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Coping with the COVID-19 pandemic had implications for athletes' mental well-being. This mixed-methods study examined the influence of self-compassion on athletes' coping during the pandemic through the mediator of cognitive appraisal. The prospective design involved 90 athletes completing two online surveys 1 week apart measuring self-compassion, cognitive appraisal, and coping strategies. The PROCESS macro was used for the mediation analysis. A qualitative thematic analysis was used to explore athletes' responses to the pandemic during the second survey. Self-compassion had an indirect negative effect on avoidance-focused coping by appraising the pandemic as less of a threat (95% confidence interval [−0.20, −0.001]) and had a total effect on emotion-focused coping (95% confidence interval [0.02, 0.40]). Based on the thematic analysis, athletes described many raw emotions and a variety of coping strategies during the pandemic. Self-compassion demonstrated promising benefits to athletes who dealt with the challenging situation of the pandemic. [ABSTRACT FROM AUTHOR]

The article explores the agreement between electronic health record (EHR)-documented and parent-reported race and ethnicity in pediatric emergency care settings. It discusses significant overall agreement but notes discrepancies, particularly for less-represented racial and ethnic groups, suggesting the need for improved methods to enhance data accuracy and equity in healthcare research and provision.

The basal macronarian sauropod Europasaurus holgeri is known only from the Late Jurassic of the Langenberg Quarry near Goslar, Lower Saxony, Germany. Europasaurus has been identified as an insular dwarf and shows a clear resemblance to Camarasaurus and Giraffatitan. This study provides a detailed description of the dentition of Europasaurus based on an array of fossils outstanding in their abundance, variety of preservation, and ontogenetic range. Dental morphology for the replacement and functional dentitions, the tooth replacement pattern, and implications for food intake are described for the Europasaurus dentition, which is characterized by broad-crowned teeth. Characteristic features for Europasaurus are the presence of denticles on replacement teeth, the wrinkled enamel, and large wear facets both on the apex and on the carinae of the tooth crowns. The partially articulated skull SNHM-2207-R and isolated tooth rows DfmMh/FV 580.1 and DfmMh/FV 896.7 suggest the presence of strong connective tissue partially covering the teeth. This connective tissue would have provided stability and protection for the teeth. Evidence for this connective tissue include exposed tooth necks, in-situ teeth with strongly resorbed roots which no longer would have been connected to the jaw bone, and wrinkled enamel and its surface pattern. The same features can be observed in other sauropod taxa as well. We therefore suggest that eusauropods in general possessed this connective tissue structure, which may be an autapomorphy of the group. Possibly, this hypothetical structure is homologous to the rhamphotheca in birds and some non-avian theropods, which, however rarely, show such a close integration of keratinous tissue and teeth that we hypothesize here. [ABSTRACT FROM AUTHOR]

Objectives Racial–ethnic disparities in experiences of economic hardship during the pandemic are well documented in the population overall and among older adults. Existing research shows that this economic hardship was much less common at older than younger ages. Little is known about the intersection of racial–ethnic and age disparities in pandemic-related hardship in later life. This research report investigated racial–ethnic gaps in economic hardship by age group among older adults. Methods Data were from the 2018 and 2020 U.S. Health and Retirement Study (HRS) including the 2020 coronavirus disease 2019 module. We estimated Heckman-corrected linear probability models to examine differences in experiences of pandemic-related economic hardship in the 2020 HRS by race–ethnicity (non-Hispanic White, non-Hispanic Black, U.S.-born Hispanic, foreign-born Hispanic) across age groups (55–64, 65–74, 75+). In the multivariable analysis, we controlled for sociodemographic characteristics, participation in social programs, pre-existing health conditions and behaviors, and economic resources from the 2018 HRS. Results Experiences of economic hardship declined with age within each racial–ethnic group. Racial–ethnic gaps in hardship remained at older ages without any controls. However, when all controls were added, racial–ethnic gaps in economic hardship were eliminated for those ages 75+. Individual characteristics prior to the pandemic explained racial–ethnic differences in hardship for the oldest adults (75+) but did not explain gaps for those ages 55–74. Discussion Results point to structural factors generating new racial–ethnic gaps in pandemic-related economic hardship among those approaching retirement (ages 55–74) that did not affect the oldest adults (ages 75+). [ABSTRACT FROM AUTHOR]

Background Population-based expanded carrier screening (ECS) involves screening for multiple recessive diseases offered to all couples considering a pregnancy or during pregnancy. Previous research indicates that in some countries primary care professionals are perceived as suitable providers for ECS. However, little is known about their perspectives. We therefore aimed to explore primary care professionals' views on population-based ECS. Methods Four online focus groups with 14 general practitioners (GPs) and 16 community midwives were conducted in the Netherlands. Results Our findings highlight various perspectives on the desirability of population-based ECS. Participants agreed that ECS could enhance reproductive autonomy and thereby prevent suffering of the child and/or parents. However, they also raised several ethical, societal, and psychological concerns, including a tendency towards a perfect society, stigmatization, unequal access to screening and negative psychosocial consequences. Participants believed that provision of population-based ECS would be feasible if prerequisites regarding training and reimbursement for providers would be fulfilled. most GPs considered themselves less suitable or capable of providing ECS, in contrast to midwives who did consider themselves suitable. Nevertheless, participants believed that, if implemented, ECS should be offered in primary care or by public health services rather than as hospital-based specialized care, because they believed a primary care ECS offer increases access in terms of time and location. Conclusions While participants believed that an ECS offer would be feasible, they questioned its desirability and priority. Studies on the desirability and feasibility of population-based ECS offered in primary care or public health settings are needed. [ABSTRACT FROM AUTHOR]

The paradigm of modernity is associated with human detachment from soil as the agricultural and affective foundation of modern societies. The focus on soil as a resource has created increasingly exhausted landscapes. Soil science is well placed to (re)build the urgently needed connection between humans and nature by generating evidence for soil functioning and, perhaps most importantly, by establishing linkages with diverse types of soil knowledge and integrating them in collaborative solutions. Such transdisciplinary solutions can be achieved by transforming current ways of doing soil science, which begin with soil scientists. Anchored in feminist and critical thinking, we used the 'reflecting and doing' framework (Lopez et al., 2023) to demonstrate how reflexivity can help soil science to become a transformative space. By partially dissolving the mind–heart and human–soil dualisms, we can foster a way of generating soil knowledge that emerges from the relations within and beyond the human Self. Such an approach is relatively new in academic soil science, which relies heavily on the scientific method as a detached form of knowing that privileges mind over body, reason over emotion, culture over nature and production over reproduction. We argue that this journey starts with (re)positioning ourselves as soil scientists in relation to our research and advance a Transformative Soil Science that recognizes soil knowledge as situated and embodied and that identifies soil as the main ally for a sustainable world. [ABSTRACT FROM AUTHOR]

