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The use of rare earth elements has increased in recent years, leading to a rise in environmental concentrations. Despite the growth in number of studies regarding toxicity, knowledge gaps remain. For Daphnia magna, standardized test methods involve exposure periods of either 48 h or 21 days to assess toxicological effects. In this study, the exposure period was adjusted to 7 days to evaluate sublethal endpoints not measurable in 48-h tests. Additionally, this approach enabled us to obtain results within a shorter time frame than that required for 21-day tests. This study focused on the individual toxicity of lanthanum (La) and gadolinium (Gd) to Daphnia magna. We assessed mortality, feeding rate, somatic growth, and maturity under static conditions, modifying the media by adding MOPS buffer to maintain an initial pH of 6.8 and providing Raphidocelis subcapitata as a daily food source. Results showed that the solubility of La decreased considerably, with the highest recovery rate dropping from 133.33% at the start to 32.73% by the end of the 7-day exposure period. In contrast, Gd solubility remained stable, with a recovery rate of 86.88% at the start and 81.30% at the end of the test. Daily lethal concentrations (LC x ) were calculated, revealing LC 10 values on the first day, LC 20 on the second day, and LC 50 by the third day for La and the second day for Gd. By the test's end, the LC 10 , LC 20 , and LC 50 values were 30.40, 78.96, and 403.67 µg L -1 for La, and 10.67, 33.73, and 241.28 µg L -1 for Gd. For the sublethal endpoints, maturity was the most sensitive endpoint with the EC 20 and EC 10 corresponding to 0.79 and 0.26 µg L -1 for La and 0.39 and 0.14 µg L -1 for Gd. Gd had a higher toxicity in all endpoints assessed. While a thorough comparison to existing literature remains challenging due to variations in endpoints assessed, the methodology employed in this study yielded a range of informative results. This approach provides a useful range-finding test for Daphnia magna toxicity assessments, particularly for preliminary screening, and may complement standardized methodologies., Competing Interests: Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Much of the current autism and gender literature has been based within a medical deficiency model; where both are seen as deficiencies rather than differences. However, there is currently minimal knowledge about the experiences of being an autistic adolescent who is both assigned female at birth and has gender dysphoria (GD), whilst even less is known about their experiences of social identity, self-concept and resilience. This study aims to explore experiences of GD with a particular focus on identity and resilience to promote parent and healthcare staff understanding; particularly around gender-affirming care, to foster positive mental health outcomes. Five assigned female at birth autistic adolescents, who identify as trans men/boys, took part in one-to-one semi-structured interviews, which were analysed using an Interpretative Phenomenological Approach. Five subordinate themes arose; "Having both autism and GD", "Finding where I belong", "Being more than labels", "Trying to cope" and "Making support successful". Our findings build on current literature and theory regarding the experience of concurrent autism and GD; highlighting its legitimacy, the ways in which autism impacts upon GD and how healthcare approaches and policy can increase accessibility and suitability of gender-affirming care., Competing Interests: Declarations. Ethical Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by The West of Scotland Research Ethics Service (WoSRES; 13th December 2021; study reference number 21/WS/0137). Informed Consent: Written Informed consent was obtained from all individual participants included in the study. Parental assent was sought from all under 16s with capacity to consent. The participants have consented to the submission of the research project to a journal. Again, parental assent was sought from all under 16s with capacity to consent. Data will be deposited in the University of Edinburgh Data Repository for a minimum of 5 years, to allow for research transparency. The following authors contributed to the study conception and design; Dr Michelle Oliver, Dr. Eimear Crowe, Flo Parkin, Dr. Emma Macey & Dr. Karri Gillespie-Smith. Material preparation was carried out by Dr Michelle Oliver and Flo Parkin. Data collection was carried out by Dr Michelle Oliver. Analysis was performed by Dr Michelle Oliver and Dr Zoe Poysden with contribution from Flo Parkin & Dr. Karri Gillespie-Smith. The first draft of the manuscript was written by Dr Michelle Oliver with initial drafts being commented on by Ally Pax Arcari Mair & Dr. Karri Gillespie-Smith. All authors commented on and approved the final manuscript. Competing Interests: The authors have no competing interests to declare that are relevant to the content of this article. The authors declare they have no other financial or non-financial interests to disclose., (© 2024. Crown.)

The self-matching task (SMT) is widely used to investigate the cognitive mechanisms underlying the self-prioritization effect (SPE), wherein performance is enhanced for self-associated stimuli compared to other-associated ones. Although the SMT robustly elicits the SPE, there is a lack of data quantifying the reliability of this paradigm. This is problematic, given the prevalence of the reliability paradox in cognitive tasks: many well-established cognitive tasks demonstrate relatively low reliability when used to evaluate individual differences, despite exhibiting replicable effects at the group level. To fill this gap, this preregistered study investigated the reliability of SPE derived from the SMT using a multiverse approach, combining all possible indicators and baselines reported in the literature. We first examined the robustness of 24 SPE measures across 42 datasets (N = 2250) using a meta-analytical approach. We then calculated the split-half reliability (r) and intraclass correlation coefficient (ICC2) for each SPE measure. Our findings revealed a robust group-level SPE across datasets. However, when evaluating individual differences, SPE indices derived from reaction time (RT) and efficiency exhibited relatively higher, compared to other SPE indices, but still unsatisfied split-half reliability (approximately 0.5). The reliability across multiple time points, as assessed by ICC2, RT, and efficiency, demonstrated moderate levels of test-retest reliability (close to 0.5). These findings revealed the presence of a reliability paradox in the context of SMT-based SPE assessment. We discussed the implications of how to enhance individual-level reliability using this paradigm for future study design., Competing Interests: Declarations. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Conflicts of Interest/Competing Interests: The authors declare no competing interests., (© 2024. The Psychonomic Society, Inc.)

