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Abstract Motility coupled to responsive behavior is essential for many microorganisms to seek and establish appropriate habitats. One of the simplest possible responses, reversing the direction of motion, is believed to enable filamentous cyanobacteria to form stable aggregates or accumulate in suitable light conditions. Here, we demonstrate that filamentous morphology in combination with responding to light gradients by reversals has consequences far beyond simple accumulation: Entangled aggregates form at the boundaries of illuminated regions, harnessing the boundary to establish local order. We explore how the light pattern, in particular its boundary curvature, impacts aggregation. A minimal mechanistic model of active flexible filaments resembles the experimental findings, thereby revealing the emergent and generic character of these structures. This phenomenon may enable elongated microorganisms to generate adaptive colony architectures in limited habitats or guide the assembly of biomimetic fibrous materials.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

IntroductionDuring the communicable coronavirus disease (COVID-19) pandemic, organizational infection control measures (oICMs) were introduced in the workplace. The employees’ positive attitudes and active participation are relevant for full effectiveness regarding disease prevention. Therefore, we explore changes in employees’ attitudes toward oICM at work from August–October 2020 (T0) over January 2021 (T1) to October–November 2021 (T2). We further investigate the role an organization can play in supporting health-related preventive behavior.MethodsWe considered repeated cross-sectional and longitudinal panel survey data from 5,554 employees of a global supplier of technology and services in Germany. A total of 16 items constitute the attitude scores toward oICM (5-point Likert scale). Via mixed-effect model, aspects associated with employees’ attitudes toward oICM were explored. Via ‘extreme-group’ approach, we compared the 20% of participants with the largest changes into less favorable to the 20% with the largest changes into more favorable attitudes toward oICM over time.ResultsThe overall positive attitudes toward work-related oICM were more favorable at T1 (mean ± SD: 4.2 ± 0.6, median (IQR): 4.3 (0.8), n = 2,515) compared to T0 (4.1 ± 0.6, 4.1 (0.8), n = 2,417) but less favorable at T2 (3.9 ± 0.7, 4.0 (0.9), n = 2,062). Among others, feeling well-informed about possible work-related risks of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), perceived psychosocial demands through work environment aspects, and perceived management’s commitment to safety and health were associated with long-term positive attitudes toward oICM. Individuals developing more favorable attitudes toward oICM reported feeling well-informed about possible work-related SARS-CoV-2 infection risks and improved COVID-19-specific resilience over time. Individuals developing less favorable attitudes toward oICM reported decreased perceptions of COVID-19-associated risks.ConclusionoICMs in the workplace were perceived appropriate even after COVID-19 vaccines were widely available although the perceived affective risks about SARS-CoV-2 decreased. Taken together, our findings highlight how organizations can support employees in adopting health-related preventive behavior. Among others, we found that feeling well-informed about possible work-related health risks was positively associated with long-term favorable attitudes toward work-related oICM. We expect that the results contribute to the development of interventions to prepare and adapt to future global public health concerns.

The development of new antimalarials is required because of the threat of resistance to current antimalarial therapies. To discover new antimalarial chemotypes, we screened the Janssen Jumpstarter library against the P. falciparum asexual parasite and identified the 7-N-substituted-3-oxadiazole quinolone hit class. We established the structure-activity relationship and optimized the antimalarial potency. The optimized analog WJM228 (17) showed robust metabolic stability in vitro, although the aqueous solubility was limited. Forward genetic resistance studies uncovered that WJM228 targets the Qo site of cytochrome b (cyt b), an important component of the mitochondrial electron transport chain (ETC) that is essential for pyrimidine biosynthesis and an established antimalarial target. Profiling against drug-resistant parasites confirmed that WJM228 confers resistance to the Qo site but not Qi site mutations, and in a biosensor assay, it was shown to impact the ETC via inhibition of cyt b. Consistent with other cyt b targeted antimalarials, WJM228 prevented pre-erythrocytic parasite and male gamete development and reduced asexual parasitemia in a P. berghei mouse model of malaria. Correcting the limited aqueous solubility and the high susceptibility to cyt b Qo site resistant parasites found in the clinic will be major obstacles in the future development of the 3-oxadiazole quinolone antimalarial class.

Abstract Background Metazoans inherited genes from unicellular ancestors that perform essential biological processes such as cell division, metabolism, and protein translation. Multicellularity requires careful control and coordination of these unicellular genes to maintain tissue integrity and homeostasis. Gene regulatory networks (GRNs) that arose during metazoan evolution are frequently altered in cancer, resulting in over-expression of unicellular genes. We propose that an imbalance in co-expression of unicellular (UC) and multicellular (MC) genes is a driving force in cancer. Results We combine gene co-expression analysis to infer changes to GRNs in cancer with protein sequence conservation data to distinguish genes with UC and MC origins. Co-expression networks created using RNA sequencing data from 31 tumor types and normal tissue samples are divided into modules enriched for UC genes, MC genes, or mixed UC-MC modules. The greatest differences between tumor and normal tissue co-expression networks occur within mixed UC-MC modules. MC and UC genes not commonly co-expressed in normal tissues form distinct co-expression modules seen only in tumors. The degree of rewiring of genes within mixed UC-MC modules increases with tumor grade and stage. Mixed UC-MC modules are enriched for somatic mutations in cancer genes, particularly amplifications, suggesting an important driver of the rewiring observed in tumors is copy number changes. Conclusions Our study shows the greatest changes to gene co-expression patterns during tumor progression occur between genes of MC and UC origins, implicating the breakdown and rewiring of metazoan gene regulatory networks in cancer development and progression.