Despite clinical advances in immunotherapy, still many therapeutics cause dose‐limiting (auto)immune‐mediated toxicities. Nanoparticle‐based drug delivery systems (DDS) can improve cancer immunotherapy through site‐specific delivery and controlled release of immunotherapeutics in the tumor microenvironment (TME). However, DDS face several challenges, including unspecific release. To address this, vaterite nanoparticles (VNPs) that selectively release immunotherapeutic proteins at low pH conditions find in the TME, are established previously. In the current study, these VNPs are further modified for active targeting without affecting the loaded protein activity, exemplified with Tumor Necrosis Factor α (TNF). Specifically, VNPs are coated with gelatin, a matrix‐metalloprotease sensitive polymer which provides functional groups for further conjugation. Subsequently, streptavidin is covalently linked to the gelatin shell by amine‐epoxy chemistry, enabling coupling of any biotinylated ligand. Exemplified by biotinylated cetuximab and rituximab, targeted VNPs selectively bind to cells expressing epidermal growth factor receptor (EGFR) or CD20, respectively. Importantly, TNF remains functionally active after the modification steps, as VNP treatment increased ICAM‐1 expression on FaDu cells and activated NFκB signaling in a Jurkat.NFκB‐luciferase cell line model. In conclusion, a targetable vaterite‐based DDS is produced that allows for easy surface modification with any biotinylated ligand that may find broad applications in tumor‐selective immunotherapy. [ABSTRACT FROM AUTHOR]

Wild crop germplasm and landrace varieties have long been considered as a source of novel genetic variation for improving domesticated crops. Due to genetic bottlenecks that occurred during domestication, dissemination, and subsequent crop improvement, many beneficial genes are absent from commercial varieties and elite breeding germplasm, yet are still present in wild populations. To catalog potential novel disease resistance genes useful for breeding more resilient dry beans, we screened wild and landrace Phaseolus vulgaris L. accessions archived in the USDA GRIN seed bank for untapped resistance to anthracnose (Colletotrichum lindemuthianum) and bean common mosaic necrosis virus (BCMNV). A population of 194 wild and 55 landrace accessions were screened for resistance to two highly virulent races of anthracnose (race 2047 and race 3481) and for resistance to the BCMNV strain NL‐3. Thirteen accessions, all wild, were resistant to both anthracnose races, with MX‐QT‐3 and PI 661812 displaying complete resistance with no disease symptoms across all replications. Surprisingly, no natural resistance to BCMNV strain NL‐3 was detected in the wild germplasm. PI 442541, PI 661891, and W6 10164 were the only three accessions that expressed the I‐gene phenotype and all three have some history of cultivation. This study provides a resource for introgression of genetic diversity for anthracnose resistance into cultivated beans and reveals that innate resistance to BCMNV may not exist in wild populations of P. vulgaris. Core Ideas: Wild Phaseolus vulgaris germplasm has genetic and phenotypic diversity not present in cultivated varieties.Resistance to two races of anthracnose exists in wild bean germplasm.Resistance to BCMNV NL‐3 was not found in wild bean germplasm, but in three landraces. [ABSTRACT FROM AUTHOR]

Introduction: A research and mentoring program was developed to provide local first-generation students, students returning to school after a professional experience, and underrepresented minority students resources and relationships to guide them toward a STEM degree from a four-year university. Methods: A multi-tiered mentoring community was formed including direct mentoring from graduate students and faculty advisors, peer mentoring among undergraduate students from different colleges and universities, and high school students to increase the accessibility of research opportunities for this demographic. Local students were recruited from Northwest Arkansas Community College and Upward Bound to combine community college and high school students in a novel manner. The programs were integrated whenever possible to emphasize peer mentoring, including mentoring lunches, research meetings, presentation sessions, conference presentations, and professional development mentoring sessions. Results: On the post-program survey, students indicated the community formed in the program supported their STEM identity development, provided them with quality relationships, and developed skills valuable to completion of a STEM degree. This identity development was further evidenced by the students presenting their work at a conference and obtaining additional research positions after the summer program ended. Conclusion: The post-program scores and continued efforts of different demographics of students to pursue STEM highlight the versatility of the multitiered mentoring community model to serve students from different ages, backgrounds, and demographics. [ABSTRACT FROM AUTHOR]

Background and Objectives The oldest adults faced the highest risk of death and hospitalization from coronavirus disease 2019 (COVID-19), but less is known about whether they also were the most likely to experience pandemic-related economic, healthcare, and mental health challenges. Guided by prior research on vulnerability versus resilience among older adults, the current study investigated age differences in economic hardship, delays in medical care, and mental health outcomes among adults aged 55 and older. Research Design and Methods Data were from the COVID-19 module and Leave Behind Questionnaire in the 2020 Health and Retirement Study (HRS). We estimated linear probability models to examine differences in experiences of pandemic-related economic and health challenges by age group (55–64, 65–74, 75+) with and without controls for preexisting sociodemographic, social program, health, and economic characteristics from the 2018 HRS. Models accounting for differential mortality also were estimated. Results Adults aged 65–74 and 75+ experienced fewer economic and mental health challenges and those aged 75+ were less likely to delay medical care than adults aged 55–64. Age gradients were consistent across a broad range of measures and were robust to including controls. For all age groups, economic challenges were less common than delays in medical care or experiences of loneliness, stress, or being emotionally overwhelmed. Discussion and Implications Even though the oldest adults were at the greatest risk of death and hospitalization from COVID-19, they experienced fewer secondary pandemic-related challenges. Future research should continue to explore the sources of this resilience for older adults. [ABSTRACT FROM AUTHOR]

