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The role of time-varying external parameters in tropical cyclone (TC) dynamics is explored through a low-order conceptual box model. Specifically, we look at stable-to-stable state transitions which may be linked to tropical cyclone intensification, dissipation, or eyewall replacement cycles (ERCs). To this end, we identify two parameters of interest: the exponent of radial decline and sea-surface temperature. We examine how variations in these parameters affect the stable states of the model and consider the behaviour of the system under different time-dependent forcing profiles for the parameters. By externally forcing the exponent of radial decline and sea-surface temperature, we show the existence of rate-dependent behaviour in the model. These findings are brought together in a case study of Hurricane Irma (2017). The results highlight the role of the radial vorticity gradient in behaviour such as rate-induced tipping and overshoot recovery. They also show that a simple model can be used to explore relatively complex tropical cyclone dynamics.

Vertical-axis wind turbines (VAWTs) are considered promising solutions for urban wind energy generation due to their design, low maintenance costs, and reduced noise and visual impact compared to horizontal-axis wind turbines (HAWTs). However, deploying these turbines close to densely populated urban areas often triggers considerable local opposition to wind energy projects. Among the primary concerns raised by communities is the issue of noise emissions. Noise annoyance should be considered in the design and decision-making process to foster the social acceptance of VAWTs in urban environments. At the same time, maximising the operational efficiency of VAWTs in terms of power generation and actuation effort is equally important. This paper balances noise and aero-servo-elastic performance by formulating and solving a multi-objective optimisation problem from a controller calibration perspective. Psychoacoustic annoyance is taken as a novel indicator for the noise objective by providing a more reliable estimate of the human perception of wind turbine noise than conventional sound metrics. The computation of the psychoacoustic annoyance metric is made feasible by integrating it with an accurate and computationally efficient low-fidelity noise prediction model. For optimisation, an advanced partial-load control scheme – often used in industrial turbines – is considered, with the Kω2 controller as a baseline for comparison. Optimal solutions balancing the defined objectives are identified using a multi-criteria decision-making method (MCDM) and are subsequently assessed using a frequency-domain controller analysis framework and mid-fidelity time-domain aero-servo-elastic simulations. The MCDM results indicate the potential application of this controller in small-scale urban VAWTs to attain power gains of up to 39 % on one side and to trade off a reduction in actuation effort of up to 25 % at the cost of only a 2 % power decrease and a 6 % increase in psychoacoustic annoyance on the other side compared to the baseline. These findings confirm the flexible structure of the optimally calibrated wind speed estimator and tip-speed ratio (WSE–TSR) tracking controller, effectively balancing aero-servo-elastic performance with noise emissions and marking the first instance of integrating residential concerns into the decision-making process.

Various applications require multi-channel high-voltage sources for their control, e.g. electrostatic adhesion, electrophoresis and artificial muscles such as piezoelectric, hydraulically amplified self-healing electrostatic(HASEL) and dielectric elastomer actuators(DEAs). Further, the ability to simultaneously monitor the state of the actuators either with images, or voltage and current sensing is crucial to characterise their behaviour. In this work, we present the design of a versatile characterisation setup, capable of generating eight HV (15 kV) arbitrary waveforms(rise time of 8 ms and fall time of 80 ms for 60 MΩ load), while synchronously monitoring voltage and current, and record high-speed (120 fps) video. The setup ensures modularity and customisability by consisting of three independent modules: (1) The imaging module includes a Raspberry Pi and a Pi Camera; (2) A 3.3 V analogue interface 16-bit resolution data acquisition module on a PCB that accommodates a microcontroller board, two 8-channel analogue-to-digital converters, and an 8-channel digital-to-analogue converter; (3) Up to 8 DC-to-HVDC converter boards powered by 12 V DC, with 3.3 V analogue interface.

Community-engaged patient navigation safety net programs are established as an evidence-based approach to address cancer prevention and early detection efforts, but barriers to expand and sustain such programs persist. In addition, few studies describe how these programs impact buy-in among communities and policy change within health care systems and government. We describe how we used the Capacity for Sustainability Framework to guide efforts for program sustainability and community, institutional, and policy level change in a breast cancer screening and patient navigation safety net program. The nine domains of the Capacity for Sustainability Framework were used to develop program logic models, to inform program implementation and quality improvement agendas, and to guide multi-level partner and stakeholder engagement, outreach, and dissemination of outcomes. The program is currently in its seventh year and continues to be annually funded by a city public health department. In 2021, additional 5-year renewable funding from a state public health department was secured. In addition, institutional program support was expanded for patients diagnosed with breast cancer. Program leaders worked with policymakers to draft legislation to support training certification and third-payor reimbursement for patient navigators and community health workers. The program is well-known and trusted among community members, community-based organizations, and providers. Community, organizational, and policy-level outcomes demonstrate that community-engaged patient navigation safety net programs can influence more than individual and interpersonal outcomes and can be sustained over time.

Abstract ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative gene for KBG syndrome, a rare developmental disorder characterized by multiple organ abnormalities, including cardiac defects. However, the role of ANKRD11 in heart development is unknown. The neural crest plays a leading role in embryonic heart development, and its dysfunction is implicated in congenital heart defects. We demonstrate that conditional knockout of Ankrd11 in the murine embryonic neural crest results in persistent truncus arteriosus, ventricular dilation, and impaired ventricular contractility. We further show these defects occur due to aberrant cardiac neural crest cell organization leading to outflow tract septation failure. Lastly, knockout of Ankrd11 in the neural crest leads to impaired expression of various transcription factors, chromatin remodelers and signaling pathways, including mTOR, BMP and TGF-β in the cardiac neural crest cells. In this work, we identify Ankrd11 as a regulator of neural crest-mediated heart development and function.

Abstract We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS) and health questionnaires were administered at inclusion and at 1, 3 and 6 months. Blood samples were collected at each visit, MRI scan at baseline and at 6 months, and, optionally, cerebrospinal fluid. Cognitive features were analyzed in relation to clinical, neuroimaging, and biochemical markers at inclusion and follow-up. Forty-nine participants, with a mean time from symptom onset of 10.4 months, showed attention-executive function (69%) and verbal memory (39%) impairment. Apathy (64%), moderate-severe anxiety (57%), and severe fatigue (35%) were prevalent. Visual memory (8%) correlated with total gray matter (GM) and subcortical GM volume. Neuronal damage and inflammation markers were within normal limits. Over time, cognitive test scores, depression, apathy, anxiety scores, MRI indexes, and fluid biomarkers remained stable, although fewer participants (50% vs. 75.5%; p = 0.012) exhibited abnormal cognitive evaluations at follow-up. Altered attention/executive and verbal memory, common in PACS, persisted in most subjects without association with structural abnormalities, elevated cytokines, or neuronal damage markers.

