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The examination of fungal secretomes has garnered attention for its potential to unveil the repertoire of secreted proteins, notably CAZymes (Carbohydrate-Active enzymes), across various microorganisms. This study presents findings on categorizing the secretome profile of CAZymes by their function and family, derived from the filamentous fungus Trichoderma longibrachiatum LMBC 172. The cultivation was performed through submerged fermentation with three distinct carbon sources: sugarcane bagasse, tamarind seeds, and a control simulating hemicellulose containing 0.5% beechwood xylan plus 0.5% oat spelt xylan. The secretome analysis revealed 206 distinct CAZymes. Each carbon source showed particularities and differences. Of these, 89 proteins were produced simultaneously with all the carbon sources; specifically, 41 proteins using only the hemicellulose simulation, 29 proteins when sugarcane bagasse was used as a carbon source, and only 3 when tamarind seeds were used. However, in this last condition, there was a high intensity of xyloglucanase GH74 production, thus reaffirming the richness of xyloglucan in the constitution of these seeds. When evaluating the proteins found in two conditions, 18 proteins were shown between the simulation of hemicellulose and sugarcane bagasse, 11 proteins between the simulation of hemicellulose and tamarind seeds, and 15 proteins between sugarcane bagasse and tamarind seeds. Among the proteins found, there are representatives of different families such as glycosyl hydrolases (GHs) that cleave cellulose, hemicellulose, pectin, or other components; carbohydrate esterases (CEs); polysaccharide lyases (PLs); carbohydrate-binding modules (CBMs); and auxiliary activity enzymes (AAs). These results demonstrate the importance of analyzing CAZymes secreted by microorganisms under different culture conditions.

Habermas verk om den ”Borgerliga offentligheten” publicerades för drygt sextio år sedan och fick stort internationellt genomslag. Författaren har själv nyligen kommenterat studiens möte med nutida medielandskap och samhälle. Habermas själv, och många med honom, ser fortfarande civilsamhällets förfall som ett hot mot dess potential som infrastruktur för diskursiv demokrati och öppenhet. Kosellecks sedermera klassiska studie av upplysningstänkande föregick Habermas, men varnade för utopism, ”despotisk moralism” och att oansvarigt kritiserande kunde bli följden av den offentlighet som han inspirerade Habermas att undersöka. Habermas mer inflytelserika analys talar om en ofullbordad modernitet och fortsätter att formulera försvar för en förnuftig offentlighet i Kants upplysningsanda. Koselleck varnade för upplysningens fullbordan såsom denna diskurs utvecklades och där han bedömde frimurare som betydligt mer framträdande än Habermas, men hans politiska position i detta är föremål för tolkning och kritik. Här ställs de två ansatserna i relation till varandra, Kosellecks position tydliggörs och såväl likheter som skillnader uppmärksammas. Avslutningsvis väcks frågan om vad som är fruktbart och vad som kanske måste uppges i dessa analyser.

In diesem Beitrag wird ein asynchrones Onlineseminarkonzept aus der universitären Lehrkräftebildung vorgestellt, das selbstgesteuertes und nachhaltiges Lernen ermöglicht. Inhaltlich steht die Vermittlung von lehramtsspezifischen Grundlagen zur schulischen Inklusion im Fokus. Darüber hinaus liegt der allgemeine Schwerpunkt der Konzeption inhaltsunabhängig auf der Förderung der Kooperations- und Kollaborationsfähigkeit, den Feedback- und Selbstlernkompetenzen sowie der Fähigkeit zum Perspektivenwechsel bei den teilnehmenden Studierenden. Das digitale Lernangebot wurde mithilfe des Learning-Management-Systems OLAT nach Prinzipien des lebendigen und nachhaltigen Lernens gestaltet und enthält mit einem Punktekonzept Elemente der Gamification. Es ist selbstgesteuert, produktiv, aktivierend, situationsbezogen und fördert die soziale Interaktion, um gemeinsames Lernen zu unterstützen. Seminarevaluationen und offene Befragungen der Teilnehmenden über mehrere Semester hinweg zeigen, dass das Konzept sehr gut aufgenommen wird und nach subjektivem Empfinden die genannten Ziele erfüllen kann.

Background: Smoking has conflicting results on outcomes following acute myocardial infarction (AMI). We evaluated the independent influence of smoking status on patient outcomes. Methods: We included patients with AMI undergoing invasive coronary angiography with available self-reported smoking status. The incidence of death of any cause was evaluated during a median follow-up of 1.14 years (range 0.36–3.40 years). Association between smoking status and long-term mortality was evaluated using multivariable adjusted Cox regression analysis. Results: From 1612 AMI patients (aged 65.7 ± 13.3 years, 72.1 % male), 378 patients (23.4 %) were current-smokers, 311 (19.3 %) ex-smokers, and 923 (57.3 %) non-smokers. Compared with non-smokers, current-smokers were younger (68.5 ± 13.0 vs. 58.6 ± 12.5, p

Background The applicability of quantitative flow ratio (QFR), a nonhyperemic, invasive coronary angiography‐derived computation of fractional flow reserve (FFR), has not been studied in coronary artery bypass grafts. We sought to explore the correlation and diagnostic agreement between QFR and FFR in saphenous vein grafts (SVGs). Methods and Results A total of 129 prospectively included patients (mean age 73±8 years, 84% male) with prior coronary artery bypass grafting underwent invasive coronary angiography and pressure‐derived functional assessment in 150 nonoccluded SVGs. QFR dedicated angiography images of the SVGs were acquired and used for offline QFR computation. The diagnostic performance of QFR was compared with 2‐dimensional quantitative coronary angiography, using FFR as a reference. A threshold of ≤0.80 was used to define functional significance. QFR was successfully computed in 140 (93%) SVGs. We found a significant correlation between QFR and FFR (r=0.72, P

Objectives The objectives of this study are to identify a therapeutic serum level for adalimumab associated with remission and low disease activity in patients with rheumatoid arthritis.Methods Associations between serum adalimumab trough levels and disease activity were examined using longitudinal data from a 48-week randomised phase III trial including patients with tumour necrosis factor inhibitor-naïve rheumatoid arthritis with active disease starting adalimumab treatment. Disease activity was classified according to 28-joint Disease Activity Score (DAS28)-erythrocyte sedimentation rate and C reactive protein (CRP) levels.Results Adalimumab trough levels were recorded longitudinally for 336, 330 and 302 patients at weeks 12, 24 and 48, respectively. All patients received concomitant methotrexate. Median adalimumab trough levels were 6.4 mg/L (IQR 3.4–9.5) at week 12, 7.5 mg/L (IQR 3.5–10.9) at week 24 and 7.6 mg/L (IQR 3.6–12.0) at week 48. In serial serum samples from weeks 12, 24 and 48, trough levels ≥3.9 mg/L were associated with DAS28 remission (OR 3.88 (95% CI 1.80, 8.38), p

Background Guidelines on endovascular therapy for acute ischemic stroke do not include isolated cervical internal carotid artery (cICA) occlusions. The effect of treating these lesions remains unclear. This study aimed to compare the baseline characteristics and treatment outcomes between patients with isolated cICA occlusions to patients who underwent endovascular therapy due to a level of occlusion supported by guidelines. Methods A retrospective cohort study was conducted on 1162 patients who underwent endovascular therapy. Of these, 115 had an isolated cICA occlusion. Univariate analysis of baseline characteristics and outcome measured by the modified Rankin scale 90 days after endovascular therapy were compared between patients with isolated cICA occlusion, those with tandem occlusions, and those with occlusions of the middle cerebral artery/top of the internal carotid artery (first segment of the middle cerebral artery/intracranial internal carotid artery). To adjust for confounders, an inverse probability of treatment weighting was performed. Results Patients with isolated cICA occlusions were more likely men (67.8% versus 50.9%; P

Summary: Cancer cachexia is a prevalent and often fatal wasting condition that cannot be fully reversed with nutritional interventions. Muscle atrophy is a central component of the syndrome, but the mechanisms whereby cancer leads to skeletal muscle atrophy are not well understood. We performed single-nucleus multi-omics on skeletal muscles from a mouse model of cancer cachexia and profiled the molecular changes in cachexic muscle. Our results revealed the activation of a denervation-dependent gene program that upregulates the transcription factor myogenin. Further studies showed that a myogenin-myostatin pathway promotes muscle atrophy in response to cancer cachexia. Short hairpin RNA inhibition of myogenin or inhibition of myostatin through overexpression of its endogenous inhibitor follistatin prevented cancer cachexia-induced muscle atrophy in mice. Our findings uncover a molecular basis of muscle atrophy associated with cancer cachexia and highlight potential therapeutic targets for this disorder.

BackgroundPatients with a positive prehospital stroke severity score and underlying intracerebral hemorrhage (ICH) may be harmed by longer onset-to-admission time. We aimed to investigate the interaction between ICH severity and time from onset to admission on functional outcome.MethodsThis is an individual patient data analysis with data from two randomized prehospital stroke trials using the same prehospital stroke scale. Patients were stratified according to the presence of a positive stroke severity score. They were grouped into early arrivers (admitted ≤ 90 min from onset) and late arrivers (admitted ≥90 min after onset). The primary outcome was a shift toward a better functional outcome on the modified Rankin Scale (mRS).ResultsA total of 212 patients had ICH. A positive stroke severity score was seen in 123 of these patients. Patients with ICH and a positive prehospital stroke severity score had a significantly worse outcome if they arrived 90 min or later at the hospital (adjusted odds ratio [aOR]: 2.02, 95% CI [1.01, 4.12]). This difference was not observed in patients without a positive severity score (aOR: 0.50, 95% CI [0.22, 1.14]). Patients with a positive score also had an increased risk of death or severe dependency (mRS of 5–6) of 9.1 percentage points (95% CI [−1.6%, 19.8%]) per hour if they were diagnosed with ICH.ConclusionLonger onset-to-admission time was harmful for patients with ICH and a positive prehospital stroke severity score.

Abstract Immune checkpoint inhibitors targeting PD-1/L1 have modest efficacy in hepatocellular carcinoma as single agents. Targeting membranous phosphatidylserine may induce pro-inflammatory and -immune stimulating effects that enhance immunotherapy activity. This hypothesis was tested in a single-arm phase 2 trial evaluating frontline bavituximab, a phosphatidylserine targeting antibody, plus pembrolizumab (anti-PD-1) in patients with unresectable hepatocellular carcinoma (NCT03519997). The primary endpoint was investigator-assessed objective response rate among evaluable patients, and secondary end points included progression-free survival, incidence of adverse events, overall survival, and duration of response. Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3–11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response. These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the pre-treatment tumor microenvironment.

Background and objective The influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown.Design, setting, participants and outcome measures A retrospective cohort study was performed, including 147 UC patients treated with infliximab at a tertiary inflammatory bowel disease (IBD) centre. Primary outcome was corticosteroid-free clinical remission (CFCR) at week 14 and week 52. Patients were grouped according to prednisolone tapering regimens: standard (≤5 mg/week), fast (>5 mg/week), direct discontinuation or no prednisolone. Patients intolerant to corticosteroids and patients stopping corticosteroids in preparation for surgery including colectomy during their initial admission were excluded.Results There was no overall association between prednisolone exposure or no exposure and CFCR at weeks 14 or 52 of infliximab. The proportion of patients with C reactive protein ≤5 mg/L was higher in the standard tapering at week 14 as compared with faster regimens or no prednisolone. In subgroup analyses, the standard tapering was associated with a higher rate of CFCR at week 14 compared with the fast-tapering regimen in patients receiving ≥40 mg prednisolone at initiation of infliximab (64.3% vs 26.3%, p=0.04) and among patients admitted with acute severe UC (66.6% vs 23.5%, p

Abstract Chemicals in the aquatic environment can be harmful to organisms and ecosystems. Knowledge on effect concentrations as well as on mechanisms and modes of interaction with biological molecules and signaling pathways is necessary to perform chemical risk assessment and identify toxic compounds. To this end, we developed criteria and a pipeline for harvesting and summarizing effect concentrations from the US ECOTOX database for the three aquatic species groups algae, crustaceans, and fish and researched the modes of action of more than 3,300 environmentally relevant chemicals in literature and databases. We provide a curated dataset ready to be used for risk assessment based on monitoring data and the first comprehensive collection and categorization of modes of action of environmental chemicals. Authorities, regulators, and scientists can use this data for the grouping of chemicals, the establishment of meaningful assessment groups, and the development of in vitro and in silico approaches for chemical testing and assessment.

Abstract Conservation gardening (CG) represents a socio-ecological approach to address the decline of native plant species and transform the gardening industry into an innovative conservation tool. However, essential information regarding amenable plants, their ecological requirements for gardening, and commercial availability remains limited and not readily available. In this study, we present a workflow using Germany as a case study to bridge this knowledge gap. We synthesized the Red Lists of all 16 federal states in Germany, and text-mined a comprehensive platform for garden plants, as well as multiple German producers of native plants. To provide accessible information, we developed a user-friendly app ( https://conservation-gardening.shinyapps.io/app-en/ ) that offers region-specific lists of CG plants, along with practical guidance for planting and purchasing. Our findings reveal that a median of 845 plant species are red-listed across federal states (ranging from 515 to 1123), with 41% of these species amenable to gardening (ranging from 29 to 53%), resulting in a total of 988 CG species. Notably, 66% of these species (650) are already available for purchase. Additionally, we observed that many CG plants exhibit drought tolerance and require less fertilizer on average, with implications for long-term urban planning and climate adaptation. Collaborating with gardening experts, we present a selection of purchasable CG balcony plants for each federal state, highlighting the feasibility of CG even for individuals without gardens. With a multitude of declining plants amenable to gardening and the vital role of gardens as refuges and green corridors, CG holds substantial potential to catalyze transformative change in bending the curve of biodiversity loss.

Abstract Herbivorous rodents in boreal, alpine and arctic ecosystems are renowned for their multi‐annual population cycles. Researchers have hypothesised that these cycles may result from herbivore–plant interactions in various ways. For instance, if the biomass of preferred food plants is reduced after a peak phase of a cycle, rodent diets can be expected to become dominated by less preferred food plants, leading the population to a crash. It could also be expected that the taxonomic diversity of rodent diets increases from the peak to the crash phase of a cycle. The present study is the first to use DNA metabarcoding to quantify the diets of two functionally important boreal rodent species (bank vole and tundra vole) to assess whether their diet changed systematically in the expected cyclic phase‐dependent manner. We found the taxonomic diet spectrum broad in both vole species but with little interspecific overlap. There was no evidence of systematic shifts in diet diversity metrics between the phases of the population cycle in either species. While both species' diet composition changed moderately between cycle phases and seasons, these changes were small compared to other sources of diet variation—especially differences between individuals. Thus, the variation in diet that could be attributed to cyclic phases is marginal relative to the overall diet flexibility. Based on general consumer‐resource theory, we suggest that the broad diets with little interspecific overlap render it unlikely that herbivore–plant interactions generate their synchronous population cycles. We propose that determining dietary niche width should be the first step in scientific inquiries about the role of herbivore–plant interactions in cyclic vole populations.

Objectives An increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke and to study the impact on stroke severity, quality of care and mortality on an individual patient level.Design This was a nationwide register-based cohort study.Setting We used data from several Danish registers which were linked at an individual patient level using the unique civil registration number assigned to all Danish citizens. Patients were identified from the Danish Stroke Registry and information on SARS-CoV-2 infection status was collected from the Danish National COVID-19 Registry. Concurrent SARS-CoV-2 infection was defined as a positive PCR test within 31 days prior to, and 1 day after, stroke admission. Information on comorbidity was collected from the Danish National Patient Registry and information on vital status was collected from the Danish Civil Registration System.Participants A total of 11 502 patients admitted with acute ischaemic stroke from 10 March 2020 to 31 May 2021 were included in the study.Results Among the included patients, the majority (84.6%) were tested for SARS-CoV-2, but only 68 had a positive test. These patients were more prone to have atrial fibrillation and were more often treated with reperfusion therapy. They had a significantly increased risk of severe stroke (adjusted relative risk (aRR) 1.93, 95% CI: 1.22 to 3.04) and a significantly increased 30-day mortality risk (aRR 2.29, 95% CI: 1.19 to 4.39). There was no difference in the proportion of patients fulfilling relevant performance measures on quality of care.Conclusion In this nationwide study, only 0.6% of patients with acute ischaemic stroke were tested positive for a concurrent SARS-CoV-2 infection. The patients with SARS-CoV-2 presented with more severe strokes.

IntroductionPersonality traits and neuropsychiatric symptoms such as neuroticism and depression share genetic overlap and have both been identified as risks factors for development of aging-related neurocognitive decline and Alzheimer’s disease (AD). This study aimed to examine revised personality factors derived from the Temperament and Character Inventory, previously shown to be associated with psychiatric disorders, as predictors of neuropsychiatric, cognitive, and brain trajectories of participants from a population-based aging study.MethodsMixed-effect linear regression analyses were conducted on data for the full sample (Nmax = 1,286), and a healthy subsample not converting to AD-dementia during 25-year follow-up (Nmax = 1,145), complemented with Cox proportional regression models to determine risk factors for conversion to clinical AD.ResultsTwo personality factors, Closeness to Experience (CE: avoidance of new stimuli, high anxiety, pessimistic anticipation, low reward seeking) and Tendence to Liabilities (TL: inability to change, low autonomy, unaware of the value of their existence) were associated with higher levels of depressive symptoms, stress (CE), sleep disturbance (TL), as well as greater decline in memory, vocabulary and verbal fluency in the full sample. Higher CE was additionally associated with greater memory decline across 25 years in the healthy subsample, and faster right hippocampal volume reduction across 8 years in a neuroimaging subsample (N = 216). Most, but not all, personality-cognition associations persisted after controlling for diabetes, hypertension and cardiovascular disease. Concerning risks for conversion to AD, higher age, and APOE-ε4, but none of the personality measures, were significant predictors.ConclusionThe results indicate that personality traits associated with psychiatric symptoms predict accelerated age-related neurocognitive declines even in the absence of neurodegenerative disease. The attenuation of some personality effects on cognition after adjustment for health indicators suggests that those effects may be partly mediated by somatic health. Taken together, the results further emphasize the importance of personality traits in neurocognitive aging and underscore the need for an integrative (biopsychosocial) perspective of normal and pathological age-related cognitive decline.

Abstract Camera traps have become popular labor‐efficient and non‐invasive tools to study animal populations. The use of camera trap methods has largely focused on large animals and/or animals with identifiable features, with less attention being paid to small mammals, including rodents. Here we investigate the suitability of camera‐trap‐based abundance indices to monitor population dynamics in two species of voles with key functions in boreal and Arctic ecosystems, known for their high‐amplitude population cycles. The targeted species—gray‐sided vole (Myodes rufocanus) and tundra vole (Microtus oeconomus)—differ with respect to habitat use and spatial‐social organization, which allow us to assess whether such species traits influence the accuracy of the abundance indices. For both species, multiple live‐trapping grids yielding capture‐mark‐recapture (CMR) abundance estimates were matched with single tunnel‐based camera traps (CT) continuously recording passing animals. The sampling encompassed 3 years with contrasting abundances and phases of the population cycles. We used linear regressions to calibrate CT indices, based on species‐specific photo counts over different time windows, as a function of CMR‐abundance estimates. We then performed inverse regression to predict CMR abundances from CT indices and assess prediction accuracy. We found that CT indices (for windows maximizing goodness‐of‐fit of the calibration models) predicted adequately the CMR‐based estimates for the gray‐sided vole, but performed poorly for the tundra vole. However, spatially aggregating CT indices over nearby camera traps enabled reliable abundance indices also for the tundra vole. Such species differences imply that the design of camera trap studies of rodent population dynamics should be adapted to the species in focus, and adequate spatial replication must be considered. Overall, tunnel‐based camera traps yield much more temporally resolved abundance metrics than alternative methods, with a large potential for revealing new aspects of the multi‐annual population cycles of voles and other small mammal species they interact with.

Abstract Background We present a case illustrating evolution of symptoms and brain magnetic resonance imaging in cortical superficial siderosis. Case presentation A 74-year-old man with no prior medical history presented with transient focal neurological episodes with subtle imaging changes. There was no evidence of cortical superficial siderosis. Two weeks later, the patient was readmitted with new episodes, and had developed cortical superficial siderosis adjacent to a cerebral microbleed. Transient focal neurological episode secondary to cortical superficial siderosis was diagnosed together with probable cerebral amyloid angiopathy. Conclusion Clinical symptoms may precede the development of cortical superficial siderosis prior to being detectable on brain MRI. This case highlights the temporal development of cortical superficial siderosis.

Abstract The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.

A wealth of observations have long suggested that the vast majority of isolated classical dwarf galaxies ( M _* = 10 ^7 –10 ^9 M _⊙ ) are currently star forming. However, recent observations of the large abundance of “ultra-diffuse galaxies” beyond the reach of previous large spectroscopic surveys suggest that our understanding of the dwarf galaxy population may be incomplete. Here we report the serendipitous discovery of an isolated quiescent dwarf galaxy in the nearby Universe, which was imaged as part of the JWST PEARLS Guaranteed Time Observation program. Remarkably, individual red-giant branch stars are visible in this near-IR imaging, suggesting a distance of 30 ± 4 Mpc, and a wealth of archival photometry point to an sSFR of 2 × 10 ^−11 yr ^−1 and star formation rate of 4 × 10 ^−4 M _⊙ yr ^−1 . Spectra obtained with the Lowell Discovery Telescope find a recessional velocity consistent with the Hubble Flow and >1500 km s ^−1 separated from the nearest massive galaxy in Sloan Digital Sky Survey suggesting that this galaxy was either quenched from internal mechanisms or had a very high-velocity (≳1000 km s ^−1 ) interaction with a nearby massive galaxy in the past. This analysis highlights the possibility that many nearby quiescent dwarf galaxies are waiting to be discovered and that JWST has the potential to resolve them.

The recent coronavirus pandemic impacted the mental health of people worldwide as it rapidly spread to most countries. Social media has provided a cost-effective method to examine these negative effects, but which aspects of the disease impacted the general population's psychology is not well understood. This study examined one potential factor that moderated people's responses to the fast-spreading, deadly coronavirus disease (COVID) during its emergence from January 2020 to March 2020. Applying sentiment analysis to 3.2 million COVID-related messages posted on Twitter from 189 countries, we examined how the physical distance to COVID impacted the attention and emotions of the general population as it spread around the globe. The spatial distance from each message's origin country to the nearest COVID-infected country was computed to use as an independent variable. Statistical analyses revealed that spatial distance significantly influenced both public attention and sentiment toward COVID, even when controlling for confounders. As the disease came closer, more tweets were posted and the average sentiment became more negative. These observations suggest that physical proximity to a threat influences how much attention people pay to the threat and how they respond to it emotionally. This is in line with previous disaster research and fits the psychological framework of construal level theory. Although these findings are limited in their generalizability, they have important implications. In practice, communicating the personal risks of a disease outbreak to distant people might increase public engagement in protective behaviors such as social distancing and hand washing, subsequently slowing disease spread.

James Webb Space Telescope NIRCam images have revealed 154 reliable globular cluster (GC) candidates around the z = 0.0513 elliptical galaxy VV 191a after subtracting 34 likely interlopers from background galaxies inside our search area. NIRCam broadband observations are made at 0.9–4.5 μ m using the F090W, F150W, F356W, and F444W filters. Using point-spread-function-matched photometry, the data are analyzed to present color–magnitude diagrams and color distributions that suggest a relatively uniform population of GCs, except for small fractions of reddest (5%–8%) and bluest (2%–4%) outliers. GC models in the F090W versus (F090W–F150W) diagram fit the NIRCam data well and show that the majority of GCs detected have a mass of ∼10 ^6.5 M _⊙ , with metallicities [Fe/H] spanning the typical range expected for GCs (−2.5 ≲ [Fe/H]≲ 0.5). However, the models predict ∼0.3–0.4 mag bluer (F356W–F444W) colors than the NIRCam data for a reasonable range of GC ages, metallicities, and reddening. Although our data do not quite reach the luminosity function turnover, the measured luminosity function is consistent with previous measurements, suggesting an estimated peak at m _AB ∼ −9.4 ± 0.2 mag in the F090W filter.

Purpose Coeliac disease (CD) is a common disorder and affects about 1% of the population worldwide. CD in the Trøndelag Health Study (HUNT) is a population-based cohort study which was established to provide new knowledge about CD that can improve the diagnostics and management, prevent the onset or progression and expand the knowledge about the role of genetics of the disease.Participants The cohort is based on the fourth wave of the population-based HUNT study (HUNT4), Norway, performed during 2017–2019, also including linkage to hospital records and the Norwegian Patient Registry (NPR). A total of 54 541 HUNT4 participants with available sera were screened for CD by serology. All seropositive participants were invited to a clinical assessment, including endoscopy with duodenal biopsies, during 2019–2023.Findings to date A total of 1107 HUNT4 participants (2%) were seropositive for CD and 1048 were eligible for clinical assessment, including biopsy. Of these, 724 participants attended the clinical assessment and 482 were identified with CD. In addition, 371 participants with CD were identified through the hospital records and NPR. In total, 853 participants in HUNT4 with biopsy-verified CD diagnosis were identified.Future plans All participants in the study will be invited to a follow-up assessment after at least 1 year, including repeated standard serological testing, endoscopy and tissue sampling. The collected data and material will be used to establish the true population-based prevalence of CD. The consequences of CD, including symptoms, deficiencies and comorbidity, will be investigated and possible triggers and predictors, will be studied. With access to serum samples from the previous HUNT surveys in HUNT Biobank, serological signs of CD in prediagnostic samples of seropositive individuals will be used. Genetic studies will identify new CD markers, assess genotype–phenotype links and explore gene–environment correlations.Registration clinicaltrials.gov identifier: NCT04041622.

Abstract Arctic tundra vegetation is affected by rapid climatic change and fluctuating herbivore population sizes. Broad‐billed geese, after their arrival in spring, feed intensively on belowground rhizomes, thereby disturbing soil, mosses, and vascular plant vegetation. Understanding of how springtime snowmelt patterns drive goose behavior is thus key to better predict the state of Arctic tundra ecosystems. Here, we analyzed how snowmelt progression affected springtime habitat selection and vegetation disturbance by pink‐footed geese (Anser brachyrhynchus) in Svalbard during 2019. Our analysis, based on GPS telemetry data and field observations of geese, plot‐based assessments of signs of vegetation disturbance, and drone and satellite images, covered two spatial scales (fine scale: extent 0.3 km2, resolution 5 cm; valley scale: extent 30 km2, resolution 10 m). We show that pink‐footed goose habitat selection and signs of vegetation disturbance were correlated during the spring pre‐breeding period; disturbances were most prevalent in the moss tundra vegetation class and areas free from snow early in the season. The results were consistent across the spatial scales and methods (GPS telemetry and field observations). We estimated that 23.4% of moss tundra and 11.2% of dwarf‐shrub heath vegetation in the valley showed signs of disturbance by pink‐footed geese during the study period. This study demonstrates that aerial imagery and telemetry can provide data to detect disturbance hotspots caused by pink‐footed geese. Our study provides empirical evidence to general notions about implications of climate change and snow season changes that include increased variability in precipitation.

Background The optimal blood pressure management strategy in patients undergoing endovascular therapy for acute ischemic stroke is unknown. This pilot study aimed to assess the feasibility of a standard versus individualized blood pressure management strategy during endovascular therapy. Methods This randomized controlled pilot trial included adult patients with acute ischemic stroke with large‐vessel occlusion in the anterior circulation undergoing endovascular therapy. Patients were randomized to either standard (mean arterial blood pressure [MABP] targeted between 70 and 90 mm Hg) or individualized (MABP targeted ±10% of a baseline value measured in the neurointerventional suite) blood pressure targets until reperfusion or removal of groin sheath. The main outcome was the modified Rankin Scale score at 90 days. Secondary outcomes included feasibility outcomes, 90‐day dichotomized modified Rankin Scale score (0–2 versus 3–6), and reperfusion rates. Results Between April 2021 and February 2022, 60 patients (median [interquartile range] age, 76 [66–84] years) were randomly assigned to standard (n=30) or individualized (n=30) blood pressure targets. Median (interquartile range) National institutes of Health Stroke Scale score was 15 (10–18). Mean (SD) MABP, mean (SD) systolic blood pressure, and median (interquartile range) cardiac output were significantly higher in the individualized group compared with the standard group (MABP: 94 [9] versus 88 [9] mm Hg; P=0.012; systolic blood pressure: 149 [21] versus 139 [17] mm Hg; P=0.032; and cardiac output: 5.82 [4.22–7.23] versus 4.35 [3.73–5.1] L/min; P=0.02). The odds ratio for improved outcome in the individualized group was 1.37 (95% CI, 0.56–3.36). The relative risk for improved dichotomized outcome in the individualized group was 1.31 (95% CI, 0.87–1.98). Full reperfusion rates were comparable between the standard and individualized groups (90% versus 93%; P=0.64). The median percentage of time outside the MABP targets was 54.3% in the standard group versus 61.4% in the individual group (P=0.30) and did not meet the feasibility target. Recruitment rate, data completeness, and safety were within feasibility limits. Conclusions The feasibility criteria were not met in this study because of difficulties in achieving the desired blood pressure targets. These findings do not support continuing with a large trial using the current protocol.

Abstract Introduction Rapid identification and treatment of stroke is crucial for the outcome of the patient. We aimed to determine the performance of glial fibrillary acidic protein (GFAP) independently and in combination with the Prehospital Stroke Score (PreSS) for identification and differentiation of acute stroke within 4.5 h after symptom onset. Patients and methods Clinical data and serum samples were collected from the Treat-Norwegian Acute Stroke Prehospital Project (Treat-NASPP). Patients with suspected stroke and symptoms lasting ≤ 4.5 h had blood samples collected and were evaluated with the National Institutes of Health Stroke Scale prospectively. In this sub study, NIHSS was retrospectively translated into PreSS and GFAP was measured using the sensitive single molecule array (SIMOA). Results A total of 299 patients with suspected stroke were recruited from Treat-NASPP and included in this study (44% acute ischemic stroke (AIS), 10% intracranial hemorrhage (ICrH), 7% transient ischemic attack (TIA), and 38% stroke mimics). ICrH was identified with a cross-fold validated area under the receiver-operating characteristic curve (AUC) of 0.73 (95% CI 0.62–0.84). A decision tree with PreSS and GFAP combined, first identified patients with a low probability of stroke. Subsequently, GFAP detected patients with ICrH with a 25.0% sensitivity (95% CI 11.5–43.4) and 100.0% specificity (95% CI 98.6–100.0). Lastly, patients with large-vessel occlusion (LVO) were detected with a 55.6% sensitivity (95% CI 35.3–74.5) and 82.4% specificity (95% CI 77.3–86.7). Conclusion In unselected patients with suspected stroke, GFAP alone identified ICrH. Combined in a decision tree, GFAP and PreSS identified subgroups with high proportions of stroke mimics, ICrH, LVO, and AIS (non-LVO strokes).

Abstract Background Long-lasting crises, such as the COVID-19 pandemic, require proper interim evaluation in order to optimize response. The World Health Organization and the European Center for Disease Control have recently promoted the in(tra)-action review (IAR) method for this purpose. We systematically evaluated the added value of two IARs performed in the Dutch point of entry (PoE) setting. Methods Two online, 4-hour IAR meetings were organized in March 2021, for ports and airports respectively, to reflect on the ongoing COVID-19 response. Topics discussed were selected through a survey among participants. Participants were mainly self-selected by the (air)port public health service. Evaluation of the IAR method consisted of participant evaluation through a questionnaire, and hot and cold debriefs of the organizing team. Evaluation of the impact of the IAR was done through analysis of the meeting results, and a 3-month follow-up of the actions proposed during the meetings. Results Thirty-nine professionals joined the IAR meetings. In the participant evaluation (n = 18), 89% agreed or totally agreed the IAR made it possible to identify challenges and problems in the COVID-19 response at PoE. Participants especially appreciated the resulting insight in regional and national partners. Regarding the online setting of the meeting, participants suggested to choose accessible and familiar online tools. After 3 months, all national actions and actions for ports had been executed; some regional actions for airports required further attention. A major result was a new meeting structure for all ports and the participating national authorities in which remaining and newly occurring issues were discussed. Conclusions Based on the evaluations, we conclude that the IAR method can be of value during long-term crises, such as the COVID-19 pandemic response. Although it is challenging to dedicate time and effort to the organization and attendance of IAR meetings during crisis, the IAR method is feasible in an online setting if appropriate organizing and technical capacity is available. A participatory set-up supports the IAR method as a starting point for continuous exchange and learning during ongoing crises.

Three common Apolipoprotein E isoforms, ApoE2, ApoE3, and ApoE4, are key regulators of lipid homeostasis, among other functions. Apolipoprotein E can interact with amyloid proteins. The isoforms differ by one or two residues at positions 112 and 158, and possess distinct structural conformations and functions, leading to isoform-specific roles in amyloid-based neurodegenerative diseases. Over 30 different amyloid proteins have been found to share similar characteristics of structure and toxicity, suggesting a common interactome. The molecular and genetic interactions of ApoE with amyloid proteins have been extensively studied in neurodegenerative diseases, but have not yet been well connected and clarified. Here we summarize essential features of the interactions between ApoE and different amyloid proteins, identify gaps in the understanding of the interactome and propose the general interaction mechanism between ApoE isoforms and amyloid proteins. Perhaps more importantly, this review outlines what we can learn from the interactome of ApoE and amyloid proteins; that is the need to see both ApoE and amyloid proteins as a basis to understand neurodegenerative diseases.

Tsp-1 in the tumor microenvironment is known to suppress tumor growth and progression. Here the authors show that PRSS2 represses Tsp-1 by binding to lipoprotein receptor-related protein 1 and suggest targeting PRSS2 mediated Tsp-1 repression as a potential therapeutic strategy.

Municipalities are key actors in reaching the sustainable development goals 9, 11, 12, 13 set by the United Nations. The aim of this paper is to develop, on a theoretical level, a sustainable building refurbishment framework for municipalities. The focal point of the framework is reduction of embodied and operational carbon emissions deriving from buildings, including travel-induced emissions. The institutional buildings governed by a Norwegian municipality are the case study objects in this study. The framework that is currently is used in the municipality value the building stock based on the quality and cost of refurbishing them. No framework currently includes travel-induced emissions in the evaluation. The intention is to provide a holistic framework that includes this aspect when deciding if a building should be refurbished or demolished. The omission of transport emissions can lead to truncation errors in assessments. The transport to and from the school generates higher emissions in certain scenarios. Based on the knowledge in the assessment, a theoretical framework that assesses this is developed.

Background Few tissue biomarkers exist to date that could enrich patient with cancer populations to benefit from immune checkpoint blockade by programmed cell death protein 1/ligand-1 (PD-/L-1) inhibitors. PD-L1 expression has value in this context in some tumor types but is an imperfect predictor of clinical benefit. In malignant pleural mesothelioma, PD-L1 expression is not predictive of the benefit from PD-1 blockade. We aimed to identify novel markers in malignant pleural mesothelioma to select patients better.Methods We performed a multiplex-immune histochemistry analysis of tumor samples from the phase III PROMISE-meso study, which randomized 144 pretreated patients to receive either pembrolizumab or standard second-line chemotherapy. Our panel focused on CD8+T cell, CD68+macrophages, and the expression of PD-1 and PD-L1 on these and cancer cells. We analyzed single and double positive cells within cancer tissues (infiltrating immune cells) and in the stroma. In addition, we performed cell neighborhood analysis. The cell counts were compared with clinical outcomes, including responses, progression-free and overall survivals.Results We confirmed the absence of predictive value for PD-L1 in this cohort of patients. Furthermore, total CD8 T cells, CD68+macrophages, or inflammatory subtypes (desert, excluded, inflamed) did not predict outcomes. In contrast, PD-1-expressing CD8+T cells (exhausted T cells) and PD-1-expressing CD68+macrophages were both independent predictors of progression-free survival benefit from pembrolizumab. Patients with tumors simultaneously harboring PD1+T cells and PD-1+macrophages benefited the most from immune therapy.Conclusion We analyzed a large cohort of patients within a phase III study and found that not only PD-1+CD8 T cells but also PD-1+CD68+ macrophages are predictive. This data provides evidence for the first time for the existence of PD-1+macrophages in mesothelioma and their clinical relevance for immune checkpoint blockade.

Aquatic environments are polluted with a multitude of organic micropollutants, which challenges risk assessment due the complexity and diversity of pollutant mixtures. The recognition that certain source-specific background pollution occurs ubiquitously in the aquatic environment might be one way forward to approach mixture risk assessment. To investigate this hypothesis, we prepared one typical and representative WWTP effluent mixture of organic micropollutants (EWERBmix) comprised of 81 compounds selected according to their high frequency of occurrence and toxic potential. Toxicological relevant effects of this reference mixture were measured in eight organism- and cell-based bioassays and compared with predicted mixture effects, which were calculated based on effect data of single chemicals retrieved from literature or different databases, and via quantitative structure-activity relationships (QSARs). The results show that the EWERBmix supports the identification of substances which should be considered in future monitoring efforts. It provides measures to estimate wastewater background concentrations in rivers under consideration of respective dilution factors, and to assess the extent of mixture risks to be expected from European WWTP effluents. The EWERBmix presents a reasonable proxy for regulatory authorities to develop and implement assessment approaches and regulatory measures to address mixture risks. The highlighted data gaps should be considered for prioritization of effect testing of most prevalent and relevant individual organic micropollutants of WWTP effluent background pollution. The here provided approach and EWERBmix are available for authorities and scientists for further investigations. The approach presented can furthermore serve as a roadmap guiding the development of archetypic background mixtures for other sources, geographical settings and chemical compounds, e.g. inorganic pollutants.

The analysis of the secretome allows us to identify the proteins, especially carbohydrate-active enzymes (CAZymes), secreted by different microorganisms cultivated under different conditions. The CAZymes are divided into five classes containing different protein families. Thermothelomyces thermophilus is a thermophilic ascomycete, a source of many glycoside hydrolases and oxidative enzymes that aid in the breakdown of lignocellulosic materials. The secretome analysis of T. thermophilus LMBC 162 cultivated with submerged fermentation using tamarind seeds as a carbon source revealed 79 proteins distributed between the five diverse classes of CAZymes: 5.55% auxiliary activity (AAs); 2.58% carbohydrate esterases (CEs); 20.58% polysaccharide lyases (PLs); and 71.29% glycoside hydrolases (GHs). In the identified GH families, 54.97% are cellulolytic, 16.27% are hemicellulolytic, and 0.05 are classified as other. Furthermore, 48.74% of CAZymes have carbohydrate-binding modules (CBMs). Observing the relative abundance, it is possible to state that only thirteen proteins comprise 92.19% of the identified proteins secreted and are probably the main proteins responsible for the efficient degradation of the bulk of the biomass: cellulose, hemicellulose, and pectin.

Abstract Tree canopies are considered to effectively buffer climate extremes and to mitigate climate change effects. Droughts, which are predicted to become more frequent in the course of climate change, might alter the microclimatic cooling potential of trees. However, our understanding of how microclimate at the tree canopy level is modulated by environmental and tree characteristics and their interactions is still limited. Here, we investigated canopy temperature regulation for five mature co-occurring tree species for two contrasting hydrological situations during the severe drought in 2018. Even though we observed a significant drought-induced decline in canopy cover and transpiration across tree species, we found evidence that differences in the water use strategies of trees affected cooling mechanisms differently. Although a large share of the variations in the cooling potential of trees was explained by direct and indirect effects of meteorological factors, we identified a gradual shift in importance from latent heat flux to components defining the magnitude of sensible heat flux on the energy budget of tree as the drought gained severity. The decrease in latent heat fluxes, approximated by sap flow rates, furthermore resulted in a reduced cooling potential and an equalization of tree species canopy temperatures.

Lignosulfonate-based admixtures (LS) obtained from sulfite pulping processes were the first dispersants added as a water-reducer to concrete. Less effective than the latest superplasticizers, the low cost and low environmental footprint of LS continue to allow these materials to compete in the building and construction market. In addition to the dispersion effect, LS is known to retard cement hydration. The aim of this paper is to characterize the effect of LS on the hydration and rheology of cement paste. The effect of the time at which the LS is added, either by immediate addition or after ten minutes of hydration, has been investigated. It appears that the immediate addition of LS is less effective than the delayed addition when it comes to dispersion of cement, likely due to the initial ettringite formation.

Summary: Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett’s oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. Funding: German Research Foundation (DFG).

Summary: Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

Climate warming allows generalist boreal consumers to expand into Arctic ecosystems. We present experimental and observational field data showing that a generalist boreal insect pest—the winter moth (Operophtera brumata Linnaeus, 1758)—is expanding its outbreak range out of the northern boreal mountain birch forest in northeast Fennoscandia and into the adjacent Low Arctic shrub tundra. This is the first documented example of an outbreaking boreal insect pest expanding into a tundra ecosystem. The expansion has coincided with a long-term advancing trend in the expected hatching date of moth eggs in spring for the study region. We show that the winter moth can complete development on Low Arctic willows and that the density of winter moth larvae in willow thickets is unrelated to the amount of mountain birch (the main host plant in northern boreal forest) in the thickets. However, we also demonstrate that larval densities on willows show a regional-scale spatial decline when moving away from the birch forest and into the shrub tundra. Continued monitoring is needed to establish whether the outbreaks will spread farther into the tundra. The expansion of outbreaking boreal pests into the tundra could alter conventional expectations of increasing vegetation productivity and shrubification in tundra ecosystems.

How the 22q11.2 deletion predisposes to psychiatric disease is unclear. Here, the authors examine living human neuronal cells and show that 22q11.2 regulates the expression of genes linked to autism during early development, and genes linked to schizophrenia and synaptic biology in neurons.

We utilize deep JWST Near Infrared Camera (NIRCam) observations for the first direct constraints on the Galaxy Stellar Mass Function (GSMF) at z > 10. Our EPOCHS v1 sample includes 1120 galaxy candidates at 6.5 < z < 13.5 taken from a consistent reduction and analysis of publicly available deep JWST NIRCam data covering the Prime Extragalactic Areas for Reionization Science, CEERS, GLASS, JADES GOOD-S, NGDEEP, and SMACS0723 surveys, totaling 187 arcmin ^2 . We investigate the impact of spectral energy distribution fitting methods, assumed star formation histories (SFHs), dust laws, and priors on galaxy masses and the resultant GSMF. While our fiducial GSMF agrees with the literature at z < 13.5, we find that the assumed SFH model has a large impact on the GSMF and stellar mass density (SMD), finding a 0.75 dex increase in the SMD at z = 10.5 between a flexible nonparametric and standard parametric SFH. Overall, we find a flatter SMD evolution at z ≥ 9 than some studies predict, suggesting a rapid buildup of stellar mass in the early Universe. We find no incompatibility between our results and those of standard cosmological models, as suggested previously, although the most massive galaxies may require a high star formation efficiency. We find that the “little red dot” galaxies dominate the z = 7 GSMF at high masses, necessitating a better understanding of the relative contributions of active galactic nucleus and stellar emission. We show that assuming a theoretically motivated top-heavy initial mass function (IMF) reduces stellar mass by 0.5 dex without affecting fit quality, but our results remain consistent with existing cosmological models with a standard IMF.

As a part of the Deciphering the Interplay between the Interstellar medium, Stars, and the Circumgalactic medium (DIISC) survey, we investigate indirect evidence of gas inflow into the disk of the galaxy NGC 99. We combine optical spectra from the Binospec spectrograph on the MMT telescope with optical imaging data from the Vatican Advanced Technology Telescope, radio H i 21 cm emission images from the NSF Karl G. Jansky’s Very Large Array, and UV spectroscopy from the Cosmic Origins Spectrograph on the Hubble Space Telescope. We measure emission lines (H α , H β , [O iii ] λ 5007, [N ii ] λ 6583, and [S ii ] λ 6717, 31) in 26 H ii regions scattered about the galaxy and estimate a radial metallicity gradient of −0.017 dex kpc ^−1 using the N2 metallicity indicator. Two regions in the sample exhibit an anomalously low metallicity (ALM) of 12 + log(O/H) = 8.36 dex, which is ∼0.16 dex lower than other regions at that galactocentric radius. They also show a high difference between their H i and H α line of sight velocities on the order of 35 km s ^−1 . Chemical evolution modeling indicates gas accretion as the cause of the ALM regions. We find evidence for corotation between the interstellar medium of NGC 99 and Ly α clouds in its circumgalactic medium, which suggests a possible pathway for low metallicity gas accretion. We also calculate the resolved Fundamental Metallicity Relation (rFMR) on subkiloparsec scales using localized gas-phase metallicity, stellar mass surface density, and star formation rate surface density. The rFMR shows a similar trend as that found by previous localized and global FMR relations.

A Type Ia supernova (SN) at z = 1.78 was discovered in James Webb Space Telescope Near Infrared Camera imaging of the galaxy cluster PLCK G165.7+67.0 (G165; z = 0.35). The SN is situated 1.5–2 kpc from the host-galaxy nucleus and appears in three different locations as a result of gravitational lensing by G165. These data can yield a value for Hubble’s constant using time delays from this multiply imaged SN Ia that we call “SN H0pe.” Over the cluster, we identified 21 image multiplicities, confirmed five of them using the Near-Infrared Spectrograph, and constructed a new lens model that gives a total mass within 600 kpc of (2.6 ± 0.3) × 10 ^14 M _⊙ . The photometry uncovered a galaxy overdensity coincident with the SN host galaxy. NIRSpec confirmed six member galaxies, four of which surround the SN host galaxy with relative velocity ≲900 km s ^−1 and projected physical extent ≲33 kpc. This compact galaxy group is dominated by the SN host galaxy, which has a stellar mass of (5.0 ± 0.1) × 10 ^11 M _⊙ . The group members have specific star formation rates of 2–260 Gyr ^−1 derived from the H α -line fluxes corrected for stellar absorption, dust extinction, and slit losses. Another group centered on a strongly lensed dusty star-forming galaxy is at z = 2.24. The total (unobscured and obscured) SFR of this second galaxy group is estimated to be (≳ 100 M _⊙ yr ^−1 ), which translates to a supernova rate of ∼1 SNe yr ^−1 , suggesting that regular monitoring of this cluster may yield additional SNe.

We present the results of our search for Lyman continuum (LyC)-emitting (weak) active galactic nuclei (AGN) at redshifts 2.3 ≲ z ≲ 4.9 from Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) F275W observations in the Ultraviolet Imaging of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (UVCANDELS) fields. We also include LyC emission from AGN using HST WFC3 F225W, F275W, and F336W imaging found in Early Release Science (ERS) and Hubble Deep UV Legacy Survey data. We performed exhaustive queries of the Vizier database to locate AGN with high-quality spectroscopic redshifts. In total, we found 51 AGN that met our criteria within the UVCANDELS and ERS footprints. Out of these 51, we find 12 AGN that had ≥4 σ detected LyC flux in the WFC3/UVIS images. Using a wide variety of space-based plus ground-based data, ranging from X-ray to radio wavelengths, we fit the multiwavelength photometric data of each AGN to a CIGALE spectral energy distribution (SED) using AGN models and correlate various SED parameters to the LyC flux. Kolmogorov–Smirnov tests of the SED parameter distributions for the LyC-detected and nondetected AGN showed they are likely not distinct samples. However, we find that the X-ray luminosity, star formation onset age, and disk luminosity show strong correlations relative to their emitted LyC flux. We also find strong correlations of the LyC flux to several dust parameters, i.e., polar and toroidal dust emission and 6 μ m luminosity, and anticorrelations with metallicity and A _FUV . We simulate the LyC escape fraction ( f _esc ) using the CIGALE and intergalactic medium transmission models for the LyC-detected AGN and find an average f _esc ≃ 18%, weighted by uncertainties. We stack the LyC fluxes of subsamples of AGN according to the wavelength continuum region in which they are detected and find no significant distinctions in their LyC emission, although our submillimeter-detected F336W sample (3.15 < z < 3.71) shows the brightest stacked LyC flux. These findings indicate that LyC production and escape in AGN are more complicated than the simple assumption of thermal emission and a 100% escape fraction. Further testing of AGN models with larger samples than presented here is needed.

We present an analysis of the ultraviolet luminosity function (UV LF) and star formation rate density of distant galaxies (7.5 < z < 13.5) in the “blank” fields of the Prime Extragalactic Areas for Reionization and Lensing Science (PEARLS) survey combined with Early Release Science data from the CEERS, GLASS, and NGDEEP surveys/fields and the first data release of JADES. We use strict quality cuts on EAZY photometric redshifts to obtain a reliable selection and characterization of high-redshift ( z > 6.5) galaxies from a consistently processed set of deep, near-infrared imaging. Within an area of 180 arcmin ^2 , we identify 1046 candidate galaxies at redshifts z > 6.5 and we use this sample to study the UV LF in four redshift bins between 7.5 < z < 13.5. The measured number density of galaxies at z = 8 and z = 9 matches those of past observations undertaken by the Hubble Space Telescope (HST). Our z = 10.5 measurements lie between early James Webb Space Telescope (JWST) results and past HST results, indicating cosmic variance may be the cause of previous high density measurements. However, the number densities of UV-luminous galaxies at z = 12.5 are high compared to predictions from simulations. When examining the star formation rate density of galaxies at this period, our observations are still largely consistent with a constant star formation efficiency, are slightly lower than previous early estimations using JWST, and support galaxy driven reionization at z ≤ 8.

We present the second NuSTAR and XMM-Newton extragalactic survey of the JWST north ecliptic pole (NEP) time-domain field (TDF). The first NuSTAR NEP-TDF survey had 681 ks total exposure time executed in NuSTAR cycle 5 in 2019 and 2020. This second survey, acquired from 2020 to 2022 in cycle 6, adds 880 ks of NuSTAR exposure time. The overall NuSTAR NEP-TDF survey is the most sensitive NuSTAR extragalactic survey to date, and a total of 60 sources were detected above the 95% reliability threshold. We constrain the hard X-ray number counts, $\mathrm{log}N$ – $\mathrm{log}S$ , down to 1.7 × 10 ^−14 erg cm ^−2 s ^−1 at 8–24 keV and detect an excess of hard X-ray sources at the faint end. About 47% of the NuSTAR-detected sources are heavily obscured ( N _H > 10 ^23 cm ^−2 ), and ${18}_{-8}^{+20}$ % of the NuSTAR-detected sources are Compton-thick ( N _H > 10 ^24 cm ^−2 ). These fractions are consistent with those measured in other NuSTAR surveys. Four sources presented >2 σ variability in the 3 yr survey. In addition to NuSTAR, a total of 62 ks of XMM-Newton observations were taken during NuSTAR cycle 6. The XMM-Newton observations provide soft X-ray (0.5–10 keV) coverage in the same field and enable more robust identification of the visible and infrared counterparts of the NuSTAR-detected sources. A total of 286 soft X-ray sources were detected, out of which 214 XMM-Newton sources have secure counterparts from multiwavelength catalogs.

The James Webb Space Telescope (JWST) North Ecliptic Pole (NEP) Time-domain Field (TDF) is a >14′ diameter field optimized for multiwavelength time-domain science with JWST. It has been observed across the electromagnetic spectrum both from the ground and from space, including with the Hubble Space Telescope (HST). As part of HST observations over three cycles (the “TREASUREHUNT” program), deep images were obtained with the Wide Field Camera on the Advanced Camera for Surveys in F435W and F606W that cover almost the entire JWST NEP TDF. Many of the individual pointings of these programs partially overlap, allowing an initial assessment of the potential of this field for time-domain science with HST and JWST. The cumulative area of overlapping pointings is ∼88 arcmin ^2 , with time intervals between individual epochs that range between 1 day and 4+ yr. To a depth of m _AB ≃ 29.5 mag (F606W), we present the discovery of 12 transients and 190 variable candidates. For the variable candidates, we demonstrate that Gaussian statistics are applicable and estimate that ∼80 are false positives. The majority of the transients will be supernovae, although at least two are likely quasars. Most variable candidates are active galactic nuclei (AGNs), where we find 0.42% of the general z ≲ 6 field galaxy population to vary at the ∼3 σ level. Based on a 5 yr time frame, this translates into a random supernova areal density of up to ∼0.07 transients arcmin ^−2 (∼245 deg ^−2 ) per epoch and a variable AGN areal density of ∼1.25 variables arcmin ^−2 (∼4500 deg ^−2 ) to these depths.