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Genome replication follows a defined temporal programme that can change during cellular differentiation and disease onset. DNA replication results in an increase in DNA copy number that can be measured by high-throughput sequencing. Here we present a protocol to determine genome replication dynamics using DNA copy-number measurements. Cell populations can be obtained in three variants of the method. First, sort-seq reveals the average replication dynamics across S phase in an unperturbed cell population; FACS is used to isolate replicating and non-replicating subpopulations from asynchronous cells. Second, sync-seq measures absolute replication time at specific points during S phase using a synchronized cell population. Third, marker frequency analysis can be used to reveal the average replication dynamics using copy-number analysis in any proliferating asynchronous cell culture. These approaches have been used to reveal genome replication dynamics in prokaryotes, archaea and a wide range of eukaryotes, including yeasts and mammalian cells. We have found this approach straightforward to apply to other organisms and highlight example studies from across the three domains of life. Here we present a Saccharomyces cerevisiae version of the protocol that can be performed in 7–10 d. It requires basic molecular and cellular biology skills, as well as a basic understanding of Unix and R. This protocol describes a suite of related approaches for genome-wide profiling of DNA replication dynamics in unperturbed or synchronized cells by measuring DNA copy-number changes using high-throughput sequencing.

Background The identification of sites of DNA replication initiation in mammalian cells has been challenging. Here, we present unbiased detection of replication initiation events in human cells using BrdU incorporation and single-molecule nanopore sequencing. Results Increases in BrdU incorporation allow us to measure DNA replication dynamics, including identification of replication initiation, fork direction, and termination on individual nanopore sequencing reads. Importantly, initiation and termination events are identified on single molecules with high resolution, throughout S-phase, genome-wide, and at high coverage at specific loci using targeted enrichment. We find a significant enrichment of initiation sites within the broad initiation zones identified by population-level studies. However, these focused initiation sites only account for ~ 20% of all identified replication initiation events. Most initiation events are dispersed throughout the genome and are missed by cell population approaches. This indicates that most initiation occurs at sites that, individually, are rarely used. These dispersed initiation sites contrast with the focused sites identified by population studies, in that they do not show a strong relationship to transcription or a particular epigenetic signature. Conclusions We show here that single-molecule sequencing enables unbiased detection and characterization of DNA replication initiation events, including the numerous dispersed initiation events that replicate most of the human genome.

Background Cip1-interacting zinc finger protein 1 (CIZ1) forms RNA-dependent protein assemblies that stabilise epigenetic state, notable at the inactive X chromosome in females. CIZ1 has been linked with a range of human cancers and in mice genetic deletion of CIZ1 manifests as hyperproliferative lymphoid lineages in females. This suggests that its role in maintenance of epigenetic stability is linked with disease. Results Here, we show that male and female CIZ1-null primary murine fibroblasts have reduced H4K20me1 and that this compromises nuclear condensation on entry to quiescence. Global transcriptional repression remains intact in condensation-deficient CIZ1-null cells; however, a subset of genes linked with chromatin condensation and homology-directed DNA repair are perturbed. Failure to condense is phenotypically mimicked by manipulation of the H4K20me1 methyltransferase, SET8, in WT cells and partially reverted in CIZ1-null cells upon re-expression of CIZ1. Crucially, during exit from quiescence, nuclear decondensation remains active, so that repeated entry and exit cycles give rise to expanded nuclei susceptible to mechanical stress, DNA damage checkpoint activation, and downstream emergence of transformed proliferative colonies. Conclusions Our results demonstrate a role for CIZ1 in chromatin condensation on entry to quiescence and explore the consequences of this defect in CIZ1-null cells. Together, the data show that CIZ1’s protection of the epigenome guards against genome instability during quiescence cycles. This identifies loss of CIZ1 as a potentially devastating vulnerability in cells that undergo cycles of quiescence entry and exit.

Objectives: The number of predatory journals is increasing in the scholarly communication realm. These journals use questionable business practices, minimal or no peer review, or limited editorial oversight and, thus, publish articles below a minimally accepted standard of quality. These publications have the potential to alter the results of knowledge syntheses. The objective of this study was to determine the degree to which articles published by a major predatory publisher in the health and biomedical sciences are cited in systematic reviews.Methods: The authors downloaded citations of articles published by a known predatory publisher. Using forward reference searching in Google Scholar, we examined whether these publications were cited in systematic reviews.Results: The selected predatory publisher published 459 journals in the health and biomedical sciences. Sixty-two of these journal titles had published a total of 120 articles that were cited by at least 1 systematic review, with a total of 157 systematic reviews citing an article from 1 of these predatory journals.Discussion: Systematic review authors should be vigilant for predatory journals that can appear to be legitimate. To reduce the risk of including articles from predatory journals in knowledge syntheses, systematic reviewers should use a checklist to ensure a measure of quality control for included papers and be aware that Google Scholar and PubMed do not provide the same level of quality control as other bibliographic databases.