Abstract Settlement is a critical period in the life cycle of marine invertebrates with a planktonic larval stage. For reef-building invertebrates such as oysters and corals, settlement rates are predictive for long-term reef survival. Increasing evidence suggests that marine invertebrates use information from ocean soundscapes to inform settlement decisions. Sessile marine invertebrates with a planktonic stage are particularly reliant on environmental cues to direct them to ideal habitats. As gregarious settlers, oysters prefer to settle amongst members of the same species. It has been hypothesized that oyster larvae from species Crassostrea virginica and Ostrea angasi use distinct conspecific oyster reef sounds to navigate to ideal habitats. In controlled laboratory experiments we exposed Pacific Oyster Magallana gigas larvae to anthropogenic sounds from conspecific oyster reefs, vessels, combined reef-vessel sounds as well as off-reef and no speaker controls. Our findings show that sounds recorded at conspecific reefs induced higher percentages of settlement by about 1.44 and 1.64 times compared to off-reef and no speaker controls, respectively. In contrast, the settlement increase compared to the no speaker control was non-significant for vessel sounds (1.21 fold), combined reef-vessel sounds (1.30 fold), and off-reef sounds (1.18 fold). This study serves as a foundational stepping stone for exploring larval sound feature preferences within this species.

Abstract The tumor microenvironment plays a crucial role in determining response to treatment. This involves a series of interconnected changes in the cellular landscape, spatial organization, and extracellular matrix composition. However, assessing these alterations simultaneously is challenging from a spatial perspective, due to the limitations of current high-dimensional imaging techniques and the extent of intratumoral heterogeneity over large lesion areas. In this study, we introduce a spatial proteomic workflow termed Hyperplexed Immunofluorescence Imaging (HIFI) that overcomes these limitations. HIFI allows for the simultaneous analysis of > 45 markers in fragile tissue sections at high magnification, using a cost-effective high-throughput workflow. We integrate HIFI with machine learning feature detection, graph-based network analysis, and cluster-based neighborhood analysis to analyze the microenvironment response to radiation therapy in a preclinical model of glioblastoma, and compare this response to a mouse model of breast-to-brain metastasis. Here we show that glioblastomas undergo extensive spatial reorganization of immune cell populations and structural architecture in response to treatment, while brain metastases show no comparable reorganization. Our integrated spatial analyses reveal highly divergent responses to radiation therapy between brain tumor models, despite equivalent radiotherapy benefit.

Abstract ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer. We further show that the rostral migratory stream has incomplete migration of neuroblasts, reduced cell proliferation as well as aberrant differentiation of neurons. This leads to reduced neuroblasts and neurons in the olfactory bulb granule cell layer. In vitro, Ankrd11-deficient neural stem cells from the postnatal subventricular zone display reduced migration, proliferation, and neurogenesis. Finally, we describe two clinically and molecularly confirmed KBG syndrome patients with anosmia and olfactory bulb and groove hypo-dysgenesis/agenesis. Our report provides evidence that Ankrd11 is a novel regulator of olfactory bulb development and neuroblast migration. Moreover, our study highlights a novel clinical sign of KBG syndrome linked to ANKRD11 perturbations in mice and humans.

Classroom videos are a common source of data for educational researchers studying classroom interactions as well as a resource for teacher education and professional development. Over the last several decades emerging technologies have been applied to classroom videos to record, transcribe, and analyze classroom interactions. With the rise of machine learning, we report on the development and validation of neural networks to classify instructional activities using video signals, without analyzing speech or audio features, from a large corpus of nearly 250 h of classroom videos from elementary mathematics and English language arts instruction. Results indicated that the neural networks performed fairly-well in detecting instructional activities, at diverse levels of complexity, as compared to human raters. For instance, one neural network achieved over 80% accuracy in detecting four common activity types: whole class activity, small group activity, individual activity, and transition. An issue that was not addressed in this study was whether the fine-grained and agnostic instructional activities detected by the neural networks could scale up to supply information about features of instructional quality. Future applications of these neural networks may enable more efficient cataloguing and analysis of classroom videos at scale and the generation of fine-grained data about the classroom environment to inform potential implications for teaching and learning.

The low-cost thermal infrared ‘THz-Torch’ concept (referred to here as ‘THz-T’) was first introduced over a decade ago, and since then the associated ‘over the THz horizon’ thermal infrared (10-100 THz) implementation technologies have continued to advance. While short range secure wireless communications links have received a great deal of attention, material spectroscopy has only briefly been introduced in a short conference abstract. Here, for the first time, we explore in depth the basic concepts behind THz-T spectroscopy. Moreover, when compared to the unvalidated results within our previous work, we demonstrate an enhanced experimental THz-T spectrometer. A detailed thermal noise power link budget model for both the transmission and reflection modes of operation has been undertaken and independently validated. As a proof of principle, a diverse array of different material types has been characterized. This includes glass sheets, semiconductor wafers, ceramic plate, plastic tape, plastic sheets, as well as polymer and cotton paper banknotes. THz-T technology has the advantages of hardware simplicity and low cost non-destructive testing for ubiquitous applications.

Chloroplasts are photosynthetic organelles in algal and plant cells that contain their own genome. Chloroplast genomes are commonly used in evolutionary studies and taxonomic identification and are increasingly becoming a target for crop improvement studies. As DNA sequencing becomes more affordable, researchers are collecting vast swathes of high-quality whole-genome sequence data from laboratory and field settings alike. Whole tissue read libraries sequenced with the primary goal of understanding the nuclear genome will inadvertently contain many reads derived from the chloroplast genome. These whole-genome, whole-tissue read libraries can additionally be used to assemble chloroplast genomes with little to no extra cost. While several tools exist that make use of short-read second generation and third-generation long-read sequencing data for chloroplast genome assembly, these tools may have complex installation steps, inadequate error reporting, poor expandability, and/or lack scalability. Here, we present CLAW (Chloroplast Long-read Assembly Workflow), an easy to install, customise, and use Snakemake tool to assemble chloroplast genomes from chloroplast long-reads found in whole-genome read libraries (https://github.com/aaronphillips7493/CLAW). Using 19 publicly available reference chloroplast genome assemblies and long-read libraries from algal, monocot and eudicot species, we show that CLAW can rapidly produce chloroplast genome assemblies with high similarity to the reference assemblies. CLAW was designed such that users have complete control over parameterisation, allowing individuals to optimise CLAW to their specific use cases. We expect that CLAW will provide researchers (with varying levels of bioinformatics expertise) with an additional resource useful for contributing to the growing number of publicly available chloroplast genome assemblies.

Health disparities persist among Black men, notably in the context of lung cancer and stress-related health outcomes. This study explores these disparities through a community-based participatory research (CBPR) approach, citizen science, and social network theory, leveraging the expertise and trust of Black barbers as community leaders. The purpose is to understand the nuanced connections between stress and lung cancer in this demographic. Engaging 161 Black men across four Chicago neighborhoods, the study successfully collected hair samples and survey data, emphasizing the importance of culturally sensitive recruitment strategies. Findings highlight the effectiveness of the collaboration, showcasing the role of barbershops as community hubs for research. The study concludes by advocating for sustained partnerships with community leaders, emphasizing transparency in research communication, and promoting culturally grounded approaches to address health disparities and enhance research participation among underrepresented populations.

Mutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS) cases. A shared effect of these mutations is that SOD1, which is normally a stable dimer, dissociates into toxic monomers that seed toxic aggregates. Considerable research effort has been devoted to developing compounds that stabilize the dimer of fALS SOD1 variants, but unfortunately, this has not yet resulted in a treatment. We hypothesized that cyclic thiosulfinate cross-linkers, which selectively target a rare, 2 cysteine-containing motif, can stabilize fALS-causing SOD1 variants in vivo. We created a library of chemically diverse cyclic thiosulfinates and determined structure-cross-linking-activity relationships. A pre-lead compound, "S-XL6," was selected based upon its cross-linking rate and drug-like properties. Co-crystallographic structure clearly establishes the binding of S-XL6 at Cys 111 bridging the monomers and stabilizing the SOD1 dimer. Biophysical studies reveal that the degree of stabilization afforded by S-XL6 (up to 24°C) is unprecedented for fALS, and to our knowledge, for any protein target of any kinetic stabilizer. Gene silencing and protein degrading therapeutic approaches require careful dose titration to balance the benefit of diminished fALS SOD1 expression with the toxic loss-of-enzymatic function. We show that S-XL6 does not share this liability because it rescues the activity of fALS SOD1 variants. No pharmacological agent has been proven to bind to SOD1 in vivo. Here, using a fALS mouse model, we demonstrate oral bioavailability; rapid engagement of SOD1G93A by S-XL6 that increases SOD1G93A's in vivo half-life; and that S-XL6 crosses the blood-brain barrier. S-XL6 demonstrated a degree of selectivity by avoiding off-target binding to plasma proteins. Taken together, our results indicate that cyclic thiosulfinate-mediated SOD1 stabilization should receive further attention as a potential therapeutic approach for fALS.

We examine Ulysses magnetic field observations from 1993 to 1996 as the spacecraft made its first fast-latitude scan from the southern to the northern hemisphere. Most of the observations we use are representative of high-latitude solar minimum conditions. We examine magnetic field power spectra characteristics of interplanetary turbulence at high frequencies, where the spectrum breaks from an inertial range into the ion dissipation range. The onset and spectral index of the dissipation spectrum are consistent with low-latitude observations at 1 au. Both ranges have a ratio of power in perpendicular magnetic field components to parallel components near 3. The power spectrum ratio test developed by Bieber et al. for single-spacecraft analyses that determines the underlying anisotropy of the wave vectors yields only marginally more energy associated with field-aligned wave vectors than perpendicular wave vectors when comparing the inertial and dissipation-range spectra. The lack of significant change in the anisotropies between the inertial and dissipation ranges contrasts strongly with the turbulence found typically for 1 au near-ecliptic observations, where significant differences in both anisotropies are observed.

We undertake a theoretical study of a finite-time quantum Otto engine cycle driven by inter-particle interactions in a weakly interacting one-dimensional (1D) Bose gas in the quasicondensate regime. Utilizing a c -field approach, we simulate the entire Otto cycle, i.e. the two work strokes and the two equilibration strokes. More specifically, the interaction-induced work strokes are modelled by treating the working fluid as an isolated quantum many-body system undergoing unitary evolution. The equilibration strokes, on the other hand, are modelled by treating the working fluid as an open quantum system tunnel-coupled to another quasicondensate which acts as either the hot or cold reservoir, albeit of finite size. We find that, unlike a uniform 1D Bose gas, a harmonically trapped quasicondensate cannot operate purely as a heat engine; instead, the engine operation is enabled by additional chemical work performed on the working fluid, facilitated by the inflow of particles from the hot reservoir. The microscopic treatment of dynamics during equilibration strokes enables us to evaluate the characteristic operational time scales of this Otto thermochemical engine, crucial for characterizing its power output, without any ad hoc assumptions about typical thermalization timescales. We analyse the performance and quantify the figures of merit of the proposed Otto thermochemical engine, finding that it offers a favourable trade-off between efficiency and power output, particularly when the interaction-induced work strokes are implemented via a sudden quench. We further demonstrate that in the sudden quench regime, the engine operates with an efficiency close to the near-adiabatic (near maximum efficiency) limit, while concurrently achieving maximum power output.

Background: The interconnected effects of maternal perinatal depression and the early mother-infant relational quality on children's executive function development are crucial yet understudied. This study addresses this gap, focusing on how perinatal depressive symptoms and emotional availability at 6 months predict child executive function performance at age four, with an emphasis on the moderating role of emotional availability., Method: This study included 282 mother-infant pairs recruited from the Mercy Pregnancy and Emotional Wellbeing Study, utilising repeated Edinburgh Postnatal Depression Scale measurement over the perinatal period, Emotional Availability Scales, and child executive function assessments (Shape School, NEPSY-II, Preschool Age Psychiatric Assessment, Attention Deficit Hyperactivity scale, inattentive subscale). Latent growth curve analysis incorporated controls for socioeconomic status and maternal cognitive abilities, and moderation effects were examined through multiplicative interaction terms., Results: We found that emotional availability influences children's executive function, specifically switching, motor inhibition, and inattentive symptoms, irrespective of maternal depressive symptom changes. This effect is further nuanced by emotional availability's moderating role in the association between depressive symptom change and switching., Limitations: The study's limitations include a relatively small sample size for moderation analysis and the exclusion of paternal influences., Conclusion: This study is a significant step in understanding the profound influence of maternal emotional availability in infancy on child executive function development, offering new avenues for research and, if replicated, a foundation for innovative intervention approaches., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: A scoping review of randomized controlled trials (RCTs) of parenting and family-based interventions that aim to reduce severe and persistent conduct problems among 10-17 year-olds. The review also examined feasibility for conducting a network meta-analysis of common therapy elements measured by RCTs., Materials and Methods: The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA- ScR). Searches were conducted in ERIC, PsycINFO, and MEDLINE without limits on publication year, language or publication country. Study methodological quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for RCTs., Results: Twenty-five eligible RCTs were identified. The studies trialed nine interventions, with Multisystemic Therapy (MST) being the most evaluated ( N  = 10), followed by Functional Family Therapy (FFT, N  = 4), and Treatment Foster Care Oregon (TFCO, N  = 3). Only 10 of the 25 RCTs revealed treatment effect on conduct problems, including 6 of 9 MST, 1 of 4 FFT and all 3 TFCO trials., Discussion: Surprisingly few RCTs of parenting and family-based interventions have been carried out exclusively with this population. Available data suggests that MST and FFT have uncertain effectiveness for reducing severe and persistent conduct problems. While the quality of the reviewed studies was generally high, only two reported substantive data on common therapy elements., Conclusion: There is need for more RCTs of parenting and family-based interventions delivered for older children and adolescents with severe and persistent conduct problems. Future RCTs should systematically measure common therapy elements with a view to advancing intervention science.

