The underestimated fraction: diversity, challenges and novel insights into unicellular cyanobionts of lichens.

Lichens are remarkable and classic examples of symbiotic organisms that have fascinated scientists for centuries. Yet, it has only been for a couple of decades that significant advances have focused on the diversity of their green algal and/or cyanobacterial photobionts. Cyanolichens, which contain cyanobacteria as their photosynthetic partner, include up to 10% of all known lichens and, as such, studies on their cyanobionts are much rarer compared to their green algal counterparts. For the unicellular cyanobionts, i.e. cyanobacteria that do not form filaments, these studies are even scarcer. Nonetheless, these currently include at least 10 different genera in the cosmopolitan lichen order Lichinales. An international consortium (International Network of CyanoBionts; INCb) will tackle this lack of knowledge. In this article, we discuss the status of current unicellular cyanobiont research, compare the taxonomic resolution of photobionts from cyanolichens with those of green algal lichens (chlorolichens), and give a roadmap of research on how to recondition the underestimated fraction of symbiotic unicellular cyanobacteria in lichens.

Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells.

Targeted therapy remains the future of anti-cancer drug development, owing to the lack of specificity of current treatments which lead to damage in healthy normal tissues. ATR inhibitors have in recent times demonstrated promising clinical potential, and are currently being evaluated in the clinic. However, despite the considerable optimism for clinical success of these inhibitors, reports of associated normal tissues toxicities remain a concern and can compromise their utility. Here, ICT10336 is reported, a newly developed hypoxia-responsive prodrug of ATR inhibitor, AZD6738, which is hypoxia-activated and specifically releases AZD6738 only in hypoxic conditions, in vitro. This hypoxia-selective release of AZD6738 inhibited ATR activation (T1989 and S428 phosphorylation) and subsequently abrogated HIF1a-mediated adaptation of hypoxic cancers cells, thus selectively inducing cell death in 2D and 3D cancer models. Importantly, in normal tissues, ICT10336 is demonstrated to be metabolically stable and less toxic to normal cells than its active parent agent, AZD6738. In addition, ICT10336 exhibited a superior and efficient multicellular penetration ability in 3D tumor models, and selectively eradicated cells at the hypoxic core compared to AZD6738. In summary, the preclinical data demonstrate a new strategy of tumor-targeted delivery of ATR inhibitors with significant potential of enhancing the therapeutic index.

Predictors of Aneurysm Obliteration in Patients Treated with the WEB Device: Results of a Multicenter Retrospective Study.

BACKGROUND AND PURPOSE: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment. MATERIALS AND METHODS: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up. RESULTS: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis was observed in 485/537 (90.3%) of nonoccluded aneurysms. At the final follow-up, complete occlusion was achieved in 497/763 (65.1%) patients, and retreatment was required for 56/763 (7.3%) patients. On multivariable analysis, history of smoking, maximal aneurysm diameter, and the presence of an aneurysm wall branch were negative predictors of complete occlusion (OR, 0.5, 0.8, and 0.4, respectively). Maximal aneurysm diameter, the presence of an aneurysm wall branch, posterior circulation location, and male sex increase the chances of retreatment (OR, 1.2, 3.8, 3.0, and 2.3 respectively). Intraprocedural occlusion resulted in a 3-fold increase in the long-term occlusion rate and a 5-fold decrease in the retreatment rate (P < .001), offering a specificity of 87% and a positive predictive value of 85% for long-term occlusion. CONCLUSIONS: Intraprocedural occlusion can be used to predict the chance of long-term aneurysm occlusion and the need for retreatment after embolization with a WEB device. Smoking, aneurysm size, and the presence of an aneurysm wall branch are associated with decreased chances of successful treatment.

Dissecting the components of error in analogue report tasks : Error in analogue report tasks.