In higher eukaryotic nuclei, DNA is periodically anchored to an extraction-resistant protein structure, via matrix attachment regions. We describe a refined and accessible method to non-subjectively, rapidly and reproducibly measure both size and stability of the intervening chromatin loops, and use it to demonstrate that malignant transformation compromises the DNA-nuclear matrix interface.

PhD-prepared nurse practitioners (NPs) bring a unique combination of attributes to work within university settings. However, models for integrating clinical practice within academia are lacking for nursing faculty. As four PhD-prepared NPs, we completed a pilot collaborative self-study to explore how PhD-NPs working in academia experience the integration of clinical practice with academic work, and how clinical practice fits within workload and academic promotion models. Following initial data collection by email, we conducted a virtual focus group and analyzed the data using Braun and Clarke’s Reflexive Thematic Analysis. Identified themes included the value of clinical work; lack of understanding of the PhD-NP role; synergy between teaching, research, and clinical practice; challenges including time constraints and competing responsibilities; and the lack of formal models for PhD-NP role organization and compensation. PhD-prepared NPs felt clinical work added value to their teaching and research, although academic-clinical role organizational models were lacking. This pilot data must be contextualized within current North American policies and practice settings. Findings can be used to inform further study on the development of models for clinical practice in academia.

Work-integrated learning (WIL) is an educational approach that aims to support students’ integration of theory to practice. These rich learning opportunities provide students with real-world experiences and introduce practice and ethical situations that help consolidate and bridge their knowledge and skill. Academic integrity has been defined as the ongoing commitment to values that are consistent with ethical practice: honesty, trust, fairness, respect, responsibility, and courage (International Centre for Academic Integrity, 2021). It is important to understand what specifically influences students’ intentions to behave with integrity in WIL settings. This paper reports on one study that explored predictors to students’ intentions to behave with integrity across three different WIL settings in their upper years of studies. The findings and recommendations from the research may help to inform other professional programs that include WIL through their educational offerings.

We propose that phenomenography is well-suited to research about nursing, given its focus on identifying variation in individuals’ experiences, and inclusion of diverse voices and perspectives. Phenomenography explores qualitatively different ways in which a group of people experience a phenomenon, often using semi-structured interviews. The use of phenomenography is especially relevant in research about nursing which provides accounts of the experiences of nurses and patients within complex practice settings. We consider the tenets of phenomenography and examine phenomenography’s relationship to and differences from phenomenology. We review literature published about phenomenographic research in nursing and reflect on the potential benefits of phenomenographic research about nursing. This paper adds to knowledge about use of phenomenography in research about nursing.