The critical relevance and importance of considering religion and spirituality (R/S) in academic and public discourse on bioethical issues and in the illness experiences of patients and families is difficult to deny. Yet, little is known about the nature and scope of R/S education in graduate bioethics training. We therefore conducted a literature review and survey of bioethics programs in the USA and a content analysis of relevant syllabi of courses. In this article, we identify the core didactic components of existing offerings, characterize their curricular trends, and consider the implications of our findings. We propose a new critical humanist approach to the study of R/S in bioethics to both expand and enhance more established pedagogies., Competing Interests: Declarations. Conflict of interest: The authors have not disclosed any conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Paxlovid® (nirmatrelvir and ritonavir) is the only licensed oral antiviral for COVID-19. Ritonavir is a potent inhibitor of cytochrome P450 enzymes causing numerous drug-drug interactions (DDIs)., Aim: To describe the frequency, type, and severity of detected drug related problems (DRPs) associated with Paxlovid®., Method: This study involved a retrospective quantitative analysis including all patients prescribed Paxlovid® at a public hospital in Vienna, Austria. Data were collected from the patients' records by a clinical pharmacist. A customised, piloted data collection form was used. A sample of data was checked for consistency by an independent clinical pharmacist. Any DDI and severity classification was recorded using an established interaction checker tool. Dosage adjustments due to renal impairment were recorded., Results: One hundred twenty-two of 140 patients (87.1%) required interventions to prevent DRPs. Pharmacists' intervention at dispensing was needed in 63.6% (n = 89) of cases. In 3 (2.1%) patients, Paxlovid® was prescribed despite being contraindicated due to severe renal impairment. The most common were DDIs (n = 80; 57.1%). Renal impairment and DDIs were noted in 24.3% (n = 34) of cases. A total of 313 DDIs were recorded in 114 (81.4%) patients, with severe interactions in 24 (17%) patients., Conclusion: Pharmacists' involvement in prescribing highly interacting drugs such as Paxlovid® is essential to enhance patient safety., Competing Interests: Conflicts of interest: The authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The human defensins are a group of cationic antimicrobial peptides that range in size from 2 to 5 kDa and share a common structural motif of six disulphide-linked cysteines. Several naturally occurring human α- and β-defensins have been identified over the past two decades. They have a wide variety of antimicrobial effects, and their potential to avoid the development of resistance to antimicrobial treatment makes them attractive as therapeutic agents. Human defensins have recently been the focus of medical and molecular biology studies due to their promising application in medicine and the pharmaceutical industry. This work aims to provide a comprehensive summary of the current developments of human defensins, including their identification, categorization, molecular features, expression, modes of action, and potential application in medical settings. Current obstacles and future opportunities for using human defensins are also covered. Furthermore, we shed light on the potential of this class as an antiviral agent, particularly against SARS CoV-2, by providing an in silico-based investigation of their plausible mechanisms of action., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

The chemical behavior of mercury (Hg) and its interactions with naturally occurring ligands shape its environmental fate and impact. The neurotoxic properties of Hg are widely known and studied both in vitro and in vivo. However, there continues to be limited information on the influence of chelation with large organic ligands on the toxicity to marine macro-organisms. This work examined the effect of Hg complexed with various types of dissolved organic matter (DOM) on the mortality and hatching success of Artemia sp. nauplii under varying marine media conditions. The results confirmed both, an alleviating as well as additive, DOM-specific, effect on mortality. DOM coexposure resulted in a compound specific decreased or increased toxicity in comparison with single exposure in artificial seawater, with LC 50 values ranging from 2.11 to 62.89 µM. Hatching success under conditions of Hg exposure was almost two orders of magnitude more sensitive than toxicity in hatched individuals. Elevated DOM concentrations had no statistically significant impact on hatching success with computed EC 50 values ranging from 196 to 324 nM., Competing Interests: Declarations. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent to publish: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: In humans, 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) tumour-to-background contrast continues to increase long after a typical uptake period of 45 - 60 min. Similar studies have not been performed in mice and the static imaging time point for most studies is arbitrarily set at 30 - 60 min post-injection of [ 18 F]FDG. Ideally, static PET imaging should be performed after the initial period of rapid uptake but this period has not been defined in mice, with previous dynamic studies in mice being limited to 60 min. This study aimed to define the kinetics of [ 18 F]FDG biodistribution over periods of 3 - 4 h in different murine tumour models, both subcutaneous and autochthonous, and to further refine fasting and warming protocols used prior to imaging., Procedures: Dynamic [ 18 F]FDG PET-CT scans lasting 3 or 4 h were performed with C57BL/6 J and Balb/c nude mice bearing subcutaneous EL4 murine T-cell lymphoma and Colo205 human colorectal tumours, respectively, and with transgenic Eμ-Myc lymphoma mice. Prior to [ 18 F]FDG injection, four combinations of different animal handling conditions were used: warming for 1 h at 31 °C; maintenance at room temperature (20 - 24 °C), fasting for 6 - 10 h and a fed state., Results: Tumour mean standardised uptake value (SUV mean ) peaked at 147 ± 48 min post injection in subcutaneous tumours and 74 ± 31 min in autochthonous Eμ-Myc lymphomas. The tumour-to-blood ratio (TBR) peaked at 171 ± 57 and 83 ± 33 min in subcutaneous and autochthonous Eμ-Myc tumours, respectively. Fasting increased tumour [ 18 F]FDG uptake and suppressed myocardial uptake in EL4 tumour-bearing mice. There was a good correlation between tumour SUV mean and K i calculated using an input function (IDIF) derived from the inferior vena cava., Conclusions: Delayed static [ 18 F]FDG-PET imaging (> 60 min) in both autochthonous and subcutaneous tumours in improved tumour-to-background contrast and increased reproducibility., Competing Interests: Declarations. Ethical Approval: All applicable institutional and/or national guidelines for the care and use of animals were followed. Conflict of Interest: The authors declare that they have no conflict of interest., (© 2024. Crown.)