Over the last two decades, the analogue report task has become a standard method for measuring the fidelity of visual representations across research domains including perception, attention, and memory. Despite its widespread use, there has been no methodical investigation of the different task parameters that might contribute to response variability. To address this gap, we conducted two experiments manipulating components of a typical analogue report test of memory for colour hue. We found that human response errors were independently affected by changes in storage and maintenance requirements of the task, demonstrated by a strong effect of set size even in the absence of a memory delay. In contrast, response variability remained unaffected by physical size of the colour wheel, implying negligible contribution of motor noise to task performance, or by its chroma radius, highlighting non-uniformity of the standard colour space. Comparing analogue report to a matched forced-choice task, we found variation in adjustment criterion made a limited contribution to analogue report variability, becoming meaningful only with low representational noise. Our findings validate the analogue report task as a robust measure of representational fidelity for most purposes, while also quantifying non-representational sources of noise that would limit its reliability in specialized settings.

Demonstrating the use of population level data to investigate trends in the rate, radiation dose and cost of Computed Tomography across clinical groups: Are there any areas of concern?

INTRODUCTION: Increases in computed tomography (CT) use may not always reflect clinical need or improve outcomes. This study aimed to demonstrate how population level data can be used to identify variations in care between patient groups, by analysing system-level changes in CT use around the diagnosis of new conditions. METHODS: Retrospective repeated cross-sectional observational study using West Australian linked administrative records, including 504,723 adults diagnosed with different conditions in 2006, 2012 and 2015. For 90 days pre/post diagnosis, CT use (any and 2+ scans), effective dose (mSv), lifetime attributable risk (LAR) of cancer incidence and mortality from CT, and costs were assessed. RESULTS: CT use increased from 209.4 per 1000 new diagnoses in 2006 to 258.0 in 2015; increases were observed for all conditions except neoplasms. Healthcare system costs increased for all conditions but neoplasms and mental disorders. Effective dose increased substantially for respiratory (+2.5 mSv, +23.1%, P < 0.001) and circulatory conditions (+2.1 mSv, +15.4%, P < 0.001). The LAR of cancer incidence and mortality from CT increased for endocrine (incidence +23.4%, mortality +18.0%) and respiratory disorders (+21.7%, +23.3%). Mortality LAR increased for circulatory (+12.1%) and nervous system (+11.0%) disorders. The LAR of cancer incidence and mortality reduced for musculoskeletal system disorders, despite an increase in repeated CT in this group. CONCLUSIONS: Use and costs increased for most conditions except neoplasms and mental and behavioural disorders. More strategic CT use may have occurred in musculoskeletal conditions, while use and radiation burden increased for respiratory, circulatory and nervous system conditions. Using this high-level approach we flag areas requiring deeper investigation into appropriateness and value of care.

Same-visit hepatitis C testing and treatment to accelerate cure among people who inject drugs (the QuickStart Study): a cluster randomised cross-over trial protocol.

INTRODUCTION: Despite universal access to government-funded direct-acting antivirals (DAAs) in 2016, the rate of hepatitis C treatment uptake in Australia has declined substantially. Most hepatitis C is related to injecting drug use; reducing the hepatitis C burden among people who inject drugs (PWID) is, therefore, paramount to reach hepatitis C elimination targets. Increasing DAA uptake by PWID is important for interrupting transmission and reducing incidence, as well as reducing morbidity and mortality and improving quality of life of PWID and meeting Australia's hepatitis C elimination targets. METHODS AND ANALYSIS: A cluster randomised cross-over trial will be conducted with three intervention arms and a control arm. Arm A will receive rapid hepatitis C virus (HCV) antibody testing; arm B will receive rapid HCV antibody and rapid RNA testing; arm C will receive rapid HCV antibody testing and same-day treatment initiation for HCV antibody-positive participants; the control arm will receive standard of care. The primary outcomes will be (a) the proportion of participants with HCV commencing treatment and (b) the proportion of participants with HCV achieving cure. Analyses will be conducted on an intention-to-treat basis with mixed-effects logistic regression models. ETHICS AND DISSEMINATION: The study has been approved by the Alfred Ethics Committee (number HREC/64731/Alfred-2020-217547). Each participant will provide written informed consent. Reportable adverse events will be reported to the reviewing ethics committee. The findings will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05016609. TRIAL PROGRESSION: The study commenced recruitment on 9 March 2022 and is expected to complete recruitment in December 2024.

