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The article discusses the use of extracorporeal cardiopulmonary resuscitation (ECPR) as a potential intervention for patients with refractory cardiac arrest. ECPR involves draining blood from the body, oxygenating it, and then returning it to the arterial system, providing better oxygen delivery than conventional CPR. The article highlights the need for a proactive approach to implementing ECPR in the UK, as it is currently underutilized. The article also discusses the selection criteria for ECPR and the challenges in implementing ECPR services. The authors emphasize the importance of developing institutional expertise and ensuring equitable access to ECPR services across the UK. [Extracted from the article]

Due to its haptic and interactive nature, virtual anatomy provides an opportunity for small‐group learning, enabling students to develop their group work skills before they graduate. However, there is currently little practical guidance supported by pedagogic principles detailing how to incorporate it into curricula. Anatomy educators at the University of Plymouth conducted action research aiming to capture students' overall perceptions of the virtual anatomy platform Anatomage. Questioning the benefits and challenges students face while interacting with Anatomage prompted the creation of evidence‐based interventions to be later evaluated. Although a plethora of themes were identified, this report specifically examines those relating to group work. Thematic analysis of initial focus group data found group size and group dynamics impacted students' experience with the platform. Following the implementation of interventions to resolve these issues, a questionnaire and second series of focus groups were conducted to determine whether they were successful. Additional subthemes found from these data included facilitation, social pressure, peer learning and working with friends. This study contributed to the improvement of small group learning and integration of virtual anatomy into curricula based on student and staff feedback. As such, these data support the development of effective group working skills which are fundamental for healthcare professionals and widely recognized by regulators such as the General Medical Council and Health and Care Professions Council. In this report, the authors provide practical advice informed by pedagogy and principles from management and psychology to provide a multidisciplinary perspective. [ABSTRACT FROM AUTHOR]

We establish a sample‐ and data‐processing pipeline that allows for high‐throughput optical microscope measurement of porous films, provided they are sufficiently optically scattering. Here, self‐limiting electrospray deposition (SLED) is used to manufacture scattering films of different morphologies. This technique compensates for the scattering of the films through background subtraction of the reflection image with the transmission image. This process is implemented through a combination of an ImageJ and MATLAB data pipeline; the Canny edge‐detector is used as the image‐processing algorithm to identify the boundaries of the film. This process is verified against manually measured images; a comparative study between cross‐sectional scanning electron microscopy (where scattering effects are diminished) and optical microscopy also verifies that our optical microscopy technique can be used to consistently, non‐destructively measure film thickness regardless of film morphology. In addition, this technique can be used in combination with dense film measurements to measure film porosity. [ABSTRACT FROM AUTHOR]

The valorization of lignin, a currently underutilized component of lignocellulosic biomass, has attracted attention to promote a stable and circular bioeconomy. Successful approaches including thermochemical, biological, and catalytic lignin depolymerization have been demonstrated, enabling opportunities for lignino‐refineries and lignocellulosic biorefineries. Although significant progress in lignin valorization has been made, this review describes unexplored opportunities in chemical and biological routes for lignin depolymerization and thereby contributes to economically and environmentally sustainable lignin‐utilizing biorefineries. This review also highlights the integration of chemical and biological lignin depolymerization and identifies research gaps while also recommending future directions for scaling processes to establish a lignino‐chemical industry. [ABSTRACT FROM AUTHOR]

This article examines a complete collection of posts made within two of the largest online peer‐to‐peer breastmilk‐sharing communities in the United States, collected during the first month after the COVID‐19 vaccine became available to all U.S. adults. I propose that such communities support not only the circulation of human milk among strangers but also the circulation of widely shared attentional norms alongside interactional rules of relevance and concern. When collectively held attentional norms are violated, Goffmanian face‐saving maneuvers become visible. This case study engages studies of cultural cognition—in particular, those on collective rules of relevance and attention—to make sense of emergent cultural blind spots. [ABSTRACT FROM AUTHOR]

Short sequences that mediate interactions with modular binding domains are ubiquitous throughout eukaryotic proteomes. Networks of short linear motifs (SLiMs) and their corresponding binding domains orchestrate many cellular processes, and the low mutational barrier to evolving novel interactions provides a way for biological systems to rapidly sample selectable phenotypes. Mapping SLiM binding specificity and the rules that govern SLiM evolution is fundamental to uncovering the pathways regulated by these networks and developing the tools to manipulate them. We used high‐throughput screening of the human proteome to identify sequences that bind to the Enabled/VASP homology 1 (EVH1) domain of the postsynaptic density scaffolding protein Homer1. This expanded our understanding of the determinants of Homer EVH1 binding preferences and defined a new motif that can facilitate the discovery of additional Homer‐mediated interactions. Interestingly, the Homer1 EVH1 domain preferentially binds to sequences containing an N‐terminally overlapping motif that is bound by the paralogous family of Ena/VASP actin polymerases, and many of these sequences can bind to EVH1 domains from both protein families. We provide evidence from orthologous EVH1 domains in pre‐metazoan organisms that the overlap in human Ena/VASP and Homer binding preferences corresponds to an incomplete divergence from a common Ena/VASP ancestor. Given this overlap in binding profiles, promiscuous sequences that can be recognized by both families either achieve specificity through extrinsic regulatory strategies or may provide functional benefits via multi‐specificity. This may explain why these paralogs incompletely diverged despite the accessibility of further diverged isoforms. [ABSTRACT FROM AUTHOR]

Education is viewed as a critical keystone in achieving the Sustainable Development Goals (SDGs). Specifically, Education for Sustainable Development (ESD) is meant to enable everyone to contribute to sustainable development (SDG 4.7). This target is monitored using the global indicator 4.7.1 – mainstreaming of ESD in policies, curricula, training of educators and student assessment. Here, we offer a conceptual and methodological framework for assessments of SDG 4.7.1 (input‐level) that addresses both quality and depth of implementation and speed of change. The approach combines document analysis with external expert evaluation and is applied to 10‐year data (>11,000 documents) from all formal areas of education in Germany (early childhood education, school education, vocational education and training, higher education). Currently, ESD is mostly implemented in Germany as an "add‐on" to the educational system, with all sub‐indicators ranging from "isolated mentioning" of ESD and related concepts to "partial integration". Across most areas of education, the sub‐indicator training of educators was evaluated as most deficient. With regard to the speed of change, it was found that the implementation of ESD is dynamic, with all sub‐indicators having been evaluated as increasing. The proposed framework can increase the validity, reliability, and comparability of both country reporting and scientific assessments of SDG 4.7.1. We argue for independent and integrative monitoring across input, process, output and outcome to complement self‐reporting and to support evidence‐informed policymaking on sustainability in education. [ABSTRACT FROM AUTHOR]

