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The term “charisma” is recognized as sociology's most successful export to common speech. While sociologists habitually dismiss popular uses of the word, we address its vernacularity head on as a worthy object of study and as a potential resource for conceptual development. Using machine learning, we locate “charisma” within the wider discursive field out of which it arises (and continues to arise) across four corpora; namely: Weber’s major writings; social scientific research (123,531 JSTOR articles); and social media (“X”) posts containing of “charisma” (n=77,161) and its 2023 variant, “rizz” (n=85,869). By capturing meaning structures that discursively suspend “charisma” across multiple dimensions, we discern three spectra that help to distinguish charisma’s sociological and non‐sociological uses. Spectrum one differentiates perspectives which see charisma as having either a structural or individual‐level range of efficacy. Spectrum two differentiates indifferent/analytical perspectives on charisma from perspectives which see it as desirable but also morally conservative. Spectrum three differentiates between relational and individualized ontologies for charisma. We find that, rather than hewing closely to the Weberian formulation, social scientific uses exist in an intermediate position vis‐à‐vis these three spectra. Thus, scholars participate in what they otherwise criticize as charisma’s vulgarization. The article concludes with recommendations for how to constructively interact with ‘popular charisma.’ [ABSTRACT FROM AUTHOR]

A diagnosis of brain metastasis (BM) significantly affects quality of life in patients with metastatic renal cell cancer (mRCC). Although systemic treatments have shown efficacy in mRCC, active surveillance (AS) is still commonly used in clinical practice. In this single‐center cohort study, we assessed the impact of different initial treatment strategies for metastatic RCC (mRCC) on the development of BM. All consecutive patients diagnosed with mRCC between 2011 and 2022 were included at the Erasmus MC Cancer Institute, the Netherlands, and a subgroup of patients with BM was selected. In total, 381 patients with mRCC (ECM, BM, or both) were identified. Forty‐six patients had BM of whom 39 had metachronous BM (diagnosed ≥1 month after ECM). Twenty‐five (64.1%) of these 39 patients with metachronous BM had received prior systemic treatment for ECM and 14 (35.9%) patients were treatment naive at BM diagnosis. The median BM‐free survival since ECM diagnosis was significantly longer (p =.02) in previously treated patients (29.0 [IQR 12.6–57.0] months) compared to treatment naive patients (6.8 [IQR 1.0–7.0] months). In conclusion, patients with mRCC who received systemic treatment for ECM prior to BM diagnosis had a longer BM‐free survival as compared to treatment naïve patients. These results emphasize the need for careful evaluation of treatment strategies, and especially AS, for patients with mRCC. [ABSTRACT FROM AUTHOR]

Centrosomal Protein 55 (CEP55) exhibits various oncogenic activities; it regulates the PI3K-Akt-pathway, midbody abscission, and chromosomal instability (CIN) in cancer cells. Here, we analyzed the mechanism of how CEP55 controls CIN in ovarian and breast cancer (OvCa) cells. Down-regulation of CEP55 reduced CIN in all cell lines analyzed, and CEP55 depletion decreased spindle microtubule (MT)-stability in OvCa cells. Moreover, recombinant CEP55 accelerated MT-polymerization and attenuated cold-induced MT-depolymerization. To analyze a potential relationship between CEP55-controlled CIN and its impact on MT-stability, we identified the CEP55 MT-binding peptides inside the CEP55 protein. Thereafter, a mutant with deficient MT-binding activity was re-expressed in CEP55-depleted OvCa cells and we could show that this mutant did not restore reduced CIN in CEP55-depleted cells. This finding strongly indicates that CEP55 regulates CIN by controlling MT dynamics. [ABSTRACT FROM AUTHOR]