Background: Dichotomisation of statistical significance, rather than interpretation of effect sizes supported by confidence intervals, is a long-standing problem., Methods: We distributed an online survey to clinical trial statisticians across the UK, Australia and Canada asking about their experiences, perspectives and practices with respect to interpretation of statistical findings from randomised trials. We report a descriptive analysis of the closed-ended questions and a thematic analysis of the open-ended questions., Results: We obtained 101 responses across a broad range of career stages (24% professors; 51% senior lecturers; 22% junior statisticians) and areas of work (28% early phase trials; 44% drug trials; 38% health service trials). The majority (93%) believed that statistical findings should be interpreted by considering (minimal) clinical importance of treatment effects, but many (61%) said quantifying clinically important effect sizes was difficult, and fewer (54%) followed this approach in practice. Thematic analysis identified several barriers to forming a consensus on the statistical interpretation of the study findings, including: the dynamics within teams, lack of knowledge or difficulties in communicating that knowledge, as well as external pressures. External pressures included the pressure to publish definitive findings and statistical review which can sometimes be unhelpful but can at times be a saving grace. However, the concept of the minimally important difference was identified as a particularly poorly defined, even nebulous, construct which lies at the heart of much disagreement and confusion in the field., Conclusion: The majority of participating statisticians believed that it is important to interpret statistical findings based on the clinically important effect size, but report this is difficult to operationalise. Reaching a consensus on the interpretation of a study is a social process involving disparate members of the research team along with editors and reviewers, as well as patients who likely have a role in the elicitation of minimally important differences., (© 2024. The Author(s).)

Background: Strong research capacity and culture (RCC) within professional groups predict engagement in high-quality research and the integration of evidence into practice. However, factors affecting RCC participation and development are currently unknown in Australian Orthopaedic Surgeons., Study Design: Cross-sectional survey., Methods: All Australian Orthopaedic Association members were invited to complete the individual domain of the validated Research Capacity and Culture tool., Results: One hundred and sixty-three Australian Orthopaedic Association members (9%) provided survey answers. Survey findings indicated that AOA members scored moderate or high for most RCC domains (14 out of 15). Barriers to the completion of research included a lack of time, other work roles taking priority, and a lack of funds for research., Conclusion: The Australian Orthopaedic Association members surveyed in this study demonstrated adequate research skills and experience, although reported they could benefit from additional support securing funding and navigating specific research tasks. Increasing future collaboration with academic institutions and clinician-researcher roles may enhance the output of high-quality orthopaedic research in Australia., (© 2024. The Author(s).)

Background: Pediatric high blood pressure (BP) predicts future cardiovascular disease events. High BP is improperly measured, underrecognized, and undermanaged especially in disadvantaged populations. In a large, diverse, academic pediatric practice, we detail the associations of a comprehensive initiative with high BP provider recognition., Methods: A comprehensive BP initiative was promulgated including (1) retraining providers and staff on BP management; (2) deploying equipment at 55+ sites; and (3) electronic decision support tool alerting staff and clinicians and suggesting management. During the 14-month preintervention and 14-month postintervention periods, data on BP and patient characteristics were collected. The outcome was incident BP recognition defined as any of the following: BP-specific International Classification of Diseases, Tenth Revision , diagnosis; problem list entry; specialty referral; diagnostic testing; repeat visit; or antihypertensives. Dichotomized as underpre versus at or over 13 years of age, analyses utilized interrupted time series and multivariable-adjusted logistic regression., Results: From preintervention (children, n=105 674; adolescents, n=54 365) to postintervention (children, n=87 917; adolescents, n=56 470), the proportion measured with high BP declined in children and adolescents (30% versus 14% and 30% versus 15%, respectively, each P <0.001). Post-intervention, high BP provider recognition was 58% higher in children (4.6%-7.3%) and 43% higher in adolescents (7.9% versus 11.3%; P <0.001 for both). The improvement was not different in disadvantaged race, ethnicity, or zip codes., Conclusions: A comprehensive BP initiative was associated with more appropriate high BP measurement and recognition including in disadvantaged populations. Future work may address the low overall and nonsustained recognition and consideration of electronic decision support for pediatric BP management and mitigating disparities.

The research presented in this paper offers insight into the availability of intermediates in the depolymerization of polyethylene terephthalate (PET) to be used as feedstock to create value-added products. Monitoring the dispersity, molecular weight, end groups, and crystallinity of reaction intermediates during the heterogeneous depolymerization of PET offers insight into the mechanism by which the polymer chains evolve during the reaction. Our results show dispersity decreases and crystallinity increases while the yield of insoluble PET remains high early in the reaction. Our interpretation of this data depicts a mechanism where chain scission targets amorphous tie chains between crystalline phases. Targeting the tie-chains lowers the M n of the polymer without changing the amount of recovered polymer flake. Chain scission of tie-chains and isolating highly crystalline PET lowers the dispersity (Đ) of the polymer chains, as the size of the crystalline lamellae guides the molecular weight of the depolymerized oligomers. When sufficient end groups of PET chains are converted to alcohol groups, the PET flakes break apart into highly crystalline and less disperse polymer. Our results also demonstrate that the oligomeric depolymerization intermediates are readily repolymerized, offering new opportunities to chemically recycle PET more effectively and efficiently, from both an energy and purification standpoint., (© 2024 Wiley-VCH GmbH.)

Introduction: Bipolar disorder is a recurrent mental health disorder with a prevalence rate of 1.4%. On average, there can be a delay of 9.5 years from the initial presentation of symptoms to a confirmed diagnosis. Individuals living with bipolar disorder have a reduced life expectancy. There is limited evidence regarding the effectiveness of antidepressants in treating bipolar disorder. The ASCEnD clinical trial will test the clinical and cost-effectiveness of the aripiprazole/sertraline combination in comparison with quetiapine for the treatment of bipolar depression (individuals who suffer from depressive episodes in bipolar disorder) and will include a nested qualitative study., Methods: The qualitative study will use semi-structured interviews to explore pilot trial participants' and clinicians' perspectives on recruitment procedures, the acceptability of the intervention, the management of bipolar disorder and attitudes to medication combinations., Conclusion: Findings will inform recruitment strategies and optimise training for the participating sites in the ASCEnD full trial. They will also help to illuminate the lived experience of people with bipolar disorder and the clinicians who work with people with bipolar disorder. The discussion will explore perspectives on the delay in diagnosis, having a diagnosis, the impact of living with bipolar disorder and attitudes to treatment, including drug combinations., Patient or Public Contribution: A Lived Experience Advisory Panel (LEAP) has been convened with the support of the McPin Foundation, which will contribute to the ASCEnD trial and its nested qualitative study to provide input on the design and delivery of the trial and qualitative study, analysis of qualitative data and dissemination of findings., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Purpose: To compare the prevalence of emotional and physical intimate partner violence (IPV) across pregnancy and the first year postpartum in those with and without clinical depression and assess the association between maternal childhood trauma, current stressful life events and depression and IPV over the perinatal period., Methods: Data were obtained from 505 pregnant women from the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a cohort study with data collected across pregnancy until 12 months postpartum. Maternal antenatal depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) with repeat measurement of perinatal depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS). Trauma was measured using the Childhood Trauma Questionnaire, and experiences of physical and emotional intimate partner violence using items in the Stressful Life Events Scale., Results: Women experiencing IPV across the perinatal period were significantly more likely to score over 13 on the EPDS (p < .001) at each timepoint in pregnancy and the postpartum and physical IPV was associated with clinical depression. Further, a history of childhood trauma and current additional stressful life events were significantly associated with reporting current IPV in the perinatal period., Conclusions: This study confirmed the risk factors of childhood trauma and current stressful life events for reporting experiences of IPV in the perinatal period. Furthermore, women experiencing IPV reported higher depressive symptoms, providing evidence supporting the value of assessing those women who screen higher on the EPDS for IPV. Together these findings also support trauma informed care across pregnancy and the postpartum., (© 2024. Crown.)