Purpose: The purpose of this study was to explore the narrative accounts of new graduate nurses reflecting upon their transition to practice and professional identity formation in order to identify how experiences of becoming and being nurses may inform nursing education, policy, and practice with relation to recruitment and retention of nurses. Background: There is a global shortage of nurses, further exacerbated by a greater desire to leave the profession since the COVID-19 pandemic. As nursing students transition into the roles of new graduate nurses, they begin to form stronger role-oriented identities. These have been associated with greater job satisfaction and indicative of retention. Individual characteristics and factors such as gender, previous health care experience, sense of teamwork, communication, and self-image are antecedents for a strong sense of professional identity while contentious relationships with colleagues and burnout are detrimental to the professional socialization required to establish role-oriented identity. Professional identity development in new nurses is an understudied phenomenon and insights may inform strategies to recruit and retain nurses. Method: We used a narrative inquiry approach to understand individuals’ experiences. We conducted interviews with five new nurses who had graduated from a school of nursing in Ontario with an average of 20 months of experience. We completed two interviews with each participant with an emphasis on gathering narrative accounts of experiences of becoming and being a nurse. Results: Four themes were identified: (1) Entering into the world of nursing: Nurses reflected upon influential events and individuals at the beginning of their journeys. (2) Journey to become a nurse: Nurses reported an evolution of skills and confidence. (3) Learning alongside others: Nurses noted influential therapeutic relationships with patients and instructors as vital in establishing professional identity. (4) Embodying nursing: Nurses shared challenges in separating professional identity from self-concept and maintaining balance in their lives. Conclusion: Supportive individuals and experiences are essential in inspiring and supporting new graduate transitions, which overall influence the evolution of professional identity of new nurses and, in turn, recruitment, and retention. These findings will be of interest to educational institutions and a variety of practice settings to support successful new graduate transitions and staff retention. Objectif : Cette étude visait à explorer les récits narratifs des réflexions des infirmières et infirmiers nouvellement diplômés sur leur transition vers la pratique et la formation de leur identité professionnelle pour déterminer la façon dont l’expérience de devenir et d’être une infirmière ou un infirmier peut influencer la formation, les politiques et la pratique infirmières par rapport au recrutement et à la fidélisation des infirmières et infirmiers. Contexte : Il y a une pénurie mondiale d’infirmières et infirmiers exacerbée par un plus grand désir de quitter la profession, depuis la pandémie de COVID-19. Une identité plus forte axée sur le rôle commence à se former pendant la transition des étudiantes et étudiants en sciences infirmières vers leur pratique d’infirmières et infirmiers nouvellement diplômés. Un parallèle a été tracé entre cette identité et une plus grande satisfaction professionnelle et la fidélisation. Des caractéristiques et des facteurs personnels, comme le genre, les expériences antérieures des soins de santé, l’esprit d’équipe, la communication et l’image de soi, contribuent à un sentiment d’identité professionnelle fort, tandis que les relations conflictuelles avec des collègues et l’épuisement professionnel nuisent à la socialisation professionnelle nécessaire pour former une identité axée sur le rôle. Le développement d’une identité professionnelle dans la profession infirmière est un phénomène peu étudié, alors que des données pourraient éclairer les stratégies de recrutement et de fidélisation des infirmières et infirmiers. Méthode : Une approche narrative a été utilisée pour comprendre les expériences individuelles. Des entrevues ont été réalisées auprès de 5 infirmières et infirmiers nouvellement diplômés d’une école de sciences infirmières en Ontario ayant en moyenne 20 mois d’expérience. Deux entrevues ont été réalisées avec chaque participante ou participant visant à recueillir des récits sur l’expérience de devenir et d’être une infirmière ou un infirmier. Résultats : Quatre thèmes ont été cernés : (1) L’arrivée dans le milieu des soins infirmiers : les infirmières et infirmiers se sont centrés sur les événements et les personnes qui ont eu une influence au début de leur parcours. (2) Le parcours pour devenir une infirmière ou un infirmier : les infirmières et infirmiers ont fait état d’une évolution d’habiletés et de confiance. (3) L’apprentissage aux côtés des autres : les infirmières et infirmiers ont indiqué que les relations thérapeutiques importantes avec des personnes soignées et des formatrices ou formateurs ont joué un rôle essentiel dans la formation d’une identité professionnelle. (4) L’appropriation de la profession infirmière : les infirmières et infirmiers ont parlé des défis liés à la séparation de l’identité professionnelle du concept de soi et au maintien de l’équilibre dans leur vie. Conclusion : Les personnes qui offrent du soutien et les expériences sont essentielles pour inspirer et soutenir les infirmières et les infirmiers nouvellement diplômés dans leur transition. Elles exercent une influence globale sur l’évolution de leur identité professionnelle, et par le fait même, sur le recrutement et la rétention. Ces constats intéresseront les établissements d’enseignement et les différents milieux de pratique afin de soutenir une transition réussie des infirmières et infirmiers nouvellement diplômés et de favoriser la rétention des recrues.

Adults with chronic pain have a lower quality of life (QOL) compared to the general population. Chronic pain requires specialized treatment to address the multitude of factors that contribute to an individual's pain experience, and effectively managing pain requires a biopsychosocial approach to improve patients' QOL. This study examined adults with chronic pain after a year of specialized treatment to determine the role of cognitive markers (i.e., pain catastrophizing, depression, pain self-efficacy) in predicting changes in QOL. Patients in an interdisciplinary chronic pain clinic (N = 197) completed measures of pain catastrophizing, depression, pain self-efficacy, and QOL at baseline and 1 year later. Correlations and a moderated mediation were completed to understand the relationships between the variables. Higher baseline pain catastrophizing was significantly associated with increased mental QOL (b = 0.39, 95% confidence interval [CI] 0.141; 0.648) and decreased depression (b = −0.18, 95% CI −0.306; −0.052) over a year. Furthermore, the relationship between baseline pain catastrophizing and the change in depression was moderated by the change in pain self-efficacy (b = −0.10, 95% CI −0.145; −0.043) over a year. Patients with high baseline pain catastrophizing reported decreased depression after a year of treatment, which was associated with greater QOL improvements but only in patients with unchanged or improved pain self-efficacy. Our findings highlight the roles of cognitive and affective factors and their impact on QOL in adults with chronic pain. Understanding the psychological factors that predict increased mental QOL is clinically useful, because medical teams can optimize these positive changes in QOL through psychosocial interventions aimed at improving patients' pain self-efficacy.