While early modern Spain may seem a world away, it is an extremely rich and relevant context for gaining a better understanding of the Rhetoric of Health, specifically the power of metaphor, in the related spheres of policy-making and public debate. It was a time and place in which the urban populace's physical well-being depended upon the fortunes of theatrical performances due to a system of alms for hospitals driven by ticket receipts. Anti-theatricalists argued that the immoral nature of theatrical performances made them spiritually and medically detrimental to society. Pro-theatricalists argued that plays were always a public good on balance because they raised much-needed funds for hospitals. Instead of producing a conflict between morality and public health, each side reinforced their connection until the two topics became nearly inseparable in the sphere of public debate. While pro-theatricalists mainly stayed with their arguments about funding hospitals, anti-theatricalists developed a new strategy of literalising the metaphor of theatre as a "plague of the republic" and arguing that immoral entertainment brought literal disease to the populace as a punishment from God. This exemplifies Stephen Pender's observation of how, in an early modern medical context, "Rhetoric as a way of perceiving probabilities and adjusting one's argument to the audience and circumstance offers a model of ethical action and interaction". This article is organised chronologically to track specific adjustments to a specific public-health debate that rely upon moral metaphors of medicine. Each side wrangled over these metaphors in an effort to break a deadlock in a public-health policy debate with entertainment, finance, and morality at its centre. By the end of the seventeenth century, anti-theatricalists finally found their best rhetorical weapon in the literalisation of the "plague of the republic" metaphor, but it only offered a short-term solution to banning theatre contingent upon the ebb and flow of epidemics. Simultaneously, the finance structure of funding hospitals began to erase the role of hospitals from the longstanding debate about the morality of public theatre. The case of early modern Spain provides valuable lessons about the power of metaphor in the Rhetoric of Healthcare that are still applicable today., (© 2024. The Author(s).)

Background: Repair of large incisional hernias is challenging, and the risks of postoperative complications have been associated with obesity, smoking, and diabetes. The present study was conducted to determine the impact of these risk factors on short and long-term outcomes following the repair with the peritoneal flap hernioplasty (PFH)., Methods: Three hundred twenty-seven patients undergoing PFH for incisional hernia repair were identified. Patient demographics and clinical data were recorded. Patients presenting signs of complications were assessed during a visit to the outpatient clinic. A multivariable regression analysis was performed to evaluate the association between BMI, smoking and diabetes, and postoperative complications., Results: The study included 157 males (48.0%) and 170 females (52.0%). Median BMI was 30.9 kg/m 2 . Diabetes was present in 13.8% of patients. 23.2% were active smokers. The recurrence rate was 2.4%. The odds ratios for postoperative complications were increased by 9% per BMI unit (P < 0.01), due predominantly to a rise in superficial wound infections (P < 0.01) and seroma production (P = 0.07). The adjusted odds ratio increased fourfold in patients with BMI > 40 kg/m 2 (P = 0.06)., Conclusion: Incisional hernia repair with the PFH technique is associated with a low risk of short and long-term complications. The risk is associated with obesity and significantly increased in patients with a BMI exceeding 40 kg/m 2 , where a fourfold increase was observed predominantly due to seroma and superficial wound infections. The recurrence rate was 2.4% and was unaltered across BMI categories. No association was established between smoking, diabetes, and the risk of all-cause complications., (© 2024. The Author(s).)

Background: While there is an accumulation of evidence that pharmacist prescribing is safe and effective, there is a lack of research on processes of implementation into practice, particularly for patients with complex clinical conditions such as chronic kidney disease (CKD)., Aim: The aim was to explore the facilitators and barriers to the implementation of pharmacist prescribing for patients with CKD in the United Kingdom (UK)., Method: Semi-structured interviews were conducted with UK Renal Pharmacy Group members who were independent prescribers. The Consolidated Framework for Implementation Research (CFIR) underpinned the interview schedule. Interviews were recorded, transcribed, and independently coded by two researchers. A thematic approach was used for analysis, with data generation continuing until saturation of themes. Ethical approval was granted., Results: Data saturation was achieved following 14 interviews. Most interviewees were female (n = 11), all had secondary care as their main practice setting, and were highly experienced prescribers with 8 having 11 or more years of prescribing practice. Interviewees were positive regarding the development of their prescribing practice. Facilitators and barriers emerged across all 5 of the CFIR domains. Key facilitators were aspects of inner setting (e.g., organisational support and communication) while key barriers were also related to inner setting, specifically the need for adequate structural and financial resources., Conclusion: This theory-based study has illuminated the facilitators and barriers for the implementation of pharmacist prescribing in CKD. There is a need to consider the resources required for implementation of prescribing practice at an early stage of planning and development., Competing Interests: Conflicts of interest Derek Stewart is the Editor-in-Chief of the International Journal of Clinical Pharmacy. He had no role in handling the manuscript, specifically the processes of editorial review, peer review and decision making., (© 2024. The Author(s).)