Background: Cariprazine has emerged as a promising augmenting treatment agent for unipolar depression and as a monotherapy option for bipolar depression. We evaluated cariprazine's efficacy in treating acute major depressive episodes in individuals with major depressive disorder (MDD) or bipolar disorder., Methods: A systematic review was conducted on MEDLINE, Embase, PsycINFO, Scopus and Web of Science, ClinicalTrials.gov and ScanMedicine. Study quality was assessed using the RoB 2 tool. Pairwise and dose-response meta-analyses were conducted with RStudio. Evidence quality was assessed with GRADE., Results: Nine RCTs meeting inclusion criteria encompassed 4889 participants. Cariprazine, compared to placebo, significantly reduced the MADRS score (MD = -1.49, 95 % CI: -2.22 to -0.76) and demonstrated significantly higher response (RR = 1.21, 95 % CI: 1.12 to 1.30) and remission (RR = 1.19, 95 % CI: 1.06 to 1.34) rates. Subgroup analysis unveiled statistically significant reductions in MADRS score in MDD (MD = -1.15, 95 % CI: -2.04 to -0.26) and bipolar I disorder (BDI) (MD = -2.53, 95 % CI: -3.61 to -1.45), higher response rates for both MDD (RR = 1.19, 95 % CI: 1.08 to 1.31) and BDI (RR = 1.27, 95 % CI: 1.10 to 1.46), and higher remission rates only for BDI (RR = 1.41, 95 % CI: 1.24 to 1.60). A higher rate of treatment discontinuation due to adverse events was observed., Limitations: Reliance solely on RCTs limits generalisability; strict criteria might not reflect real-world diversity., Conclusions: Cariprazine demonstrates efficacy in treating major depressive episodes, although variations exist between MDD and BDI and tolerability may be an issue., Competing Interests: Declaration of competing interest João Martins-Correia reports personal fees from Jaba and Lundbeck, outside this work. Luís Afonso Fernandes reports personal fees from Jaba, Janssen and Lundbeck, outside this work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The use of monoclonal antibodies for the control of drug resistant nosocomial bacteria may alleviate a reliance on broad spectrum antimicrobials for treatment of infection. We identify monoclonal antibodies that may prevent infection caused by carbapenem resistant Acinetobacter baumannii. We use human immune repertoire mice (Kymouse platform mice) as a surrogate for human B cell interrogation to establish an unbiased strategy to probe the antibody-accessible target landscape of clinically relevant A. baumannii. After immunisation of the Kymouse platform mice with A. baumannii derived outer membrane vesicles (OMV) we identify 297 antibodies and analyse 26 of these for functional potential. These antibodies target lipooligosaccharide (OCL1), the Oxa-23 protein, and the KL49 capsular polysaccharide. We identify a single monoclonal antibody (mAb1416) recognising KL49 capsular polysaccharide to demonstrate prophylactic in vivo protection against a carbapenem resistant A. baumannii lineage associated with neonatal sepsis mortality in Asia. Our end-to-end approach identifies functional monoclonal antibodies with prophylactic potential against major lineages of drug resistant bacteria accounting for phylogenetic diversity and clinical relevance without existing knowledge of a specific target antigen. Such an approach might be scaled for a additional clinically important bacterial pathogens in the post-antimicrobial era., (© 2024. The Author(s).)

Dedifferentiated and Well-differentiated liposarcoma are characterized by a systematic amplification of the Murine Double Minute 2 (MDM2) oncogene. We demonstrate that p53-independent metabolic functions of chromatin-bound MDM2 are exacerbated in liposarcoma and mediate an addiction to serine metabolism to sustain tumor growth. However, the origin of exogenous serine remains unclear. Here, we show that elevated serine levels in mice harboring liposarcoma-patient derived xenograft, released by distant muscle is essential for liposarcoma cell survival. Repressing interleukine-6 expression, or treating liposarcoma cells with Food and Drugs Administration (FDA) approved anti-interleukine-6 monoclonal antibody, decreases de novo serine synthesis in muscle, impairs proliferation, and increases cell death in vitro and in vivo. This work reveals a metabolic crosstalk between muscle and liposarcoma tumor and identifies anti-interleukine-6 as a plausible treatment for liposarcoma patients., (© 2024. The Author(s).)

Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It is characterized by a component of undifferentiated tumor cells coexisting with a component of well-differentiated adipocytic tumor cells. Both dedifferentiated (DD) and well-differentiated (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing, DNA sequencing, in situ multiplex immunofluorescence and functional assays in paired WD and DD components from primary DDLPS tumors, we characterize the cellular heterogeneity of DDLPS tumor and micro-environment. We identify a population of tumor adipocyte stem cells (ASC) showing striking similarities with adipocyte stromal progenitors found in white adipose tissue. We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-β-high immunosuppressive tumor micro-environment., (© 2024. The Author(s).)

