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Background: Use of heart failure-exacerbating medications (HFEMs) may lead to preventable episodes of acute decompensated heart failure (HF). HFEMs use is common in patients with HF, and there may be opportunities to reduce their use from the emergency department (ED). Methods: We performed an observational study on patients with HF presenting to EDs within a healthcare system between 1 January 2016 and 31 December 2020. Patients with chronic HF were identified using diagnostic codes within the electronic health record. The cohort was restricted to ambulatory (i.e., discharged to home) ED encounters. Medications, either ordered in the ED or prescribed at ED discharge, were extracted from the medication administration record and identified as potential HFEMs based on the 2016 American Heart Association Scientific Statement. Descriptive statistics were used to summarize the prevalence of HFEM use during ambulatory ED encounters. Exploratory analyses to identify correlates of HFEM use were performed. Results: The study cohort included 23,907 ED encounters. ED administration or prescription of HFEMs occurred during 20% of ambulatory ED encounters. HFEM administration in the ED (17%) was more common than HFEM prescription at ED discharge (6%). The most common HFEMs administered in the ED included nonsteroidal anti-inflammatory drugs (11%) and albuterol (7%). Conclusion: HFEM use is common in patients with HF seeking ED care, occurring in roughly one-fifth of ambulatory ED encounters. There may be opportunities to optimize medication use among patients with HF in the ED. [ABSTRACT FROM AUTHOR]

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70–80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork. Teams should ideally include adult and paediatric endocrinologists, oncologists, cardiologists, surgeons, geneticists, pathologists, radiologists, clinical psychologists and nuclear medicine physicians. Provision of an international Consensus Statement should improve care and outcomes for children and adolescents with these tumours. Phaeochromocytomas and paragangliomas (PPGL) are rare endocrine tumours that can affect paediatric patients as well as adults. In this first international Consensus Statement on PPGL in paediatric patients, the authors discuss the diagnosis, management and long-term surveillance of these tumours in children and adolescents. [ABSTRACT FROM AUTHOR]

Introduction: There is a lack of biomarkers of clinically important diets, such as the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. Objectives: Our study explored serum metabolites associated with adherence to the MIND diet. Methods: In 3,908 Atherosclerosis Risk in Communities (ARIC) study participants, we calculated a modified MIND diet score based on a 66-item self-reported food frequency questionnaire (FFQ). The modified score did not include berries and olive oil, as these items were not assessed in the FFQ. We used multivariable linear regression models in 2 subgroups of ARIC study participants and meta-analyzed results using fixed effects regression to identify significant metabolites after Bonferroni correction. We also examined associations between these metabolites and food components of the modified MIND diet. C-statistics evaluated the prediction of high modified MIND diet adherence using significant metabolites beyond participant characteristics. Results: Of 360 metabolites analyzed, 27 metabolites (15 positive, 12 negative) were significantly associated with the modified MIND diet score (lipids, n = 13; amino acids, n = 5; xenobiotics, n = 3; cofactors and vitamins, n = 3; carbohydrates n = 2; nucleotide n = 1). The top 4 metabolites that improved the prediction of high dietary adherence to the modified MIND diet were 7-methylxanthine, theobromine, docosahexaenoate (DHA), and 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF). Conclusion: Twenty-seven metabolomic markers were correlated with the modified MIND diet. The biomarkers, if further validated, could be useful to objectively assess adherence to the MIND diet. [ABSTRACT FROM AUTHOR]

Background: Smartphone use in medicine is nearly universal despite a dearth of research assessing utility in clinical performance. We sought to identify and define smartphone use during simulated neuroemergencies. Methods: In this retrospective review of a prospective observational single-center simulation-based study, participants ranging from subinterns to attending physicians and stratified by training level (novice, intermediate, and advanced) managed a variety of neurological emergencies. The primary outcome was frequency and purpose of smartphone use. Secondary outcomes included success rate of smartphone use and performance (measured by completion of critical tasks) of participants who used smartphones versus those who did not. In subgroup analyses we compared outcomes across participants by level of training using t-tests and χ2 statistics. Results: One hundred and three participants completed 245 simulation scenarios. Smartphones were used in 109 (45%) simulations. Of participants using smartphones, 102 participants looked up medication doses, 52 participants looked up management guidelines, 11 participants looked up hospital protocols, and 13 participants used smartphones for assistance with an examination scale. Participants found the correct answer 73% of the time using smartphones. There was an association between participant level and smartphone use with intermediate participants being more likely to use their smartphones than novice or advanced participants, 53% versus 29% and 26%, respectively (p < 0.05). Of the intermediate participants, those who used smartphones did not perform better during the simulation scenario than participants who did not use smartphones (smartphone users' mean score [standard deviation] = 12.3 [2.9] vs. nonsmartphone users' mean score [standard deviation] = 12.9 (2.7), p = 0.85). Conclusions: Participants commonly used smartphones in simulated neuroemergencies but use didn't confer improved clinical performance. Less experienced participants were the most likely to use smartphones and less likely to arrive at correct conclusions, and thus are the most likely to benefit from an evidence-based smartphone application for neuroemergencies. [ABSTRACT FROM AUTHOR]

Purpose of Review: Stress urinary incontinence is a common condition and approximately 14% will undergo surgical intervention for treatment. Midurethral sling (MUS) is commonly indicated for the treatment of SUI, but up to 8% of women will under sling revision within 15 years of placement for complications. In this review, the current literature on functional outcomes after mid-urethral sling removal will be reviewed. Topics of focus include pain, dyspareunia, stress urinary incontinence, urgency urinary incontinence, and mixed incontinence. Recent Findings: Sling revision may be indicated for women who developed voiding dysfunction, pain, or mesh-related complications such as exposure or extrusion following MUS placement. There are multiple case series, retrospective and prospective studies describing the many aspects of this complex clinical scenario. Most are focused on identifying and reporting functional outcomes through urodynamics and validated questionnaires. The indication prompting sling revision does often improve following the revision, but the issue may persist, and additional treatments may be required. Summary: Development or resolution of any functional issues after MUS removal rely on the indication for removal, certain patient-specific factors, and the severity of symptoms prior to MUS removal. Although there is a significant number of studies concerning urethral sling removal management, more studies with a larger number of patients and more detailed data stratification are needed for addressing discreet functional outcomes after removal of mid-urethral sling. [ABSTRACT FROM AUTHOR]

We compare the abilities of earnings and cash flows to predict future cash flows. We take a novel approach in that we perform apples-to-apples comparisons of five earnings components measured on an accrual basis with their equivalents measured on a cash basis. On the one hand, we find that the operating profit component (sales net of cost of goods sold and SG&A expense) outperforms its cash-basis equivalent in predicting future cash flows. On the other hand, we find that the depreciation expense and non-operating income components underperform their cash-basis equivalents in predicting future cash flows. Additionally, we fail to find significant differences between the predictive abilities of the interest expense and income tax expense components and their cash-basis equivalents. The inconsistent findings across earnings components suggest that unequivocal all-or-nothing conclusions on the relative predictive abilities of earnings and cash flows are unwarranted. [ABSTRACT FROM AUTHOR]

Delineating voting districts is one of the most salient concerns of contemporary American society, and the creation of new voting maps, along with their subsequent legal challenges, speaks for much of our modern political discourse. The legal, societal, and political debate over serviceable voting districts demands a concept of fairness, which is a loosely characterized, but amorphous, concept that has evaded precise definition. We advance a new paradigm to compare voting maps that avoids the pitfalls associated with an a priori metric being used to uniformly assess maps. Our evaluative method instead shows how to use uncertain data envelopment analysis to assess maps on a variety of metrics, a tactic that permits each district to be assessed separately and optimally. We test our methodology on a collection of proposed and publicly available maps to illustrate our assessment strategy. [ABSTRACT FROM AUTHOR]

In this paper, we prove a global bifurcation result for the existence of non-radial branches of solutions to the paramterized family of Γ -symmetric equations - Δ u = f (α , z , u) , u | ∂ D = 0 on the unit disc D : = { z ∈ C : | z | < 1 } with u (z) ∈ R k , where R k is an orthogonal Γ -representation, f : R × D ¯ × R k → R k is a sub-linear Γ -equivariant continuous function, differentiable with respect to u at zero and satisfying the conditions f (α , e i θ z , u) = f (α , z , u) for all θ ∈ R and f (z , - u) = - f (z , u) . [ABSTRACT FROM AUTHOR]

Rates of ecosystem metabolic properties, such as plankton community respiration, can be used as an assessment of the eutrophication state of a waterbody and are the primary biogeochemical rates causing oxygen depletion in coastal waters. However, given the additional labor involved in measuring biogeochemical rate processes, few monitoring programs regularly measure these properties, and thus, few long-term monitoring records of plankton respiration exist. An 8-year, biweekly plankton community respiration rate time series was analyzed as part of a monitoring program situated in the lower Patuxent River estuary, a tributary of Chesapeake Bay. We found that particulate nutrients (nitrogen and phosphorus) were the most highly correlated covariates with respiration rate. Additionally, statistical and kinetic models including variables both water temperature and particulate nitrogen were able to explain 74% of the variability in respiration. Over the long-term record, both particulate nutrients and respiration rate were elevated when measured at higher tides. Separate measurements of respiration rate during 10 consecutive days and during high and low tide on three separate days also support the enhancement of respiration with high tide. The enhancement was likely due to the import of particulate nutrients from the highly productive mid-bay region. This analysis of the longest consistently measured community respiration rate dataset in Chesapeake Bay has implications for how to interpret long-term records of measurements made at fixed locations in estuaries. [ABSTRACT FROM AUTHOR]

To conserve or restore juvenile fish habitat, resource managers, restoration practitioners, and engineers need fine-scale information to understand what conditions they need to preserve or what specifications are needed to create new habitat. The objective of this study was to develop statistical models using a dataset of 18 coastal ponds in Southwest Florida, USA, to predict the abundance of juvenile common snook Centropomus undecimalis (hereafter snook) and presence of juvenile tarpon Megalops atlanticus, both of which are flagship species used for conservation and restoration of subtropical and tropical wetlands. Model predictors included water conditions and characteristics of vegetation, sediment, and geographic position. Modeling results indicated that juvenile snook used coastal ponds that were directly connected to tidal creeks. In contrast, juvenile tarpon were more likely to be present in coastal ponds that were separated from tidal creeks by dense mangrove forest (e.g., elevation > 0.48 m above Mean Low Water) characterized by highly organic sediment and low dissolved oxygen, to which tarpon are well adapted. Overlap between snook abundance and tarpon presence was greatest where connections between ponds and the nearest tidal creek were at a relatively low elevation (e.g., -0.12 m relative to Mean Low Water). Although these findings are most applicable to management and conservation of populations in areas along the Gulf coast of Florida (i.e., in areas of similar tidal range and coastal geomorphology), incorporating more detailed habitat surveys to better capture landscape context, geomorphology, and connectivity into fish sampling designs should be broadly applicable to estuarine fish ecology. [ABSTRACT FROM AUTHOR]

Parkinson's Disease (PD) is a debilitating neurodegenerative disorder, characterized by motor and cognitive impairments, that affects >1% of the population over the age of 60. The pathogenesis of PD is complex and remains largely unknown. Due to the cellular heterogeneity of the human brain and changes in cell type composition with disease progression, this complexity cannot be fully captured with bulk tissue studies. To address this, we generated single-nucleus RNA sequencing and whole-genome sequencing data from 100 postmortem cases and controls, carefully selected to represent the entire spectrum of PD neuropathological severity and diverse clinical symptoms. The single nucleus data were generated from five brain regions, capturing the subcortical and cortical spread of PD pathology. Rigorous preprocessing and quality control were applied to ensure data reliability. Committed to collaborative research and open science, this dataset is available on the AMP PD Knowledge Platform, offering researchers a valuable tool to explore the molecular bases of PD and accelerate advances in understanding and treating the disease. [ABSTRACT FROM AUTHOR]

The human cerebral cortex shows hemispheric asymmetry, yet the microstructural basis of this asymmetry remains incompletely understood. Here, we probe layer-specific microstructural asymmetry using one post-mortem male brain. Overall, anterior and posterior regions show leftward and rightward asymmetry respectively, but this pattern varies across cortical layers. A similar anterior-posterior pattern is observed using in vivo Human Connectome Project (N = 1101) T1w/T2w microstructural data, with average cortical asymmetry showing the strongest similarity with post-mortem-based asymmetry of layer III. Moreover, microstructural asymmetry is found to be heritable, varies as a function of age and sex, and corresponds to intrinsic functional asymmetry. We also observe a differential association of language and markers of mental health with microstructural asymmetry patterns at the individual level, illustrating a functional divergence between inferior-superior and anterior-posterior microstructural axes, possibly anchored in development. Last, we could show concordant evidence with alternative in vivo microstructural measures: magnetization transfer (N = 286) and quantitative T1 (N = 50). Together, our study highlights microstructural asymmetry in the human cortex and its functional and behavioral relevance. The human cortex displays an anterior-to-posterior asymmetry, identified via both post-mortem and in vivo microstructural measurements. Microstructural asymmetry is heritable, varies across cortical layers and between sexes, and relates to functional asymmetry and behavior. [ABSTRACT FROM AUTHOR]

The Colorado River drains about 8% of the conterminous United States, provides water for 40 million people, and is one of the most overallocated rivers in the world. As the upper Colorado River Basin (UCOL) contributes an estimated 92% of the total basin natural streamflow, knowledge of the location and amount of surface water withdrawals in the UCOL is important for managing the Colorado River system. Since the UCOL encompasses portions of five states, water use data are dispersed among numerous federal and state agency databases, and there is no centralized dataset that documents surface water use within the entire UCOL at a fine spatial and temporal resolution. This article presents an inventory of 1,358 major structures that divert surface water from and within the UCOL with corresponding daily time series withdrawal records from 1980 through 2022. Data compilation efforts, processing methods, and contents of this diversion database are documented, and summary information is provided. [ABSTRACT FROM AUTHOR]

