Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So... Show moreAngiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes. This 15-fold increase in genus-level sampling relative to comparable nuclear studies provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade. Show less
Objectives Multiple studies have proven the prognostic value of molecular classification for stage I–III endometrial cancer patients. However, studies on the relevance of molecular classification... Show moreObjectives Multiple studies have proven the prognostic value of molecular classification for stage I–III endometrial cancer patients. However, studies on the relevance of molecular classification for stage IV endometrial cancer patients are lacking. Hypothetically, poor prognostic molecular subtypes are more common in higher stages of endometrial cancer. Considering the poor prognosis of stage IV endometrial cancer patients, it is questionable whether molecular classification has additional prognostic value. Therefore, we determined which molecular subclasses are found in stage IV endometrial cancer and if there is a correlation with progression-free and overall survival.Methods A retrospective multicenter cohort study was conducted using data from five Dutch hospitals. Patients with stage IV endometrial cancer at diagnosis who were treated with primary cytoreductive surgery or cytoreductive surgery after induction chemotherapy between January 2000 and December 2018 were included. Exclusion criteria were age <18 years or recurrent disease. The molecular classification was performed centrally on all tumor samples according to the World Health Organization 2020 classification (including POLE and estrogen receptor status). The Kaplan–Meier method was used to calculate progression free and overall survival in the molecular subclasses, for the different histological subtypes and for estrogen receptor positive versus estrogen receptor negative tumors. Groups were compared using the log-rank test.Results 164 stage IV endometrial cancer patients were molecularly classified. Median age of the patients was 67 years (range 33–86). Most patients presented with a non-endometrioid histological subtype (58%). Intra-abdominal complete cytoreductive surgery was achieved in 60.4% of the patients. 101 tumors (61.6%) were classified as p53 abnormal, 35 (21.3%) as no specific molecular profile, 21 (12.8%) as mismatch repair deficient, and 6 (3%) as POLE mutated. Molecular classification had no significant impact on progression free (p=0.056) or overall survival (p=0.12) after cytoreductive surgery. Overall survival was affected by histologic subtype (p<0.0001) and estrogen receptor status (p=0.013).Conclusion The distribution of the molecular subclasses in stage IV endometrial cancer patients differed substantially from the distribution in stage I–III endometrial cancer patients, with the unfavorable subclasses being more frequently present. Although the molecular classification was not prognostic in stage IV endometrial cancer, it could guide adjuvant treatment decisions. Show less
Fishman, T.; Mastrucci, A.; Peled, Y.; Saxe, S.; Ruijven, B. van 2024
The construction materials used in buildings have large and growing implications for global material flows and emissions. Material Intensity (MI) is a metric that measures the mass of construction... Show moreThe construction materials used in buildings have large and growing implications for global material flows and emissions. Material Intensity (MI) is a metric that measures the mass of construction materials per unit of a building’s floor area. MIs are used to model buildings’ materials and assess their resource use and environmental performance, critical to global climate commitments. However, MI data availability and quality are inconsistent, incomparable, and limited, especially for regions in the Global South. To address these challenges, we present the Regional Assessment of buildings’ Material Intensities (RASMI), a new dataset and accompanying method of comprehensive and consistent representative MI value ranges that embody the variability inherent in buildings. RASMI consists of 3072 MI ranges for 8 construction materials in 12 building structure and function types across 32 regions covering the entire world. The dataset is reproducible, traceable, and updatable, using synthetic data when required. It can be used for estimating historical and future material flows and emissions, assessing demolition waste and at-risk stocks, and evaluating urban mining potentials. Show less
Background: Knowledge of the psychosocial impact of facial skin surgery on patients can help improve counselling strategies.Objectives: The objective was to measure the psychological impact... Show moreBackground: Knowledge of the psychosocial impact of facial skin surgery on patients can help improve counselling strategies.Objectives: The objective was to measure the psychological impact of facial skin cancer surgery on patients over a 1-year period. Secondary objective was to meas-ure the difference between Mohs micrographic surgery (MMS) and conventional excision (CE) on these parameters.Methods: This observational survey study was conducted between March 2019 and July 2020. Patients who had facial skin surgery using MMS or CE were selected. Five surveys were conducted on four timepoints (preoperative, 1 week, 3 months and 1 year post-operative) measuring the quality of life, perceived stigmatization, body image, satisfaction with facial appearance and psychosocial distress.Results: A total of 228 patients (MMS 154 patients, CE 74 patients) were included for the analysis. Scores for quality of life did not significantly change, in the year after surgery (PCS-12 mean 50.5, SD 9.3 and MCS-12 50.6, SD 9.4); however, stigmatiza-tion (F (3, 235,39) 7,26, p < 0.01, d = −0.07), body image concerns (F (3, 198,28) = 3.75, p < 0.01, d = −0.14), satisfaction with facial appearance (F (3, 205,18) = 10.74, p < 0.01, d = 0.43) and psychosocial distress (F (3, 208,69) = 9.26, p < 0.01, d = −0.15) did change over time. The use of MMS or CE did not significantly affect outcome scores after 1 year.Conclusion: Patients receiving facial skin cancer surgery exhibited low scores for perceived stigmatization and body image concerns. Their quality of life was not statistically inf luenced by facial surgery, and their satisfaction with their facial appearance and psychosocial distress even improved after 1 year. The results suggest that the surgical treatment type (MMS or CE) does not inf luence the outcome. The overall results can help in counselling strategies to improve expectations for patients receiving facial surgery. Show less
Until the 17th century, the Dutch coastal region of Zeeland ranked among Europe's most urbanized areas, driven by thriving international trade networks. People living in this time of flourishing... Show moreUntil the 17th century, the Dutch coastal region of Zeeland ranked among Europe's most urbanized areas, driven by thriving international trade networks. People living in this time of flourishing economy benefitted enormously from it in terms of employment opportunities and working conditions, which were reportedly better than in the rest of the Low Countries. However, the rapid growth of Zeeland's urban centers likely presented increasing challenges for the population in terms of accessing essential resources, including food, clean water, and housing. In the 19th century, Zeeland's economy ultimately faced a significant downturn due to the decline in the maritime trade, leading to a substantial reduction in its urban population. Examining patterns of urbanization and economic histories that differ from the commonly studied thriving industrial contexts in bioarcheological research, as exemplified by Zeeland, is a crucial yet relatively underexplored facet in our efforts to understanding the human past. To address this gap, this study investigates the impact of urbanization on the health of Zeeland's inhabitants over time by analyzing nonspecific stress markers (i.e., cribra orbitalia, porotic hyperostosis, and linear enamel hypoplasia) and chronic maxillary sinusitis in a sample of 246 individuals from three urban sites dating from 1030 to 1800 CE. Our analysis of skeletal remains reveals significant differences in the prevalence of porotic hyperostosis, linear enamel hypoplasia, and sinusitis between the medieval and post-medieval periods. These findings suggest that de-urbanization and economic decline adversely affected the health and well-being of the populations under study, influenced by factors such as working conditions and food availability. This study provides a new perspective on bioarcheological approaches to urbanization, shedding light on the intricate realities of urbanization in Zeeland and offering important insights into its complexities. Show less
ObjectiveTo assess the differences between endoscopic and radiological methods of analysis for diagnosing chronic maxillary sinusitis (CMS) in archaeological skeletal remains.Materials32 crania... Show moreObjectiveTo assess the differences between endoscopic and radiological methods of analysis for diagnosing chronic maxillary sinusitis (CMS) in archaeological skeletal remains.Materials32 crania from a Dutch post-medieval rural population.MethodsWe assessed the presence of bone changes indicative of CMS (i.e., bone growth and bone resorption) both endoscopically and through computed tomography (CT), and then compared results.ResultsWe observed moderate agreement between bone growth scores obtained through endoscopy and CT, and fair agreement when assessing bone resorption.ConclusionsCMS prevalence rates observed through CT may be comparable to rates assessed endoscopically, although caution is needed when making direct comparisons.SignificanceThis is the first study comparing data obtained through endoscopy and radiological methods in the study of CMS, informing paleopathologists about potential biases in data comparison.LimitationsOur small sample size likely impacted results.Suggestions for further researchFurther research is advised to fully explore the comparability of endoscopic and radiological method of analysis in the study of sinusitis.Data AvailabilityThe datasets generated and analyzed during the current study are available upon request. Show less
Rakers, M.; Hattem, N. van; Simic, I.; Chavannes, N.; Peet, P. van; Bonten, T.; ... ; Os, H. van 2024
Background While remote patient management (RPM) has the potential to assist in achieving treatment targets for cardiovascular risk factors in primary care, its effectiveness may vary among... Show moreBackground While remote patient management (RPM) has the potential to assist in achieving treatment targets for cardiovascular risk factors in primary care, its effectiveness may vary among different patient subgroups. Panel management, which involves proactive care for specific patient risk groups, could offer a promising approach to tailor RPM to these groups. This study aims to (i) assess the perception of healthcare professionals and other stakeholders regarding the adoption and (ii) identify the barriers and facilitators for successfully implementing such a panel management approach. Methods In total, nineteen semi-structured interviews and two focus groups were conducted in the Netherlands. Three authors reviewed the audited transcripts. The Consolidated Framework for Implementation Strategies (CFIR) domains were used for the thematic analysis. Results A total of 24 participants (GPs, nurses, health insurers, project managers, and IT consultants) participated. Overall, a panel management approach to RPM in primary care was considered valuable by various stakeholders. Implementation barriers encompassed concerns about missing necessary risk factors for patient stratification, additional clinical and technical tasks for nurses, and reimbursement agreements. Facilitators included tailoring consultation frequency and early detection of at-risk patients, an implementation manager accountable for supervising project procedures and establishing agreements on assessing implementation metrics, and ambassador roles. Conclusion Panel management could enhance proactive care and accurately identify which patients could benefit most from RPM to mitigate CVD risk. For successful implementation, we recommend having clear agreements on technical support, financial infrastructure and the criteria for measuring evaluation outcomes. Show less
T cells are the most common immune cells in atherosclerotic plaques, and the function of T cells can be altered by fatty acids. Here, we show that pre-exposure of CD4+ T cells to oleic acid, an... Show moreT cells are the most common immune cells in atherosclerotic plaques, and the function of T cells can be altered by fatty acids. Here, we show that pre-exposure of CD4+ T cells to oleic acid, an abundant fatty acid linked to cardiovascular events, upregulates core metabolic pathways and promotes differentiation into interleukin-9 (IL-9)-producing cells upon activation. RNA sequencing of non-activated T cells reveals that oleic acid upregulates genes encoding key enzymes responsible for cholesterol and fatty acid biosynthesis. Transcription footprint analysis links these expression changes to the differentiation toward TH9 cells, a pro-atherogenic subset. Spectral flow cytometry shows that pre-exposure to oleic acid results in a skew toward IL-9+-producing T cells upon activation. Importantly, pharmacological inhibition of either cholesterol or fatty acid biosynthesis abolishes this effect, suggesting a beneficial role for statins beyond cholesterol lowering. Taken together, oleic acid may affect inflammatory diseases like atherosclerosis by rewiring T cell metabolism. Show less
Chemokine receptors are relevant targets for a multitude of immunological diseases, but drug attrition for these receptors is remarkably high. While many drug discovery programs have been pursued,... Show moreChemokine receptors are relevant targets for a multitude of immunological diseases, but drug attrition for these receptors is remarkably high. While many drug discovery programs have been pursued, most prospective drugs failed in the follow-up studies due to clinical inefficacy, and hence there is a clear need for alternative approaches. Allosteric modulators of receptor function represent an excellent opportunity for novel drugs, as they modulate receptor activation in a controlled manner and display increased selectivity, and their pharmacological profile can be insurmountable. Here, we discuss allosteric ligands and their pharmacological characterization for modulation of chemokine receptors. Ligands are included if (1) they show clear signs of allosteric modulation in vitro and (2) display evidence of binding in a topologically distinct manner compared to endogenous chemokines. We discuss how allosteric ligands affect binding of orthosteric (endogenous) ligands in terms of affinity as well as binding kinetics in radioligand binding assays. Moreover, their effects on signaling events in functional assays and how their binding site can be elucidated are specified. We substantiate this with examples of published allosteric ligands targeting chemokine receptors and hypothetical graphs of pharmacological behavior. This review should serve as an effective starting point for setting up assays for characterizing allosteric ligands to develop safer and more efficacious drugs for chemokine receptors and, ultimately, other G protein-coupled receptors. Show less