Interferon-gamma (IFNγ) is traditionally recognized for its pro-inflammatory role during intestinal inflammation. Here, we demonstrate that IFNγ also functions as a pro-repair molecule by increasing TNFα receptor 2 (TNFR2 protein/TNFRSF1B gene) expression on intestinal epithelial cells (IEC) following injury in vitro and in vivo. In silico analyses identified binding sites for the IFNγ signaling transcription factor STAT1 in the promoter region of TNFRSF1B. Scratch-wounded IEC exposed to IFNγ exhibited a STAT1-dependent increase in TNFR2 expression. In situ hybridization revealed elevated Tnfrsf1b mRNA levels in biopsy-induced colonic mucosal wounds, while intraperitoneal administration of IFNγ neutralizing antibodies following mucosal injury resulted in impaired IEC Tnfrsf1b mRNA and inhibited colonic mucosal repair. These findings challenge conventional notions that "pro-inflammatory" mediators solely exacerbate damage by highlighting latent pro-repair functions. Moreover, these results emphasize the critical importance of timing and amount in the synthesis and release of IFNγ and TNFα during the inflammatory process, as they are pivotal in restoring tissue homeostasis., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Politicization and misinformation or disinformation of unproven COVID-19 therapies have resulted in communication challenges in presenting science to the public, especially in times of heightened public trepidation and uncertainty., Objective: This study aims to examine how scientific evidence and uncertainty were portrayed in US news on 3 unproven COVID-19 therapeutics, prior to the development of proven therapeutics and vaccines., Methods: We conducted a media analysis of unproven COVID-19 therapeutics in early 2020. A total of 479 discussions of unproven COVID-19 therapeutics (hydroxychloroquine, remdesivir, and convalescent plasma) in traditional and online US news reports from January 1, 2020, to July 30, 2020, were systematically analyzed for theme, scientific evidence, evidence details and limitations, safety, efficacy, and sources of authority., Results: The majority of discussions included scientific evidence (n=322, 67%) although only 24% (n=116) of them mentioned publications. "Government" was the most frequently named source of authority for safety and efficacy claims on remdesivir (n=43, 35%) while "expert" claims were mostly mentioned for convalescent plasma (n=22, 38%). Most claims on hydroxychloroquine (n=236, 79%) were offered by a "prominent person," of which 97% (n=230) were from former US President Trump. Despite the inclusion of scientific evidence, many claims of the safety and efficacy were made by nonexperts. Few news reports expressed scientific uncertainty in discussions of unproven COVID-19 therapeutics as limitations of evidence were infrequently included in the body of news reports (n=125, 26%) and rarely found in headlines (n=2, 2%) or lead paragraphs (n=9, 9%; P<.001)., Conclusions: These results highlight that while scientific evidence is discussed relatively frequently in news reports, scientific uncertainty is infrequently reported and rarely found in prominent headlines and lead paragraphs., (©Sara Watson, Tyler J Benning, Alessandro R Marcon, Xuan Zhu, Timothy Caulfield, Richard R Sharp, Zubin Master. Originally published in JMIR Infodemiology (https://infodemiology.jmir.org), 29.08.2024.)

Aim: To explore the experiences of undergraduate nursing students in navigating daily micro-transitions between nursing and non-nursing roles., Background: Nursing students develop professional role identity through socialization, experience, and practice while simultaneously managing pre-existing personal roles. This dynamic creates a training ground for future sustainable practice., Design: Qualitative, cross-sectional, interpretive phenomenological design with hermeneutics., Methods: Seventeen undergraduate nursing students participated online in semi-structured, audiovisual-recorded interviews until data saturation was reached., Results: Three main themes emerged: 1) Strategies for Getting In and Out of Nurse Mode, 2) Cultivating Mindful Nursing Practice, and 3) Nursing Student Socialization and Immersion. Findings indicated that nursing students noticed benefits in their personal and professional lives as they developed this skill. Findings also suggested that students need support from their educators to ensure they are not trapped in nurse mode while learning to navigate nurse role identity., Conclusions: Understanding and supporting nursing students in managing role micro-transitions are crucial. Findings indicated a functional need for nursing students to understand and apply knowledge and skills regarding a) when to initiate a role micro-transition and b) how to complete a micro-transition effectively between a nursing and non-nursing role. Educational strategies and support systems addressing this need may improve future nursing professionals' quality of life and clinical practice., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Suicide is a leading cause of death in children and adolescents worldwide and a major public health concern. While suicidal behaviours place a significant demand on mental health and emergency services, data regarding suicide-related contacts with police and paramedics are an underutilised resource. The aim of the present study was to identify the demographic profile of young individuals (aged 5-17) and had a suicide-related contact with police or paramedics in Queensland (Australia)., Methods: The present study utilised a population-wide linked dataset, including data from police and paramedics and health administrative data, between 1 February 2013 and 31 January 2018., Results: The identified cohort of 7929 children had a median age of 15 years and mainly comprised females (63.2%). Over the study period, 64 children died, most by suicide (76.6%). Less than a third of the cohort were responsible for almost two-thirds of the total number of contacts with police or paramedics., Conclusion: Findings provide a comprehensive profile of children and adolescents in suicidal crisis and highlight the substantial number of interactions that occur with police and paramedics. Due to the way the linked dataset was constructed, it must be assumed that the number of young persons in suicidal crisis is higher. Findings highlight the value of considering pre-hospital alternatives to presenting to emergency departments (EDs) for this cohort, to reduce impost on EDs and improve outcomes. Further examination of re-presentations by young persons is warranted to inform prevention and intervention strategies., (© 2024 Australasian College for Emergency Medicine.)

Background: Large biobanks that link biological specimens with specimen donors' health histories are a critical tool for precision medicine, and many health care institutions have invested significant resources in setting up and building up large collections for this purpose. As biobanks require consented participation from thousands of individual donors, much research has focused on the values and preferences of new and prospective donors who are actively contemplating an invitation to participate in the collection. Few studies, however, have focused on participants' opinions about their biobank participation in the months and years following enrollment. Methods: We conducted a survey in a large, established biobank and evaluated participants' levels of decisional regret regarding their decision to enroll in the biobank. Results: We found very low levels of decisional regret among established biobank participants. Multivariable regression analysis found that age, length of time in the biobank, lower educational attainment, inadequate health literacy, and previous invitations to research participation were all significant predictors of elevated regret. Discussion: Among those with elevated regret, several demographic factors may point to elevated likelihood of decisional regret. More research is needed to identify factors associated with long-term satisfaction with biobank participation and with elevated risk of regret and/or withdrawal from the collection.

Metastatic carcinoma of presumed renal origin (rCUP) has recently emerged as a new entity within the heterogeneous entity of Cancers of Unknown Primary (CUP) but their biological features and optimal therapeutic management remain unknown. We report the molecular characteristics and clinical outcome of a series of 25 rCUP prospectively identified within the French National Multidisciplinary Tumor Board for CUP. This cohort strongly suggests that rCUP share similarities with common RCC subtypes and benefit from renal-tailored systemic treatment. This study highlights the importance of integrating clinical and molecular data for optimal diagnosis and management of CUP., (© 2024. The Author(s).)