Improving health system responses when patients are harmed: a protocol for a multistage mixed-methods study.

INTRODUCTION: At least 10% of hospital admissions in high-income countries, including Australia, are associated with patient safety incidents, which contribute to patient harm ('adverse events'). When a patient is seriously harmed, an investigation or review is undertaken to reduce the risk of further incidents occurring. Despite 20 years of investigations into adverse events in healthcare, few evaluations provide evidence of their quality and effectiveness in reducing preventable harm.This study aims to develop consistent, informed and robust best practice guidance, at state and national levels, that will improve the response, learning and health system improvements arising from adverse events. METHODS AND ANALYSIS: The setting will be healthcare organisations in Australian public health systems in the states of New South Wales, Queensland, Victoria and the Australian Capital Territory. We will apply a multistage mixed-methods research design with evaluation and in-situ feasibility testing. This will include literature reviews (stage 1), an assessment of the quality of 300 adverse event investigation reports from participating hospitals (stage 2), and a policy/procedure document review from participating hospitals (stage 3) as well as focus groups and interviews on perspectives and experiences of investigations with healthcare staff and consumers (stage 4). After triangulating results from stages 1-4, we will then codesign tools and guidance for the conduct of investigations with staff and consumers (stage 5) and conduct feasibility testing on the guidance (stage 6). Participants will include healthcare safety systems policymakers and staff (n=120-255) who commission, undertake or review investigations and consumers (n=20-32) who have been impacted by adverse events. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Northern Sydney Local Health District Human Research Ethics Committee (2023/ETH02007 and 2023/ETH02341).The research findings will be incorporated into best practice guidance, published in international and national journals and disseminated through conferences.

Standardized reporting for Head CT Scans in patients suspected of traumatic brain injury (TBI): An international expert endeavor.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) is a major source of health loss and disability worldwide. Accurate and timely diagnosis of TBI is critical for appropriate treatment and management of the condition. Neuroimaging plays a crucial role in the diagnosis and characterization of TBI. Computed tomography (CT) is the first-line diagnostic imaging modality typically utilized in patients with suspected acute mild, moderate and severe TBI. Radiology reports play a crucial role in the diagnostic process, providing critical information about the location and extent of brain injury, as well as factors that could prevent secondary injury. However, the complexity and variability of radiology reports can make it challenging for healthcare providers to extract the necessary information for diagnosis and treatment planning. METHODS/RESULTS/CONCLUSION: In this article, we report the efforts of an international group of TBI imaging experts to develop a clinical radiology report template for CT scans obtained in patients suspected of TBI and consisting of fourteen different subdivisions (CT technique, mechanism of injury or clinical history, presence of scalp injuries, fractures, potential vascular injuries, potential injuries involving the extra-axial spaces, brain parenchymal injuries, potential injuries involving the cerebrospinal fluid spaces and the ventricular system, mass effect, secondary injuries, prior or coexisting pathology).

One- and 2-year outcomes of lumbar facet arthroplasty versus spinal fusion in young (<65 years) and old (≥65 years) patients for the treatment of degenerative spondylolisthesis and stenosis.

Background: Facet arthroplasty, an alternative to lumbar fusion, offers stabilization and preserves range of motion. This subanalysis of the TOPS IDE trial (FDA #G160168) compared facet arthroplasty, using the TOPS device, with a standard single-level transforaminal lumbar interbody fusion (TLIF) in patients stratified by age (<65 and ≥65 years) with symptomatic grade 1 degenerative spondylolisthesis with moderate to severe spinal stenosis at L2-5. Methods: Patient-reported outcomes (PROMS), including Oswestry disability index (ODI), visual analog pain scales (VAS), and Zurich claudication questionnaires (ZCQ), were assessed at baseline and multiple postoperative timepoints. Radiographic evaluation of flexion/extension range of motion (ROM) occurred at baseline, 12 months, and 24 months. Data were analyzed following an intention-to-treat model. Significance was defined as p<.05. Results: About 299 patients were included (TOPS=206, TLIF=93). The groups were similar at baseline. At 2 years, the TOPS group had a greater proportion of patients report ≥15-point improvement for ODI (93.8% versus 77.1%, p=.011) and ≥20-point improvement for VAS back (84.4% versus 61.8%, p=.014). At 1 year, TOPS group had a greater proportion of patients report clinically significant improvements in all ZCQ categories (91.6% versus 78.5%, p=.012). In patients <65 years, the TOPS group had improved PROMS compared to TLIF at 2 years; however, these differences were less pronounced in patients ≥65 years old. The TOPS groups preserved more ROM at 12 (2.8° 95%CI [1.87; 3.74], p<.0001) and 24 (2.99° 95%CI [1.82; 4.15], p<.0001) months compared to TLIF. ROM was similarly preserved in patients aged <65 and ≥65. The rate of adverse events did not differ significantly between treatment groups. Conclusions: Facet arthroplasty preserves more ROM in all ages and leads to improved PROMS compared to TLIF, particularly in younger patients.