Although tissue stiffness is known to play an important role in aortic dilatation, the current guidelines for offering preventative surgery in patients with Marfan syndrome rely solely on the aortic diameter. In this systematic review and meta-analysis, we analyze and compare literature on in vivo aortic stiffness measures in Marfan patients. Our aim is to assess the potential of these measurements as early indicators of aortic dilatation. Following the PRISMA guidelines, we collected literature on diameter and three in vivo stiffness measures: Pulse wave velocity (PWV), β -stiffness index (SI) and distensibility, at five different aortic locations in patients with Marfan syndrome. Results were reviewed and compared against each other. For meta-analysis, an augmented dataset was created by combining data from the literature. Regression with respect to age and statistical comparisons were performed. Thirty articles reporting data from 1925 patients with Marfan and 836 patients without Marfan were reviewed. PWV was found to be higher in Marfan, but only in dilated aortas. Distensibility was found to be lower even in non-dilated aortas, and its decrease was associated with higher chances of developing aortic dilatation. β -SI was higher in Marfan patients and was positively correlated with the rate of aortic dilatation, emphasizing its role as a valuable indicator. In our meta-analysis, all stiffness measures showed a significant variation with age. Distensibility and β -stiffness index were different in Marfan patients at all locations, and the difference was more pronounced after accounting for age-related variation. From the literature, β -SI and distensibility emerge as the best predictors of future aortic dilatation. Our meta-analysis quantifies age-related changes in aortic stiffness and highlights the importance of accounting for age in comparing these measurements. Missing diameter values in the literature limited our analysis. Further investigation of criteria combining stiffness and diameter is recommended to better assist clinical decisions for prophylactic surgery., Competing Interests: Declarations Conflict of interest The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Fish diversity and water quality are vital indicators of the health of freshwater ecosystems, however these systems are increasingly threatened by environmental changes and anthropogenic activities. This investigation aimed to assess the fish diversity and evaluate the physicochemical parameters of water at Ghazi Swabi near Tarbela Dam, River Indus, Khyber Pakhtunkhwa, Pakistan, between March and June 2020. Monthly water samples were collected and analyzed for various physicochemical parameters such as temperature, dissolved oxygen (DO), total dissolved solids (TDS), pH, turbidity, salinity, and concentrations of heavy metals including lead (Pb), copper (Cu), cadmium (Cd), and mercury (Hg). Using various nets and traps the fish specimens were collected with the help of local fishermen. Morphometric and meristic analyses were conducted to identify the species, while systematic keys were used to remove misidentifications. A total of 110 fish specimens were collected, representing 7 species across 6 genera, 3 families, and 3 orders. The family Cyprinidae was the most abundant, with species including Puntius conchonius, Puntius waageni, Crossocheilus diplocheilus, Barilius modestus, and Aspidoparia morar. The Belonidae family was represented by Xenentodon cancila, and the Ambassidae family by Chanda nama. Physicochemical analysis showed that the water quality remained within permissible limits for aquatic life, however higher levels of certain heavy metals were detected, which may pose long-term risks. The study concluded that the fish diversity at Ghazi Swabi near Tarbela Dam reflects a moderately healthy ecosystem, the presence of heavy metals in the water raises concerns about future ecological health. Regular monitoring and mitigation efforts are recommended to preserve biodiversity and maintain water quality. The study suggests the need for sustainable management practices to protect freshwater ecosystems from anthropogenic impacts., Competing Interests: Declarations Ethics approval and consent to participate Not applicable.All authors have read, understood, and have complied as applicable with the statement on “Ethical responsibilities of authors” as found in the Instructions for Authors and are aware that with minor exceptions, no changes can be made to authorship once the paper is submitted. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Intelligence is a fundamental property for all life enabling an increased probability of survival and reproduction under wild circumstances. Kingsland and Taiz (2024) think that plants are not intelligent but seem unaware of the extensive literature about intelligence, memory, learning and chromatin topology in plants. Their views are consequently rejected. Their claim of fake quotations is shown to result from faulty reasoning and lack of understanding of practical biology. Their use of social media as scholarly evidence is unacceptable. Darwin's views on intelligence are described, and their pertinence to the adaptive responses of plants is discussed. Justifications for comments I have made concerning McClintock and her "thoughtful" cell, von Sachs writings as indicating purpose (teleonomy) to plant behaviour, Went and Thimann's allusions to plant intelligence and Bose legacy as the father of plant electrophysiology are described. These scientists were usually first in their field of knowledge, and their understanding was consequently deeper. The article finishes with a brief critical analysis of the 36 scientists who were used to condemn plant neurobiology as of no use. It is concluded that participants signed up to a false prospectus because contrary evidence was omitted., (© 2024. The Author(s).)

Evidence indicates that poly-victimization relates to greater victim impacts than single-type victimization. A separate body of research finds that victimization motivated by bias is associated with elevated harm. However, little empirical work has assessed whether youth who experience biased victimization are poly-victims, and studies have not sufficiently examined the potentially deleterious effects of experiencing both types of victimization. This study uses nationally representative data to examine the prevalence of school-based crime and bullying victimization among hate speech victims. I then assess the odds of experiencing fear and avoiding places at school across victimization types. The findings reveal that a considerable number of hate speech victims are also bullied and that experiencing any two types of victimization is associated with increased odds of fear and avoidance. These results highlight the importance of targeting biased victimization in anti-bullying programming., (© 2024 Springer Publishing Company.)

Forecasting mortality rates is crucial for evaluating life insurance company solvency, especially amid disruptions caused by phenomena like COVID-19. The Lee-Carter model is commonly employed in mortality modelling; however, extensions that can encompass count data with diverse distributions, such as the Generalized Autoregressive Score (GAS) model utilizing the COM-Poisson distribution, exhibit potential for enhancing time-to-event forecasting accuracy. Using mortality data from 29 countries, this research evaluates various distributions and determines that the COM-Poisson model surpasses the Poisson, binomial, and negative binomial distributions in forecasting mortality rates. The one-step forecasting capability of the GAS model offers distinct advantages, while the COM-Poisson distribution demonstrates enhanced flexibility and versatility by accommodating various distributions, including Poisson and negative binomial. Ultimately, the study determines that the COM-Poisson GAS model is an effective instrument for examining time series data on mortality rates, particularly when facing time-varying parameters and non-conventional data distributions., (© 2024. Crown.)

EMOKINE is a software package and dataset creation suite for emotional full-body movement research in experimental psychology, affective neuroscience, and computer vision. A computational framework, comprehensive instructions, a pilot dataset, observer ratings, and kinematic feature extraction code are provided to facilitate future dataset creations at scale. In addition, the EMOKINE framework outlines how complex sequences of movements may advance emotion research. Traditionally, often emotional-'action'-based stimuli are used in such research, like hand-waving or walking motions. Here instead, a pilot dataset is provided with short dance choreographies, repeated several times by a dancer who expressed different emotional intentions at each repetition: anger, contentment, fear, joy, neutrality, and sadness. The dataset was simultaneously filmed professionally, and recorded using XSENS® motion capture technology (17 sensors, 240 frames/second). Thirty-two statistics from 12 kinematic features were extracted offline, for the first time in one single dataset: speed, acceleration, angular speed, angular acceleration, limb contraction, distance to center of mass, quantity of motion, dimensionless jerk (integral), head angle (with regards to vertical axis and to back), and space (convex hull 2D and 3D). Average, median absolute deviation (MAD), and maximum value were computed as applicable. The EMOKINE software is appliable to other motion-capture systems and is openly available on the Zenodo Repository. Releases on GitHub include: (i) the code to extract the 32 statistics, (ii) a rigging plugin for Python for MVNX file-conversion to Blender format (MVNX=output file XSENS® system), and (iii) a Python-script-powered custom software to assist with blurring faces; latter two under GPLv3 licenses., (© 2024. The Author(s).)

Allergic disease is a major global health concern that imposes significant life-altering and economic burdens on affected individuals. However, there is still no cure. Polymer-based nanoparticles (NP) have shown the potential to induce antigen (Ag)-specific immune tolerance in various Th1/17 and Th2-mediated immune disorders including autoimmunity and allergy. Common methods by which Ags are associated with NPs are through surface conjugation or encapsulation. However, these Ag delivery strategies can be associated with several caveats that dampen their effectiveness such as uncontrolled Ag loading, a high Ag burst release, and an increased immune recognition profile. We previously developed Ag-polymer conjugate NPs (acNPs) to overcome those noted limitations, while allowing for controlled delivery of precise quantities of Ag to innate immune cells for Ag-specific CD4 T cell modulation. Here, we utilized ovalbumin (OVA) protein-poly(lactic-co-glycolic acid) (PLGA) conjugate NPs (acNP-OVA) to elucidate the impact of Ag loading on the induction of Th2 tolerance using a prophylactic and therapeutic OVA/ALUM-induced mouse model of allergic lung inflammation (ALI) in comparison to Ag-encapsulated PLGA NPs (NP(Ag)). We demonstrate that acNP-OVA formulations reduced OVA-specific IgE and inhibited Th2 cytokine secretions in an Ag loading-dependent manner when administered prophylactically. Administration of acNP-OVA to pre-sensitized mice did not affect OVA-specific IgE and Th2 cytokines tended to be reduced, however, there was no clear Ag loading dependency. acNP-OVA with medium-to-low Ag loadings were well tolerated, while formulations with high Ag loadings, including NP(Ag) resulted in anaphylaxis. Overall, our results clarify the relationship between Ag loading and Ag-specific IgE and Th2 cytokine responses in a murine model of ALI, which provides insight useful for future design of tolerogenic NP-based immunotherapies., (© 2024. Controlled Release Society.)