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. The current standard treatment for AMD involves frequent intravitreal administrations of therapeutic agents. While effective, this approach presents challenges, including patient discomfort, inconvenience, and the risk of adverse complications. Nanoparticle-based intravitreal drug delivery platforms offer a promising solution to overcome these limitations. These platforms are engineered to target the retina specifically and control drug release, which enhances drug retention, improves drug concentration and bioavailability at the retinal site, and reduces the frequency of injections. This review aims to uncover the design principles guiding the development of highly effective nanoparticle-based intravitreal drug delivery platforms for AMD treatment. By gaining a deeper understanding of the physiology of ocular barriers and the physicochemical properties of nanoparticles, we establish a basis for designing intravitreal nanoparticles to optimize drug delivery and drug retention in the retina. Furthermore, we review recent nanoparticle-based intravitreal therapeutic strategies to highlight their potential in improving AMD treatment efficiency. Lastly, we address the challenges and opportunities in this field, providing insights into the future of nanoparticle-based drug delivery to improve therapeutic outcomes for AMD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known conflict of interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: The purpose of this study was to evaluate interocular predictors of progression in patients with untreated keratoconus., Methods: This is a multicenter longitudinal observational study with real-world data collected through the Save Sight Keratoconus Registry. Patients between the period of June 2000 and September 2022 were included in this study. Parameters such as patient age, sex, ocular history, visual acuity, K2, Max-K, and thinnest corneal thickness pachymetry (TCT) were analyzed., Results: There were 4342 untreated eyes from 2171 patients with keratoconus. A total of 333 patients showed progression of either Max-K, TCT, or both, whereas 1838 patients showed stable parameters. Factors associated with a higher incidence of progression in Max-K were younger baseline age (HR 0.96 per year older; 95% CI 0.95-0.98, P < 0.0001) and a higher baseline intereye asymmetry in Max-K (HR 1.02 per higher diopter; 95% CI 1.00-1.04, P = 0.04). A younger baseline age was the only predictor of progression in TCT (HR 0.97 per year older; 95% CI 0.95-0.99, P = 0.001)., Conclusions: Age is the most significant predictor of progression for both corneal thinning and progression of Max-K. Interocular asymmetry in Max-K at baseline could be used as part of an algorithm for determining the risk of keratoconus progression. It is recommended that patients with higher interocular asymmetry in Max-K have a closer follow-up of both eyes as they are at a higher risk of progression., Competing Interests: The author declares that there is no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1::WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on 12 samples from five patients, we find that DSRCT tumor cells cluster into consistent subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs. In vitro modeling shows that high EWSR1::WT1 DNA-binding activity associates with most lineage-related states, in contrast to glycolytic and profibrotic states. Single-cell chromatin accessibility analysis suggests that EWSR1::WT1 binding site variability may drive distinct lineage-related transcriptional programs, supporting some level of cell-intrinsic plasticity. Spatial transcriptomics reveals that glycolytic and profibrotic states specifically localize within hypoxic niches at the periphery of tumor cell islets, suggesting an additional role of tumor cell-extrinsic microenvironmental cues. We finally identify a single-cell transcriptomics-derived epithelial signature associated with improved patient survival, highlighting the clinical relevance of our findings., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Recent evidence suggests that the first consultation with a general practitioner (GP) for symptoms of depression may be more than just a vehicle for assessment and management planning (as current guidelines imply)., Objectives: To identify what patients find helpful, or otherwise, in their first consultation for low mood with a GP., Methods: A cross-sectional questionnaire and interview study of patients with low mood who had recently consulted their GP, in the North of England. Patients were asked to complete a questionnaire regarding the consultation, and a Patient Health Questionnaire-9 (PHQ-9), within 2 weeks. They were also invited to take part in a face-face interview with a researcher. Both sources of data were subjected to qualitative thematic analysis., Results: Thirty-seven questionnaires were returned; 5 interviews took place. The majority of participants felt better after consulting a GP for the first time for low mood. The factors most commonly cited as helpful were "being listened to" and "understanding or empathy from the GP." Others included "admitting the problem," "being reassured of normality," and "being provided with optimism or hope for change." The most commonly reported difficulty was the patients' struggle to express themselves. Patients often felt that GP follow-up was inadequate., Conclusions: These results suggest that the therapeutic benefit of the GP consultation is under-recognized in current guidelines. The results of our study will provide crucial information as to how such consultations can be tailored to improve patient satisfaction., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: This study will examine the role of childhood experience of parental divorce on later perinatal depression and parenting stress., Methods: 546 women were recruited at less than 20 weeks pregnancy into an ongoing pregnancy cohort study and followed up in pregnancy and the postpartum. Depression at recruitment was measured using the Structured Clinical Interview for the DSM and the Edinburgh Postnatal Depression Scale repeated in pregnancy and the postpartum. Parenting stress was measured at 12 months postpartum using Parenting Stress Index., Results: This study found 33% of women had experienced parental divorce. While we did not find a statistically significant relationship between the experience of parental divorce and perinatal depression, there was a higher rate of perinatal depression when parental divorce occured at a younger age. There was no association with parental divorce and parenting stress. Childhood divorce was significantly associated with other adverse childhood experiences., Conclusions: Our findings did not support an impact of parental divorce on either maternal perinatal depression or on parenting stress, suggesting the experience of parental divorce for children may not inevitably impact their later experiences as parents. Further research on the association with age of parental divorce and later perinatal mental health is warranted., Competing Interests: DisclosureThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Visual changes due to hyperglycemia in diabetes are not uncommon. While blurred vision is a well-established sequela of chronic hyperglycemia, homonymous hemianopia with or without electroclinical seizures is much rarer and can be mistaken for migraine, temporal arteritis, or ischemia of the central nervous system., Methods: This article analyzed case studies for 3 patients (67M, 68M, 52F) presenting with complex visual phenomena, from 3 to 42 days duration, including pathogenesis, clinical findings, management, and follow-up., Results: Examinations demonstrated dense left homonymous hemianopias in 2 patients and a left inferior homonymous quadrantanopia in one, with no other abnormalities. Patients described vivid, nonstereotyped intermittent hallucinations in the affected fields. Blood glucose levels ranged from 13.5 to 35.0 mmol/L (243-630 mg/dL) without ketosis and HbA1c from 14.6% to 16.8%. Computed tomography of the brain showed no acute intracranial pathology. MRI of the brain either detected no abnormalities or demonstrated changes consistent with seizure activity. Electroencephalogram (EEG) demonstrated seizures over the right occipital region in each patient. EEG seizures coincided with patients' hallucinations, while they remained otherwise conscious. Oral hypoglycemic and antiepileptic medications were commenced with rapid and complete reversal of the seizures and visual field deficits, confirmed by repeat Automated 30-2 and MRI., Conclusions: Hyperglycemia-induced occipital lobe seizures with visual hallucinations and interictal homonymous visual field defects represent a rare but clinically important diagnosis. This article highlights the importance of prompt recognition and treatment to facilitate recovery., Competing Interests: M. T. Coroneo reports ongoing relationships with Katena/Corza and Allgenesis, and a past relationship with ASCRS. The remaining authors report no conflicts of interest., (Copyright © 2024 by North American Neuro-Ophthalmology Society.)

Interstitial lung diseases (ILDs) are a heterogeneous group of conditions characterised by non-infective inflammation and scarring of the lung parenchyma. They are not infrequently encountered by the general radiologist in both acute and outpatient reporting settings who may even be the first to make the diagnosis. In the acute setting, patients with ILD can present with respiratory deterioration due to a number of causes and in addition to the common causes of dyspnoea, an acute exacerbation of ILD needs to be considered. An exacerbation can be initiated by common triggers such as infection, pulmonary embolism (PE), and heart failure, and it can also be initiated by an insult to the lung or occur due to an unknown cause. Particular care needs to be taken when interpreting computed tomography (CT) examinations in these patients as the findings of an acute exacerbation are non-specific and patient and technical factors can cause spurious appearances including dependent changes, breathing artefact and contrast medium opacification. In the non-acute setting, patients with ILD are at increased risk of lung cancer and pulmonary hypertension (PH), with lung cancer being a particularly important consideration as treatments carry the risk of triggering an acute exacerbation or deterioration in lung function. Overall, this review aims to provide an overview for the general radiologist of additional factors to consider when interpreting scans in patients with ILD and how the presence of ILD impacts the differential diagnoses and complications that can occur in these patients in both acute and non-acute settings., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

