival in rural Alabama. The prevalence of diabetes in Alabama is approximately 1.6 times higher than the national average. A glycated hemoglobin (HbA1c) test is the gold standard for diabetes diagnosis and is relatively quick and inexpensive. At the event, 38 participants received point of care HbA1c testing, results, and counseling. Seven participants had an HbA1c level of 5.7% to 6.4%, which indicates prediabetes, and one participant had an HbA1c level of 6.5% or higher, which indicates possible diabetes mellitus. Many patients were surprised by their results and by the simplicity of the test. The purpose of this article is to describe a cost-effective interdisciplinary educational event to increase diabetes awareness in a rural community.

The 21st Century Echocardiography Laboratory in Australia and New Zealand: Rapid Evolution of Training and Workforce, Practice and Technology.

Echocardiography is a common and increasingly used noninvasive imaging tool in medicine. In this paper, we imagine the echocardiography laboratory of the future and consider the challenges we face currently, and may face in the future, and how these might be overcome; challenges such as training enough sonographers to meet the increasing demands of the ageing population living with chronic cardiovascular disease and the need for surveillance in other clinical scenarios. We consider the changing qualification framework and the requirements for accreditation and registration in Australia and New Zealand and the potential for migrant sonographers to meet some of the increasing demand. Advanced scopes of practice are likely to be a feature of the future workforce and we consider some of the ways these may evolve. Lastly, we consider how the evolving clinical landscape and technology may change the way echocardiography is delivered.

Self-Regulated E-Learning Modules for Prenursing Success.

To be successful in their courses, nursing students must possess and routinely practice a wide range of self-regulated learning skills. Self-monitoring and regulation of cognition, metacognition, and behaviors influence learning for nursing practice. As reading and studying for comprehension, effective note taking, and taking tests successfully are challenging for many students, faculty at a rural community college created five self-regulated e-learning modules to equip prenursing students with evidence-based techniques to facilitate learning. This article describes the framework of self-regulated learning, the learning modules, student feedback, and implications for nurse educators.

Consensus Recommendations for Developing IQ Script Enabled Radiation Oncology Care Plans in the MOSAIQ Oncology Information System.

BACKGROUND: IQ script enabled radiation oncology (RO) Care Plans are a unique functionality of the MOSAIQ oncology information system and enables standardization of clinical workflow via predefined order sets, strategic launching of assessment forms, and automated forwarding of clinical tasks. However, the development of RO Care Plans is center-specific and must be adapted to each center's clinical workflow. To our knowledge, little to no guidelines exist for RO Care Plan implementation. This article is a collaborative article from 5 different centers of varying sizes and adoption stage that provides consensus strategies for RO Care Plan development. METHODS: In 2016, 5 different centers of varying sizes and adoption stages met to develop strategies for RO Care Plan development. Before the meeting, an initial draft was circulated to all participating centers for feedback and incorporated into a refined document. The refined recommendations underwent a formal, 3-stage consensus process mediated by a radiation therapist to arrive at the final document. RESULTS: Overall, 17 recommendations were provided that focused on 7 areas of Care Plan development: (1) predevelopment planning, (2) current-state RO workflow evaluation, (3) future-state RO integration planning, (4) Care Plan authoring, (5) pre-implementation, (6) implementation, and (7) post-implementation evaluation and review. CONCLUSIONS: Care Plan development is a center-specific process, and the resulting recommendations provide a blueprint for a broad range of cancer centers for implementing Care Plans, or similar oncology information system modules, into their clinical processes.

Nurses' perceptions and experiences of mentoring.

Pre-registration education programmes provide nursing students with the skills and knowledge to become safe and proficient practitioners. Assessment of students' competence is a fundamental part of these programmes and mentors play a crucial role. Mentors are registered nurses who have completed an appropriate mentorship programme in an approved higher education institution, and their main role includes teaching, supervising and assessing students' clinical competence. The role can be demanding and stressful, and mentors must maintain their workloads while supporting students. This article reports the results of the qualitative findings of a survey of mentorship practices ( Brown et al 2012 ). The findings suggest that mentors value support from link lecturers and practice education facilitators, especially when they experience difficulties with nursing students who do not have the required competencies to pass their placement.

Untangling Polypharmacy in Older Adults.

Polypharmacy, the use of five or more medications at one time, is increasingly prevalent in older adults. The nurse's role in education, care coordination, communication, and regular medication recon- ciliation is vital to improve outcomes.