Canadian midwives' perspectives on the clinical impacts of point of care ultrasound in obstetrical care: A concurrent mixed-methods study.

Introduction: Point of Care Ultrasound (POCUS) is used globally in obstetrics to conduct real time bedside ultrasound scans to answer a clinical question, and it may be conducted by a non-sonography healthcare practitioner. The College of Midwives of Ontario expanded the scope of practice in 2018 to allow registered midwives to perform POCUS during clinical assessments. In response, a POCUS training curriculum for practicing midwives was developed. This paper reports on the perceptions of learners about the impact of this training on their clinical practice. Methods: We conducted a mixed-methods study to understand learner perceptions. Data collection included surveys at four time points over a year, and semi-structured interviews. Quantitative data were analyzed through descriptive statistics, and qualitative analyses used a constructivist approach to grounded theory. Results: The frequency of POCUS use within antenatal care increased among learners, with common applications including assessment of fetal presentation and confirmation of viability. POCUS was seen to holistically aid practitioners care by providing additional skills and knowledge to improve care quality and access to care, particularly for remote areas where ultrasounds are not easily available. However, participants articulated a need for clearer regulatory guidelines outlining how this technology should be applied in midwifery. Equipment purchasing and maintaining costs were a barrier for many midwives. Conclusions: Participants who had access to a device are continuing to use sonography within their clinics to provide comprehensive midwifery care informed by real-time ultrasound assessments. POCUS scans were seen to offer many benefits to improve patient care.

PIGA mutations and glycosylphosphatidylinositol anchor dysregulation in polyposis-associated duodenal tumorigenesis.

The pathogenesis of duodenal tumours in the inherited tumour syndromes Familial Adenomatous Polyposis (FAP) and MUTYH-associated Polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumours and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of PIGA in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyses the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of GPI anchors in duodenal epithelial cells and transcriptional profiling of duodenal adenomas revealed transcriptional signatures associated with loss of PIGA. Implications: PIGA somatic mutation in duodenal tumours from patients with FAP and MAP and loss of membrane GPI-anchors may present new opportunities for understanding and intervention in duodenal tumorigenesis.

Mobile health biometrics to prescribe immediate remote physical activity for enhancing uptake to cardiac rehabilitation (MOTIVATE-CR+): protocol for a randomised controlled feasibility trial.

INTRODUCTION: Cardiac rehabilitation (CR) can reduce cardiovascular mortality and improve health-related quality of life. In the United Kingdom, patient uptake of CR remains low (52%), falling well short of the target in the 2019 National Health Service long-term plan (85%). Mobile health (mHealth) technologies, offering biometric data to patients and healthcare professionals, may bridge the gap between supervised exercise and physical activity advice, enabling patients to engage in regular long-term physically active lifestyles. This randomised controlled trial (RCT) will evaluate the feasibility of mHealth technology when incorporated into a structured home-based walking intervention, in people with recent myocardial infarction. METHODS AND ANALYSIS: This is a feasibility, assessor blinded, parallel group RCT. Participants will be allocated to either CR standard care (control group) or CR standard care+mHealth supported exercise counselling (mHealth intervention group). Feasibility outcomes will include the number of patients approached, screened and eligible; the percentage of patients who decline CR (including reasons for declining), agree to CR and consent to being part of the study; the percentage of patients who enrol in standard CR and reasons for drop out; and the percentage of participants who complete clinical, physical and psychosocial outcomes to identify a suitable primary outcome for a future definitive trial. ETHICS AND DISSEMINATION: The trial was approved in the UK by the Northwest-Greater Manchester East Research Ethics Committee (22/NW/0301) and is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results will be published in peer-reviewed journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBERS: NCT05774587.

Validation of a Tool to Evaluate Nursing Students' Electronic Health Record Competency in Simulation.

AIM: The aim of the study was to establish reliability and validity of the Competency Assessment in Simulation of Electronic Health Records (CASE) tool. BACKGROUND: Effective teaching and learning practices, including valid and reliable assessment of students' electronic health record (EHR) competency, contribute to safe, high-quality, efficient nursing care. METHOD: The study used a mixed-methods design to test reliability and validity of the CASE tool. RESULTS: A nationally representative sample of faculty from universities representing 27 states provided scores for videos using the CASE tool. Forty-seven participants completed the first scoring survey; 22 of the 47 participants (47%) completed the second-round scoring. Intraclass correlation for the final score between the first and second responses shows the consistency of test-retest reliability (ICC = .78, p < .001). CONCLUSION: The CASE tool provided evidence of validity and reliability in evaluating EHR competency in simulation.

Patient and Staff Perspectives on the Impacts and Challenges of Hospital-Based Harm Reduction.

Importance: Harm reduction is associated with improved health outcomes among people who use substances. As overdose deaths persist, hospitals are recognizing the need for harm reduction services; however, little is known about the outcomes of hospital-based harm reduction for patients and staff. Objective: To evaluate patient and staff perspectives on the impact and challenges of a hospital-based harm reduction program offering safer use education and supplies at discharge. Design, Setting, and Participants: This qualitative study consisted of 40-minute semistructured interviews with hospitalized patients receiving harm reduction services and hospital staff at an urban, safety-net hospital in California from October 2022 to March 2023. Purposive sampling allowed inclusion of diverse patient racial and ethnic identities, substance use disorders (SUDs), and staff roles. Exposure: Receipt of harm reduction education and/or supplies (eg, syringes, pipes, naloxone, and test strips) from an addiction consult team, or providing care for patients receiving these services. Main Outcomes and Measures: Interviews were analyzed using thematic analysis to identify key themes. Results: A total of 40 participants completed interviews, including 20 patients (mean [SD] age, 43 [13] years; 1 American Indian or Alaska Native [5%], 1 Asian and Pacific Islander [5%], 6 Black [30%]; 6 Latine [30%]; and 6 White [30%]) and 20 staff (mean [SD] age 37 [8] years). Patients were diagnosed with a variety of SUDs (7 patients with opioid and stimulant use disorder [35%]; 7 patients with stimulant use disorder [35%]; 3 patients with opioid use disorder [15%]; and 3 patients with alcohol use disorder [15%]). A total of 3 themes were identified; respondents reported that harm reduction programs (1) expanded access to harm reduction education and supplies, particularly for ethnically and racially minoritized populations; (2) built trust by improving the patient care experience and increasing engagement; and (3) catalyzed culture change by helping destigmatize care for individuals who planned to continue using substances and increasing staff fulfillment. Black and Latine patients, those who primarily used stimulants, and those with limited English proficiency (LEP) reported learning new harm reduction strategies. Program challenges included hesitancy regarding regulations, limited SUD education among staff, remaining stigma, and the need for careful assessment of patient goals. Conclusions and Relevance: In this qualitative study, patients and staff believed that integrating harm reduction services into hospital care increased access for populations unfamiliar with harm reduction, improved trust, and reduced stigma. These findings suggest that efforts to increase access to harm reduction services for Black, Latine, and LEP populations, including those who use stimulants, are especially needed.

Broadening the Environmental Lens to Include Social and Structural Determinants of Women's Health Disparities.

BACKGROUND: Due to the physical, metabolic, and hormonal changes before, during, and after pregnancy, women-defined here as people assigned female at birth-are particularly susceptible to environmental insults. Racism, a driving force of social determinants of health, exacerbates this susceptibility by affecting exposure to both chemical and nonchemical stressors to create women's health disparities. OBJECTIVES: To better understand and address social and structural determinants of women's health disparities, the National Institute of Environmental Health Sciences (NIEHS) hosted a workshop focused on the environmental impacts on women's health disparities and reproductive health in April 2022. This commentary summarizes foundational research and unique insights shared by workshop participants, who emphasized the need to broaden the definition of the environment to include upstream social and structural determinants of health. We also summarize current challenges and recommendations, as discussed by workshop participants, to address women's environmental and reproductive health disparities. DISCUSSION: The challenges related to women's health equity, as identified by workshop attendees, included developing research approaches to better capture the social and structural environment in both human and animal studies, integrating environmental health principles into clinical care, and implementing more inclusive publishing and funding approaches. Workshop participants discussed recommendations in each of these areas that encourage interdisciplinary collaboration among researchers, clinicians, funders, publishers, and community members. https://doi.org/10.1289/EHP12996.