Methodological quality of umbrella reviews in endodontics: A cross-sectional study.

INTRODUCTION: In endodontics, the number of umbrella reviews has increased significantly over the last few years, but there is no evidence that they were methodologically sound. The aim of the current study was to appraise the methodological quality of umbrella reviews in endodontics, and to identify possible predictive factors associated with methodological quality. METHODS: Umbrella reviews published in the discipline of endodontics until December 2023 were included. The methodological quality of the reviews was evaluated using a checklist consisting of 11 items. Each item in the checklist was evaluated by two independent assessors who assigned a score of '1' if it was fully addressed, '0.5' if it was partially ddressed, and '0' if it was not addressed. Bootstrapped multiple linear regression analysis was used to examine the association between the total scores awarded and five predictor variables (a priori protocol registration, year of publication, number of authors, journal impact factor (IF) and continent of the corresponding author). The statistical significance level was set as 5%. RESULTS: A total of 27 reviews were included. Ninety-six per cent of the reviews adequately reported: eligibility criteria for selecting the reviews, details of the reviews, techniques for assessing the risk of bias or methodological quality of the individual systematic reviews they included. Only 30% of the reviews adequately managed overlapping primary studies within individual systematic reviews. Among the five predictors analysed, a priori protocol registration and journals with IFs were associated with significantly greater total methodological quality scores. DISCUSSION: Several methodological shortcomings in the umbrella reviews published within the field of endodontics were revealed. Umbrella reviews published in journals with IFs and those with protocols registered a priori had significantly superior methodological quality scores. CONCLUSION: In endodontics, authors intending to publish umbrella reviews should consider the limitations revealed in this study and follow the appropriate rules to ensure their reviews comply with the highest standards and provide accurate and dependable information and conclusions.

Skeletal muscle composition, power, and mitochondrial energetics in older men and women with knee osteoarthritis.

OBJECTIVE: To investigate the overall and sex-specific relationship between presence and severity of knee osteoarthritis (KOA) with muscle composition, power, and energetics in older adults. METHODS: Males and females (n=655, 76.1±4.9yrs; 57% females) enrolled in the Study of Muscle, Mobility and Aging (SOMMA) completed standing knee radiographs and knee pain assessments. Participants were divided into three groups by Kellgren-Lawrence grade (KLG) of KOA severity (0-1; 2, or 3-4). Outcome measures included whole-body muscle mass, thigh fat free muscle (FFM) volume and muscle fat infiltration (MFI), leg power, specific power (power normalized to muscle volume), and muscle mitochondrial energetics. RESULTS: Overall, presence and severity of KOA is associated with greater MFI, lower leg power and specific power, and reduced oxidative phosphorylation (p trend<0.036). Sex-specific analysis revealed reduced energetics only in females with KOA (p trend<0.007) compared to females with no KOA. In models adjusted for age, sex, race, NSAIDS use, site/technician, physical activity, height, and abdominal adiposity participants with KLG 3-4 had greater MFI (0.008% (0.004, 0.011) and lower leg power (-51.56W (-74.03, -29.10)) and specific power (-5.38W/L (-7.31, -3.45)) than KLG 0-1. No interactions were found between pain and KLG status. Among those with KOA, MFI and oxidative phosphorylation were associated with thigh FFM volume, leg power and specific power. CONCLUSION: Muscle health is associated with presence and severity of KOA and differs by sex. While muscle composition and power are lower in both males and females with KOA, regardless of pain status, mitochondrial energetics is reduced only in females.