Background: Champions of AI-facilitated clinical documentation have suggested that the emergent technology may decrease the administrative loads of physicians, thereby reducing cognitive burden and forestalling burnout. Explorations of physicians' experiences with automated documentation are critical in evaluating these claims. Objective: To evaluate physicians' experiences with DAX Copilot (DAXC), a generative AI-facilitated clinical documentation tool. Design: Semi-structured interviews were conducted in August and September of 2023 with physician-users of DAXC. Participants: A purposive sample of 12 interviewees, selected from 116 primary care physicians, employed at a multi-site academic learning health system. Approach: After completing all 12 interviews, three study personnel independently analyzed and coded the transcripts. Reconciliation sessions were then held to merge the three analyses into one summary, eliminating redundant codes, and grouping findings into themes. Key Results: For a majority of interviewees, DAXC reduced the amount of time spent documenting encounters, and alleviated anxieties of having to retain important clinical details until there was time to make notes. DAXC also allowed physicians to be more engaged during appointments, resulting in more personable provider-patient encounters. However, some physicians weighed these benefits against an uneasy feeling that interviewees might be asked to see more patients if DAXC was mandated. Physicians also noted that the tool would occasionally imagine or misgender patients, offer unsolicited and inappropriate diagnoses, and mistake critical details in transcription. The few physicians less enthusiastic about the generative technology portrayed themselves as creatures of habit who had cultivated long-standing workflows and particular notation practices that DAXC could neither improve upon nor reproduce. Conclusions: According to physician interviewees, automated AI-driven clinical documentation has the potential to significantly reduce the administrative burden associated with particular types of provider-patient encounters. Addressing the growing pains of the incipient technology, identified here, may allow for a broader applicability for clinical practice. [ABSTRACT FROM AUTHOR]

Mutations in ITM2B cause familial British, Danish, Chinese, and Korean dementias. In familial British dementia (FBD), a mutation in the stop codon of the ITM2B gene (also known as BRI2) causes a C-terminal cleavage fragment of the ITM2B/BRI2 protein to be extended by 11 amino acids. This fragment, termed amyloid-Bri (ABri), is highly insoluble and forms extracellular plaques in the brain. ABri plaques are accompanied by tau pathology, neuronal cell death and progressive dementia, with striking parallels to the aetiology and pathogenesis of Alzheimer's disease. The molecular mechanisms underpinning FBD are ill-defined. Using patient-derived induced pluripotent stem cells, we show that expression of ITM2B/BRI2 is 34-fold higher in microglia than neurons and 15-fold higher in microglia compared with astrocytes. This cell-specific enrichment is supported by expression data from both mouse and human brain tissue. ITM2B/BRI2 protein levels are higher in iPSC-microglia compared with neurons and astrocytes. The ABri peptide was detected in patient iPSC-derived microglial lysates and conditioned media but was undetectable in patient-derived neurons and control microglia. The pathological examination of post-mortem tissue supports the presence of ABri in microglia that are in proximity to pre-amyloid deposits. Finally, gene co-expression analysis supports a role for ITM2B/BRI2 in disease-associated microglial responses. These data demonstrate that microglia are major contributors to the production of amyloid forming peptides in FBD, potentially acting as instigators of neurodegeneration. Additionally, these data also suggest ITM2B/BRI2 may be part of a microglial response to disease, motivating further investigations of its role in microglial activation. These data have implications for our understanding of the role of microglia and the innate immune response in the pathogenesis of FBD and other neurodegenerative dementias including Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Wolverine distribution contracted along the southern periphery of its range in North America during the 19th and 20th centuries due primarily to human influences. This history, along with low densities, sensitivity to climate change, and concerns about connectivity among fragmented habitats spurred the recent US federal listing of threatened status and special concern status in Canada. To help inform large scale landscape connectivity, we collected 882 genetic samples genotyped at 19 microsatellite loci. We employed multiple statistical models to assess the landscape factors (terrain complexity, human disturbance, forest configuration, and climate) associated with wolverine genetic connectivity across 2.2 million km2 of southwestern Canada and the northwestern contiguous United States. Genetic similarity (positive spatial autocorrelation) of wolverines was detected up to 555 km and a high-to-low gradient of genetic diversity occurred from north-to-south. Landscape genetics analyses confirmed that wolverine genetic connectivity has been negatively influenced by human disturbance at broad scales and positively influenced by forest cover and snow persistence at fine- and broad–scales, respectively. This information applied across large landscapes can be used to guide management actions with the goal of maintaining or restoring population connectivity. [ABSTRACT FROM AUTHOR]

Extreme short-duration rainfall is intensifying with climate warming, and growing evidence suggests that subhourly rainfall extremes are increasing faster than more widely studied durations at hourly and daily timescales. In this case study, we used 55 years (1968–2022) of 5-min precipitation data from Mahantango Creek, a long-term experimental agricultural watershed in east-central Pennsylvania, United States, to examine annual and seasonal changes in subhourly (15-min), hourly, and daily rainfall extremes. Specifically, we evaluated temporal trends in the magnitude and frequency of subhourly, hourly, and daily rainfall extremes. We then estimated apparent scaling rates between rainfall extremes and dew point temperature (Td) and compared these rates to the Clausius-Clapeyron (CC) rate (∼ 7% per °C). We also determined the coincidence of extreme rainfall trends with indicators of atmospheric instability and convective-type precipitation. Overall, we found the most significant changes in rainfall extremes at 15-min durations during the spring, with magnitudes of these subhourly extremes increasing by 0.6 to 0.9% per year, and frequencies rising by 3.4% per year. Apparent scaling rates in the spring showed that 15-min rainfall extremes transitioned from sub-CC scaling to greater than 2CC scaling when Td reached 11° C, implying a possible shift from stratiform rains to more intense convective rains above this Td threshold. Notably, trends in maximum hourly convective available potential energy (CAPE) increased during spring, as did the ratio of 15-min rainfall extremes to their corresponding daily rainfall totals. Findings indicate that convective-type precipitation may be playing an increasing role in the intensification of springtime 15-min rainfall extremes in Mahantango Creek. [ABSTRACT FROM AUTHOR]

Accurately identifying periodontal landmarks via acoustic imaging is increasingly important. Here, we evaluated the accuracy of cementoenamel junction (CEJ) identification using ultrasound by comparing it to clinical methods in 153 extracted human teeth. The distance between the CEJ to a reference point was measured using two clinical methods (visual examination and tactile sensation) as well as ultrasound imaging. Statistical analyses were performed across all teeth and sub-groups, including tooth types (incisors, cuspids, and molars/premolars), and two classifications: A- vs. B- (visually detectable or undetectable CEJ, respectively); and CL-S vs. CL-D (shallow or deep cervical lesions). In A- or CL-S teeth, ultrasound measurements highly agreed with clinical measurements, showing a 1.72-mm 95% CI for A- and 1.99-mm 95% CI for CL-S compared to visual examination, and a 1.77-mm 95% CI for A- and a 2.10-mm 95% CI for CL-S compared to tactile sensation, respectively. For 80% of A- and 76% of CL-S teeth, the difference between ultrasound and visual examination was within ± 20%. For 81% of A- and 80% of CL-S teeth, the difference between ultrasound and tactile sensation was within ± 20%. The variance of ultrasound versus clinical CEJ identifications showed a significant correlation (r = 0.6607) to the cervical lesion depth. The errors between ultrasound and clinical measurements show no significant bias across different tooth types. [ABSTRACT FROM AUTHOR]

Fast radio bursts (FRBs) are millisecond-duration events detected from beyond the Milky Way. FRB emission characteristics favour highly magnetized neutron stars, or magnetars, as the sources1, as evidenced by FRB-like bursts from a galactic magnetar2,3, and the star-forming nature of FRB host galaxies4,5. However, the processes that produce FRB sources remain unknown6. Although galactic magnetars are often linked to core-collapse supernovae (CCSNe)7, it is uncertain what determines which supernovae result in magnetars. The galactic environments of FRB sources can be used to investigate their progenitors. Here, we present the stellar population properties of 30 FRB host galaxies discovered by the Deep Synoptic Array (DSA-110). Our analysis shows a marked deficit of low-mass FRB hosts compared with the occurrence of star formation in the Universe, implying that FRBs are a biased tracer of star formation, preferentially selecting massive star-forming galaxies. This bias may be driven by galaxy metallicity, which is positively correlated with stellar mass8. Metal-rich environments may favour the formation of magnetar progenitors through stellar mergers9,10, as higher-metallicity stars are less compact and more likely to fill their Roche lobes, leading to unstable mass transfer. Although massive stars do not have convective interiors to generate strong magnetic fields by dynamo11, merger remnants are thought to have the requisite internal magnetic-field strengths to result in magnetars11,12. The preferential occurrence of FRBs in massive star-forming galaxies suggests that a core-collapse supernova of merger remnants preferentially forms magnetars.Analysis of the stellar population properties of 30 host galaxies of fast radio bursts (FRBs) suggests an abundance of FRBs in massive star-forming galaxies, and implies that the formation of FRB sources—magnetars—is linked to core-collapse supernovae of stellar merger remnants. [ABSTRACT FROM AUTHOR]

Purpose: Pediatric brain tumor survivors can experience detrimental effects from radiation treatment. This cross-sectional, large cohort study examined late psychosocial and executive functioning effects in pediatric patients treated ≥ 3 years after proton radiation therapy (PRT). Methods: Parents of 101 pediatric brain tumor survivors completed the Behavior Assessment System for Children and the Behavior Rating Inventory of Executive Function. Standard scores were compared to published normative means, rates of impairment (T-score > 65) were calculated, and demographic and clinical characteristics were examined. Results: Mean age at PRT was 8.12 years and mean interval from PRT to assessment was 6.05 years. Half were female (49.5%), 45.5% received craniospinal irradiation (CSI), and 58.4% were diagnosed with infratentorial tumors. All mean T-scores were within normal range. Mean T-scores were significantly elevated compared to the norm on the withdrawal, initiate, working memory, and plan/organize scales. Rates of impairment were notably high in working memory (24.8%), initiate (20.4%), withdrawal (18.1%), and plan/organize (17.0%). Greater withdrawal was significantly associated with CSI and also with chemotherapy and diagnosis of hearing loss. Mean T-scores were significantly lower than the norm on the hyperactivity, aggression, conduct problems, and inhibition scales. No significant problems were identified with social skills or depression. Interval since treatment was not correlated with any scale. Conclusion: Although psychosocial and executive functioning was within the normal range, on average, social withdrawal and metacognitive executive functioning (working memory, initiating, planning/organizing) were areas of concern. Targeted yearly screening and proactive executive skill and social interventions are needed for this population. [ABSTRACT FROM AUTHOR]

Purpose: To report osteoporosis screening utilization rates among Asian American (AsA) populations in the USA. Methods: We retrospectively assessed the use of dual-energy X-ray absorptiometry (DXA) screening using the Medicare 5% Research Identifiable Files. Using Current Procedural Terminology (CPT) codes indicative of a DXA scan, we identified patients recommended for DXA screening according to the ACR-SPR-SSR Practice Parameters (females ≥ 65 years, males ≥ 70 years). Sociodemographic factors and their association with screening were evaluated using chi-square tests. Results: There were 80,439 eligible AsA beneficiaries, and 12,102 (15.1%) received osteoporosis screening. DXA rate for women was approximately four times greater than the rate for men (19.8% vs. 5.0%; p < 0.001). AsA beneficiaries in zip codes with higher mean household income (MHI) were more likely to have DXA than those in lower MHI areas (17.6% vs. 14.3%, p < 0.001). AsA beneficiaries aged < 80 were more likely to receive DXA (15.5%) than those aged ≥ 80 (14.1%, p < 0.001). There were 2,979,801 eligible non-AsA beneficiaries, and 496,957 (16.7%) received osteoporosis screening during the study period. Non-Hispanic white beneficiaries had the highest overall screening rate (17.5%), followed by North American Native (13.0%), Black (11.8%), and Hispanic (11.1%) beneficiaries. Comparing AsA to non-AsA populations, there were significantly lower DXA rates among AsA beneficiaries when controlling for years of Medicare eligibility, patient age, sex, location, and mean income (p < 0.001). Conclusion: We found lower than expected DXA screening rates for AsA patients. A better understanding of the barriers and facilitators to AsA osteoporosis screening is needed to improve patient care. [ABSTRACT FROM AUTHOR]

Accelerating text input in augmentative and alternative communication (AAC) is a long-standing area of research with bearings on the quality of life in individuals with profound motor impairments. Recent advances in large language models (LLMs) pose opportunities for re-thinking strategies for enhanced text entry in AAC. In this paper, we present SpeakFaster, consisting of an LLM-powered user interface for text entry in a highly-abbreviated form, saving 57% more motor actions than traditional predictive keyboards in offline simulation. A pilot study on a mobile device with 19 non-AAC participants demonstrated motor savings in line with simulation and relatively small changes in typing speed. Lab and field testing on two eye-gaze AAC users with amyotrophic lateral sclerosis demonstrated text-entry rates 29–60% above baselines, due to significant saving of expensive keystrokes based on LLM predictions. These findings form a foundation for further exploration of LLM-assisted text entry in AAC and other user interfaces. Individuals with severe motor impairments use gaze to type and communicate. This paper presents a large language model-based user interface that enables gaze typing in highly abbreviated forms, achieving significant motor saving and speed gain. [ABSTRACT FROM AUTHOR]

Purpose: This brief report examined associations between animal consumption and intimate partner aggression in a sample of undergraduates. Two possible explanatory variables for these associations, depressive symptoms and speciesism, were also examined. Methods: Participants included 245 undergraduate students who provided electronic consent and completed a one-time anonymous survey. Results: Results indicated that animal consumption was associated with higher use of physical and psychological intimate partner aggression, even after accounting for other correlates. Animal consumption was also associated with higher speciesism, and speciesism was associated with higher use of physical and psychological intimate partner aggression. Conclusions: Results extend findings from prior studies documenting links between animal consumption and negative outcomes and further suggest that speciesism may play a role in understanding links between animal consumption and intimate partner aggression. [ABSTRACT FROM AUTHOR]