Background: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy., Methods: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS., Results: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07)., Conclusions: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality., (© 2024. The Author(s).)

Microplastics (MPs) are emerging and ubiquitous contaminants, known to accumulate in river sediments. In many developing nations, the absence of policies for managing plastic waste puts the inland river ecosystems at risk of excessive abundance of plastics and MPs. However, only limited studies have reported MPs in river environments in these countries. The current study therefore examined the abundance and nature of MPs and potentially toxic elements (PTEs) in the sediments of the Odo-Ona and Ogun Rivers in Southwest Nigeria. MPs were extracted from the sediments using the density separation method and categorized according to their size, colour and shapes. The range of MP abundances found in the Ogun River sediments was 66.6 ± 12.2 to 311 ± 20.8 particles/kg, while that of the Odo-Ona River ranged from 133 ± 50 to 433 ± 100 particles/kg. The MPs polymer analyses revealed the presence of polyethylene (PE), polypropylene (PP) and polyamide (PA) particles in the sediments. PE was most abundant in the two rivers, constituting 72.8% and 59.7% of MPs (with 0.5 - 5 mm size), recovered from the Odo-Ona and Ogun Rivers, respectively. High concentrations of Cr and Pb with ranges of 10.3 - 48.3 and 10.1 - 211 mg/kg, respectively, were detected in the sediments and were associated with anthropogenic effects. This study reveals the impact of indiscriminate waste dumping on the water bodies, and calls for strict enforcement of environmental laws in the country., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: The aim of this study is to explore the feasibility of using machine learning approaches to objectively differentiate the mobilization patterns, measured via accelerometer sensors, of patients pre- and post-intervention., Methods: The intervention tested the implementation of a Frailty Care Bundle to improve mobilization, nutrition and cognition in older orthopedic patients. The study recruited 120 participants, a sub-group analysis was undertaken on 113 patients with accelerometer data (57 pre-intervention and 56 post-intervention), the median age was 78 years and the majority were female. Physical activity data from an ankle-worn accelerometer (StepWatch 4) was collected for each patient during their hospital stay. These data contained daily aggregated gait variables. Data preprocessing included the standardization of step counts and feature computation. Subsequently, a binary classification model was trained. A systematic hyperparameter optimization approach was applied, and feature selection was performed. Two classifier models, logistic regression and Random Forest, were investigated and Shapley values were used to explain model predictions., Results: The Random Forest classifier demonstrated an average balanced accuracy of 82.3% (± 1.7%) during training and 74.7% (± 8.2%) for the test set. In comparison, the logistic regression classifier achieved a training accuracy of 79.7% (± 1.9%) and a test accuracy of 77.6% (± 5.5%). The logistic regression model demonstrated less overfitting compared to the Random Forest model and better performance on the hold-out test set. Stride length was consistently chosen as a key feature in all iterations for both models, along with features related to stride velocity, gait speed, and Lyapunov exponent, indicating their significance in the classification., Conclusion: The best performing classifier was able to distinguish between patients pre- and post-intervention with greater than 75% accuracy. The intervention showed a correlation with higher gait speed and reduced stride length. However, the question of whether these alterations are part of an adaptive process that leads to improved outcomes over time remains., (© 2024. The Author(s).)

Introduction: Venous thromboembolisms (VTEs), including deep vein thrombosis (DVT) and pulmonary embolisms (PE), are common after total knee (TKA) and hip arthroplasty (THA). Recent studies suggest that aspirin effectively prevents VTE following major orthopaedic surgery. This meta-analysis compares randomised controlled trials (RCTs) evaluating aspirin versus direct oral anticoagulants (DOACs) for VTE prevention after primary THA and TKA., Methods: We included RCTs from 2017 to 2023 that looked at aspirin versus DOACs for VTE prophylaxis in primary THA and TKA. A search strategy was conducted which used Boolean operators and MESH terms. Primary outcomes included VTE rates, symptomatic, asymptomatic DVT and PE. Secondary outcomes were mortality and bleeding complications. Statistical analysis was performed using REVMAN software. An odds ratio with a 95% confidence interval was generated for the pooled studies. Heterogeneity was assessed using the I 2 variable, and publication bias was evaluated with a funnel plot., Results: Seven RCTs with 3967 patients were included for analysis. Rivaroxaban 10 mg OD was compared to varying doses of aspirin (81-300 mg). There were no significant differences between the groups in the incidence of VTE (OR: 1.21, 95% CI: 0.72-2.01), PE (OR: 1.01, 95% CI: 0.39-2.61), asymptomatic DVT (OR: 1.39, 95% CI: 0.64-3.00), suspected DVT (OR: 1.13, 95% CI: 0.49-2.61) and major bleeding (OR: 0.84, 95% CI: 0.55-1.27)., Discussion: Aspirin is as effective as rivaroxaban for primary thromboprophylaxis post-THA and TKA, without increased incidence of complications. Further research is needed to determine the optimal dosing regimen of aspirin and its long-term efficacy in preventing VTE., Level of Evidence: Level I., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior., Methods: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC., Results: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P  =  0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size., Conclusions: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies., (© 2024. Society of Surgical Oncology.)