The effect of information integration on team communication in a simulated submarine control room task.

Submarine control rooms are characterised by dedicated individual roles for information types (e.g. Sonar operator processes sound energy), with individuals verbally reporting the information that they receive to other team members to help resolve uncertainty in the operational environment (low information integration). We compared this work design with one that ensured critical information was more readily available to all team members (high information integration). We used the Event Analysis of Systemic Teamwork (EAST) method to analyse task, information, and social networks for novice teams operating within a simulated submarine control room under low versus high information integration. Integration impacted team member centrality (importance relative to other operators) and the nature of information shared. Team members with greater centrality reported higher workload. Higher integration across consoles altered how team members interacted and their relative status, the information shared, and how workload was distributed. However, overall network structures remained intact.

Wider integration (distribution) of information within teams in a simulated submarine control room altered the content of the information shared between team members and the centrality and workload of team members. Practitioners must consider how to integrate information in sociotechnical systems such that information traditionally held by specialist positions can be distributed within teams to benefit team performance and other outcomes.

The Chartered Institute of Ergonomics and Human Factors at 75: perspectives on contemporary challenges and future directions for Ergonomics and Human Factors.

As the UK's Chartered Institute of Ergonomics and Human Factors (CIEHF) celebrates its 75th anniversary, it is worth reflecting on our discipline's contribution, current state, and critical future endeavours. We present the perspectives of 18 EHF professionals who were asked to respond to five questions regarding the impact of EHF, contemporary challenges, and future directions. Co-authors were in agreement that EHF's impact has been only limited to date and that critical issues require resolution, such as increasing the number of suitably qualified practitioners, resolving the research-practice gap, and increasing awareness of EHF and its benefits. Frequently discussed future directions include advanced emerging technologies such as artificial intelligence, the development of new EHF methods, and enhancing the quality and reach of education and training. The majority felt there will be a need for EHF in 75 years; however, many noted that our methods will need to adapt to meet new needs.Practitioner statement: This article provides the perspectives of 18 Ergonomics and Human Factors (EHF) professionals on the impact of EHF, contemporary challenges and critical future directions, and changes that are necessary to ensure EHF remains relevant in future. As such, it provides important guidance on future EHF research and practice.

Polymerization of ZBTB transcription factors regulates chromatin occupancy.

BCL6, an oncogenic transcription factor (TF), forms polymers in the presence of a small-molecule molecular glue that stabilizes a complementary interface between homodimers of BCL6's broad-complex, tramtrack, and bric-à-brac (BTB) domain. The BTB domains of other proteins, including a large class of TFs, have similar architectures and symmetries, raising the possibility that additional BTB proteins self-assemble into higher-order structures. Here, we surveyed 189 human BTB proteins with a cellular fluorescent reporter assay and identified 18 ZBTB TFs that show evidence of polymerization. Through biochemical and cryoelectron microscopy (cryo-EM) studies, we demonstrate that these ZBTB TFs polymerize into filaments. We found that BTB-domain-mediated polymerization of ZBTB TFs enhances chromatin occupancy within regions containing homotypic clusters of TF binding sites, leading to repression of target genes. Our results reveal a role of higher-order structures in regulating ZBTB TFs and suggest an underappreciated role for TF polymerization in modulating gene expression.

Team Approach: Neuromuscular Training for Primary and Secondary Prevention of Anterior Cruciate Ligament Injury.

Neuromuscular training is a method of performance optimization-typically combining plyometrics, balancing training, agility, and dynamic stabilization-predicated on improving the efficiency of fundamental movement patterns. Neuromuscular training has consistently been shown to reduce the risk of anterior cruciate ligament injury, particularly for athletes engaged in activities associated with noncontact knee injuries (i.e., women's soccer). Successful implementation of neuromuscular training programs requires input from coaches, physical therapists, athletic trainers, and physicians to generate efficacious programs with high rates of adherence.