The island of Newfoundland, Canada, is known as an area with high lichen species richness; however, most of this diversity is known from coastal regions where the ocean creates a maritime climate. The central part of the island has a more continental climate and is also the part of the province with the highest levels of industrial forest harvest and mining activities. For these reasons, it has not been an area considered to have high lichen diversity. Here, we show how local Mi'kmaw knowledge in collaboration with western scientific expertise facilitated a two-eyed seeing approach (Etuaptmumk) that yielded the discovery of overlooked lichen diversity in Central Newfoundland. Surveys by the authors throughout 2023 yielded collections of 175 species of lichenized, lichenicolous and allied fungi from the area known as Charlie's Place. Of these, there is a high proportion of cyanolichens (13%) and calicioids (11%), indicating high ecological value and potential old growth/ancient forest status. In addition, we report 19 new species records for the province, two of which (Chaenothecopsis vainioana and Myrionora albidula) are new records for Canada. Overall, the survey work reported here suggests that Charlie's Place should be a priority area for protection within the context of Central Newfoundland. This work also illustrates the value of research under the framework of Etuaptmumk and the benefits of combining local Indigenous and western scientific knowledge. The political, logistical, and financial support of Qalipu First Nation was key to the success of this work. [ABSTRACT FROM AUTHOR]

Inspired by recent developments in the theory of Banach and operator algebras of locally compact groups, we construct several new classes of bifunctors (A,B)\mapsto A\otimes _{\alpha } B, where A\otimes _\alpha B is a cross norm completion of A\odot B for each pair of C*-algebras A and B. For the first class of bifunctors considered (A,B)\mapsto A{\otimes _p} B (1\leq p\leq \infty), A{\otimes _p} B is a Banach algebra cross-norm completion of A\odot B constructed in a fashion similar to p-pseudofunctions \text {PF}^*_p(G) of a locally compact group. Taking a cue from the recently introduced symmetrized p-pseudofunctions due to Liao and Yu and later by the second and the third named authors, we also consider {\otimes _{p,q}} for Hölder conjugate p,q\in [1,\infty ] – a Banach *-algebra analogue of the tensor product {\otimes _{p,q}}. By taking enveloping C*-algebras of A{\otimes _{p,q}} B, we arrive at a third bifunctor (A,B)\mapsto A{\otimes _{\mathrm C^*_{p,q}}} B where the resulting algebra A{\otimes _{\mathrm C^*_{p,q}}} B is a C*-algebra. For G_1 and G_2 belonging to a large class of discrete groups, we show that the tensor products \mathrm C^*_{\mathrm r}(G_1){\otimes _{\mathrm C^*_{p,q}}}\mathrm C^*_{\mathrm r}(G_2) coincide with a Brown-Guentner type C*-completion of \mathrm \ell ^1(G_1\times G_2) and conclude that if 2\leq p'

Background: Intrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to this brain injury is dysregulation of neurovascular coupling. We have shown that intrauterine inflammation induced by intra-amniotic lipopolysaccharide (LPS) in preterm lambs, and postnatal dopamine administration, disrupts neurovascular coupling and the functional cerebral haemodynamic responses, potentially leading to impaired brain development. In this study, we aimed to characterise the structural changes of the neurovascular unit following intrauterine LPS exposure and postnatal dopamine administration in the brain of preterm lambs using cellular and molecular analyses. Methods: At 119–120 days of gestation (term = 147 days), LPS was administered into the amniotic sac in pregnant ewes. At 126-7 days of gestation, the LPS-exposed lambs were delivered, ventilated and given either a continuous intravenous infusion of dopamine at 10 µg/kg/min or isovolumetric vehicle solution for 90 min (LPS, n = 6; LPSDA, n = 6). Control preterm lambs not exposed to LPS were also administered vehicle or dopamine (CTL, n = 9; CTLDA, n = 7). Post-mortem brain tissue was collected 3–4 h after birth for immunohistochemistry and RT-qPCR analysis of components of the neurovascular unit. Results: LPS exposure increased vascular leakage in the presence of increased vascular density and remodelling with increased astrocyte "end feet" vessel coverage, together with downregulated mRNA levels of the tight junction proteins Claudin-1 and Occludin. Dopamine administration decreased vessel density and size, decreased endothelial glucose transporter, reduced neuronal dendritic coverage, increased cell proliferation within vessel walls, and increased pericyte vascular coverage particularly within the cortical and deep grey matter. Dopamine also downregulated VEGFA and Occludin tight junction mRNA, and upregulated dopamine receptor DRD1 and oxidative protein (NOX1, SOD3) mRNA levels. Dopamine administration following LPS exposure did not exacerbate any effects induced by LPS. Conclusion: LPS exposure and dopamine administration independently alters the neurovascular unit in the preterm brain. Alterations to the neurovascular unit may predispose the developing brain to further injury. [ABSTRACT FROM AUTHOR]

This paper studies how organizational leaders' early private‐sector leadership experiences impact adopting a contested organizational practice, temporary employment, in public organizations. We employed unique organization/year‐level register panel data on the executive careers of the directors of Dutch public organizations and the prevalence of temporary employment in organizations they lead. Fixed‐effect regression analyses of 29,031 organization/year observations between 2006 and 2019 show greater use of temporary employment in public organizations when directors have early private‐sector executive experience. We found a similar impact of leaders' imprinted experiences in "fully" public and "hybrid" organizations that combine public and private sector elements. We discuss implications and suggestions for future studies on organizational leaders' role in contested practice adoption in the public sector. [ABSTRACT FROM AUTHOR]

Context: Long-term multi-environment trials (METs) could improve genomic prediction models for plant breeding programs by better representing the target population of environments (TPE). However, METs are generally highly unbalanced because genotypes are routinely dropped from trials after a few years. Furthermore, in the presence of genotype × environment interaction (GEI), selection of the environments to include in a prediction set becomes critical to represent specific TPEs. Aims: The goals of this study were to compare strategies for modelling GEI in genomic prediction, using large METs from oat (Avena sativa L.) breeding programs in the Midwest United States, and to develop a variety decision tool for farmers and plant breeders. Methods: The performance of genotypes in TPEs was predicted by using different strategies for handling GEI in genomic prediction models including systematic and/or random GEI components. These strategies were also used to build the variety decision tool for farmers. Key results: Genomic prediction for unknown genotypes, locations and years within TPEs had moderate to high predictive ability, accuracy and reliability. Modelling GEI was beneficial in small, but not in large, mega-environments. The latest 3 years were highly predictive of performance in an upcoming year for most years but not for years with unusual weather patterns. High predictive ability, accuracy and reliability were obtained when large datasets were used in TPEs. Conclusions: Deployment of historical datasets can be accomplished through meaningful delineation and prediction for TPEs. Implications: We have shown the performance of a simple modelling strategy for handling prediction for TPEs when deploying large historical datasets. Rankings of genotypic performance may change from one environment to the next, creating genotype × environment interaction (GEI), which can impact genomic prediction and complicate identification of superior genotypes. We compared strategies for predicting the performance of individuals in the presence of GEI. The results provide useful tools for the optimisation of training populations and testing environments for the prediction of individuals in the targeted populations of environments. [ABSTRACT FROM AUTHOR]

Objective and Methods: The study examined sexual victimization among college students with disabilities (n = 187) using an online survey at a large southern university. Students reported one or multiple disabilities: physical disabilities, Attention Deficit Hyperactivity Disorder (ADHD)/Attention Deficit Disorder (ADD), learning disabilities, and emotional disabilities, with most students reporting more than one disability. Results: Overall, 71% of the sample experienced one or more types of lifetime sexual assault and/or rape, and 51% reported sexual victimization since attending the university. There were no significant differences in experiencing sexual assault and/or rape between students with one disability compared to students with more than one disability. Conclusions: Considering the high rates of sexual victimization among students with disabilities, and the dearth of research focusing on the context of sexual assault in this population, future research and research-based prevention initiatives are needed. Findings can inform future prevention efforts to address sexual violence among students with disabilities on campuses. [ABSTRACT FROM AUTHOR]

Background: VISTA is a well-known immune checkpoint in T cell biology, but its role in innate immunity is less established. Here, we investigated the role of VISTA on anticancer macrophage immunity, with a focus on phagocytosis, macrophage polarization and concomitant T cell activation. Methods: Macrophages, differentiated from VISTA overexpressed THP-1 cells and cord blood CD34+ cell-derived monocytes, were used in phagocytosis assay using B lymphoma target cells opsonized with Rituximab. PBMC-derived macrophages were used to assess the correlation between phagocytosis and VISTA expression. qRT-PCR, flow cytometry, and enzyme-linked immunosorbent assay were performed to analyze the impact of VISTA on other checkpoints and M1/M2-like macrophage biology. Additionally, flow cytometry was used to assess the frequency of CD14+ monocytes expressing VISTA in PBMCs from 65 lymphoma patients and 37 healthy donors. Results: Ectopic expression of VISTA in the monocytic model cell line THP-1 or in primary monocytes triggered differentiation towards the macrophage lineage, with a marked increase in M2-like macrophage-related gene expression and decrease in M1-like macrophage-related gene expression. VISTA expression in THP-1 and monocyte-derived macrophages strongly downregulated expression of SIRPα, a prominent 'don't eat me' signal, and augmented phagocytic activity of macrophages against cancer cells. Intriguingly, expression of VISTA's extracellular domain alone sufficed to trigger phagocytosis in ∼ 50% of cell lines, with those cell lines also directly binding to recombinant human VISTA, indicating ligand-dependent and -independent mechanisms. Endogenous VISTA expression was predominantly higher in M2-like macrophages compared to M0- or M1-like macrophages, with a positive correlation observed between VISTA expression in M2c macrophages and their phagocytic activity. VISTA-expressing macrophages demonstrated a unique cytokine profile, characterized by reduced IL-1β and elevated IL-10 secretion. Furthermore, VISTA interacted with MHC-I and downregulated its surface expression, leading to diminished T cell activation. Notably, VISTA surface expression was identified in monocytes from all lymphoma patients but was less prevalent in healthy donors. Conclusions: Collectively, VISTA expression associates with and drives M2-like activation of macrophages with a high phagocytic capacity yet a decrease in antigen presentation capability to T cells. Therefore, VISTA is a negative immune checkpoint regulator in macrophage-mediated immune suppression. [ABSTRACT FROM AUTHOR]

Alcohol intoxication may influence how bystanders interpret other people's consent and refusal cues. We examined the effects of alcohol intoxication on participants' perceptions of characters' consent and refusal indicators in a fictional vignette depicting an alcohol-involved sexual encounter. Young adults (n = 119, 52% women) participated in an alcohol administration experiment examining the influence of acute intoxication on bystander perceptions during a vignette depicting a character who is intoxicated and declines a sexual advance from another character, who ignores her refusal and continues to pursue sexual activity. Participants were randomly assigned to an alcohol or non-alcohol condition and then guided through a semi-structured interview in which we asked about the characters' consent and refusal cues. Interviews were analyzed using both inductive and deductive coding. Most participants eventually indicated the encounter was nonconsensual, but approximately 9% of participants described the encounter as entirely consensual and another 42% of participants described the interaction as initially consensual and then nonconsensual. Participants discussed nuanced accounts of consent and refusal cues, including indicators related to alcohol consumption. Disregarding intoxication and gender, participants eventually recognized the situation as nonconsensual and thus potentially risky. However, some participants recognized this risk earlier in the encounter than others. Consequently, bystanders who recognize risk later in a situation may have fewer opportunities to intervene before a situation escalates. We recommend sexual assault prevention educators take a more nuanced approach when discussing consent and refusal indicators, emphasizing contextual factors that may indicate risk. [ABSTRACT FROM AUTHOR]

Pluripotent stem cell‐derived kidney organoids hold great promise as a potential auxiliary transplant tissue for individuals with end‐stage renal disease and as a platform for studying kidney diseases and drug discovery. To establish accurate models, it is crucial to thoroughly characterize the morphological features and maturation stages of the cellular components within these organoids. Nephrons, the functional units of the kidney, possess distinct morphological structures that directly correlate with their specific functions. High spatial resolution imaging emerges as a powerful technique for capturing ultrastructural details that may go unnoticed with other methods such as immunofluorescent imaging and scRNA sequencing. In our study, we have applied software capable of seamlessly stitching virtual slides generated from electron microscopy, resulting in high‐definition overviews of tissue slides. With this technology, we can comprehensively characterize the development and maturation of kidney organoids when transplanted under the renal capsule of mice. These organoids exhibit advanced ultrastructural developments upon transplantation, including the formation of the filtration barrier in the renal corpuscle, the presence of microvilli in the proximal tubule, and various types of cell sub‐segmentation in the connecting tubule similarly to those seen in the adult kidney. Such ultrastructural characterization provides invaluable insights into the structural development and functional morphology of nephron segments within kidney organoids and how to advance them by interventions such as a transplantation. Research HighlightsHigh‐resolution imaging is crucial to determine morphological maturation of hiPSC‐derived kidney organoids. Upon transplantation, refined ultrastructural development of nephron segments was observed, such as the development of the glomerular filtration barrier. [ABSTRACT FROM AUTHOR]

Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating age-dependent diseases. Such systems are particularly needed for TDP-43 proteinopathies1, which involve human-specific mechanisms2–5 that cannot be directly studied in animal models. Here, to explore the emergence and consequences of TDP-43 pathologies, we generated induced pluripotent stem cell-derived, colony morphology neural stem cells (iCoMoNSCs) via manual selection of neural precursors6. Single-cell transcriptomics and comparison to independent neural stem cells7 showed that iCoMoNSCs are uniquely homogenous and self-renewing. Differentiated iCoMoNSCs formed a self-organized multicellular system consisting of synaptically connected and electrophysiologically active neurons, which matured into long-lived functional networks (which we designate iNets). Neuronal and glial maturation in iNets was similar to that of cortical organoids8. Overexpression of wild-type TDP-43 in a minority of neurons within iNets led to progressive fragmentation and aggregation of the protein, resulting in a partial loss of function and neurotoxicity. Single-cell transcriptomics revealed a novel set of misregulated RNA targets in TDP-43-overexpressing neurons and in patients with TDP-43 proteinopathies exhibiting a loss of nuclear TDP-43. The strongest misregulated target encoded the synaptic protein NPTX2, the levels of which are controlled by TDP-43 binding on its 3′ untranslated region. When NPTX2 was overexpressed in iNets, it exhibited neurotoxicity, whereas correcting NPTX2 misregulation partially rescued neurons from TDP-43-induced neurodegeneration. Notably, NPTX2 was consistently misaccumulated in neurons from patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration with TDP-43 pathology. Our work directly links TDP-43 misregulation and NPTX2 accumulation, thereby revealing a TDP-43-dependent pathway of neurotoxicity. A neural stem cell culture system derived from induced pluripotent stem cells forms a network of synaptically connected and electrophysiologically active neurons that were used as a model system to identify a mechanism of TDP-43-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

To investigate the relationship between language and diagnostic errors (DxE) in the pediatric emergency department (ED). Electronic trigger identified ED encounters resulting in unplanned hospital admission that occurred within 10 days of an index visit from January 2018 through February 2022. Manual screening of each triggered encounter identified cases where the index visit diagnosis and hospitalization discharge diagnosis differed, and these were screened in for review using the Revised Safer Dx instrument to determine if a diagnostic error (DxE) occurred. Non-English primary language (NEPL) and English-proficient (EP) groups were established based on caregiver language. The primary outcome was the proportion of DxE each group. Data were analyzed using univariate analysis and multivariable logistic regression to identify independent predictors of DxE. Electronic trigger identified 3,551 patients, of which 806 (22.7 %) screened in for Safer Dx review. 172 (21.3 %) experienced DxE. The proportion of DxE was similar between EP and NEPL groups (21.5 vs. 21.7 %; p=0.97). Age≥12 years and fewer prior admissions in the preceding 6 months predicted higher odds of DxE. NEPL did not predict higher odds of DxE. NEPL was not associated with increased odds DxE resulting in unplanned admission. [ABSTRACT FROM AUTHOR]

Species-focused conservation requires a thorough understanding of species' distributions. Delineating a species' distribution requires taxonomic knowledge and adequate occurrence data. For plants and fungi, herbaria represent a valuable source of large-scale occurrence data. Advances in digital technology mean that data from many herbarium collections worldwide are now easily accessible. However, species concepts can change over time requiring herbarium records to be re-examined and databases updated, which does not always occur synchronously across all collections. Therefore, non-critical use of these data can promote inaccuracies in understanding species distributions. Taxonomic revisions are common in understudied organisms, such as lichens. Here, we illustrate how changing taxonomy and non-critical acceptance of online data affects our understanding of disjunct distributions, using the lichen Brodoa oroarctica (Krog) Goward as an example. Defining the distribution of the arctic lichen B. oroarctica is confounded by changing taxonomy and uncertainty of herbarium records that pre-date taxonomic revisions. We review the distribution of this species in the literature and in aggregate occurrence databases, and verify herbarium specimens that represent disjunct occurrences in eastern North America to present an updated account of its distribution and frequency in eastern North America. We show that knowledge of changing species taxonomy is essential to depicting accurate species distributions. [ABSTRACT FROM AUTHOR]

'MN‐Torgy' (Reg. no. CV‐1203, PI 698205) hard red spring wheat (Triticum aestivium L.) was released by the University of Minnesota Agricultural Experiment Station in 2020 because of its high grain yield, disease resistance, and end‐use quality characteristics. MN‐Torgy is a medium‐maturity cultivar with above average plant height despite containing the semi‐dwarfing allele Rht24b. MN‐Torgy has moderate resistance to Fusarium head blight (caused primarily by Fusarium graminearum Schwabe) and good resistance to prevalent races of pathogens causing leaf rust (Puccinia triticina Eriks.) and stem rust (Puccinia graminis Pers.:Pers. f. sp. tritici Eriks. & E. Henn.) and is well adapted to the north‐central United States. MN‐Torgy also has good adult plant resistance to the Ug99 family of stem rust races. Core Ideas: MN‐Torgy is a new hard red spring wheat cultivar.MN‐Torgy spring wheat has field resistance to the Ug99 family of stem rust races.MN‐Torgy spring wheat is moderately resistant to Fusarium head blight. [ABSTRACT FROM AUTHOR]

In recent years, the therapeutic (re)activation of innate anticancer immunity has gained prominence, with therapeutic blocking of the interaction of Signal Regulatory Protein (SIRP)-a with its ligand CD47 yielding complete responses in refractory and relapsed B cell lymphoma patients. SIRP-a has as crucial inhibitory role on phagocytes, with e.g., its aberrant activation enabling the escape of cancer cells from immune surveillance. SIRP-a belongs to a family of paired receptors comprised of not only immune-inhibitory, but also putative immune-stimulatory receptors. Here, we report that an as yet uninvestigated SIRP family member, SIRP-beta 2 (SIRP-ß2), is strongly expressed under normal physiological conditions in macrophages and granulocytes at protein level. Endogenous expression of SIRP-ß2 on granulocytes correlated with trogocytosis of cancer cells. Further, ectopic expression of SIRP-ß2 stimulated macrophage adhesion, differentiation and cancer cell phagocytosis as well as potentiated macrophage-mediated activation of T cell Receptor-specific T cell activation. SIRP-ß2 recruited the immune activating adaptor protein DAP12 to positively regulate innate immunity, with the charged lysine 202 of SIRP-ß2 being responsible for interaction with DAP12. Mutation of lysine 202 to leucine lead to a complete loss of the increased adhesion and phagocytosis. In conclusion, SIRPß2 is a novel positive regulator of innate anticancer immunity and a potential costimulatory target for innate immunotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to assess the feasibility of online adaptive radiotherapy (oART) for bladder cancer using a focal boost by focusing on the quality of the online treatment plan and automatic target delineation, duration of the workflow and performance in the presence of fiducial markers for tumor bed localization. Methods: Fifteen patients with muscle invasive bladder cancer received daily oART with Cone Beam CT (CBCT), artificial intelligence (AI)-assisted automatic delineation of the daily anatomy and online plan reoptimization. The bladder and pelvic lymph nodes received a total dose of 40 Gy in 20 fractions, the tumor received an additional simultaneously integrated boost (SIB) of 15 Gy. The dose distribution of the reference plan was calculated for the daily anatomy, i.e. the scheduled plan. Simultaneously, a reoptimization of the plan was performed i.e. the adaptive plan. The target coverage and V95% outside the target were evaluated for both plans. The need for manual adjustments of the GTV delineation, the duration of the workflow and the influence of fiducial markers were assessed. Results: All 300 adaptive plans met the requirement of the CTV-coverage V95%≥98% for both the boost (55 Gy) and elective volume (40 Gy). For the scheduled plans the CTV-coverage was 53.5% and 98.5%, respectively. Significantly less tissue outside the targets received 55 Gy in case of the adaptive plans as compared to the scheduled plans. Manual corrections of the GTV were performed in 67% of the sessions. In 96% of these corrections the GTV was enlarged and resulted in a median improvement of 1% for the target coverage. The median on-couch time was 22 min. A third of the session time consisted of reoptimization of the treatment plan. Fiducial markers were visible on the CBCTs and aided the tumor localization. Conclusions: AI-driven CBCT-guided oART aided by fiducial markers is feasible for bladder cancer radiotherapy treatment including a SIB. The quality of the adaptive plans met the clinical requirements and fiducial markers were visible enabling consistent daily tumor localization. Improved automatic delineation to lower the need for manual corrections and faster reoptimization would result in shorter session time. [ABSTRACT FROM AUTHOR]

In this article, we reflect on our experiences of teaching sustainability in management education in an emergent context of increasing and pervasive eco-anxiety. Our collaborative autoethnographic enquiry stemmed from the tensions we experienced in our desire to present a realistic view of the future to students, while still maintaining their (and our) sense of hope and agency. While sustainability in management education has long acknowledged the need to engage learners' hearts and hands as well as their heads, the challenges of effectively integrating the emotional (heart) dimension in the classroom have remained under-explored in the literature. We develop the findings of our collaborative autoethnography into a framework that provides insights for educators navigating the range of emotional responses evoked in the sustainability in management education classroom. This framework acts as a roadmap, based around five spheres of practice, that will aid sustainability in management education educators in making more conscious and deliberate choices about their teaching practice within the complex context of eco-anxiety. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to assess the feasibility of online adaptive radiotherapy (oART) for bladder cancer using a focal boost by focusing on the quality of the online treatment plan and automatic target delineation, duration of the workflow and performance in the presence of fiducial markers for tumor bed localization. Methods: Fifteen patients with muscle invasive bladder cancer received daily oART with Cone Beam CT (CBCT), artificial intelligence (AI)-assisted automatic delineation of the daily anatomy and online plan reoptimization. The bladder and pelvic lymph nodes received a total dose of 40 Gy in 20 fractions, the tumor received an additional simultaneously integrated boost (SIB) of 15 Gy. The dose distribution of the reference plan was calculated for the daily anatomy, i.e. the scheduled plan. Simultaneously, a reoptimization of the plan was performed i.e. the adaptive plan. The target coverage and V95% outside the target were evaluated for both plans. The need for manual adjustments of the GTV delineation, the duration of the workflow and the influence of fiducial markers were assessed. Results: All 300 adaptive plans met the requirement of the CTV-coverage V95%≥98% for both the boost (55 Gy) and elective volume (40 Gy). For the scheduled plans the CTV-coverage was 53.5% and 98.5%, respectively. Significantly less tissue outside the targets received 55 Gy in case of the adaptive plans as compared to the scheduled plans. Manual corrections of the GTV were performed in 67% of the sessions. In 96% of these corrections the GTV was enlarged and resulted in a median improvement of 1% for the target coverage. The median on-couch time was 22 min. A third of the session time consisted of reoptimization of the treatment plan. Fiducial markers were visible on the CBCTs and aided the tumor localization. Conclusions: AI-driven CBCT-guided oART aided by fiducial markers is feasible for bladder cancer radiotherapy treatment including a SIB. The quality of the adaptive plans met the clinical requirements and fiducial markers were visible enabling consistent daily tumor localization. Improved automatic delineation to lower the need for manual corrections and faster reoptimization would result in shorter session time. [ABSTRACT FROM AUTHOR]

Many people living with dementia are 'on the margins', not accessing services and support, despite policy and care advancements. The COVID-19 pandemic exacerbated this, with the closure of face-to-face support during lockdowns in the UK and globally. The aim of the 'Beyond the Margins' project was to develop, implement, and evaluate a face-face programme of support with, by and for people with direct experience of dementia who are on the margins of existing services and support. In March 2020 the project was interrupted by the outbreak of the COVID-19 pandemic and it changed to an online format. The three-phase participatory action research project included 40 people living with dementia, 26 care partners and 31 health and social care practitioners. A seven-week online personal development programme called Getting On with Life (GO) was developed, delivered, and evaluated. This paper focuses on the participatory approaches used to develop and implement the GO programme, and the resulting aspects of its approach to facilitation and content. Key features include the GO Programme's principles of providing a safe and a respectful space, and the programme's values of: Everyone who comes already knows things, can learn things and can teach things; Doing things 'with' each other, rather than 'for' or 'to' each other; Personalised goals—led by the needs of participants rather than an imposed agenda. A key finding was the importance of developing post-diagnostic programmes as a 'sandwich', providing a safe space for learning that is preceded by understanding pathways to access the programme and followed by explicit consideration of the next steps in increasing social engagement. [ABSTRACT FROM AUTHOR]

Photonic crystals owe their multitude of optical properties to the way their structure creates interference effects. It is therefore possible to influence the photonic response by acting on their physical structure. In this article, tunable photonic crystals made by elastic polymers that respond to their environment are explored, in particular with a physical deformation under temperature variation. This creates a feedback process in which the photonic response depends on its physical structure, which itself is influenced by the environmental changes. By using a multi‐photon polymerization process specifically optimized for soft responsive polymers such as Liquid Crystalline Networks, highly resolved, reproducible, and mechanically self‐standing photonic crystals are fabricated. The physical structure of the 3D woodpile can be tuned by an external temperature variation creating a reversible spectral tuning of 50 nm in the telecom wavelength range. By comparing these results with finite element calculations and temperature induced shape‐change, it is confirmed that the observed tuning is due to an elastic deformation of the structure. The achieved nanometric patterning of tunable anisotropic photonic materials will further foster the development of reconfigurable photonic crystals with point defects acting as tunable resonant cavities and, more in general, of 4D nanostructures. [ABSTRACT FROM AUTHOR]

Aggregation of the RNA‐binding protein TAR DNA‐binding protein 43 (TDP‐43) is the key neuropathological feature of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). In physiological conditions, TDP‐43 is predominantly nuclear, forms oligomers, and is contained in biomolecular condensates assembled by liquid–liquid phase separation (LLPS). In disease, TDP‐43 forms cytoplasmic or intranuclear inclusions. How TDP‐43 transitions from physiological to pathological states remains poorly understood. Using a variety of cellular systems to express structure‐based TDP‐43 variants, including human neurons and cell lines with near‐physiological expression levels, we show that oligomerization and RNA binding govern TDP‐43 stability, splicing functionality, LLPS, and subcellular localization. Importantly, our data reveal that TDP‐43 oligomerization is modulated by RNA binding. By mimicking the impaired proteasomal activity observed in ALS/FTLD patients, we found that monomeric TDP‐43 forms inclusions in the cytoplasm, whereas its RNA binding‐deficient counterpart aggregated in the nucleus. These differentially localized aggregates emerged via distinct pathways: LLPS‐driven aggregation in the nucleus and aggresome‐dependent inclusion formation in the cytoplasm. Therefore, our work unravels the origins of heterogeneous pathological species reminiscent of those occurring in TDP‐43 proteinopathy patients. Synopsis: Loss of TDP‐43 oligomerization and RNA binding promotes diverse TDP‐43 pathologies providing insight into the origins of heterogeneous pathological species occurring in human disease. TDP‐43 oligomerization and RNA binding govern its stability, splicing regulation, LLPS, and subcellular localization.TDP‐43 oligomerization is modulated by RNA binding.Monomeric TDP‐43 forms inclusions in the cytoplasm, whereas its RNA binding‐deficient counterpart aggregates in the nucleus.TDP‐43 aggregates emerge via distinct pathways: LLPS‐driven aggregation in the nucleus and aggresome‐dependent inclusion formation in the cytoplasm.Our work unravels the origins of heterogeneous TDP‐43 inclusions reminiscent of those occurring in TDP‐43 proteinopathy patients. [ABSTRACT FROM AUTHOR]

Gastrointestinal nematode (GIN) parasites play an important role in the ecological dynamics of many animal populations. Recent studies suggest that fine‐scale spatial variation in GIN infection dynamics is important in wildlife systems, but the environmental drivers underlying this variation remain poorly understood.We used data from over two decades of GIN parasite egg counts, host space use, and spatial vegetation data from a long‐term study of Soay sheep on St Kilda to test how spatial autocorrelation and vegetation in an individual's home range predict parasite burden across three age groups. We developed a novel approach to quantify the plant functional traits present in a home range to describe the quality of vegetation present.Effects of vegetation and space varied between age classes. In immature lambs, strongyle parasite faecal egg counts (FEC) were spatially structured, being highest in the north and south of our study area. Independent of host body weight and spatial autocorrelation, plant functional traits predicted parasite egg counts. Higher egg counts were associated with more digestible and preferred plant functional traits, suggesting the association could be driven by host density and habitat preference.In contrast, we found no evidence that parasite FEC were related to plant functional traits in the host home range in yearlings or adult sheep. Adult FEC were spatially structured, with highest burdens in the north‐east of our study area, while yearling FEC showed no evidence of spatial structuring.Parasite burdens in immature individuals appear more readily influenced by fine‐scale spatial variation in the environment, highlighting the importance of such heterogeneity for our understanding of wildlife epidemiology and health. Our findings support the importance of fine‐scale environmental variation for wildlife disease ecology and provides new evidence that such effects may vary across demographic groups within a population. [ABSTRACT FROM AUTHOR]

A higher density of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment, particularly cytotoxic CD8+ T cells, is associated with improved clinical outcome in various cancers. However, local inhibitory factors can suppress T cell activity and hinder anti-tumor immunity. Notably, TILs from various cancer types express the co-stimulatory Tumor Necrosis Factor receptor CD27, making it a potential target for co-stimulation and re-activation of tumorinfiltrated and tumor-reactive T cells. Anti-cancer therapeutics based on exploiting CD27-mediated T cell co-stimulation have proven safe, but clinical responses remain limited. This is likely because current monoclonal antibodies fail to effectively activate CD27 signaling, as this receptor requires higher-order receptor cross-linking. Here, we report on a bispecific antibody, CD27xEGFR, that targets both CD27 and the tumor antigen, epidermal growth factor receptor (EGFR). By targeting EGFR, which is commonly expressed on carcinomas, CD27xEGFR induced cancer cell-localized crosslinking and activation of CD27. The design of CD27xEGFR includes an Fc-silent domain, which is designed to minimize potential toxicity by reducing Fc gamma receptor-mediated binding and activation of immune cells. CD27xEGFR bound to both of its targets simultaneously and triggered EGFR-restricted co-stimulation of T cells as measured by T cell proliferation, T cell activation markers, cytotoxicity and IFN-g release. Further, CD27xEGFR augmented T cell cytotoxicity in a panel of artificial antigen-presenting carcinoma cell line models, leading to Effector-to-Target ratio-dependent elimination of cancer cells. Taken together, we present the in vitro characterization of a novel bispecific antibody that re-activates T cell immunity in EGFR-expressing cancers through targeted co-stimulation of CD27. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant systemic treatment (NST) leads to pathologic complete response (pCR) in 10–89% of breast cancer patients depending on subtype. The added value of surgery is uncertain in patients who reach pCR; however, current imaging and biopsy techniques aiming to predict pCR are not accurate enough. This study aims to quantify the residual disease remaining after NST in patients with a favorable response on MRI and residual disease missed with biopsies. Methods: In the MICRA trial, patients with a favorable response to NST on MRI underwent ultrasound-guided post-NST 14G biopsies followed by surgery. We analyzed pathology reports of the biopsies and the surgical specimens. Primary outcome was the extent of residual invasive disease among molecular subtypes, and secondary outcome was the extent of missed residual invasive disease. Results: We included 167 patients. Surgical specimen showed residual invasive disease in 69 (41%) patients. The median size of residual invasive disease was 18 mm (interquartile range [IQR] 12–30) in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) patients, 8 mm (IQR 3–15) in HR+/HER2-positive (HER2+) patients, 4 mm (IQR 2–9) in HR-negative (HR−)/HER2+ patients, and 5 mm (IQR 2–11) in triple-negative (TN) patients. Residual invasive disease was missed in all subtypes varying from 4 to 7 mm. Conclusion: Although the extent of residual invasive disease is small in TN and HER2+ subtypes, substantial residual invasive disease is left behind in all subtypes with 14G biopsies. This may hamper local control and limits adjuvant systemic treatment options. Therefore, surgical excision remains obligatory until accuracy of imaging and biopsy techniques improve. [ABSTRACT FROM AUTHOR]

Objectives: The Building Capacity Project is an asset‐based community development initiative that aims to reduce stigma and promote social inclusion for people with dementia. Using a community‐based participatory approach, we conducted research to examine the relational patterns and participatory practices within and across project sites in two different regions of Canada (Vancouver and Thunder Bay). Methods: Five focus groups and five individual interviews were conducted with team members and community partners (n = 29) and analysed for themes. Results: The overarching theme of Making Space at the Table explains how the participation of people with dementia has served both as a value and a practice shaping the relational work throughout the project. Three sub‐themes include: Maintaining a common foundation; Creating communication pathways; and Fostering personal connections. Conclusions: Together, these findings show how community development can support the meaningful participation of people with dementia in their communities through processes of collaboration that focus on individual and collective strengths, that allow time for the work to unfold, and for building relationships that foster trust and respect for diversity. Key points: Collaborations that are based on common values help foster diverse ways for people with dementia to participate and contribute in their communities.Building on existing networks is an effective way to scale out new ideas for engaging participation of people with dementia in their communities.Ensuring opportunities for people with dementia to develop strong personal ties with each other and work together as a group builds confidence and motivation to engage in community development work. [ABSTRACT FROM AUTHOR]

This study evaluates to what extent symptoms are present before, during, and after a positive SARS-CoV-2 polymerase chain reaction (PCR) test, and to evaluate how the symptom burden and quality of Life (QoL) compares to those with a negative PCR test. Participants from the Dutch Lifelines COVID-19 Cohort Study filled-out as of March 2020 weekly, later bi-weekly and monthly, questions about demographics, COVID-19 diagnosis and severity, QoL, and symptoms. The study population included those with one positive or negative PCR test who filled out two questionnaires before and after the test, resulting in 996 SARS-CoV-2 PCR positive and 3978 negative participants. Nearly all symptoms were more often reported after a positive test versus the period before the test (p < 0.05), except fever. A higher symptom prevalence after versus before a test was also found for nearly all symptoms in negatives (p < 0.05). Before the test, symptoms were already partly present and reporting of nearly all symptoms before did not differ between positives and negatives (p > 0.05). QoL decreased around the test for positives and negatives, with a larger deterioration for positives. Not all symptoms after a positive SARS-CoV-2 PCR test might be attributable to the infection and symptoms were also common in negatives. [ABSTRACT FROM AUTHOR]

Downsizing surface-enhanced Raman spectroscopy (SERS) within microfluidic devices has opened interesting perspectives for the development of low-cost and portable (bio)sensors for the optical analysis of liquid samples. Despite the research efforts, SERS-fluidic devices still rely either on the use of expensive bulky set-ups or on polymeric devices giving spurious background signals fabricated via expensive manufacturing processes. Here, polymeric platforms integrating fluidics and optics were fabricated with versatile designs allowing easy coupling with fiber-based Raman systems. For the first time, anti-fouling photocurable perfluoropolyether (PFPE) was explored for high-throughput SERS-integrating chip fabrication via replica molding of negative stamps obtained through standard and advanced fabrication processes. The PFPE devices comprised networks of channels for fluid handling and for optical fiber housing with multiple orientations. Embedded microfeatures were used to control the relative positioning of the fibers, thus guaranteeing the highest signal delivering and collection. The feasibility of PFPE devices as fiber-based SERS fluidic platforms was demonstrated through the straightforward acquisition of Raman-SERS spectra of a mixture of gold nanoparticles as SERS substrates with rhodamine 6G (Rh6G) at decreasing concentrations. In the presence of high-performing gold nanostars, the Rh6G signal was detectable at dilutions down to the nanomolar level even without tight focusing and working at low laser power—a key aspect for analyte detection in real-world biomedical and environmental applications. [ABSTRACT FROM AUTHOR]

Background: The multidisciplinary management of patients with brain metastases consists of surgical resection, radiation treatment and systemic treatment. Tailoring and timing these treatment modalities is challenging. This study presents real-world data from consecutively treated patients and assesses the impact of all treatment strategies and their relation with survival. The aim is to provide new insights to improve multidisciplinary decisions towards individualized treatment strategies in patients with brain metastases. Methods: A retrospective consecutive cohort study was performed. Patients with brain metastases were included between June 2018 and May 2020. Brain metastases of small cell lung carcinoma were excluded. Overall survival was analyzed in multivariable models. Results: 676 patients were included in the study, 596 (88%) received radiotherapy, 41 (6%) awaited the effect of newly started or switched systemic treatment and 39 (6%) received best supportive care. Overall survival in the stereotactic radiotherapy group was 14 months (IQR 5–32) and 32 months (IQR 11–43) in patients who started or switched systemic treatment and initially did not receive radiotherapy. In patients with brain metastases without options for local or systemic treatment best supportive care was provided, these patients had an overall survival of 0 months (IQR 0–1). Options for systemic treatment, Karnofsky Performance Score ≥ 70 and breast cancer were prognostic for a longer overall survival, while progressive extracranial metastases and whole-brain-radiotherapy were prognostic for shorter overall survival. Conclusions: Assessing prognosis in light of systemic treatment options is crucial after the diagnosis of brain metastasis for the consideration of radiotherapy versus best supportive care. [ABSTRACT FROM AUTHOR]