Introduction: The emergence of the COVID-19 pandemic has served as a call for enhanced global cooperation and a more robust pandemic preparedness and response framework. As a result of this pressing demand, dialogues were initiated to establish a pandemic treaty designed to foster a synchronized global strategy for addressing forthcoming health emergencies. In this review, we discussed the main obstacles to this treaty., Results: Among several challenges facing the pandemic treaty, we highlighted (1) global cooperation and political will, (2) equity in access to resources and treatments, (3) sustainable financing, (4) compliance and enforcement mechanisms, (5) sovereignty concerns, and (6) data sharing and transparency., Conclusion: Navigating the hurdles facing the development of the pandemic treaty requires concerted efforts, diplomatic finesse, and a shared commitment to global solidarity. Addressing challenges in global cooperation, equitable access, transparency, compliance, financing, and sovereignty is essential for forging a comprehensive and effective framework for pandemic preparedness and response on the global stage., (© 2024. The Author(s).)

The ring-like peripheral light-harvesting complex 2 (LH2) expressed by many phototrophic purple bacteria is a popular model system in biological light-harvesting research due to its robustness, small size, and known crystal structure. Furthermore, the availability of structural variants with distinct electronic structures and optical properties has made this group of light harvesters an attractive testing ground for studies of structure-function relationships in biological systems. LH2 is one of several pigment-protein complexes for which a link between functionality and effects such as excitonic coherence and vibronic coupling has been proposed. While a direct connection has not yet been demonstrated, many such interactions are highly sensitive to resonance conditions, and a dependence of intra-complex dynamics on detailed electronic structure might be expected. To gauge the sensitivity of energy-level structure and relaxation dynamics to naturally occurring structural changes, we compare the photo-induced dynamics in two structurally distinct LH2 variants. Using polarization-controlled 2D electronic spectroscopy at cryogenic temperatures, we directly access information on dynamic and static disorder in the complexes. The simultaneous optimal spectral and temporal resolution of these experiments further allows us to characterize the ultrafast energy relaxation, including exciton transport within the complexes. Despite the variations in PPC molecular structure manifesting as clear differences in electronic structure and disorder, the energy-transport and-relaxation dynamics remain remarkably similar. This indicates that the light-harvesting functionality of purple bacteria within a single LH2 complex is highly robust to structural perturbations and likely does not rely on finely tuned electronic- or electron-vibrational resonance conditions., (© 2024. The Author(s).)

This study investigated the effects of dietary supplements, citrus (CTS) and cucumber (CMB), on the jejunum and cecum microbiota of 14- and 28-days old broiler chickens to evaluate their impact on the gut health and assess their role as alternatives to antibiotic growth promoters (ABGPs). 16SrRNA gene sequencing revealed the overall bacterial microbiota composition was significantly affected by the gut site (p?

Background: Early reports suggested that previous abdominal surgery was a relative contraindication to laparoscopic cholecystectomy (LC) on account of difficulty and potential access complications. This study analyses different types/systems of previous surgery and locations of scars and how they affect access difficulties. As modified access techniques to minimise risk of complications are under-reported the study details and evaluates them., Method: Prospectively collected data from consecutive LC and common bile duct explorations (LCBDE) performed by a single surgeon over 30 years was analysed. Previous abdominal surgery was documented and peri-operative outcomes were compared with patients who had no previous surgery using Chi-squared analysis., Results: Of 5916 LC and LCBDE, 1846 patients (31.2%) had previous abdominal surgery. The median age was 60 years. Those with previous surgery required more frequent duodenal (RR 1.07; p = 0.023), hepatic flexure (RR 1.11; p = 0.043) and distal adhesiolysis (RR 3.57; p < 0.001) and had more access related bowel injuries (0.4% vs. 0.0%; p < 0.001). Previous upper gastrointestinal and biliary surgery had the highest rates of adhesiolysis (76.3%), difficult cystic pedicles (58.8%), fundus-first approach (7.2%), difficulty grades (64.9% Grades 3-5) and utilisation of abdominal drains (71.1%). Previous open surgery resulted in longer operative time compared to previous laparoscopic procedures (65vs.55 min; p < 0.001), increased difficulty of pedicle dissection (42.4% vs. 36.0%; p < 0.05) and required more duodenal, hepatic flexure and distant adhesiolysis (p < 0.05) and fundus-first dissection (4% vs 2%; p < 0.05). Epigastric and supraumbilical access and access through umbilical and other hernias were used in 163 patients (8.8%) with no bowel complications., Conclusion: The risks of access and adhesiolysis in patients with previous abdominal scars undergoing biliary surgery are dependent on the nature of previous surgery. Previous open, upper gastrointestinal and biliary surgery carried the most significant risks. Modified access techniques can be adopted to safely mitigate these risks., (© 2024. The Author(s).)