Objectives: Sealers are an important component in root canal obturation to provide the seal of the root canal system. In recent years, there has been an increase in the use of hydraulic silicate sealers, commonly referred to as bioceramic sealers, due to their many advantageous properties. NeoSealer Flo (NS; Avalon Biomed USA, Houston TX) is a recently introduced premixed bioceramic sealer. There is limited evidence on its properties and clinical performance. Therefore, the purpose of this study was to evaluate the outcome of root canal treatment using NS in a sealer-based obturation technique. Materials and Methods: The records of patients in a private practice between 2017 and 2022 were analyzed to identify both initial and retreatment cases obturated with either EndoSequence BC sealer or NS using sealer-based obturation with a minimum of one-year follow-up. Treatment outcome between NS and BC was compared with chi-square test. Logistic regression was used to identify additional prognostic factors. Results: Six hundred and eighty-seven teeth met the inclusion criteria for the study. The success rate of cases obturated with BC was 94.9% and 96.5% for the cases obturated with NS. No statistically significant differences were found between the two sealer types. Presence of a periapical radiolucency or periapical radiolucency > 5.00 mm were statistically significant prognostic factors. Conclusions: Endodontic treatment using BC or NS with sealer-based obturation method is a viable treatment option. Clinical Relevance: Root canal obturation with bioceramic sealers, such as NeoSealer Flo and Endosequence BC sealer, provide favorable clinical outcomes. [ABSTRACT FROM AUTHOR]

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Multinucleated skeletal muscle cells need to acquire additional nuclei through fusion with activated skeletal muscle stem cells when responding to both developmental and adaptive growth stimuli. A fundamental question in skeletal muscle biology has been the reason underlying this need for new nuclei in cells that already harbor hundreds of nuclei. Here we utilize nuclear RNA-sequencing approaches and develop a lineage tracing strategy capable of defining the transcriptional state of recently fused nuclei and distinguishing this state from that of pre-existing nuclei. Our findings reveal the presence of conserved markers of newly fused nuclei both during development and after a hypertrophic stimulus in the adult. However, newly fused nuclei also exhibit divergent gene expression that is determined by the myogenic environment to which they fuse. Moreover, accrual of new nuclei through fusion is required for nuclei already resident in adult myofibers to mount a normal transcriptional response to a load-inducing stimulus. We propose a model of mutual regulation in the control of skeletal muscle development and adaptations, where newly fused and pre-existing myonuclear populations influence each other to maintain optimal functional growth. Skeletal muscle cells contain hundreds of nuclei, but can also add new nuclei in response to various stimuli. Here, the authors perform lineage tracing on the newly fused nuclei showing that these exhibit unique transcriptional states depending on the stimulus. [ABSTRACT FROM AUTHOR]

Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a few other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad spectrum of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers. In particular, CAST/EiJ, a wild-derived strain, developed high lung viral burdens, more severe lung pathology than seen in other CC strains, and a dysregulated cytokine profile resulting in morbidity and mortality. These inbred mouse strains may serve as a valuable platform to evaluate therapeutic countermeasures against severe COVID-19 and other coronavirus pandemics in the future. [ABSTRACT FROM AUTHOR]

Background: The number of Hospital-at-Home (HaH) programs rapidly increased during the COVID-19 pandemic and after issuance of Centers for Medicare and Medicaid Services' (CMS) Acute Hospital Care at Home (AHCaH) waiver. However, there remains little evidence on effective strategies to equitably expand HaH utilization. Objective: Evaluate the effects of a multifaceted implementation strategy on HaH utilization over time. Design: Before and after implementation evaluation using electronic health record (EHR) data and interrupted time series analysis, complemented by qualitative interviews with key stakeholders. Participants: Between December 2021 and December 2022, we identified adults hospitalized at six hospitals in North Carolina approved by CMS to participate in the AHCaH waiver program. Eligible adults met criteria for HaH transfer (HaH-eligible clinical condition, qualifying home environment). We conducted semi-structured interviews with 12 HaH patients and 10 referring clinicians. Interventions: Two strategies were studied. The discrete implementation strategy (weeks 1–12) included clinician-directed educational outreach. The multifaceted implementation strategy (weeks 13–54) included ongoing clinician-directed educational outreach, local HaH assistance via nurse navigators, involvement of clinical service line executives, and individualized audit and feedback. Measures: We assessed weekly averaged HaH capacity utilization, weekly counts of unique referring providers, and patient characteristics. We analyzed themes from qualitative data to determine barriers and facilitators to HaH use. Results: Our evaluation showed week-to-week increases in HaH capacity utilization during the multifaceted implementation strategy period, compared to discrete-period trends (slope-change odds ratio—1.02, 1.01–1.04). Counts of referring providers also increased week to week, compared to discrete-period trends (slope-change means ratio—1.05, 1.03–1.07). The increase in HaH utilization was largest among rural residents (11 to 34%). Barriers included HaH-related information gaps and referral challenges; facilitators included patient-centeredness of HaH care. Conclusions: A multifaceted implementation strategy was associated with increased HaH capacity utilization, provider adoption, and patient diversity. Health systems may consider similar, contextually relevant multicomponent approaches to equitably expand HaH. [ABSTRACT FROM AUTHOR]

Video recordings accurately capture facial expression movements; however, they are difficult for face perception researchers to standardise and manipulate. For this reason, dynamic morphs of photographs are often used, despite their lack of naturalistic facial motion. This study aimed to investigate how humans perceive emotions from faces using real videos and two different approaches to artificially generating dynamic expressions – dynamic morphs, and AI-synthesised deepfakes. Our participants perceived dynamic morphed expressions as less intense when compared with videos (all emotions) and deepfakes (fearful, happy, sad). Videos and deepfakes were perceived similarly. Additionally, they perceived morphed happiness and sadness, but not morphed anger or fear, as less genuine than other formats. Our findings support previous research indicating that social responses to morphed emotions are not representative of those to video recordings. The findings also suggest that deepfakes may offer a more suitable standardized stimulus type compared to morphs. Additionally, qualitative data were collected from participants and analysed using ChatGPT, a large language model. ChatGPT successfully identified themes in the data consistent with those identified by an independent human researcher. According to this analysis, our participants perceived dynamic morphs as less natural compared with videos and deepfakes. That participants perceived deepfakes and videos similarly suggests that deepfakes effectively replicate natural facial movements, making them a promising alternative for face perception research. The study contributes to the growing body of research exploring the usefulness of generative artificial intelligence for advancing the study of human perception. [ABSTRACT FROM AUTHOR]

Pragma-Dialectics (PD) is an approach to argumentation that can be described as disagreement-centric. On PD, disagreement is the condition which defines argument, it is the practical problem to be solved by it, and disagreement's management is the ultimate source of argument's normativity. On PD, arguing in the context of agreement is taken to be "incorrect" and arguments where agreement already reigns are "pointless." Even the PD account of fallacies is disagreement-centered: a fallacy is something that impedes resolution of a dispute. We argue here that the disagreement-focus of PD yields procedural errors of application in cases of arguments given explicitly for agreement-management, that there are explanations of fallacies better understood as agreement-focused (straw man and ad hominem in particular), and that there are unique meta-argumentative errors emergent in instances of agreement. [ABSTRACT FROM AUTHOR]