Background: A growing number of older adults live in senior affordable housing, many with limited support systems and representing underserved or disadvantaged populations. Staff in these buildings are in a unique position to identify and address the healthcare and biopsychosocial needs of their residents and link them to services and supports. Methods: Staff in four affordable housing sites received training on the 4Ms approach to caring for older adults and conducting resident health assessments. They learned to collect comprehensive health information using a 4Ms Resident Health Risk Assessment (4Ms‐RHRA) and results are entered into a customized electronic database. Embedded flags identify potential risk factors and initiate a follow‐up process for documenting interventions and tracking referrals to healthcare and supportive services. Results: Eighty‐one percent of the 221 4Ms‐RHRAs completed with residents (63% female, mean age 71.1 years, 73% live alone) were flagged for at least one concern (Mean = 2.2 flags). Items addressing What Matters were most frequently flagged: resident's "most important health issue" (55%) and Advance Care Planning (ACP: 48%). In response, staff provided Advance Directive forms and Five Wishes pamphlets to interested residents and reminded residents to review ACP documents annually. Conclusion: Training affordable housing staff, precepting faculty, and students to conduct health assessments based on the 4Ms framework and longitudinally track interventions related to resident‐centered needs and manage long‐term service and supports is a first step in creating an interprofessional workforce capable of addressing the complex needs of older individuals in affordable housing. [ABSTRACT FROM AUTHOR]

Passive acoustic monitoring (PAM) has gained increasing popularity to study behaviour, habitat preferences, distribution and community assembly of birds and other animals. Automated species classification algorithms like 'BirdNET' are capable of detecting and classifying avian vocalizations within extensive audio data, covering entire species assemblages. PAM reveals substantial potential for biodiversity monitoring that informs evidence‐based conservation. Nevertheless, fully realizing this potential remains challenging, especially due to the issue of false‐positive species detections. Here, we introduce an optimized thresholding framework, which incorporates contextual information extracted from the time‐series of automated species detections (i.e. covariates on quality and quantity of species' detections measured at varying time intervals) to improve the differentiation of true and false positives. We verified a sample of BirdNET detections per species and modelled species‐specific thresholds using conditional inference trees. These thresholds were designed to minimize false‐positive detections while maximizing the preservation of true positives in the dataset. We tested this framework for a large dataset of BirdNET detections (5760 h of audio data, 60 sites) recorded over an entire breeding season. Our results revealed considerable interspecific variability of precision (percentage of true positives) within raw BirdNET data. Our optimized thresholding approach achieved high precision (≥0.9) for 70% of the 61 detected species, while species‐specific thresholds solely relying on the BirdNET confidence scores achieved high precision for only 31% of the species. Conservative universal thresholds (not species‐specific) reached high precision for 48% of the species. Our thresholding approach outperformed previous thresholding approaches and enhanced interspecific comparability for bird community analyses. By incorporating contextual information from the time‐series of species detections, the differentiation of true and false positives was substantially improved. Our approach may enhance a straightforward application of PAM in biodiversity research, landscape planning and evidence‐based conservation. [ABSTRACT FROM AUTHOR]

The successful utilization of innovative sulfide‐based solid‐state batteries in energy storage hinges on developing scalable technologies and machinery for upscaling their production. While multiple Gigafactories for lithium‐ion batteries are already operational worldwide, the upscaling of solid‐state batteries exhibiting their full potential remains to be seen in the near future. In this study, the conventional production of lithium‐ion batteries is reconsidered, and the feasibility of seamlessly integrating sulfide‐based solid‐state batteries into the existing process chains is discussed. Scalable technologies and key challenges along the process chain of sulfide‐based solid‐state batteries are accordingly addressed. Experimental investigations yield crucial insights into enabling large‐scale production of sulfide‐based battery components while highlighting remaining challenges from a production perspective. An overview of the roll‐to‐roll machinery housed in microenvironments under an inert atmosphere in the "Sulfidic Cell Production Advancement Center" at the Institute for Machine Tools and Industrial Management at the Technical University of Munich is given. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pericardial sarcoidosis is an uncommon cause of chest pain to consider, and it requires a heightened level of suspicion and thorough history gathering. If there is suspicion of inflammatory disease, pursuing advanced imaging and biopsies is crucial, as early immunosuppressive treatment can enhance outcomes. Pericardial involvement in sarcoidosis is a rare condition with limited research. This case study discusses a 52‐year‐old African American woman who presented with subacute chest pain and was diagnosed with pericardial sarcoidosis. Diagnostic evaluation revealed extensive lymphadenopathy and pericardial effusion, and a pericardial biopsy confirmed non‐caseating granulomatous inflammation. Treatment with steroids and methotrexate resulted in clinical improvement. Eight months follow‐up showed near resolution of pericardial disease. This case emphasizes the importance of considering cardiac sarcoidosis in sarcoidosis patients, utilizing advanced imaging for accurate diagnosis, and tailoring treatment to the level of cardiac involvement. [ABSTRACT FROM AUTHOR]

It has been shown previously that a set of three modifications—termed S1, Crystal Kappa, and elbow—act synergistically to improve the crystallizability of an antigen‐binding fragment (Fab) framework. Here, we prepared a phage‐displayed library and performed crystallization screenings to identify additional substitutions—located near the heavy‐chain elbow region—which cooperate with the S1, Crystal Kappa, and elbow modifications to increase expression and improve crystallizability of the Fab framework even further. One substitution (K141Q) supports the signature Crystal Kappa‐mediated Fab:Fab crystal lattice packing interaction. Another substitution (E172G) improves the compatibility of the elbow modification with the Fab framework by alleviating some of the strain incurred by the shortened and bulkier elbow linker region. A third substitution (F170W) generates a split‐Fab conformation, resulting in a powerful crystal lattice packing interaction comprising the biological interaction interface between the variable heavy and light chain domains. In sum, we have used K141Q, E172G, and F170W substitutions—which complement the S1, Crystal Kappa, and elbow modifications—to generate a set of highly crystallizable Fab frameworks that can be used as chaperones to enable facile elucidation of Fab:antigen complex structures by x‐ray crystallography. [ABSTRACT FROM AUTHOR]