Background: Independent prescribing (IP) has not been extensively investigated in community pharmacy (CP). Normalization process theory (NPT) constructs help explain how interventions are integrated into practice and include: 'coherence' (understanding), 'cognitive participation' (what promotes engagement), 'collective action' (integration with existing systems), and 'reflexive monitoring' (evaluation)., Aim: To use NPT to investigate the integration of pharmacist IP in CP., Method: NHS Scotland Pharmacy First Plus (PFP) is a community pharmacy IP service. Questionnaire items were developed using the NPT derived Normalisation MeAsure Development (NoMAD) tool for an online survey of all PFP IP pharmacists. Demographic data were analysed descriptively and scale scores (calculated from item scores for the 4 NPT constructs) were used for inferential analysis., Results: There was a 73% (88/120) response rate. Greater than 90% 'strongly agreed'/'agreed' to NoMAD items relating to most NPT constructs. However, responses to 'collective action' items were diverse with more participants answering 'neither agree nor disagree' or 'disagree'. A statistically significant difference in NPT construct scale scores with significant p-values (ranging from p < 0.001 to p = 0.033) was shown on all the NPT constructs for the variable 'On average, how often do you consult with patients under the PFP service?'., Conclusion: This theory-based work offers perspectives on IP integration within CP. Despite its geographic focus this work offers insights relevant to wider contexts on IP integration. It shows 'collective action' focused 'organisation' and 'group process' challenges with a need for further work on staff training, resource availability and utilisation, working relationships, communication and management., (© 2024. The Author(s).)

The prevalence of informal caregiving is increasing as populations across the world age. Caregiving has been found to be associated with poor mental health outcomes including depressive symptoms. The purpose of this study is to examine the mean trajectory of depressive symptomatology in older caregivers in a large European sample over an eight-year period, the effects of time-varying and time-invariant covariates on this trajectory, and the mean trajectory of depressive symptomatology according to pattern of caregiving. The results suggest that depressive symptoms in the full sample of caregivers follow a nonlinear trajectory characterized by an initial decrease which decelerates over time. Caregiver status and depressive symptoms were significantly associated such that depressive symptoms increased as a function of caregiver status. The trajectory in caregivers who report intermittent or consecutive occasions of caregiving remained stable over time. Significant associations were found between sociodemographic, health and caregiving characteristics and the initial levels and rates of change of these trajectories. While these results point to the resilience of caregivers, they also highlight the factors that are related to caregivers' adaptation over time. This can help in identifying individuals who may require greater supports and, in turn, ensuring that caregivers preserve their well-being., (© 2024. The Author(s).)

This paper reconsiders several results of historical and current importance to nonparametric estimation of the survival distribution for failure in the presence of right-censored observation times, demonstrating in particular how Volterra integral equations help inter-connect the resulting estimators. The paper begins by considering Efron's self-consistency equation, introduced in a seminal 1967 Berkeley symposium paper. Novel insights provided in the current work include the observations that (i) the self-consistency equation leads directly to an anticipating Volterra integral equation whose solution is given by a product-limit estimator for the censoring survival function; (ii) a definition used in this argument immediately establishes the familiar product-limit estimator for the failure survival function; (iii) the usual Volterra integral equation for the product-limit estimator of the failure survival function leads to an immediate and simple proof that it can be represented as an inverse probability of censoring weighted estimator; (iv) a simple identity characterizes the relationship between natural inverse probability of censoring weighted estimators for the survival and distribution functions of failure; (v) the resulting inverse probability of censoring weighted estimators, attributed to a highly influential 1992 paper of Robins and Rotnitzky, were implicitly introduced in Efron's 1967 paper in its development of the redistribution-to-the-right algorithm. All results developed herein allow for ties between failure and/or censored observations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Extrachromosomal DNA (ecDNA) are circular regions of DNA that are found in many cancers. They are an important means of oncogene amplification, and correlate with treatment resistance and poor prognosis. Consequently, there is great interest in exploring and targeting ecDNA vulnerabilities as potential new therapeutic targets for cancer treatment. However, the biological significance of ecDNA and their associated regulatory control remains unclear. Light microscopy has been a central tool in the identification and characterisation of ecDNA. In this review we describe the different cellular models available to study ecDNA, and the imaging tools used to characterise ecDNA and their regulation. The insights gained from quantitative imaging are discussed in comparison with genome sequencing and computational approaches. We suggest that there is a crucial need for ongoing innovation using imaging if we are to achieve a full understanding of the dynamic regulation and organisation of ecDNA and their role in tumourigenesis., (© 2024. The Author(s).)

Purpose: This study aims to describe the phenomenon of unperceived pregnancy followed by neonaticide with a focus on the lack of awareness of reproductive potential in an Austrian sample., Methods: An explorative comparative study of neonaticide cases with single and repeat perpetrators was conducted using nationwide register-based data from 1995 to 2017. A total number of 55 cases out of 66 were included in the analysis. A standardized coding sheet was used and calculations were performed., Results: 48 women gave birth to 101 children, of which 55 were killed, 23 children lived out of home care and 23 lived with the perpetrator We found a higher fertility rate in both neonaticide perpetrators in the single (1,9) and the repeat group (4,25) in comparison to the general population (1,4). The use of contraception was only 31% among neonaticide perpetrators, deviating substantially from the general Austrian population age group (16-29yrs) which used contraception in 91%. The neonaticide perpetrators used an effective contraception method (pearl-index < 4) in only 2%, whereas 20% of the general population did so. The number of unperceived pregnancies was high in both groups (50/55) 91%., Conclusion: Future case reports and forensic evaluations should take reproductive behavior into account, as it may offer valuable insights into the events leading up to neonaticide. Our findings suggest that denial of reproductive potential often precedes unperceived pregnancies. In the Austrian cohort, women who experienced unperceived pregnancies resulting in unassisted births and subsequent neonaticide showed a low prevalence of contraceptive use. This is particularly noteworthy given that the primary motive for neonaticide is unwanted pregnancy., (© 2024. The Author(s).)