MANAGEMENT OF GASTROINTESTINAL STROMAL TUMORS. Gastrointestinal stromal tumors (GIST) are the most frequent sarcoma subtype. More than 80% of GIST are characterized by activating mutations in KIT or PDGFRA genes, but rare molecular subtypes exist. Localized GIST can be cured by surgery. Adjuvant treatment with imatinib is the gold standard in high-risk GIST presenting mutations sensitive to this tyrosine kinase inhibitor. The development of tyrosine kinase inhibitors targeting KIT and PDGFRA has revolutionized the prognosis of metastatic GIST, by increasing the median overall survival: from less than 18 months to more than 70 months within 20 years. Similary to other histological subtypes, the diagnostic and therapeutic management of GIST must be referred to sarcoma reference centers., Competing Interests: S. Watson déclare avoir participé à des interventions ponctuelles pour Deciphera, Amgen, AstraZeneca et avoir été prise en charge, à l’occasion de déplacements pour congrès, par Amgen, PharmaMar, Deciphera. C. Bonnet déclare avoir participé à des interventions ponctuelles pour GSK et avoir été pris en charge, à l’occasion de déplacements pour congrès, par Amgen.

Single-cell RNA sequencing (scRNAseq) is a rapidly advancing field enabling the characterisation of heterogeneous gene expression profiles within a population. The cell cycle phase is a major contributor to gene expression variance between cells and computational analysis tools have been developed to assign cell cycle phases to cells within scRNAseq datasets. Whilst these tools can be extremely useful, all have the drawback that they classify cells as only G1, S or G2/M. Existing discrete cell phase assignment tools are unable to differentiate between G2 and M and continuous-phase-assignment tools are unable to identify a region corresponding specifically to mitosis in a pseudo-timeline for continuous assignment along the cell cycle. In this study, bulk RNA sequencing was used to identify differentially expressed genes between mitotic and interphase cells isolated based on phospho-histone H3 expression using fluorescence-activated cell sorting. These gene lists were used to develop a methodology which can distinguish G2 and M phase cells in scRNAseq datasets. The phase assignment tools present in Seurat were modified to allow for cell cycle phase assignment of all stages of the cell cycle to identify a mitotic-specific cell population.

Introduction: Infective Endocarditis (IE) is a rare, life-threatening infection of the endocardium with multisystem effects. Culprit microorganisms derived from different niches circulate through the bloodstream and attach to the endocardium, particularly the heart valves. This study aimed to investigate culprit microorganisms among a cross-sectional cohort of IE patients, their associated factors, and to explore the potential relationship to the oral microbiome., Methods: In this observational study, we undertook a cross-sectional analysis of 392 medical records from patients diagnosed with IE. The primary outcome of this study was to analyse the association between the IE culprit microorganisms and the underlying anatomical types of IE (native valve (NVE), prosthetic valve (PVE), or cardiac device-related (CDE)). Secondary outcomes encompassed a comparative analysis of additional factors, including: the treatment approaches for IE, and the categorisation of blood cultures, extending to both genus and species levels. Additionally, we cross-referenced and compared the species-level identification of IE bacteraemia outcome measures with data from the expanded Human Oral Microbiome Database (eHOMD)., Results: A culprit microorganism was identified in 299 (76.28%) case participants. Staphylococcal infections were the most common ( p  < 0.001), responsible for 130 (33.16%) hospitalisations. There were 277 (70.66%) cases of NVE, 104 (26.53%) cases of PVE, and 11 (2.81%) cases of CDE. The majority of PVE occurred on prosthetic aortic valves (78/104, 75%), of which 72 (93.5%) were surgical aortic valve replacements (SAVR), 6 (7.8%) were transcatheter aortic valve implants, and one transcatheter pulmonary valve implant. Overall, underlying anatomy ( p  = 0.042) as well as the treatment approaches for IE ( p  < 0.001) were significantly associated with IE culprit microorganisms. Cross-reference between IE bacteraemia outcomes with the eHOMD was observed in 267/392 (68.11%) cases., Conclusions: This study demonstrated that IE patients with a history of stroke, smoking, intravenous drug use, or dialysis were more likely to be infected with Staphylococcus aureus . CDE case participants and patients who had previous SAVR were most associated with Staphylococcus epidermidis . IE patients aged 78+ were more likely to develop enterococci IE than other age groups. Oral microorganisms indicated by the eHOMD are significantly observed in the IE population. Further research, through enhanced dental and medical collaboration, is required to correlate the presence of oral microbiota as causative factor for IE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Ismail, Yogarajah, Falconer, Dworakowski, Watson, Breeze, Gunning, Khan, Hussain, Howard, Cheong, Shah, Nibali and Sousa.)

Background and Objectives: Exome sequencing (ES) demonstrates a 20-50 percent diagnostic yield for patients with a suspected monogenic neurologic disease. Despite the proven efficacy in achieving a diagnosis for such patients, multiple barriers for obtaining exome sequencing remain. This study set out to assess the efficacy of ES in patients with primary neurologic phenotypes who were appropriate candidates for testing but had been unable to pursue clinical testing., Methods: A total of 297 patients were identified from the UCLA Clinical Neurogenomics Research Center Biobank, and ES was performed, including bioinformatic assessment of copy number variation and repeat expansions. Information regarding demographics, clinical indication for ES, and reason for not pursuing ES clinically were recorded. To assess diagnostic efficacy, variants were interpreted by a multidisciplinary team of clinicians, bioinformaticians, and genetic counselors in accordance with the American College of Medical Genetics and Genomics variant classification guidelines. We next examined the specific barriers to testing for these patients, including how frequently insurance-related barriers such as coverage denials and inadequate coverage of cost were obstacles to pursuing exome sequencing., Results: The cohort primarily consisted of patients with sporadic conditions (n = 126, 42.4%) of adult-onset (n = 239, 80.5%). Cerebellar ataxia (n = 225, 75.8%) was the most common presenting neurologic phenotype. Our study found that in this population of mostly adult patients with primary neurologic phenotypes that were unable to pursue exome sequencing clinically, 47 (15.8%) had diagnostic results while an additional 24 patients (8.1%) had uncertain results. Of the 297 patients, 206 were initially recommended for clinical exome but 88 (42.7%) could not pursue ES because of insurance barriers, of whom 14 (15.9%) had diagnostic findings, representing 29.8% of all patients with diagnostic findings. In addition, the incorporation of bioinformatic repeat expansion testing was valuable, identifying a total of 8 pathogenic repeat expansions (17.0% of all diagnostic findings) including 3 of the common spinocerebellar ataxias and 2 patients with Huntington disease., Discussion: These findings underscore the importance and value of clinical ES as a diagnostic tool for neurogenetic disease and highlight key barriers that prevent patients from receiving important clinical information with potential treatment and psychosocial implications for patients and family members., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010., Patients and Methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020., Results: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers., Conclusions: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)