Multimodal neuroimaging grants a powerful in vivo window into the structure and function of the human brain. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends – or gradients – in brain structure and function, offering a framework to unify principles of brain organization across multiple scales. Strong community enthusiasm for these techniques has been instrumental in their widespread adoption and implementation to answer key questions in neuroscience. Following a brief review of current literature on this framework, this perspective paper will highlight how pragmatic steps aiming to make gradient methods more accessible to the community propelled these techniques to the forefront of neuroscientific inquiry. More specifically, we will emphasize how interest for gradient methods was catalyzed by data sharing, open-source software development, as well as the organization of dedicated workshops led by a diverse team of early career researchers. To this end, we argue that the growing excitement for brain gradients is the result of coordinated and consistent efforts to build an inclusive community and can serve as a case in point for future innovations and conceptual advances in neuroinformatics. We close this perspective paper by discussing challenges for the continuous refinement of neuroscientific theory, methodological innovation, and real-world translation to maintain our collective progress towards integrated models of brain organization. [ABSTRACT FROM AUTHOR]

Purpose: Our study aimed to provide consensus and expert clinical practice statements related to airway management in critically ill adults with a physiologically difficult airway (PDA). Methods: An international Steering Committee involving seven intensivists and one Delphi methodology expert was convened by the Society of Critical Care Anaesthesiologists (SOCCA) Physiologically Difficult Airway Task Force. The committee selected an international panel of 35 expert clinician–researchers with expertise in airway management in critically ill adults. A Delphi process based on an iterative approach was used to obtain the final consensus statements. Results: The Delphi process included seven survey rounds. A stable consensus was achieved for 53 (87%) out of 61 statements. The experts agreed that in addition to pathophysiological conditions, physiological alterations associated with pregnancy and obesity also constitute a physiologically difficult airway. They suggested having an intubation team consisting of at least three healthcare providers including two airway operators, implementing an appropriately designed checklist, and optimizing hemodynamics prior to tracheal intubation. Similarly, the experts agreed on the head elevated laryngoscopic position, routine use of videolaryngoscopy during the first attempt, preoxygenation with non-invasive ventilation, careful mask ventilation during the apneic phase, and attention to cardiorespiratory status for post-intubation care. Conclusion: Using a Delphi method, agreement among a panel of international experts was reached for 53 statements providing guidance to clinicians worldwide on safe tracheal intubation practices in patients with a physiologically difficult airway to help improve patient outcomes. Well-designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties. [ABSTRACT FROM AUTHOR]

Background: Acetaminophen toxicity remains one of the most common causes of liver failure and is treated with a course of n-acetylcysteine (NAC). This exceptionally effective medication is traditionally administered using a complicated three-bag protocol that is prone to administration errors. Objective: We aimed to assess whether switching to a novel two-bag protocol (150 mg/kg over 1 h followed by 150 mg/kg over 20 h) reduced administration errors while not increasing liver injury or anaphylactoid reactions. Methods: This was a retrospective chart review of hospital encounters for patients with acetaminophen toxicity, comparing outcomes before and after the change from a three-bag protocol to a two-bag protocol at two affiliated institutions. The primary outcome was incidence of medication errors with secondary outcomes including acute liver injury (ALI) and incidence of non-anaphylactoid allergic reactions (NAAR). The study was approved by the health system's Institutional Review Board. Results: 483 encounters were included for analysis (239 in the three-bag and 244 in the two-bag groups). NAAR were identified in 11 patients with no difference seen between groups. Similarly, no differences were seen in ALI. Medication administration errors were observed significantly less often in the two-bag group (OR 0.24) after adjusting for confounders. Conclusion: Transitioning to a novel two-bag NAC regimen decreased administration errors. This adds to the literature that two-bag NAC regimens are not only safe but also may have significant benefits over the traditional NAC protocol. [ABSTRACT FROM AUTHOR]

Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative1–6, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 107 chemical synapses7 between 139,255 neurons reconstructed from an adult female Drosophila melanogaster8,9. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities10–12. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome—a map of projections between regions—from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.FlyWire presents a neuronal wiring diagram of the whole fly brain with annotations for cell types, classes, nerves, hemilineages and predicted neurotransmitters, with data products and an open ecosystem to facilitate exploration and browsing. [ABSTRACT FROM AUTHOR]

Reliable electricity, elevators, heat, hot water, and water are aspects of safe and accessible housing. Interruptions to these services represent a persistent challenge faced by public housing residents in the New York City Housing Authority (NYCHA). We compiled outage data spanning 2020–2022 from NYCHA's online service interruptions portal and paired these data with demographic and meteorological sources to understand the burden of these outages. To ease dissemination of these data—a spatiotemporally granular outage dataset that could fill gaps surrounding urban outage health impacts—we provide a public dashboard for visualization and download of the service interruption data in an analysis-ready format. We demonstrated that (1) outages often exceeded health-relevant restoration windows (e.g., 8 h for electrical interruptions); (2) senior developments (exclusively residents 62 +) had the longest duration of elevator, heat, and hot water outages; and (3) outages sometimes overlapped with temperature extremes—potentially increasing their health risk. Residents of NYCHA, who are predominately low-income, Black, and Hispanic face a disproportionate burden of service interruptions. Like all New Yorkers, NYCHA residents deserve to live in dignified housing that is safe and accessible. Addressing service interruptions are one way to make public housing safer and push toward climate and environmental justice. [ABSTRACT FROM AUTHOR]

Concerns have been raised that cross-agency differences in the definition and measurement of juvenile recidivism may hamper the generalizability of knowledge and comparisons across jurisdictions. However, it is unclear whether measurement choices do impact the conclusions of studies of juvenile recidivism. This study examined whether the rates and the demographic, risk, and contextual predictors of juvenile recidivism varied by the operationalization of recidivism. The sample included 14,537 terms of probation of youths who completed probation in Florida between 2012 and 2016. Recidivism rates differed depending on the type of system contact and the follow-up length. Rates were comparable when adult system data were and were not included. Three-level multivariate multilevel models showed that the predictors were more strongly associated with commitment than with referral or adjudication. The directions and significance of the predictors' effects were consistent across types of system contact, follow-up lengths, and data sources. Researchers should use varied measurement strategies, clearly describe their approach, and test for robustness across measures. [ABSTRACT FROM AUTHOR]