In the last decade, storytelling has been popularised as a method for societal sustainability transformations. With this growing popularity, there has also been a rapid increase in those identifying as storytellers. Perhaps because storytelling for sustainability has an innocent ring to it, it has not yet been studied from a power perspective. However, as it is fast-spreading and has explicit change purposes, it is important to clarify assumptions about knowledge, power and change. This article offers a first step towards understanding and evaluating the wide variety of applications behind the label of storytelling for sustainability. We perform a frame analysis of how storytellers describe their storytelling for sustainability. Our findings demonstrate that the label of storytelling for sustainability encompasses fundamentally different ideas about whose knowledge counts. The article raises critical questions that can help assess the legitimacy and appropriateness of different applications of storytelling for sustainability. [ABSTRACT FROM AUTHOR]

Social media and other platforms have become an essential part of outdoor activities as they influence how nature is experienced and engaged with, but also what good nature is seen as. In this article, we explore how social understandings of nature and digital technologies are mutually performed. Using the empirical case of nature selfies—an archetype of imagery on social media platforms—posted on Instagram, Facebook, and Tripadvisor, and a small participatory "breaching experiment" aimed at collecting "ugly nature selfies," we analyse and interrogate nature/society relationships displayed online within the platform contexts of attention economy and affordances. We conclude that nature selfies reinforce the desirability of consuming "beautiful" nature, while attention economy and platform affordances limit the possibilities for alternative nature/society relationships to be developed and promoted. [ABSTRACT FROM AUTHOR]

Governmental organizations face the challenge to integrate different sectoral policy perspectives and interests to deal effectively with the wicked issues of late-modern societies. This article delves into attempts of governmental organizations to realize such integrated policies and unravels the intra-organizational dynamics of collaborating on policy integration. Based on two in-depth case studies from The Netherlands, one focusing on public transport for specific target groups in the city of Rotterdam and the other focusing on a national policy program for criminal youth groups, we show how attempts at policy integration take place in the periphery of bureaucracies by temporary program teams. After the abolishment of the program team, the integrated policy easily volatilizes because of the lack of foothold and ownership in the line organization. Ironically, policy integration becomes a differentiated activity in the margins of public organizations rather than a joint exercise of sectoral organizational units. We present three explanatory hypotheses of this dynamic of marginalization. First, from a system-psychodynamic perspective, the line organization and the program team maintain distance from each other to reduce the tensions that are inherent in policy integration. Second, from an institutional perspective, the line organization marginalizes policy integration to protect their sectoral and vested interests. Third, from an innovation perspective, however, innovative policy integration does need the margins of organizations to protect itself against conservative reflexes from bureaucracies at risk of becoming marginalized and alienated. To facilitate a productive dynamic of policy integration in governmental organizations, this article concludes with providing the components for such an organizational design. [ABSTRACT FROM AUTHOR]

Abstract Background Proximal femoral fractures are strongly associated with morbidity and mortality in elderly patients. Mortality is highest among frail institutionalized elderly with both physical and cognitive comorbidities who consequently have a limited life expectancy. Evidence based guidelines on whether or not to operate on these patients in the case of a proximal femoral fracture are lacking. Practice variation occurs, and it remains unknown if nonoperative treatment would result in at least the same quality of life as operative treatment. This study aims to determine the effect of nonoperative management versus operative management of proximal femoral fractures in a selected group of frail institutionalized elderly on the quality of life, level of pain, rate of complications, time to death, satisfaction of the patient (or proxy) and the caregiver with the management strategy, and health care consumption. Methods This is a multicenter, observational cohort study. Frail institutionalized elderly (70 years or older with a body mass index

Abstract Background The incidence of brain metastases in breast cancer (BCBM) patients is increasing. These patients have a very poor prognosis, and therefore, identification of blood-based biomarkers, such as circulating tumor cells (CTCs), and understanding the genomic heterogeneity could help to personalize treatment options. Methods Both EpCAM-dependent (CellSearch® System) and EpCAM-independent Ficoll-based density centrifugation methods were used to detect CTCs from 57 BCBM patients. DNA from individual CTCs and corresponding primary tumors and brain metastases were analyzed by next-generation sequencing (NGS) in order to evaluate copy number aberrations and single nucleotide variations (SNVs). Results CTCs were detected after EpCAM-dependent enrichment in 47.7% of the patients (≥ 5 CTCs/7.5 ml blood in 20.5%). The CTC count was associated with ERBB2 status (p = 0.029) of the primary tumor as well as with the prevalence of bone metastases (p = 0.021). EpCAM-independent enrichment revealed CTCs in 32.6% of the patients, especially among triple-negative breast cancer (TNBC) patients (70.0%). A positive CTC status after enrichment of either method was significantly associated with decreased overall survival time (p

Abstract Background In solid organ transplant (SOT) recipients, transplant rejection during immune checkpoint inhibitor (ICI) treatment for cancer is a clinical problem. Donor-derived cell-free DNA (dd-cfDNA) can be detected in blood and is a sensitive biomarker for diagnosis of acute rejection in SOT recipients. To our best knowledge, this is the first case report of a kidney transplant recipient with advanced cancer treated with ICI who was monitored with dd-cfDNA. Case presentation A 72-year old female with a long-standing renal transplant was diagnosed with advanced melanoma in 2018 and was treated with the anti-PD1 antibody nivolumab. Within 12 days after the first administration of nivolumab, dd-cfDNA ratio increased to 23%, suggesting allograft rejection. Her kidney transplant function deteriorated and acute rejection was confirmed by renal transplant biopsy. As the rejection could not be controlled despite immunosuppressive treatment, a transplant nephrectomy was necessary and haemodialysis was started. Immunological analysis of the renal explant showed infiltration of alloreactive, nivolumab-saturated, PD1+ cytotoxic T cells. After transplant nephrectomy, she experienced nivolumab-related toxicity and rapid disease progression. Conclusion Clinicians prescribing ICIs should be aware that SOT recipients are at risk of transplant rejection as a result of T cell activation. Dd-cfDNA is a sensitive biomarker and should be further studied for early detection of transplant rejection. Immunological analysis of the kidney explant showed marked graft infiltration with alloreactive PD-1+ cytotoxic T cells that were saturated with nivolumab.

Currently, sensitive and specific methods for the detection and prognosis of early stage PCa are lacking. To establish the diagnosis and further identify an appropriate treatment strategy, prostate specific antigen (PSA) blood test followed by tissue biopsy have to be performed. The combination of tests is justified by the lack of a highly sensitive, specific, and safe single test. Tissue biopsy is specific but invasive and may have severe side effects, and therefore is inappropriate for screening of the disease. At the same time, the PSA blood test, which is conventionally used for PCa screening, has low specificity and may be elevated in the case of noncancerous prostate tumors and inflammatory conditions, including benign prostatic hyperplasia and prostatitis. Thus, diverse techniques of liquid biopsy have been investigated to supplement or replace the existing tests of prostate cancer early diagnosis and prognostics. Here, we provide a review on the advances in diagnosis and prognostics of non-metastatic prostate cancer by means of various biomarkers extracted via liquid biopsy, including circulating tumor cells, exosomal miRNAs, and circulating DNAs.

This article presents empirical research on how local protestant churches in the city of Utrecht organized their Sunday church services during the first weeks of the COVID-19 crisis in the Netherlands. After the first lockdown Sunday, on which many services were cancelled, most members took part in digital services of their own congregation on subsequent Sundays. Community with one another was missed most, while many still felt connected to God. Online services were considered a fine alternative, but also as one that cannot possibly replace meeting in real life. These findings arguably need theological reflection regarding the phenomenon of digital liturgical community formation. We reflect on the (dis)continuity between digital and o.ffline services as this relates to community formation, embodiedness, and the mediation of salvation. Concludingly, we point to three issues that may help local churches in drawing lessons from the COVID-19 pandemic regarding (digital) community formation.