Existing research on the security of the supply of critical materials for clean energy generally aggregates information at the country level, a practice that obscures the extensive role of foreign... Show moreExisting research on the security of the supply of critical materials for clean energy generally aggregates information at the country level, a practice that obscures the extensive role of foreign direct investment (FDI) in the production of critical materials. FDI refers to an ownership stake in a company or project by an overseas investor. Here we establish a database for global mining of lithium, cobalt, nickel and platinum at company level, covering 240 countries and regions. We show that 47% of lithium, 71% of cobalt, 41% of nickel and 34% of platinum mined in 2019 were under FDI. We then explore how FDI may affect supply risks by proposing a supply risk index that allocates production of the critical materials to the country of origin of investors instead of the country where production is located. We present upper and lower bounds of the supply risk index that reflect scenarios where either all investors or only state investors prioritize the home-country demand, respectively. This study presents an approach for assessing the national supply risks of critical materials, considering the geographical allocation of FDI. Show less
Tissue resident memory T (TRM) cells are a T-cell subset that resides at the site of prior antigen recognition to protect the body against reoccurring encounters. Besides their protective function,... Show moreTissue resident memory T (TRM) cells are a T-cell subset that resides at the site of prior antigen recognition to protect the body against reoccurring encounters. Besides their protective function, TRM cells have also been implicated in inflammatory disorders. TRM cells are characterized by the expression of CD69 and transcription factors Hobit (homolog of Blimp-1 [B lymphocyte-induced maturation protein 1] in T cells) and Blimp-1. As the majority of T cells in the arterial intima expresses CD69, TRM cells may contribute to the pathogenesis of atherosclerosis as well. Here, we aimed to assess the presence and potential role of TRM cells in atherosclerosis.To identify TRM cells in human atherosclerotic lesions, a single-cell RNA-sequencing data set was interrogated, and T-cell phenotypes were compared with that of integrated predefined TRM cells. The presence and phenotype of TRM in atherosclerotic lesions was corroborated using a mouse model that enabled tracking of Hobit-expressing TRM cells. To explore the function of TRM cells during atherogenesis, RAG1-/- (RAG1 deficient) LDLr-/- (low-density lipoprotein receptor knockout) mice received a bone marrow transplant from HobitKO/CREBlimp-1flox/flox mice, which exhibit abrogated TRM cell formation, whereafter the mice were fed a Western-type diet for 10 weeks.Human atherosclerotic lesions contained T cells that exhibited a TRM cell-associated gene signature. Moreover, a fraction of these T cells clustered together with predefined TRM cells upon integration. The presence of Hobit-expressing TRM cells in the atherosclerotic lesion was confirmed in mice. These lesion-derived TRM cells were characterized by the expression of CD69 and CD49α. Moreover, we demonstrated that this small T-cell subset significantly affects lesion composition, by reducing the amount of intralesional macrophages and increasing collagen content.TRM cells, characterized by the expression of CD69 and CD49α, constitute a minor population in atherosclerotic lesions and are associated with increased lesion stability in a Hobit and Blimp-1 knockout mouse model. Show less
Wright, K.; Koenders, M.; Douglas, K.M.; Faurholt-Jepsen, M.; Lewandowski, K.E.; Miklowitz, D.J.; ... ; Mesman, E. 2024
Feeling loved by one's parents is critical for children's health and well-being. How can such feelings be fostered? A vital feature of loving interactions is reciprocal self-disclosure, where... Show moreFeeling loved by one's parents is critical for children's health and well-being. How can such feelings be fostered? A vital feature of loving interactions is reciprocal self-disclosure, where individuals disclose intimate information about themselves. In a proof-of-concept experiment, we examined whether encouraging reciprocal self-disclosure in parent-child dyads would make children feel more loved during the conversation. Participants were 218 children (ages 8-13, 50% girls, 94% Dutch) and one of their parents (ages 28-56, 62% women, 90% Dutch). Parent-child dyads received a list of 14 questions and took turns asking them each other for 9 min. Dyads were assigned randomly to engage in self-disclosure (questions invoking escalated intimacy) or small talk (questions invoking minimal intimacy). Before and after, children reported how loved they felt by their parent during the conversation. Self-disclosure made children feel more loved during the conversation than did small talk. Compared to small talk, self-disclosure did not instigate conversations that were lengthier or more positive; rather, it instigated conversations that were more emotionally charged (reflecting anger, anxiety, and sadness), social (discussing family and friends), reflective (creating insight), and meaningful (addressing deeply personal topics, including the passing of loved ones). The dyad's gender composition did not significantly moderate these effects. Our research suggests that reciprocal self-disclosure can make children feel more loved in the moment, uncovers linguistic signatures of reciprocal self-disclosure, and offers developmental scientists a tool to examine causal effects of reciprocal self-disclosure in parent-child dyads. Future work should examine long-term effects in everyday parent-child interactions. RESEARCH HIGHLIGHTS: How can parents make children feel more loved by them in the moment? We theorize that these feelings can be cultivated through reciprocal self-disclosure. In a proof-of-concept experiment, we examined effects of reciprocal self-disclosure versus small talk in 218 parent-child dyads, with children aged 8-13. Self-disclosure (vs. small talk) made children feel more loved during the conversation. Linguistically, self-disclosure instigated conversations that were more emotionally charged, social, reflective, and meaningful. This research provides an experimental method to study self-disclosure in parent-child dyads and suggests that self-disclosure can make children feel more loved in the moment. Show less
Masquerades form an important part of indigenous African religions, and headpieces of masks are found all over the world as an iconic African art form. Contrary to expectation, however, the... Show moreMasquerades form an important part of indigenous African religions, and headpieces of masks are found all over the world as an iconic African art form. Contrary to expectation, however, the geographical distribution of masking is very restricted, occurring only in three areas of the continent, mainly situated in the forested zones. I explain this peculiar distribution by tracing the ecological and historical parameters of the societies that harbor mask rituals. The main ecological factors are the absence of cattle and the type of horticulture, while a crucial historical element is the long history of slave raiding and trading to which the continent has been subjected. These factors have led to societies in which both gender and local power arrangements show a marked indeterminacy, operating as internal arenas between men and women, and between different groups of men. Crucial in the explanation of masquerades is the fact that masking is completely absent from societies that practice cattle husbandry with the Bos indicus species (zebu). Since sleeping sickness prohibits cattle husbandry, wherever the tsetse fly thrives, masks appear. Show less
This interdisciplinary study, coupling philosophy of law with empirical cognitive science, presents preliminary insight into the role of emotion in criminalization decisions, for both laypeople and... Show moreThis interdisciplinary study, coupling philosophy of law with empirical cognitive science, presents preliminary insight into the role of emotion in criminalization decisions, for both laypeople and legal professionals. While the traditional approach in criminalization theory emphasizes the role of deliberative and reasoned argumentation, this study hypothesizes that affective and emotional processes (i.e., disgust, as indexed by a dispositional proneness to experience disgust) are also associated with the decision to criminalize behavior, in particular virtual child pornography. To test this empirically, an online study (N = 1402) was conducted in which laypeople and legal professionals provided criminalization ratings on four vignettes adapted from criminal law, in which harmfulness and disgustingness were varied orthogonally. They also completed the 25-item Disgust Scale-Revised (DS-R-NL). In line with the hypothesis, (a) the virtual child pornography vignette (characterized as low in harm, high in disgust) was criminalized more readily than the financial harm vignette (high in harm, low in disgust), and (b) disgust sensitivity was associated with the decision to criminalize behavior, especially virtual child pornography, among both lay participants and legal professionals. These findings suggest that emotion can be relevant in shaping criminalization decisions. Exploring this theoretically, the results could serve as a stepping stone towards a new perspective on criminalization, including a “criminalization bias”. Study limitations and implications for legal theory and policymaking are discussed. Show less
Adaptive immunity plays a profound role in atherosclerosis pathogenesis by regulating antigen-specific responses, inflammatory signaling and antibody production. However, as we age, our immune... Show moreAdaptive immunity plays a profound role in atherosclerosis pathogenesis by regulating antigen-specific responses, inflammatory signaling and antibody production. However, as we age, our immune system undergoes a gradual functional decline, a phenomenon termed "immunosenescence". This decline is characterized by a reduction in proliferative naïve B- and T cells, decreased B- and T cell receptor repertoire and a pro-inflammatory senescence associated secretory profile. Furthermore, aging affects germinal center responses and deteriorates secondary lymphoid organ function and structure, leading to impaired T-B cell dynamics and increased autoantibody production. In this review, we will dissect the impact of aging on adaptive immunity and the role played by age-associated B- and T cells in atherosclerosis pathogenesis, emphasizing the need for interventions that target age-related immune dysfunction to reduce cardiovascular disease risk. Show less