Purpose: To better understand preferences and attitudes that adult-aged survivors of childhood cancer have toward survivorship care plans (SCP) and related SCP-based counseling. Methods: Semi-structured qualitative interviews were conducted with 20 survivors participating in the Childhood Cancer Survivor Study who were at increased risk for cardiovascular disease secondary to their original cancer treatment. All participants were part of a larger randomized clinical trial (NCT03104543) testing the efficacy of an SCP-based counseling intervention with goal-setting designed to improve control of cardiovascular risk factors (i.e., hypertension, dyslipidemia, diabetes). A primarily deductive thematic analysis methodology guided interpretation; coded interview segments were grouped into primary themes of facilitators, barriers, suggestions, and positive sentiments. Results: Participants described benefits of the intervention including facilitation of accountability, goal-setting, and increased knowledge of their health. Many participants also noted improved knowledge of their cancer treatment and subsequent risks, and they were interested in sharing this information with their primary care provider. However, several participants were disappointed when they did not achieve their goals or felt that they had low motivation. Participants generally wanted increased flexibility in the intervention, whether in the duration, frequency, or method of delivery. Conclusions: The SCP-based intervention was generally well-received by those interviewed and appears promising for promoting goal-setting and accountability as part of an SCP-based intervention to improve control of cardiovascular risk factors. Implications for Cancer Survivors: Many survivors are at risk for cardiovascular disease or other potentially modifiable effects of their treatment. SCP-based interventions may facilitate improved control of these late effects. [ABSTRACT FROM AUTHOR]

Spiritual wellbeing is known to be a predictor of increased patient coping in hospital settings. Therefore, access to a valid and reliable measure of spiritual wellbeing amongst general hospital patients is highly recommended. The aim of this study was to investigate the dimensionality, reliability, and validity of the Functional Assessment of Chronic Illness Therapy Spiritual Wellbeing scale (FACIT-Sp-12) in a heterogeneous cohort of hospital patients. A cross-sectional survey was administered to 897 adult patients across six hospitals in Sydney, Australia. Confirmatory factor analysis for the three-factor FACIT-12-Sp indicated a poor fit, but after removal of Item 12, the three-factor FACIT-11-Sp presented a good fit to the data. Reliability testing indicated acceptable to good internal consistency. Validity was supported by statistically significant differences between patients who considered themselves 'both spiritual and religious' and 'not religious or spiritual'. While some caution should be taken when using the FACIT-Sp due to several limitations, nevertheless, in a general hospital population in Australia, the three-factor FACIT-11-Sp indicated good dimensionality, reliability, and validity. [ABSTRACT FROM AUTHOR]

As launch capabilities and interest in Cislunar missions expand for commercial, government, and military actors alike, so grows the necessity for a robust architecture in the Cislunar region for conducting Space Domain Awareness (SDA). Among the numerous objectives associated with constructing a robust Cislunar SDA architecture, of particular interest is creating an architecture that is cost effective for both architecture users and maintainers. This paper builds on previous work of using reinforcement learning methods to solve the multi-objective Cislunar architecture design problem by modeling a cooperative architecture user that seeks to maximize detectability by the architecture while minimizing total delta-v needed to do so. We also introduce a novel clustering method by which architectures explored during optimization are be grouped together, allowing us to better understand how observers must work in concert to produce optimal results. Through the interactions between the cooperative agent and architectures, we can further our understanding of the architecture design process while gaining insights into the fundamental qualities of a robust Cislunar architecture. [ABSTRACT FROM AUTHOR]

Purpose: Specialised group-based exercise rehabilitation is beneficial for cancer survivors but access to these services is limited. Telerehabilitation provides an opportunity to expand reach, but we do not know about the experiences of those who participate in this way. This study explored participant experiences of an exercise-based telerehabilitation program for people with cancer. Method: A qualitative study using semi-structured interviews was completed. Twenty-two cancer survivors were purposively sampled from the experimental group of a randomised controlled trial evaluating exercise-based cancer telerehabilitation delivered in groups using synchronous videoconferencing. Interviews were audio-recorded and transcribed verbatim. Data were coded independently by two reviewers and analysed inductively by thematic analysis. Results: ‘A feeling of connection’ was the overarching theme. Participants perceived they connected with the health service, expert health professionals, and peers through participating in the telerehabilitation program. These connections provided a personalised rehabilitation experience and improved perceptions of physical and emotional well-being. Two subthemes suggested connection was facilitated by (1) the acceptability of telerehabilitation and (2) enhanced accountability to exercise. Participants felt disconnected when they were unable to participate in the program due to cancer treatment and side effects (e.g. fatigue), feeling unwell, and co-morbidities. Conclusion: We identified that telerehabilitation facilitated connections that enhanced the reach of exercise to cancer survivors. Our findings support using telerehabilitation to deliver specialised group-based exercise programs alongside more traditional models of care to increase participation in exercise among people with cancer. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Understanding the impact of the overall construct of ultra-processed foods on diabetes risk can inform dietary approaches to diabetes prevention. In this study, we aimed to evaluate the association between ultra-processed food consumption and risk of diabetes in a community-based cohort of middle-aged adults in the USA. We hypothesised that a higher intake of ultra-processed foods is associated with a higher risk of incident diabetes. Methods: The study included 13,172 participants without diabetes at baseline (1987–1989) in the Atherosclerosis Risk in Communities (ARIC) study. Dietary intake was assessed with a 66-item semiquantitative food frequency questionnaire, and foods were categorised by processing level using the Nova classification system. Ultra-processed food was analysed categorically (quartiles of energy-adjusted intake) and continuously (per one additional serving/day). We used Cox regression to evaluate the association of ultra-processed food intake with risk of diabetes with adjustment for sociodemographic characteristics, total energy intake, health behaviours and clinical factors. Results: Over a median follow-up of 21 years, there were 4539 cases of incident diabetes. Participants in the highest quartile of ultra-processed food intake (8.4 servings/day on average) had a significantly higher risk of diabetes (HR 1.13; 95% CI 1.03, 1.23) compared with participants in the lowest quartile of intake after adjustment for sociodemographic, lifestyle and clinical factors. Each additional serving of ultra-processed food consumed daily was associated with a 2% higher risk of diabetes (HR 1.02; 95% CI 1.00, 1.04). Highest quartile consumption of certain ultra-processed food groups, including sugar- and artificially sweetened beverages, ultra-processed meats and sugary snacks, was associated with a 29%, 21% and 16% higher risk of diabetes, respectively, compared with the lowest quartile. Conclusions/interpretation: We found that a higher intake of ultra-processed food was associated with higher risk of incident diabetes, particularly sugar- and artificially sweetened beverages, ultra-processed meats and sugary snacks. Our findings suggest interventions reducing ultra-processed food consumption and specific food groups may be an effective strategy for diabetes prevention. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Strategies to augment functional beta cell mass include directed differentiation of stem cells towards a beta cell fate, which requires extensive knowledge of transcriptional programs governing endocrine progenitor cell differentiation in vivo. We aimed to study the contributions of the Brahma-related gene-1 (BRG1) and Brahma (BRM) ATPase subunits of the SWI/SNF chromatin remodelling complex to endocrine cell development. Methods: We generated mice with endocrine progenitor-specific Neurog3-Cre BRG1 removal in the presence of heterozygous (Brg1Δendo;Brm+/−) or homozygous (double knockout: DKOΔendo) BRM deficiency. Whole-body metabolic phenotyping, islet function characterisation, islet quantitative PCR and histological characterisation were performed on animals and tissues postnatally. To test the mechanistic actions of SWI/SNF in controlling gene expression during endocrine cell development, single-cell RNA-seq was performed on flow-sorted endocrine-committed cells from embryonic day 15.5 control and mutant embryos. Results: Brg1Δendo;Brm+/− mice exhibit severe glucose intolerance, hyperglycaemia and hypoinsulinaemia, resulting, in part, from reduced islet number; diminished alpha, beta and delta cell mass; compromised islet insulin secretion; and altered islet gene expression programs, including reductions in MAFA and urocortin 3 (UCN3). DKOΔendo mice were not recovered at weaning; however, postnatal day 6 DKOΔendo mice were severely hyperglycaemic with reduced serum insulin levels and beta cell area. Single-cell RNA-seq of embryonic day 15.5 lineage-labelled cells revealed endocrine progenitor, alpha and beta cell populations from SWI/SNF mutants have reduced expression of Mafa, Gcg, Ins1 and Ins2, suggesting limited differentiation capacity. Reduced Neurog3 transcripts were discovered in DKOΔendo endocrine progenitor clusters, and the proliferative capacity of neurogenin 3 (NEUROG3)+ cells was reduced in Brg1Δendo;Brm+/− and DKOΔendo mutants. Conclusions/interpretation: Loss of BRG1 from developing endocrine progenitor cells has a severe postnatal impact on glucose homeostasis, and loss of both subunits impedes animal survival, with both groups exhibiting alterations in hormone transcripts embryonically. Taken together, these data highlight the critical role SWI/SNF plays in governing gene expression programs essential for endocrine cell development and expansion. Data availability: Raw and processed data for scRNA-seq have been deposited into the NCBI Gene Expression Omnibus (GEO) database under the accession number GSE248369. [ABSTRACT FROM AUTHOR]

Platinum and ruthenium nanoparticles stabilised by an amine modified polymer immobilised ionic liquid (MNP@NH2-PEGPIILS, M = Pt, Ru) catalyse the hydrolytic liberation of hydrogen from dimethylamine borane (DMAB), ammonia borane (AB) and NaBH4 under mild conditions. While RuNP@NH2-PEGPIILS and PtNP@NH2-PEGPIILS catalyse the hydrolytic evolution of hydrogen from NaBH4 with comparable initial TOFs of 6,250 molesH2.molcat−1.h−1 and 5,900 molesH2.molcat−1.h−1, respectively, based on the total metal content, RuNP@NH2-PEGPIILS is a markedly more efficient catalyst for the dehydrogenation of DMAB and AB than its platinum counterpart, as RuNP@NH2-PEGPIILS gave initial TOFs of 8,300 molesH2.molcat−1.h−1 and 21,200 molesH2.molcat−1.h−1, respectively, compared with 3,050 molesH2.molcat−1.h−1 and 8,500 molesH2.molcat−1.h−1, respectively, for PtNP@NH2-PEGPIILS. Gratifyingly, for each substrate tested RuNP@NH2-PEGPIILS and PtNP@NH2-PEGPIILS were markedly more active than commercial 5wt % Ru/C and 5wt% Pt/C, respectively. The apparent activation energies of 55.7 kJ mol−1 and 27.9 kJ mol−1 for the catalytic hydrolysis of DMAB and AB, respectively, with RuNP@NH2-PEGPIILS are significantly lower than the respective activation energies of 74.6 kJ mol−1 and 35.7 kJ mol−1 for its platinum counterpart, commensurate with the markedly higher initial rates obtained with the RuNPs. In comparison, the apparent activation energies of 44.1 kJ mol−1 and 46.5 kJ mol−1, for the hydrolysis NaBH4 reflect the similar initial TOFs obtained for both catalysts. The difference in apparent activation energies for the hydrolysis of DMAB compared with AB also reflect the higher rates of hydrolysis for the latter. Stability and reuse studies revealed that RuNP@NH2-PEGPIILS recycled efficiently as high conversions for the hydrolysis of DMAB were maintained across five runs with the catalyst retaining 97% of its activity. [ABSTRACT FROM AUTHOR]

Prions are proteinaceous infectious particles implicated in fatal neurodegenerative disorders known as prion diseases. Herein, we provide an overview of prion biology, emphasizing the structural, functional, and evolutionary aspects of prions, along with their potential applications in protein engineering. Understanding the structure-function relationships of both healthy and disease-associated prion proteins enables a deeper understanding of the mechanisms of prion-induced neurotoxicity. Furthermore, we describe how insights into prion evolution have begun to shed light on their ancient origins and evolutionary resilience, offering deeper insights into the potential roles of prions in primordial chemical processes. [ABSTRACT FROM AUTHOR]

Early expansion and long-term persistence predict efficacy of chimeric antigen receptor T cells (CARTs)1–7, but mechanisms governing effector versus memory CART differentiation and whether asymmetric cell division induces differential fates in human CARTs remain unclear. Here we show that target-induced proximity labelling enables isolation of first-division proximal-daughter and distal-daughter CD8 CARTs that asymmetrically distribute their surface proteome and transcriptome, resulting in divergent fates. Target-engaged CARs remain on proximal daughters, which inherit a surface proteome resembling activated-undivided CARTs, whereas the endogenous T cell receptor and CD8 enrich on distal daughters, whose surface proteome resembles resting CARTs, correlating with glycolytic and oxidative metabolism, respectively. Despite memory-precursor phenotype and in vivo longevity, distal daughters demonstrate transient potent cytolytic activity similar to proximal daughters, uncovering an effector-like state in distal daughters destined to become memory CARTs. Both partitioning of pre-existing transcripts and changes in RNA velocity contribute to asymmetry of fate-determining factors, resulting in diametrically opposed transcriptional trajectories. Independent of naive, memory or effector surface immunophenotype, proximal-daughter CARTs use core sets of transcription factors known to support proliferation and effector function. Conversely, transcription factors enriched in distal daughters restrain differentiation and promote longevity, evidenced by diminished long-term in vivo persistence and function of distal-daughter CARTs after IKZF1 disruption. These studies establish asymmetric cell division as a framework for understanding mechanisms of CART differentiation and improving therapeutic outcomes.We show that target-induced proximity labelling enables isolation of first-division CD8 chimeric antigen receptor T cells that asymmetrically distribute their surface proteome and transcriptome, resulting in distinct phenotypic, metabolic and functional profiles in proximal and distal daughter cells. [ABSTRACT FROM AUTHOR]

Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of the variance associated with a lifespan model of regional cortical thickness trajectories. In contrast, modeled cortical thickness change patterns during adulthood are best explained by cholinergic and glutamatergic neurotransmitter receptor and transporter distributions. These relationships are supported by developmental gene expression trajectories and translate to individual longitudinal data from over 8000 adolescents, explaining up to 59% of developmental change at cohort- and 18% at single-subject level. Integrating neurobiological brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand brain development and aging in living humans. The neurobiology of human brain development and aging is hard to study in vivo. The authors report on distinct spatial associations between brain morphology and cellular as well as molecular brain properties throughout neurodevelopment and aging. [ABSTRACT FROM AUTHOR]