Antigen-specific B cells (ASBCs) can drive autoimmune disease by presenting autoantigen to cognate T cells to drive their activation, proliferation, and effector cell differentiation and/or by differentiating into autoantibody-secreting cells. Autoantibodies are frequently used to predict risk and diagnose several autoimmune diseases. ASBCs can drive type 1 diabetes even when immune tolerance mechanisms block their differentiation into antibody-secreting cells. Furthermore, anti-histidyl tRNA synthetase syndrome patients have expanded IgM+ Jo-1-binding B cells, which clinically diagnostic IgG Jo-1 autoantibodies may not fully reflect. Given the potential disconnect between the pathologic function of ASBCs and autoantibody secretion, direct study of ASBCs is a necessary step towards developing better therapies for autoimmune diseases, which often have no available cure. We therefore developed a high-throughput screening pipeline to 1) phenotypically identify specific B cell subsets, 2) expand them in vitro, 3) drive them to secrete BCRs as antibody, and 4) identify wells enriched for ASBCs through ELISA detection of antibody. We tested the capacity of several B cell subset(s) to differentiate into antibody-secreting cells following this robust stimulation. IgM+ and/or IgD+, CD27- memory, memory, switched memory, and BND B cells secreted B cell receptor (BCR) as antibody following in vitro stimulation, whereas few plasmablasts responded. Bimodal responses were observed across autoimmune donors for IgM+ CD21lo and IgM- CD21lo B cells, consistent with documented heterogeneity within the CD21lo subset. Using this approach, we detected insulin-binding B cell bias towards CD27- memory and CD27+ memory subsets in pre-symptomatic type 1 diabetes donors. We took advantage of routine detection of Jo-1-binding B cells in Jo-1+ anti-histidyl tRNA synthetase syndrome patients to show that Jo-1-binding B cells and total B cells expanded 20-30-fold using this culture system. Overall, these studies highlight technology that is amenable to small numbers of cryopreserved peripheral blood mononuclear cells that enables interrogation of phenotypic and repertoire attributes of ASBCs derived from autoimmune patients.

Abstract Background The BIG score (Admission base deficit (B), International normalized ratio (I), and Glasgow Coma Scale (G)) has been shown to predict mortality on admission in pediatric trauma patients. The objective of this study was to assess its performance in predicting mortality in an adult trauma population, and to compare it with the existing Trauma and Injury Severity Score (TRISS) and probability of survival (PS09) score. Materials and methods A retrospective analysis using data collected between 2005 and 2010 from seven trauma centers and registries in Europe and the United States of America was performed. We compared the BIG score with TRISS and PS09 scores in a population of blunt and penetrating trauma patients. We then assessed the discrimination ability of all scores via receiver operating characteristic (ROC) curves and compared the expected mortality rate (precision) of all scores with the observed mortality rate. Results In total, 12,206 datasets were retrieved to validate the BIG score. The mean ISS was 15 ± 11, and the mean 30-day mortality rate was 4.8%. With an AUROC of 0.892 (95% confidence interval (CI): 0.879 to 0.906), the BIG score performed well in an adult population. TRISS had an area under ROC (AUROC) of 0.922 (0.913 to 0.932) and the PS09 score of 0.825 (0.915 to 0.934). On a penetrating-trauma population, the BIG score had an AUROC result of 0.920 (0.898 to 0.942) compared with the PS09 score (AUROC of 0.921; 0.902 to 0.939) and TRISS (0.929; 0.912 to 0.947). Conclusions The BIG score is a good predictor of mortality in the adult trauma population. It performed well compared with TRISS and the PS09 score, although it has significantly less discriminative ability. In a penetrating-trauma population, the BIG score performed better than in a population with blunt trauma. The BIG score has the advantage of being available shortly after admission and may be used to predict clinical prognosis or as a research tool to risk stratify trauma patients into clinical trials.