Rivers form meta‐ecosystems, in which disturbance and connectivity control biodiversity, ecosystem functioning and their interactions across the river network, but also across connected instream and riparian ecosystems. This aquatic–terrestrial linkage is modified by drying, a disturbance that also naturally fragments river networks and thereby modifies organism dispersal and organic matter (OM) transfers across the river network. However, little evidence of the effects of drying on river network‐scale OM cycling exists. Here, we assessed the effects of fragmentation by drying at the river meta‐ecosystem scale by monitoring leaf resource stocks, invertebrate communities and decomposition rates, across three seasons and 20 sites, in the instream and riparian habitats of a river network naturally fragmented by drying. Although instream leaf resource quantity and quality increased, leaf‐shredder invertebrate richness and abundance decreased with flow intermittence. Decomposition was, however, mainly driven by network‐scale fragmentation and connectivity. Shredder richness and invertebrate‐driven decomposition both peaked at sites with intermediate amounts of intermittent reaches upstream, suggesting that upstream drying can promote the biodiversity and functioning of downstream ecosystems. Shredder richness, however, had a negative effect on decomposition in perennial sites, likely due to interspecific competition. Leaf quantity, invertebrate communities and invertebrate‐driven decomposition became more similar between instream and riparian habitats as drying frequency increased, likely due to homogenization of environmental conditions between both habitats as the river dried. Our study demonstrates the paramount effects of drying on the dynamics of resources, communities and ecosystem functioning in rivers and presents evidence of one of the first network‐scale examples of the co‐drivers of ecosystem functions across terrestrial–aquatic boundaries. [ABSTRACT FROM AUTHOR]

Introduction: Vaginal surgery has a superior outcome profile compared with other surgical routes, yet skills are declining because of low case volumes. Graduating residents' confidence and preparedness for vaginal surgery has plummeted in the past decade. The objective of the present study was to investigate whether procedure‐specific simulation skills, vs usual training, result in improved operative competence. Material and methods: We completed a randomized controlled trial of didactic and procedural training via low fidelity vaginal surgery models for anterior repair, posterior repair (PR), vaginal hysterectomy (VH), recruiting novice gynecology residents at three academic centers. We evaluated performance via global rating scale (GRS) in the real operating room and for corresponding procedures by attending surgeon blinded to group. Prespecified secondary outcomes included procedural steps knowledge, overall performance, satisfaction, self‐confidence and intraoperative parameters. A priori sample size estimated 50 residents (20% absolute difference in GRS score, 25% SD, 80% power, alpha 0.05). Clinicaltrials.gov: Registration no. NCT05887570. Results: We randomized 83 residents to intervention or control and 55 completed the trial (2011–23). Baseline characteristics were similar, except for more fourth‐year control residents. After adjustment of confounders (age, level, baseline knowledge), GRS scores showed significant differences overall (mean difference 8.2; 95% confidence interval [CI]: 0.2–16.1; p = 0.044) and for VH (mean difference 12.0; 95% CI: 1.8–22.3; p = 0.02). The intervention group had significantly higher procedural steps knowledge and self‐confidence for VH and/or PR (p < 0.05, adjusted analysis). Estimated blood loss, operative time and complications were similar between groups. Conclusions: Compared to usual training, procedure‐specific didactic and low fidelity simulation modules for vaginal surgery resulted in significant improvements in operative performance and several other skill parameters. [ABSTRACT FROM AUTHOR]

The current registered report focused on the temporal dynamics of the relationship between expectancy and attention toward threat, to better understand the mechanisms underlying the prioritization of threat detection over expectancy. In the current event‐related potentials experiment, a‐priori expectancy was manipulated, and attention bias was measured, using a well‐validated paradigm. A visual search array was presented, with one of two targets: spiders (threatening) or birds (neutral). A verbal cue stating the likelihood of encountering a target preceded the array, creating congruent and incongruent trials. Following cue presentation, preparatory processes were examined using the contingent negative variation (CNV) component. Following target presentation, two components were measured: early posterior negativity (EPN) and late positive potential (LPP), reflecting early and late stages of natural selective attention toward emotional stimuli, respectively. Behaviorally, spiders were found faster than birds, and congruency effects emerged for both targets. For the CNV, a non‐significant trend of more negative amplitudes following spider cues emerged. As expected, EPN and LPP amplitudes were larger for spider targets compared to bird targets. Data‐driven, exploratory, topographical analyses revealed different patterns of activation for bird cues compared to spider cues. Furthermore, 400–500 ms post‐target, a congruency effect was revealed only for bird targets. Together, these results demonstrate that while expectancy for spider appearance is evident in differential neural preparation, the actual appearance of spider target overrides this expectancy effect and only in later stages of processing does the cueing effect come again into play. This study examined online expectancy and subsequent emotional attention to threat at early as well as late processing stages using event‐related potentials and topographical analyses. This comprehensive study can facilitate the development of better treatments aimed at reducing attention bias and anxiety/phobia symptoms by focusing on the manipulation of expectancies. [ABSTRACT FROM AUTHOR]

Background: Tooth loss is associated with suboptimal nutrient intake and greater risk of malnutrition. Objective: To develop and field‐test a stakeholder‐informed diet education tool that addresses the unique needs of older adults with tooth loss who do not wear dentures. Methods: An iterative user‐centered approach was used. Initial content was developed based on findings from previous research. Stakeholder panels of older adults with 20 or fewer teeth, and dentists, were conducted at two time points to obtain feedback on the tool, which was revised following each panel. The tool was field‐tested in a dental school clinic and evaluated using the Patient Education Materials Assessment Tool; it was further revised based on feedback. Results: A diet education tool entitled "Eating Healthier With Tooth Loss" was developed. Sections for fruits and vegetables, grains, and proteins food groups, and one addressing socioemotional aspects of eating with missing teeth were included. Panel members provided constructive, positive feedback; recommendations for editing text, images, design, and content were integrated. Field‐testing in the dental clinic with 27 pairs of student dentists and their patients resulted in scores of 95.7% for understandability and 96.6% for actionability, with over 85% agreement with each item. The tool was revised based on field‐testing feedback. Conclusion: A diet education tool for older adults with tooth loss was developed using a user‐centered approach, integrating the 'patient voice' and patient experiences with US dietary guidelines. Use of this tool is feasible in a dental clinic setting. Future research should explore usage in larger settings. [ABSTRACT FROM AUTHOR]