Neopagans in Mexico City started to communitise only about 20 years ago. An initial analysis of related interview material shows that the narratives they develop about their first contact with neopagan content and their access to the field are framed as a conversion-like process, often connoted as a home-coming or a rebellion against predominant Catholicism. Both narratives are usually mixed with a notion of intuition that led to their further involvement in neopagan groups. Nevertheless, Mexican “folk magic” and vernacular healing traditions, Afro-American religions, and the flourishing esoteric scene in the Mexican capital are already offering links to beliefs and practices that are common in neopaganism, like ritualised ways to interact with transcendent entities, magic, and ideas of an “otherworld”. This raises various questions related to the underlying dynamics, in brief: how do heterogeneous sociohistorical situations influence emerging religious fields like the neopagan one in the Mexican capital, and how do these interactions shape personal religious transformation processes in the wider context of glocalisation, transcultural dynamics, digitalisation and the diversification of the religious field overall? In the light of Adler’s (1979) influential concept of home-coming and Luhrmann’s (1989) theory of the interpretative drift, it remains clear that becoming neopagan is rarely understood as a conversion, and therefore the two contested theoretical approaches are discussed critically and in relation to conversion. Using a grounded theory approach and thus emphasising the emic perspectives of my interviewees, I show how they construct their first encounter narratives and frame them as intuition, rebellion, or tradition, considering the underpinning sociocultural circumstances.

Religious conversion is a phenomenon that has intrigued scholars, theologians, and sociologists for centuries. As the conscious choice of a particular form of religion over another, it is eminently a form of religious contact. Religious conversion may be approached psychologically, sociologically, and conceptually. The contributions of this special issue show all three approaches and cover a wide array of geographical, social, and religious contexts.

Background: To enhance patient safety in healthcare, it is crucial to address the underreporting of issues in Critical Incident Reporting Systems (CIRSs). This study aims to evaluate the effectiveness of generative Artificial Intelligence and Natural Language Processing (AI/NLP) in reviewing CIRS cases by comparing its performance with human reviewers and categorising these cases into relevant topics. Methods: A case–control feasibility study was conducted using CIRS cases from the German CIRS-Anaesthesiology subsystem. Each case was reviewed by a human expert and by an AI/NLP model (ChatGPT-3.5). Two CIRS experts blindly assessed these reviews, rating them on linguistic quality, recognisable expertise, logical derivability, and overall quality using six-point Likert scales. Results: On average, the CIRS experts correctly classified 80% of human CIRS reviews as created by a human and misclassified 45.8% of AI reviews as written by a human. Ratings on a scale of 1 (very good) to 6 (failed) revealed a comparable performance between human- and AI-generated reviews across the dimensions of linguistic expression (p = 0.39), recognisable expertise (p = 0.89), logical derivability (p = 0.84), and overall quality (p = 0.87). The AI model was able to categorise the cases into relevant topics independently. Conclusions: This feasibility study demonstrates the potential of generative AI/NLP in analysing and categorising cases from the CIRS. This could have implications for improving incident reporting in healthcare. Therefore, additional research is required to verify and expand upon these discoveries.

Abstract Radon (222Rn) and its progeny are responsible for half of the annual dose from natural radiation and the most frequent cause for lung cancer induction after smoking. During inhalation, progeny nuclides accumulate in the respiratory tract while most of the radon gas is exhaled. The decay of progeny nuclides in the lung together with the high radiosensitivity of this tissue lead to equivalent doses implying a significant cancer risk. Here, we use gamma spectroscopy to measure the attachment of radon progeny on an air-ventilated filter system within a radon enriched atmosphere, mimicking the respiratory tract. A mathematical model was developed to describe the measured time-dependent activities of radon progeny on the filter system. We verified a linear relation between the ambient radon activity concentration during exposure and the amount of decay products on the filter system. The measured activities on the filters and its mathematical description are in good agreement. The developed experimental set-up can thus serve to further investigate the deposition of radon progeny in the respiratory tract under varying conditions for determination of dose conversion factors in radiation protection, which we demonstrate by deriving dose estimations in mouse lung.