Action does not drive visual biases in peri-tool space.

Observers experience visual biases in the area around handheld tools. These biases may occur when active use leads an observer to incorporate a tool into the body schema. However, the visual salience of a handheld tool may instead create an attentional prioritization that is not reliant on body-based representations. We investigated these competing explanations of near-tool visual biases in two experiments during which participants performed a target detection task. Targets could appear near or far from a tool positioned next to a display. In Experiment 1, participants showed facilitation in detecting targets that appeared near a simple handheld rake tool regardless of whether they first used the rake to retrieve objects, but participants who only viewed the tool without holding it were no faster to detect targets appearing near the rake than targets that appeared on the opposite side of the display. In a second experiment, participants who held a novel magnetic tool again showed a near-tool bias even when they refrained from using the tool. Taken together, these results suggest active use is unnecessary, but visual salience is not sufficient, to introduce visual biases in peri-tool space.

Characteristics and effectiveness of mentoring programmes for specialized and advanced practice nurses: A systematic review.

AIMS: (1) To identify, evaluate and summarize evidence about the objectives and characteristics of mentoring programmes for specialized nurses (SNs) or nurse navigators (NNs) and advanced practice nurses (APNs) and (2) to identify the effectiveness of these programmes. DESIGN: A systematic review based on PRISMA guidelines. DATA SOURCES: From November 2022 until 7 December 2022, four databases were searched: PubMed, EMBASE, CINAHL and The Cochrane Library. REVIEW METHODS: Study selection was performed independently by two researchers. Disagreements were discussed until consensus was reached. Data extraction was undertaken for included studies. Data synthesis was conducted using narrative analysis. Quality appraisal was performed using the Critical Appraisal Skill Programme (CASP) and Mixed Methods Appraisal Tool (MMAT). RESULTS: Twelve articles were included, all of which focused on mentoring programmes for APNs. Different forms of mentorship (e.g. (in)formal mentorship, work shadowing, workshops) were reported. Studies reported positive outcomes on job retention (n = 5), job satisfaction (n = 6), skills improvement (n = 7), satisfaction with the programme (n = 7) and confidence improvement (n = 4) among participants of mentoring programmes. CONCLUSION: There is a lack of uniformity and consistency in various elements of mentoring programmes. Further research is needed to develop mentoring programmes for both APNs and SNs/NNs in a systematic and theoretically underpinned manner. It is necessary to establish a thorough evaluation methodology, preferably using a mixed methods design that includes both a qualitative process evaluation and a comprehensive outcome evaluation using validated questionnaires, taking into account the NN/APN, the interprofessional team and organizational level. IMPACT: The synthesis of evidence may be useful to organizations developing and implementing mentoring programmes for both SN/NN and APN. The development of a mentoring programme for nursing experts should be considered a complex intervention that requires theoretical frameworks and contextual considerations. NO PATIENT OR PUBLIC CONTRIBUTION: Not applicable, as no patients or public were involved.

The PIG-A gene mutation assay in human biomonitoring and disease.

The blood cell phosphatidylinositol glycan class A (PIG-A) gene mutation assay has been extensively researched in rodents for in vivo mutagenicity testing and is now being investigated in humans. The PIG-A gene is involved in glycosyl phosphatidylinositol (GPI)-anchor biosynthesis. A single mutation in this X-linked gene can lead to loss of membrane-bound GPI anchors, which can be enumerated via corresponding GPI-anchored proteins (e.g., CD55) using flow cytometry. The studies published to date by different research groups demonstrate a remarkable consistency in PIG-A mutant frequencies. Moreover, with the low background level of mutant erythrocytes in healthy subjects (2.9-5.56 × 10-6 mutants), induction of mutation post genotoxic exposure can be detected. Cigarette smoking, radiotherapy, and occupational exposures, including lead, have been shown to increase mutant levels. Future applications of this test include identifying new harmful agents and establishing new exposure limits. This mutational monitoring approach may also identify individuals at higher risk of cancer development. In addition, identifying protective agents that could mitigate these effects may reduce baseline somatic mutation levels and such behaviors can be encouraged. Further technological progress is required including establishing underlying mechanisms of GPI anchor loss, protocol standardization, and the development of cryopreservation methods to improve GPI-anchor stability over time. If successful, this assay has the potential be widely employed, for example, in rural and low-income countries. Here, we review the current literature on PIG-A mutation in humans and discuss the potential role of this assay in human biomonitoring and disease detection.

Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement.

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.

Putting the "learning" in "pre-learning": effects of a self-directed study hall on skill acquisition in a simulation-based central line insertion course.

BACKGROUND: Opportunities to practice procedural skills in the clinical learning environment are decreasing, and faculty time to coach skills is limited, even in simulation-based training. Self-directed learning with hands-on practice early in a procedural skill course might help maximize the benefit of later faculty coaching and clinical experience. However, it may also lead to well-learned errors if learners lack critical guidance. The present study sought to investigate the effects of a hands-on, self-directed "study hall" for central line insertion among first-year residents. METHODS: Learner cohorts before vs. after introduction of the study hall (n = 49) were compared on their pre- and post-test performance of key procedural behaviors that were comparable across cohorts, with all learners receiving traditional instructor-led training between tests. RESULTS: Study hall participants spent a median of 116 min in hands-on practice (range 57-175). They scored higher at pre-test (44% vs. 27%, p = .00; Cohen's d = 0.95) and at post-test (80% vs. 72%, p = .02; Cohen's d = 0.69). A dose-response relationship was found, such that 2 h of study hall were roughly equivalent to the performance improvement seen with four clinical observations or supervised insertions of central lines. CONCLUSIONS: Self-directed, hands-on "study hall" supported improved procedural skill learning in the context of limited faculty availability. Potential additional benefits make the approach worth further experimentation and evaluation.

An Automatically Adaptive Digital Health Intervention to Decrease Opioid-Related Risk While Conserving Counselor Time: Quantitative Analysis of Treatment Decisions Based on Artificial Intelligence and Patient-Reported Risk Measures.

BACKGROUND: Some patients prescribed opioid analgesic (OA) medications for pain experience serious side effects, including dependence, sedation, and overdose. As most patients are at low risk for OA-related harms, risk reduction interventions requiring multiple counseling sessions are impractical on a large scale. OBJECTIVE: This study evaluates whether an intervention based on reinforcement learning (RL), a field of artificial intelligence, learned through experience to personalize interactions with patients with pain discharged from the emergency department (ED) and decreased self-reported OA misuse behaviors while conserving counselors' time. METHODS: We used data representing 2439 weekly interactions between a digital health intervention ("Prescription Opioid Wellness and Engagement Research in the ED" [PowerED]) and 228 patients with pain discharged from 2 EDs who reported recent opioid misuse. During each patient's 12 weeks of intervention, PowerED used RL to select from 3 treatment options: a brief motivational message delivered via an interactive voice response (IVR) call, a longer motivational IVR call, or a live call from a counselor. The algorithm selected session types for each patient each week, with the goal of minimizing OA risk, defined in terms of a dynamic score reflecting patient reports during IVR monitoring calls. When a live counseling call was predicted to have a similar impact on future risk as an IVR message, the algorithm favored IVR to conserve counselor time. We used logit models to estimate changes in the relative frequency of each session type as PowerED gained experience. Poisson regression was used to examine the changes in self-reported OA risk scores over calendar time, controlling for the ordinal session number (1st to 12th). RESULTS: Participants on average were 40 (SD 12.7) years of age; 66.7% (152/228) were women and 51.3% (117/228) were unemployed. Most participants (175/228, 76.8%) reported chronic pain, and 46.2% (104/225) had moderate to severe depressive symptoms. As PowerED gained experience through interactions over a period of 142 weeks, it delivered fewer live counseling sessions than brief IVR sessions (P=.006) and extended IVR sessions (P<.001). Live counseling sessions were selected 33.5% of the time in the first 5 weeks of interactions (95% CI 27.4%-39.7%) but only for 16.4% of sessions (95% CI 12.7%-20%) after 125 weeks. Controlling for each patient's changes during the course of treatment, this adaptation of treatment-type allocation led to progressively greater improvements in self-reported OA risk scores (P<.001) over calendar time, as measured by the number of weeks since enrollment began. Improvement in risk behaviors over time was especially pronounced among patients with the highest risk at baseline (P=.02). CONCLUSIONS: The RL-supported program learned which treatment modalities worked best to improve self-reported OA risk behaviors while conserving counselors' time. RL-supported interventions represent a scalable solution for patients with pain receiving OA prescriptions. TRIAL REGISTRATION: Clinicaltrials.gov NCT02990377; https://classic.clinicaltrials.gov/ct2/show/NCT02990377.

Mechanisms of nuclear pore complex disassembly by the mitotic Polo-like kinase 1 (PLK-1) in C. elegans embryos.

The nuclear envelope, which protects and organizes the genome, is dismantled during mitosis. In the Caenorhabditis elegans zygote, nuclear envelope breakdown (NEBD) of the parental pronuclei is spatially and temporally regulated during mitosis to promote the unification of the maternal and paternal genomes. Nuclear pore complex (NPC) disassembly is a decisive step of NEBD, essential for nuclear permeabilization. By combining live imaging, biochemistry, and phosphoproteomics, we show that NPC disassembly is a stepwise process that involves Polo-like kinase 1 (PLK-1)-dependent and -independent steps. PLK-1 targets multiple NPC subcomplexes, including the cytoplasmic filaments, central channel, and inner ring. PLK-1 is recruited to and phosphorylates intrinsically disordered regions (IDRs) of several multivalent linker nucleoporins. Notably, although the phosphosites are not conserved between human and C. elegans nucleoporins, they are located in IDRs in both species. Our results suggest that targeting IDRs of multivalent linker nucleoporins is an evolutionarily conserved driver of NPC disassembly during mitosis.

Insights from Drug Checking Programs: Practicing Bootstrap Public Health Whilst Tailoring to Local Drug User Needs.

The year 2021 was the most deadly year for overdose deaths in the USA and Canada. The stress and social isolation stemming from the COVID-19 pandemic coupled with a flood of fentanyl into local drug markets created conditions in which people who use drugs were more susceptible to accidental overdose. Within territorial, state, and local policy communities, there have been longstanding efforts to reduce morbidity and mortality within this population; however, the current overdose crisis clearly indicates an urgent need for additional, easily accessible, and innovative services. Street-based drug testing programs allow individuals to learn the composition of their substances prior to use, averting unintended overdoses while also creating low threshold opportunities for individuals to connect to other harm reduction services, including substance use treatment programs. We sought to capture perspectives from service providers to document best practices around fielding community-based drug testing programs, including optimizing their position within a constellation of other harm reduction services to best serve local communities. We conducted 11 in-depth interviews from June to November 2022 via Zoom with harm reduction service providers to explore barriers and facilitators around the implementation of drug checking programs, the potential for integration with other health promotion services, and best practices for sustaining these programs, taking the local community and policy landscape into account. Interviews lasted 45-60 min and were recorded and transcribed. Thematic analysis was used to reduce the data, and transcripts were discussed by a team of trained analysts. Several key themes emerged from our interviews: (1) the instability of drug markets amid an inconsistent and dangerous drug supply; (2) implementing drug checking services in dynamic environments in response to the rapidly changing needs of local communities; (3) training and ongoing capacity building needed to create sustainable programs; and (4) the potential for integrating drug checking programs into other services. There are opportunities for this service to make a difference in overdose deaths as the contours of the drug market itself have changed over time, but a number of challenges remain to implement them effectively and sustain the service over time. Drug checking itself represents a paradox within the larger policy context, putting the sustainability of these programs at risk and challenging the potential to scale these programs as the overdose epidemic worsens.

Integrated therapist and online CBT for depression in primary care (INTERACT): study protocol for a multi-centre randomised controlled trial.

BACKGROUND: Cognitive behavioural therapy (CBT) is an effective treatment for depression. Self-directed online CBT interventions have made CBT more accessible at a lower cost. However, adherence is often poor and, in the absence of therapist support, effects are modest and short-term. Delivering CBT online using instant messaging is clinically and cost-effective; however, most existing platforms are limited to instant messaging sessions, without the support of between-session "homework" activities. The INTERACT intervention integrates online CBT materials and 'high-intensity' therapist-led CBT, delivered remotely in real-time. The INTERACT trial will evaluate this novel integration in terms of clinical and cost-effectiveness, and acceptability to therapists and clients. METHODS: Pragmatic, two parallel-group multi-centre individually randomised controlled trial, with 434 patients recruited from primary care practices in Bristol, London and York. Participants with depression will be identified via General Practitioner record searches and direct referrals. INCLUSION CRITERIA: aged ≥ 18 years; score ≥ 14 on Beck Depression Inventory (BDI-II); meeting International Classification of Diseases (ICD-10) criteria for depression. EXCLUSION CRITERIA: alcohol or substance dependency in the past year; bipolar disorder; schizophrenia; psychosis; dementia; currently under psychiatric care for depression (including those referred but not yet seen); cannot complete questionnaires unaided or requires an interpreter; currently receiving CBT/other psychotherapy; received high-intensity CBT in the past four years; participating in another intervention trial; unwilling/unable to receive CBT via computer/laptop/smartphone. Eligible participants will be randomised to integrated CBT or usual care. Integrated CBT utilises the standard Beckian intervention for depression and comprises nine live therapist-led sessions, with (up to) a further three if clinically appropriate. The first session is 60-90 min via videocall, with subsequent 50-min sessions delivered online, using instant messaging. Participants allocated integrated CBT can access integrated online CBT resources (worksheets/information sheets/videos) within and between sessions. Outcome assessments at 3-, 6-, 9- and 12-month post-randomisation. The primary outcome is the Beck Depression Inventory (BDI-II) score at 6 months (as a continuous variable). A nested qualitative study and health economic evaluation will be conducted. DISCUSSION: If clinically and cost-effective, this model of integrated CBT could be introduced into existing psychological services, increasing access to, and equity of, CBT provision. TRIAL REGISTRATION: ISRCTN, ISRCTN13112900. Registered on 11/11/2020. Currently recruiting participants. Trial registration data are presented in Table 1.

Nucleoporin foci are stress-sensitive condensates dispensable for C. elegans nuclear pore assembly.

Nucleoporins (Nups) assemble nuclear pores that form the permeability barrier between nucleoplasm and cytoplasm. Nucleoporins also localize in cytoplasmic foci proposed to function as pore pre-assembly intermediates. Here, we characterize the composition and incidence of cytoplasmic Nup foci in an intact animal, C. elegans. We find that, in young non-stressed animals, Nup foci only appear in developing sperm, oocytes and embryos, tissues that express high levels of nucleoporins. The foci are condensates of highly cohesive FG repeat-containing nucleoporins (FG-Nups), which are maintained near their solubility limit in the cytoplasm by posttranslational modifications and chaperone activity. Only a minor fraction of FG-Nup molecules concentrate in Nup foci, which dissolve during M phase and are dispensable for nuclear pore assembly. Nucleoporin condensation is enhanced by stress and advancing age, and overexpression of a single FG-Nup in post-mitotic neurons is sufficient to induce ectopic condensation and organismal paralysis. We speculate that Nup foci are non-essential and potentially toxic condensates whose assembly is actively suppressed in healthy cells.

Smoke and mirrors? Conflict of interest declarations in tobacco and e-cigarette-related academic publications.

OBJECTIVE: This research explored international tobacco control experts' level of satisfaction with conflict of interest (COI) declaration processes; and the transparency of COI declarations of identified authors publishing in the tobacco, e-cigarette, and related novel products academic literature. METHODS: This case study profiled 10 authors' (identified by expert panel) COIs pertaining to the tobacco industry; identified the 10 authors' publications (2010-2021); and assessed the transparency of the COI declarations within the publications. RESULTS: All authors received indirect or direct funding from the tobacco industry. On review of the authors' 553 publications, 61% of COI and funding declarations were accessible, 33% were partially accessible and 6% were inaccessible. Overall, 33% of authors provided complete COI declarations, 51% provided incomplete declarations, and 16% provided no declaration. CONCLUSION: This research demonstrates existing guidelines and recommendations for reporting COI declarations are not sufficiently robust to ensure transparency in reporting of COI declarations within the field. IMPLICATIONS FOR PUBLIC HEALTH: Research outcomes have the potential to define public health discourse and influence public opinion, practices, and policy. It is critical that research remains independent and protected from the influence of the tobacco industry. Processes for monitoring and enforcing accurate reporting of COI declarations are needed.

RNA granules: functional compartments or incidental condensates?

RNA granules are mesoscale assemblies that form in the absence of limiting membranes. RNA granules contain factors for RNA biogenesis and turnover and are often assumed to represent specialized compartments for RNA biochemistry. Recent evidence suggests that RNA granules assemble by phase separation of subsoluble ribonucleoprotein (RNP) complexes that partially demix from the cytoplasm or nucleoplasm. We explore the possibility that some RNA granules are nonessential condensation by-products that arise when RNP complexes exceed their solubility limit as a consequence of cellular activity, stress, or aging. We describe the use of evolutionary and mutational analyses and single-molecule techniques to distinguish functional RNA granules from "incidental condensates."

Mechanisms of Nuclear Pore Complex disassembly by the mitotic Polo-Like Kinase 1 (PLK-1) in C. elegans embryos.

The nuclear envelope, which protects and organizes the interphase genome, is dismantled during mitosis. In the C. elegans zygote, nuclear envelope breakdown (NEBD) of the parental pronuclei is spatially and temporally regulated during mitosis to promote the unification of the parental genomes. During NEBD, Nuclear Pore Complex (NPC) disassembly is critical for rupturing the nuclear permeability barrier and removing the NPCs from the membranes near the centrosomes and between the juxtaposed pronuclei. By combining live imaging, biochemistry, and phosphoproteomics, we characterized NPC disassembly and unveiled the exact role of the mitotic kinase PLK-1 in this process. We show that PLK-1 disassembles the NPC by targeting multiple NPC sub-complexes, including the cytoplasmic filaments, the central channel, and the inner ring. Notably, PLK-1 is recruited to and phosphorylates intrinsically disordered regions of several multivalent linker nucleoporins, a mechanism that appears to be an evolutionarily conserved driver of NPC disassembly during mitosis. (149/150 words). One-Sentence Summary: PLK-1 targets intrinsically disordered regions of multiple multivalent nucleoporins to dismantle the nuclear pore complexes in the C. elegans zygote.

Germ granules in development.

A hallmark of all germ cells is the presence of germ granules: assemblies of proteins and RNA that lack a delineating membrane and are proposed to form via condensation. Germ granules across organisms share several conserved components, including factors required for germ cell fate determination and maintenance, and are thought to be linked to germ cell development. The molecular functions of germ granules, however, remain incompletely understood. In this Development at a Glance article, we survey germ granules across organisms and developmental stages, and highlight emerging themes regarding granule regulation, dynamics and proposed functions.