Objective: To examine the association with adverse pregnancy outcomes of: (1) American College of Cardiology/American Heart Association blood pressure (BP) thresholds, and (2) visit‐to‐visit BP variability (BPV), adjusted for BP level. Design: An observational study. Setting: Analysis of data from the population‐based UK Southampton Women's Survey (SWS). Population or sample: 3003 SWS participants. Methods: Generalised estimating equations were used to estimate crude and adjusted relative risks (RRs) of adverse pregnancy outcomes by BP thresholds, and by BPV (as standard deviation [SD], average real variability [ARV] and variability independent of the mean [VIM]). Likelihood ratios (LRs) were calculated to evaluate diagnostic test properties, for BP at or above a threshold, compared with those below. Main outcome measures: Gestational hypertension, severe hypertension, pre‐eclampsia, preterm birth (PTB), small‐for‐gestational‐age (SGA) infants, neonatal intensive care unit (NICU) admission. Results: A median of 11 BP measurements were included per participant. For BP at ≥20 weeks' gestation, higher BP was associated with more adverse pregnancy outcomes; however, only BP <140/90 mmHg was a good rule‐out test (negative LR <0.20) for pre‐eclampsia and BP ≥140/90 mmHg a good rule‐in test (positive LR >8.00) for the condition. BP ≥160/110 mmHg could rule‐in PTB, SGA infants and NICU admission (positive LR >5.0). Higher BPV (by SD, ARV, or VIM) was associated with gestational hypertension, severe hypertension, pre‐eclampsia, PTB, SGA and NICU admission (adjusted RRs 1.05–1.39). Conclusions: While our findings do not support lowering the BP threshold for pregnancy hypertension, they suggest BPV could be useful to identify elevated risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

The deployment of small‐molecule fluorescent agents plays an ever‐growing role in medicine and drug development. Herein, we complement the portfolio of powerful fluorophores, reporting the serendipitous discovery and development of a novel class with an imidazo[1,2‐a]pyridinium triflate core, which we term PyrAtes. These fluorophores are synthesized in a single step from readily available materials (>60 examples) and display Stokes shifts as large as 240 nm, while also reaching NIR−I emissions at λmax as long as 720 nm. Computational studies allow the development of a platform for the prediction of λmax and λEm. Furthermore, we demonstrate the compatibility of these novel fluorophores with live cell imaging in HEK293 cells, suggesting PyrAtes as potent intracellular markers. [ABSTRACT FROM AUTHOR]

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This article discusses the importance of improving the quality of multiple-choice questions in assessments to measure current learning rather than prior learning. The use of multiple-choice questions is common in many assessment plans and has various benefits, such as evaluating large classes and being useful for adaptive learning platforms. The article provides guidelines for faculty to improve the quality of multiple-choice questions, including clarity, logical arrangement of answer choices, simplicity in language, and maintaining item independence. By implementing these improvements, instructors can identify gaps in student understanding and make improvements in pedagogy. The goal is to promote equitable evaluation practices and drive rapid and equitable improvements in pedagogy. [Extracted from the article]

Floral features, the pollination process, the breeding system, and fruiting success are documented in the Andean terrestrial orchid Gomphichis valida. Studies were performed at the Department of Ancash, Peru, at ca. 4250 m a.s.l., from June to November 2022. The breeding system was studied through controlled pollinations in plants excluded from pollinators (bagged). Natural pollination was studied in the field and through photos and videos. The flowers are nectariferous and non‐protandrous and present the longest lifespan reported so far for a neotropical terrestrial orchid (53–80 days). This species is pollinator dependent (unable to set fruit and seed without the agency of pollinators) and self‐compatible. The observed pollinators belong to three functional groups that appeared successively (in order of appearance): hummingbirds (Chalcostigma stanleyi), bumblebees (Bombus coccineus and Bombus rubicundus), and solitary Halictidae bees (Augochlorella sp.). All recorded pollinators probe the flowers for nectar. The pollinaria adhere to the bee mouthparts and onto the lateral side of the hummingbird bill. Bumblebees were the most frequent and efficient functional group (up to 62.07% of the observed pollination events), followed by Halictidae (31.03%) and hummingbirds (6.90%). Natural fruiting success is high (66.66%–94.49%). Such high natural fruiting success is unexpected at high altitudes, but it is likely explained by a combination of factors, including the long floral lifespan, nectar secretion, and self‐compatibility. This is the first report of hummingbirds as pollinators of Cranichidinae orchids, and G. valida is, to the best of our knowledge, a neotropical orchidoid orchid with the most generalist pollination biology recorded so far. [ABSTRACT FROM AUTHOR]

Purpose: This work aims to assess the association of sleep duration with cardiometabolic risk (adiposity, blood pressure, lipids, albuminuria and A1C) and to investigate lifestyle factors (physical activity, light exposure, caffeine consumption and sugar consumption) associated with sleep duration in children. Methods: A nationally representative sample of 3907 children ages 6–17 years enrolled in NHANES from 2011 to 2014 was included in this cross‐sectional study. Sleep duration was defined as the daily average time spent sleeping over 7 days as measured by a physical activity monitor (PAM). Participants without valid sleep data for ≥95% of the study were excluded. Regression models were adjusted for age, sex, race, body mass index (BMI) Z score, physical activity and light exposure. Results: In adjusted regression models, longer sleep duration was associated with lower systolic blood pressure index (β = −3.63 * 10−5, 95% CI −6.99 * 10−5, −2.78 * 10−6, p = 0.035) and BMI Z score (β = −0.001, 95% CI −0.001, 0.000, p = 0.002). In logistic regression models, longer sleep duration was associated with lower odds of obesity (OR = 0.998, 95% CI 0.997, 0.999, p < 0.001) and overweight status (OR = 0.998, 95% CI 0.997, 0.999, p = 0.004). Greater light exposure (β = 6.64 * 10−5, 95% CI 3.50 * 10−5, 9.69 * 10−5, p < 0.001) and physical activity (β = 0.005, 95% CI 0.004, 0.006, p < 0.001) were associated with longer sleep. Conclusion: Longer sleep duration was associated with lower blood pressure and adiposity measures in children. Improving sleep quality by increasing physical activity and light exposure in childhood may decrease the lifetime risk of cardiometabolic disease. [ABSTRACT FROM AUTHOR]

Fish serve as indicators of exposure to contaminants of emerging concern (CECs)—chemicals such as pharmaceuticals, hormones, and personal care products—which are often designed to impact vertebrates. To investigate fish health and CECs in situ, we evaluated the health of wild fish exposed to CECs in waterbodies across northeastern Minnesota with varying anthropogenic pressures and CEC exposures: waterbodies with no human development along their shorelines, those with development, and those directly receiving treated wastewater effluent. Then, we compared three approaches to evaluate the health of fish exposed to CECs in their natural environment: a refined fish health assessment index, a histopathological index, and high‐throughput (ToxCast) in vitro assays. Lastly, we mapped adverse outcome pathways (AOPs) associated with identified ToxCast assays to determine potential impacts across levels of biological organization within the aquatic system. These approaches were applied to subsistence fish collected from the Grand Portage Indian Reservation and 1854 Ceded Territory in 2017 and 2019. Overall, 24 CECs were detected in fish tissues, with all but one of the sites having at least one detection. The combined implementation of these tools revealed that subsistence fish exposed to CECs had histological and macroscopic tissue and organ abnormalities, although a direct causal link could not be established. The health of fish in undeveloped sites was as poor, or sometimes poorer, than fish in developed and wastewater effluent‐impacted sites based on gross and histologic tissue lesions. Adverse outcome pathways revealed potential hazardous pathways of individual CECs to fish. A better understanding of how the health of wild fish harvested for consumption is affected by CECs may help prioritize risk management research efforts and can ultimately be used to guide fishery management and public health decisions. Integr Environ Assess Manag 2024;20:846–863. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Key Points: 1.Fish exposed to contaminants of emerging concern had histological and macroscopic tissue and organ abnormalities.2.Adverse outcome pathways revealed potential hazardous pathways of individual contaminants of emerging concern to fish.3.The health of fish in undeveloped sites was as poor, or sometimes poorer, than fish in developed and wastewater effluent‐impacted sites based on gross and histologic tissue lesions. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether MR fingerprinting (MRF) scans provide motion‐robust and quantitative brain tissue measurements for non‐sedated infants with prenatal opioid exposure (POE). Study Type: Prospective. Population: 13 infants with POE (3 male; 12 newborns (age 7–65 days) and 1 infant aged 9‐months). Field Strength/Sequence: 3T, 3D T1‐weighted MPRAGE, 3D T2‐weighted TSE and MRF sequences. Assessment: The image quality of MRF and MRI was assessed in a fully crossed, multiple‐reader, multiple‐case study. Sixteen image quality features in three types—image artifacts, structure and myelination visualization—were ranked by four neuroradiologists (8, 7, 5, and 8 years of experience respectively), using a 3‐point scale. MRF T1 and T2 values in 8 white matter brain regions were compared between babies younger than 1 month and babies between 1 and 2 months. Statistical Tests: Generalized estimating equations model to test the significance of differences of regional T1 and T2 values of babies under 1 month and those older. MRI and MRF image quality was assessed using Gwet's second order auto‐correlation coefficient (AC2) with confidence levels. The Cochran–Mantel–Haenszel test was used to assess the difference in proportions between MRF and MRI for all features and stratified by the type of features. A P value <0.05 was considered statistically significant. Results: The MRF of two infants were excluded in T1 and T2 value analysis due to severe motion artifact but were included in the image quality assessment. In infants under 1 month of age (N = 6), the T1 and T2 values were significantly higher compared to those between 1 and 2 months of age (N = 4). MRF images showed significantly higher image quality ratings in all three feature types compared to MRI images. Conclusions: MR Fingerprinting scans have potential to be a motion‐robust and efficient method for nonsedated infants. Level of Evidence: 2 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

GOES‐16 and GOES‐17 are the first of NOAA's Geostationary Operational Environmental Satellite (GOES)‐R series of satellites. Each GOES‐R satellite has a magnetometer mounted on the end (outboard) and one part‐way down a long boom (inboard). This paper demonstrates the relative accuracy and stability of the measurements on a daily and long‐term basis. The GOES‐16 and GOES‐17 magnetic field observations from 2017 to 2020 have been compared to simultaneous magnetic field observations from each other and from the previous GOES‐NOP series satellites (GOES‐13, GOES‐14 and GOES‐15). These comparisons provide assessments of relative accuracy and stability. We use a field model to facilitate the inter‐satellite comparisons at different longitudes. GOES‐16 inboard and outboard magnetometers data suffer daily variations which cannot be explained by natural phenomena. Long‐term‐averaged GOES‐16 outboard (OB) data has daily variations of ±3 nT from average values with one‐sigma uncertainty of ±1.5 nT. Long‐term averaged GOES‐17OB magnetometer data have minimal daily variations. Daily average of the difference between the GOES‐16 outboard or GOES‐17 outboard measurements and the measurements made by another GOES satellite are computed. The long‐term averaged results show the GOES‐16OB and GOES‐17OB measurements have long‐term stability (±2 nT or less) and match measurements from magnetometers on other GOES within limits stated herein. The GOES‐17OB operational offset (zero field value) was refined using the GOES‐17 satellite rotated 180° about the Earth pointing axis (known as a yaw flip). Plain Language Summary: GOES‐16 and GOES‐17 are the first two of the R‐series of the NOAA's Geostationary Operational Environmental Satellite (GOES). Like previous GOES satellites, they carry two magnetometers (inboard and outboard on a long boom) to measure the magnetic field at geosynchronous orbit (an altitude of approximately 35,786 km above mean sea level). Because these data are used to provide users of space‐based assets with the knowledge of the space environment and to provide input for research, the accuracy and stability of the new data sets relative to previous data sets are important. There are known variations in the data from the station‐keeping thrusters which are removed from the data studied. Previous studies showed that the GOES‐16 measurements contain artificial diurnal variations. This study shows that the diurnal variations of the outboard magnetometer data are useful and within specified limits. The GOES‐17 measurements do not have significant daily variations. Based on simultaneous measurements from the other GOES satellites, GOES‐16 and GOES‐17 outboard data are stable over a period of years. Key Points: GOES‐16 magnetic field data have artificial diurnal variations which are larger than in other GOES satellites and which change with seasonDaily averages of corrected magnetic field of GOES‐16/17 match simultaneous data from GOES‐13/14/15 nT except for eastward componentThe corrected GOES‐17 data match the GOES‐18 data when GOES‐17 and GOES‐18 are separated by 0.2° of longitude [ABSTRACT FROM AUTHOR]

Objective: The primary goal of this study was to determine in patients with normohormonal primary hyperparathyroidism (NHHPT) what percent reduction in post‐excision intraoperative parathyroid hormone (IOPTH) from baseline would yield a rate of cure comparable to that in patients with classical primary hyperparathyroidism (PHPT). Methods: This is a retrospective cohort study of patients who underwent parathyroidectomy between July 2013 and February 2020. Demographic data, preoperative, intraoperative, and postoperative metrics were collected. Patients with NHHPT were compared to those with classical PHPT. Subgroup analyses were performed. Results: Of the 496 patients included in the study, 66 (13.3%) were of the normohormonal variant based on preoperative intact parathyroid hormone (PTH) levels and 28 (5.6%) based on baseline IOPTH levels. The cure rates in the two normohormonal groups were not significantly different from their classical counterparts (98.4% and 100.0% vs. 97.1%, p = 1.000). The median percent decline in post‐excision IOPTH from baseline that achieved cure in the normohormonal groups were 82.6% and 80.4% compared to their respective controls at 87.3%, p = 0.011 and p = 0.001. Although the rate of multiglandular disease was higher in one of the normohormonal variant groups, this difference was due to a higher rate of double adenomas, not four‐gland hyperplasia. Conclusion: Patients with NHHPT undergoing parathyroidectomy can expect cure rates similar to that in patients with classical PHPT. The results of this study indicate that achieving an 80% drop or more in IOPTH levels predicts a high likelihood of cure. This is true irrespective of whether the patient is deemed normohormonal based on preoperative or intraoperative testing. Level of Evidence: 3 Laryngoscope, 134:2480–2484, 2024 [ABSTRACT FROM AUTHOR]

The EU Nature Restoration Law represents an important opportunity for freshwater habitat restoration and, consequently, freshwater biodiversity protection. However, a number of challenges must be anticipated in its implementation, which may compromise its success. Some aspects, particularly those relating to freshwater ecosystems, require more clarification. We use riverine ecosystems to illustrate existing ambiguities in the proposed legislation and the potential consequences of leaving these aspects open to interpretation during the implementation process. We also discuss potential solutions to these problems which could help ensure that the law's objectives are met. We argue that river network structure and connectivity dimensions, which result into river meta‐ecosystems, must be explicitly considered. For that purpose, we ask for clear definitions of the critical terms "free‐flowing rivers," "barriers," and "reference areas." In addition, we recommend developing methods for integrated assessment of connectivity across river networks. As a key property of river ecosystems, this must be used to prioritize actions to increase the length and number of free‐flowing rivers. Adequate restoration planning at larger spatial scales will benefit from a meta‐ecosystem perspective and accurate representation of aquatic‐terrestrial linkages, which will significantly improve the efficacy of restoration efforts. Furthermore, stakeholder and citizen engagement offer important opportunities at local, national, and European scales, and should be fostered to ensure inclusive decision‐making. The conservation challenges outlined here are particularly important for rivers, but they also have implications for other ecosystems. These considerations are useful for policymakers, conservationists, and other stakeholders involved in the Nature Restoration Law and related policy initiatives. This article is categorized under:Water and Life > Stresses and Pressures on EcosystemsWater and Life > Conservation, Management, and AwarenessHuman Water > Water Governance [ABSTRACT FROM AUTHOR]

Electrospray deposition (ESD) is a technique with emerging relevance for applications requiring micro‐/nano‐scaled coatings. Self‐limiting electrospray deposition (SLED) is a regime of ESD where upon satisfying the criteria for self‐limiting behavior, the charge buildup of the material will eventually begin to repel itself until an asymptotic thickness is achieved, based primarily on the properties of the spray solution and deposited material. This work focuses on controlling the coating thickness further to achieve sub‐micron thicknesses. By applying a voltage bias of the same polarity of the spray onto the target substrate while providing a secondary grounded surface, the thickness of a payload can be manipulated for thinner and more precise thicknesses. The magnitude of the voltage bias is varied to show the effect of voltage bias on thickness, and 2‐D and 3‐D structures are used to demonstrate the generality of this technique for complex substrates. The results show how SLED can be included as a potential alternative for conformal coatings deposited at ambient conditions at the sub‐micron scale. [ABSTRACT FROM AUTHOR]

A CoMoS composite is synthesized to combine the benefits of cobalt and molybdenum sulfides as an anodic material for advanced lithium‐ion batteries (LIBs). The synthesis is accomplished using a simple two‐step hydrothermal method and the resulting CoMoS nanocomposites are subsequently encapsulated in a carbonized polydopamine shell. The synthesis procedure exploited the self‐polymerization ability of dopamine to create nitrogen‐doped carbon‐coated cobalt molybdenum sulfide, denoted as CoMoS@NC. Notably, the de‐lithiation capacity of CoMoS and CoMoS@NC is 420 and 709 mAh g⁻1, respectively, even after 100 lithiation/de‐lithiation cycles at a current density of 200 mA g⁻1. Furthermore, excellent capacity retention ability is observed for CoMoS@NC as it withstood 600 consecutive lithiation/de‐lithiation cycles with 94% capacity retention. Moreover, a LIB full‐cell assembly incorporating the CoMoS@NC anode and an NMC‐532 cathode is subjected to comprehensive electrochemical and practical tests to evaluate the performance of the anode. In addition, the density functional theory showcases the increased lithium adsorption for CoMoS@NC, supporting the experimental findings. Hence, the use of dopamine as a nitrogen‐doped carbon shell enhanced the performance of the CoMoS nanocomposites in experimental and theoretical tests, positioning the material as a strong candidate for LIB anode. [ABSTRACT FROM AUTHOR]

Rivers significantly contribute to global biogeochemical cycles; however, we have a limited understanding of how drying may influence these cycles. Drying fragments river networks, thereby influencing important ecosystem functions such as the processing of carbon and nitrogen, and associated fluxes of greenhouse gases (GHGs) both locally, and at the river network scale. Our objective was to assess, using a network‐scale approach, the lateral, longitudinal, and temporal dynamics of GHG fluxes in a river network naturally fragmented by drying. We used a closed‐loop chamber with automated analyzers to measure carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) fluxes from dry sediments, flowing waters, isolated pools, and riparian soils, along with a suite of environmental variables, over 9 months at 20 sites across a non‐perennial river network in France. Network‐scale drying had a spatial and temporal legacy effect on GHG fluxes. On average, CO2 fluxes were up to 29 times higher from perennial than non‐perennial sites under flowing conditions. At non‐perennial sites, CO2 and N2O fluxes positively covaried with time since rewetting. In addition, CO2 and N2O fluxes at perennial sites positively covaried with the percent of non‐perennial reaches upstream, indicating a spatial effect of drying. GHG fluxes from riparian soil and dry riverbed sediments had markedly different magnitudes and covariates. This research demonstrates that drying not only has a local‐scale impact but also influences GHG fluxes at the network scale, contributing valuable insights for upscaling global riverine GHG estimates. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to develop a measure of readiness to be trained as a supporting parent volunteer for the Parent to Parent USA Network. Background: Parents of children with disabilities may suffer from isolation, stress, and depression due to increased burden of caregiving, lack of knowledge about disability, stigmatization by community and family and/or reduced family income. Peer support can serve as a buffer to stress. Methods: Measure items are based on qualitative findings and a review of relevant literature. Exploratory factor analysis was employed to determine the factor structure, and predictive validity was assessed using two‐sample t tests. Results: The 17‐item measure comprised three factors—Into Action, Wellbeing, and Skills and Navigation—and demonstrated good internal consistency. Additionally, significant differences in readiness score were found between parents who had and those who had not been trained to be peer supports and parents who had and had not received support from P2P. Implications: This measure may facilitate further study and evaluation of P2P and may be useful to other programs serving families of children with special educational or health care needs. [ABSTRACT FROM AUTHOR]

Drought‐induced groundwater decline and warming associated with climate change are primary threats to dryland riparian woodlands. We used the extreme 2012–2019 drought in southern California as a natural experiment to assess how differences in water‐use strategies and groundwater dependence may influence the drought susceptibility of dryland riparian tree species with overlapping distributions. We analyzed tree‐ring stable carbon and oxygen isotopes collected from two cottonwood species (Populus trichocarpa and P. fremontii) along the semi‐arid Santa Clara River. We also modeled tree source water δ18O composition to compare with observed source water δ18O within the floodplain to infer patterns of groundwater reliance. Our results suggest that both species functioned as facultative phreatophytes that used shallow soil moisture when available but ultimately relied on groundwater to maintain physiological function during drought. We also observed apparent species differences in water‐use strategies and groundwater dependence related to their regional distributions. P. fremontii was constrained to more arid river segments and ostensibly used a greater proportion of groundwater to satisfy higher evaporative demand. P. fremontii maintained ∆13C at pre‐drought levels up until the peak of the drought, when trees experienced a precipitous decline in ∆13C. This response pattern suggests that trees prioritized maintaining photosynthetic processes over hydraulic safety, until a critical point. In contrast, P. trichocarpa showed a more gradual and sustained reduction in ∆13C, indicating that drought conditions induced stomatal closure and higher water use efficiency. This strategy may confer drought avoidance for P. trichocarpa while increasing its susceptibility to anticipated climate warming. Key Points: Dryland riparian cottonwoods used shallow soil moisture when available but ultimately relied on groundwater for survival during droughtSpecies had different water‐use strategies related to their distribution along a gradient of increasing aridity with distance from coastPopulus trichocarpa appears more susceptible to warming, and P. fremontii more vulnerable to groundwater decline due to high water demand [ABSTRACT FROM AUTHOR]

Strong positive Indian Ocean Dipole (pIOD) events like those in 1997 and 2019 caused significant flooding in East Africa. While future projections indicate an increase in pIOD events, limited historical data hinders a comprehensive understanding of these extremes, particularly for unprecedented events. To overcome this we utilize a large ensemble of seasonal reforecast simulations, which show that regional rainfall continues to increase with pIOD magnitude, with no apparent limit. In particular we find that extreme rain days are highly sensitive to the pIOD index and their seasonal frequency increases super‐linearly with higher pIOD magnitudes. It is vital that socio‐economic systems and infrastructure are able to handle not only the increasing frequency of events like 1997 and 2019 but also unprecedented seasons of extreme rainfall driven by as‐yet‐unseen pIOD events. Future studies should prioritize understanding the hydrological implications and population exposure to these unprecedented extremes in East Africa. Plain Language Summary: The Indian Ocean Dipole is a pattern of climate variability in the Indian Ocean, characterized by opposite‐signed sea surface temperature differences from normal in the west and east. During positive events (pIOD), the western Indian Ocean is warmer than usual, which disrupts the normal circulation of the atmosphere. When pIOD is strong, extreme rainfall and flooding are common in East Africa. This happened in 1997 and 2019. According to future predictions, the frequency of extreme pIOD events will increase. However, our understanding of these events is limited as there is not a large enough sample of past events in the historical data to study. To address this, we evaluate a large collection of climate model simulations called seasonal reforecasts. The results show no evidence of an upper limit to the impact of pIOD on regional rainfall. The frequency of rain days increases during pIOD, whilst extremely heavy rain days increase even more. This means that more frequent extreme pIOD seasons will likely bring more heavy rainfall impacts. It also means that if pIOD reaches a high magnitude which has not yet been recorded, the rainfall impacts are likely to be even larger than those seen in 1997 or 2019. Key Points: Unprecedented strong positive Indian Ocean Dipole (IOD) events are likely to bring extreme rainfall to East AfricaThe extreme component of the seasonal distribution of rain days is particularly sensitive to the magnitude of the IODThe impact of larger IOD events on extreme rainfall frequency increases non‐linearly with the IOD magnitude [ABSTRACT FROM AUTHOR]

The occupation of commercial fishing is recognized as a comparatively stressful and hazardous job characterized by a myriad of risks to health, including high rates of job‐related injury, morbidity, and mortality. Nonetheless, systematic study of fisher health is limited. This paper examines a particularly understudied aspect of illness among fishers: the physical and social contexts, pathways, and potential for adverse disease interactions. The focus of the paper is on a biosocial disease process called syndemics, which increases the health burdens of this population. The paper is presented as an initial testing of the hypothesis that a "lens" of syndemics improves occupational health research and advocacy for commercial fishermen who face a substantial burden of biosocial challenges. [ABSTRACT FROM AUTHOR]

Background: Young‐onset multiple system atrophy (YOMSA) is defined as the onset of multiple system atrophy (MSA) before the age of 40 years old. YOMSA is rare and there is much uncertainty of the phenotype and natural history in patients with YOMSA. Objective: The objective is to evaluate the characteristics and disease course of patients with YOMSA. Methods: We retrospectively reviewed medical records of patients with MSA who were evaluated at all Mayo Clinic sites from 1998 to 2021. We identified patients with YOMSA and evaluated clinical characteristics, autonomic function testing results, and disease course. Results: Of 1496 patients with a diagnosis of clinically probable or clinically established MSA, 20 patients had YOMSA. The median age of onset was 39.1 (interquartile range [IQR] = 37.1, 40.1) years; 13 patients (65%) were male. MSA‐parkinsonism was the most common subtype (65%). The median duration of symptom onset to YOMSA diagnosis was 4.9 (IQR = 3.7, 9) years. At the time of medical record review, 17 patients were deceased with a median survival of 8.3 (IQR = 7, 10.9) years. Univariate analysis showed that initial onset of autonomic failure predicted unfavorable survival (hazard ratio = 2.89, P = 0.04) compared to those who presented with motor impairment only at onset. At the time of YOMSA diagnosis, composite autonomic severity score was available in 19 patients with a median of 5 (IQR = 4, 6.5). Conclusions: YOMSA resembles MSA in most aspects including phenotype and prognosis, although the diagnosis is usually delayed. The presence of autonomic failure at symptom onset may be a poor predictor for survival. [ABSTRACT FROM AUTHOR]

Plasmodium sporozoites are the highly motile and invasive forms of the malaria parasite transmitted by mosquitoes. Sporozoites form within oocysts at the midgut wall of the mosquito, egress from oocysts and enter salivary glands prior to transmission. The GPI‐anchored major surface protein, the circumsporozoite protein (CSP) is important for Plasmodium sporozoite formation, egress, migration and invasion. To visualize CSP, we previously generated full‐length versions of CSP internally tagged with the green fluorescent protein, GFP. However, while these allowed for imaging of sporogony in oocysts, sporozoites failed to egress. Here, we explore different strategies to overcome this block in egress and obtain salivary gland resident sporozoites that express CSP‐GFP. Replacing the N‐terminal and repeat region with GFP did not allow sporozoite formation. Lowering expression of CSP‐GFP at the endogenous locus allowed sporozoite formation but did not overcome egress block. Crossing of CSP‐GFP expressing parasites that are blocked in egress with wild‐type parasites yielded a small fraction of parasites that entered salivary glands and expressed various levels of CSP‐GFP. Expressing CSP‐GFP constructs from a silent chromosome region from promoters that are active only post salivary gland invasion yielded normal numbers of fluorescent salivary gland sporozoites, albeit with low levels of fluorescence. We also show that lowering CSP expression by 50% allowed egress from oocysts but not salivary gland entry. In conclusion, Plasmodium berghei parasites with normal CSP expression tolerate a certain level of CSP‐GFP without disruption of oocyst egress and salivary gland invasion. [ABSTRACT FROM AUTHOR]

Background: Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU) which require specific physical or non‐physical triggers to occur. They may be isolated or may coexist with chronic spontaneous urticaria (CSU). Despite their frequent appearance in dermatology clinics, there is scarce information on the distinguishing features among the most common subtypes of CIndU as well as isolated CIndU versus CSU plus CIndU. Objectives: To compare clinical and laboratory characteristics, and comorbid conditions among the most common CIndU types and isolated CIndU versus CSU plus CIndU. Methods: We retrospectively analysed CIndU patients and compared patients' demographic, clinical and laboratory characteristics across isolated CIndU, CSU plus CIndU, symptomatic dermographism (SD), cold urticaria (ColdU) and cholinergic urticaria (ChoU). Results: A total of 423 patients (~70% isolated CIndU, ~30% CSU plus CIndU, ~5% mixed CIndU subtypes) were included in the study. The most frequent CIndU subtypes were SD (68.6%; 290/423), ColdU (11.4%; 48/423) and ChoU (10.9%; 46/423). Isolated CIndU patients were younger than CSU plus CIndU (33.74 ± 12.72 vs. 37.06 ± 11.84, p = 0.010). Angioedema, emergency referrals, need for systemic steroids, comorbid systemic disorders were more frequent and baseline urticaria control test scores were lower in CSU plus CIndU patients (vs. CIndU, p < 0.001, p = 0.008, p < 0.001, p = 0.031, p = 0.036, respectively). Among CIndU subtypes, ChoU patients were younger (24.9 ± 12.2 vs. 34.47 ± 12.12 vs. 31.38 ± 14.95; p < 0.001) and had male predominance (p < 0.001) while SD patients had no angioedema (p < 0.001) and had higher frequency of increased total IgE levels (p = 0.006). Conclusions: Isolated CIndU and CSU plus CIndU seems to be different endotypes of CU where CSU plus CIndU presents a more severe and refractory course. There are distinctive features of each CIndU subtype. These suggest involvement of different pathomechanistic pathways in these subtypes that need to be clarified in future studies. [ABSTRACT FROM AUTHOR]

Internalizing symptoms such as elevated stress and sustained negative affect can be important warning signs for developing mental disorders. A recent theoretical framework suggests a complex interplay of empathy, theory of mind (ToM), and negative thinking processes as a crucial risk combination for internalizing symptoms. To disentangle these relationships, this study utilizes neural, behavioral, and self‐report data to examine how the interplay between empathy, ToM, and negative thinking processes relates to stress and negative affect. We reanalyzed the baseline data of N = 302 healthy participants (57% female, Mage = 40.52, SDage = 9.30) who participated in a large‐scale mental training study, the ReSource project. Empathy and ToM were assessed using a validated fMRI paradigm featuring naturalistic video stimuli and via self‐report. Additional self‐report scales were employed to measure internalizing symptoms (perceived stress, negative affect) and negative thinking processes (rumination and self‐blame). Our results revealed linear associations of self‐reported ToM and empathic distress with stress and negative affect. Also, both lower and higher, compared to average, activation in the anterior insula during empathic processing and in the middle temporal gyrus during ToM performance was significantly associated with internalizing symptoms. These associations were dependent on rumination and self‐blame. Our findings indicate specific risk constellations for internalizing symptoms. Especially people with lower self‐reported ToM and higher empathic distress may be at risk for more internalizing symptoms. Quadratic associations of empathy‐ and ToM‐related brain activation with internalizing symptoms depended on negative thinking processes, suggesting differential effects of cognitive and affective functioning on internalizing symptoms. Using a multi‐method approach, these findings advance current research by shedding light on which complex risk combinations of cognitive and affective functioning are relevant for internalizing symptoms. [ABSTRACT FROM AUTHOR]

Smurf1 and Smurf2 are two closely related member of the HECT (homologous to E6AP carboxy terminus) E3 ubiquitin ligase family and play important roles in the regulation of various cellular processes. Both were initially identified to regulate transforming growth factor‐β and bone morphogenetic protein signaling pathways through regulating Smad protein stability and are now implicated in various pathological processes. Generally, E3 ligases, of which over 800 exist in humans, are ideal targets for inhibition as they determine substrate specificity; however, there are few inhibitors with the ability to precisely target a particular E3 ligase of interest. In this work, we explored a panel of ubiquitin variants (UbVs) that were previously identified to bind Smurf1 or Smurf2. In vitro binding and ubiquitination assays identified a highly specific Smurf2 inhibitor, UbV S2.4, which was able to inhibit ligase activity with high potency in the low nanomolar range. Orthologous cellular assays further demonstrated high specificity of UbV S2.4 toward Smurf2 and no cross‐reactivity toward Smurf1. Structural analysis of UbV S2.4 in complex with Smurf2 revealed its mechanism of inhibition was through targeting the E2 binding site. In summary, we investigated several protein‐based inhibitors of Smurf1 and Smurf2 and identified a highly specific Smurf2 inhibitor that disrupts the E2–E3 protein interaction interface. [ABSTRACT FROM AUTHOR]