Abstract Background Uterine leiomyosarcoma (uLMS) is a rare and aggressive gynaecological malignancy, with individuals with advanced uLMS having a five-year survival of 0.2) but only two samples had a CHORD score > 50%, one of which had a homozygous pathogenic alteration in an HR gene (deletion in BRCA2). A further three samples harboured homozygous HRD alterations (all deletions in BRCA2), detected by WES or panel sequencing, with 5/58 (9%) individuals having HRD uLMS. All five individuals gained access to PARPi therapy. Two of three individuals with mature clinical follow up achieved a complete response or durable partial response (PR) with the subsequent addition of platinum to PARPi upon minor progression during initial PR on PARPi. Corresponding PDX responses were most rapid, complete and sustained with the PARP1-specific PARPi, AZD5305, compared with either olaparib alone or olaparib plus cisplatin, even in a paired sample of a BRCA2-deleted PDX, derived following PARPi therapy in the patient, which had developed PARPi-resistance mutations in PRKDC, encoding DNA-PKcs. Conclusions Our work demonstrates the value of identifying HRD for therapeutic targeting by PARPi and platinum in individuals with the aggressive rare malignancy, uLMS and suggests that individuals with HRD uLMS should be included in trials of PARP1-specific PARPi.

This study investigated the public acceptance of drones in six European countries. For this purpose, an online questionnaire was created, which was completed by 2998 participants. The general attitude towards drones, concerns, approval for different use cases, minimum tolerable flight altitude, acceptable flight areas, and the impact of personal and demographic attributes on drone acceptance were analyzed. Overall, attitudes towards drones were quite positive in the entire sample and even improved slightly in a second measurement at the end of the questionnaire. However, the results also show that acceptance strongly depends on the use case. Drones for civil and public applications are more widely accepted than those for private and commercial applications. Moreover, the population still has high concerns about privacy and safety. Knowledge about drones, interest in technologies, and age proved essential to predicting acceptance. Thus, tailored communication strategies, for example, through social media, can enhance public awareness and acceptance.

Background: Despite initial response to platinum-based chemotherapy and PARP inhibitor therapy (PARPi), nearly all recurrent high-grade serous ovarian cancer (HGSC) will acquire lethal drug resistance; indeed, ~15% of individuals have de novo platinum-refractory disease. Objectives: To determine the potential of anti-microtubule agent (AMA) therapy (paclitaxel, vinorelbine and eribulin) in platinum-resistant or refractory (PRR) HGSC by assessing response in patient-derived xenograft (PDX) models of HGSC. Design and methods: Of 13 PRR HGSC PDX, six were primary PRR, derived from chemotherapy-naïve samples (one was BRCA2 mutant) and seven were from samples obtained following chemotherapy treatment in the clinic (five were mutant for either BRCA1 or BRCA2 ( BRCA1/2) , four with prior PARPi exposure), recapitulating the population of individuals with aggressive treatment-resistant HGSC in the clinic. Molecular analyses and in vivo treatment studies were undertaken. Results: Seven out of thirteen PRR PDX (54%) were sensitive to treatment with the AMA, eribulin (time to progressive disease (PD) ⩾100 days from the start of treatment) and 11 out of 13 PDX (85%) derived significant benefit from eribulin [time to harvest (TTH) for each PDX with p

Abstract Background Malignant pleural effusions (MPEs) are a common complication of advanced cancers, particularly those adjacent to the pleura, such as lung and breast cancer. The pathophysiology of MPE formation remains poorly understood, and although MPEs are routinely used for the diagnosis of breast cancer patients, their composition and biology are poorly understood. It is difficult to distinguish invading malignant cells from resident mesothelial cells and to identify the directionality of interactions between these populations in the pleura. There is a need to characterize the phenotypic diversity of breast cancer cell populations in the pleural microenvironment, and investigate how this varies across patients. Methods Here, we used single‐cell RNA‐sequencing to study the heterogeneity of 10 MPEs from seven metastatic breast cancer patients, including three Miltenyi‐enriched samples using a negative selection approach. This dataset of almost 65 000 cells was analysed using integrative approaches to compare heterogeneous cell populations and phenotypes. Results We identified substantial inter‐patient heterogeneity in the composition of cell types (including malignant, mesothelial and immune cell populations), in expression of subtype‐specific gene signatures and in copy number aberration patterns, that captured variability across breast cancer cell populations. Within individual MPEs, we distinguished mesothelial cell populations from malignant cells using key markers, the presence of breast cancer subtype expression patterns and copy number aberration patterns. We also identified pleural mesothelial cells expressing a cancer‐associated fibroblast‐like transcriptomic program that may support cancer growth. Conclusions Our dataset presents the first unbiased assessment of breast cancer‐associated MPEs at a single cell resolution, providing the community with a valuable resource for the study of MPEs. Our work highlights the molecular and cellular diversity captured in MPEs and motivates the potential use of these clinically relevant biopsies in the development of targeted therapeutics for patients with advanced breast cancer.

We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone's performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity.