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Genome editing (GE) technology holds significant promise for advancements in crop development and medical applications. However, public acceptance of GE in Japan remains uncertain. This study aimed to examine how knowledge impacts public acceptance of GE technology, focusing on differences across diffusion stages and application purposes. Using ordinary least squares regression on repeated survey data collected from 2018 to 2023 in Japan ( n  = 6,234), we investigated the influence of knowledge on support for GE in consumer benefits, producer benefits, and medical technology. Our findings revealed that the effect of knowledge on technology acceptance has strengthened over time. Consumers with greater knowledge of GE are increasingly supportive of its advancement, emphasizing the growing importance of information as the technology becomes more widespread. This research highlights the role of transparent policy discussions in fostering public trust and support, thereby promoting the successful integration of new technologies into society.

For many biopharmaceuticals, subcutaneous (sc) administration is the only viable route. However, there is no in vitro method available accurately predicting the absorption profiles of subcutaneously injected pharmaceuticals. In this work, we show that a recently developed microfluidics method for interaction studies (MIS) has the potential to be useful in this respect. The method utilises the responsiveness of polyelectrolyte microgel networks to oppositely charged molecules as a means to monitor the interaction between peptides and hyaluronic acid (HA), a major constituent of the subcutaneous extracellular matrix. We use the method to determine parameters describing the strength of interaction between peptide and HA as well as the peptide's aggregation tendency and transport properties in HA networks. The results from MIS studies of the peptide drugs exenatide, pramlintide, vancomycin, polymyxin B, lanreotide, MEDI7219 and AZD2820 are compared with results from measurements with the commercially available SCISSOR system and in vivo absorption and bioavailability data from the literature. We show that both MIS and SCISSOR reveal differences in the peptides' diffusivity and tendency to aggregate in the presence of HA. We show that MIS is particularly good at discriminating between peptides forming aggregates stabilised by non-electrostatic forces in the presence of HA, and peptides forming complexes stabilised by electrostatic interactions with HA. The method provides two parameters that can be used to quantify the peptides' aggregation tendency, the one describing the peptide packing density in complexes with HA and the other the apparent diffusivity upon release in a medium of physiological ionic strength and pH. The order of the peptides when ranked by increasing binding strength at pH 7.4 determined with MIS is shown to be in agreement with the order when ranked by the apparent 1st order absorption rate constant (k a ) after sc administration in humans: lanreotide (Autogel) < exenatide (IRF) < AZD2820 < pramlintide < lanreotide (IRF) (IRF: Immediate release formulation). A correlation is found between the 1st order release rate constant determined with SCISSOR and k a for lanreotide (Autogel), exenatide and AZD2820. A mechanism relating the magnitude of k a to the peptides' charge is proposed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study examined the role of waste management authorities in promoting public awareness of municipal solid waste management (MSWM) through the lens of the expansion diffusion theory (EDT). EDT emphasizes the spread of new ideas and practices within a society through various communication channels and distinct individuals within each system. We employed a mixed-method approach using 116 survey responses from Lagos residents and five semi-structured in-depth interviews. Our findings reveal the need for a more structured approach to create public awareness of MSWM, considering the distinct groups of residents in Lagos and their responses to innovation and knowledge diffusion. We propose four pillars on which waste management authorities in developing countries can sustain their MSWM awareness campaigns, as well as an awareness campaign strategy flowchart. Our findings add to the expanding body of research on public awareness and participation in MSWM, emphasizing the critical role that waste management authorities can play in fostering sustainable waste management awareness and practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In recent years, "black swan" events have increasingly occurred across climate, epidemics, geopolitics, and economics, leading to a gradual coupling of different types of risk. Different from isolated shocks as a single type of risk affecting a specific industry, a nexus of risks allows one risk area to quickly relate to others, resulting in more catastrophic impacts. Utilizing an integrated framework, we investigate the contagion effects among climate policy uncertainty, the infectious disease equity market volatility tracker, geopolitical risk, and economic policy uncertainty using volatility, skewness, and kurtosis as risk measures. The results indicate that: (1) The contagion effect of different types of risk increases with higher order risk measures, suggesting that more extreme events are more likely to be contagious across domains. (2) Approximately two-thirds of risk contagion occurs contemporaneously, while about one-third occurs with a lag, indicating that risk contagion combines both immediacy and continuity. (3) Risk contagion exhibits significant time-varying and heterogeneous characteristics. Our study elucidates the inherent contagion characteristics between different types of risk, transforming the understanding of risk from a one-dimensional to a multidimensional perspective. This underscores that risk management should not be confined to a single domain; it is crucial to consider the potential impacts of risks from other industries on one's own., (© 2024 Society for Risk Analysis.)

Objective: Few epidemiological studies are reported in the published literature on the incidence or prevalence of antiphospholipid syndrome (APS), and available results are heterogeneous. This study aimed to estimate the incidence and prevalence of APS in the USA, overall and by APS subtype., Design: A retrospective analysis of APS disease incidence and a cross-sectional analysis of disease prevalence., Setting: Merative MarketScan Commercial Claims and Encounters Database, and the Medicare Supplemental and Coordination of Benefits Database., Participants: All individuals with claims for at least two antiphospholipid antibody tests undertaken at least 12 weeks apart and a diagnosis claim for APS as a primary or secondary diagnosis on or after the second antibody test, during the period 1 January 2016 to 31 December 2019., Main Outcome Measures: Annual incidence and prevalence of APS and APS subtypes., Results: In total, 1708 cases of APS were identified during the study period (2016-2019), of which 83% were women. The overall annual standardised incidence rate of APS per 100 000 person-years increased slightly over the study period, from 2.31 in 2016 to 2.71 in 2019. In 2019, the estimated annual prevalence of APS per 100 000 persons was 10.42 per 100 000 persons (95% CI 9.96-10.90). Based on this and US census data, we have estimated that 34 000 persons in the USA were affected by APS in 2019., Conclusions: These data add to the estimates of prevalence and incidence of APS in the literature, all of which have different strengths and limitations of the different data sources and case ascertainment methods., Competing Interests: Competing interests: MK, PZ and AJ are contractors employed by UCB. PM, MS and AS are employees and stockholders of UCB., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

With the decrease in fertility rate and the extension of life expectancy, China's ageing degree is deepening, and there is a decrease in the number of labor force individuals, leading to an increase in the burden of old-age care and constraining economic growth. The improvement of human capital can promote economic growth. Research is rquired to determine whether factors such as the teacher-student ratio (quality of education) and the average number of years of schooling (quantity of education) can help alleviate the negative impacts of ageing. The findings demonstrate that education, both in terms of quantity and quality, can successfully reduce the detrimental consequences of ageing. The threshold effect model's findings indicate that both the amount and quality of education can be more effective in reducing the negative impacts of ageing when average years of education surpass 10.87 years and the teacher-student ratio hits 7.80 (780 instructors per 1000 pupils). The results of heterogeneity analysis reveal that both the quantity and quality of education could potentially mitigate the negative effects of ageing in the eastern and western regions, although these factors do not seem to have the same effect in the central region. In the northern and southern regions, it is found that while the quantity of education can help alleviate the negative effects of ageing, the quality of education is effective only in the southern region and not in the northern region. Therefore, one potential strategy to counteract the adverse effects of ageing with a declining number of children is to increase the teacher-student ratio and extend the duration of free education., Competing Interests: The authors declare no conflicts of interest., (Copyright: © 2024 Meng, Wen. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Renin-angiotensin-aldosterone system inhibitors (RAASi) are foundational in the management of heart failure (HF) and chronic kidney disease (CKD) but increase the risk of hyperkalaemia. To facilitate continuation of RAASi therapy, guidelines suggest managing hyperkalaemia using newer potassium binders such as sodium zirconium cyclosilicate (SZC). This observational study describes the likelihood of continued RAASi therapy by duration of SZC treatment., Methods: The study population included non-dialysis-dependent adults diagnosed with HF and/or CKD who initiated outpatient SZC treatment while receiving RAASi therapy. Patients were identified using healthcare registers and claims data from the United States, Japan and Spain. SZC treatment duration was described using the Kaplan-Meier method. Hernán's clone-censor-weight (CCW) approach, using principles of trial emulation, was applied to evaluate the likelihood of continued RAASi therapy at specific time points by distinct SZC treatment durations, using a weighted Kaplan-Meier method and Z-tests., Results: The study included 7980 patients, from the United States (n = 4849), Japan (n = 2759) and Spain (n = 372). Across the three countries, mean patient age was 73.1-75.0 years, 53.2%-66.4% of patients were male, 39.0%-75.0% had HF and 76.9%-95.3% had CKD. Between Days 30 and 120, the percentage of patients remaining on SZC treatment decreased from 36.5% to 12.8% in the United States, from 63.8% to 33.7% in Japan, and from 81.9% to 65.0% in Spain. In the United States, patients who continued SZC treatment beyond 30 days had a higher likelihood of continuing RAASi therapy for up to 90 days (P < 0.001), and continuing SZC treatment beyond 60 days was superior for continuing RAASi therapy for up to 6 months (P < 0.001), versus earlier SZC discontinuation. At 120 days, the likelihood of remaining on RAASi therapy was 69%-70% for SZC treatment durations exceeding 60 days, versus 59% for shorter durations (1-30 days) (P < 0.001). Similar patterns were observed in Japan. At 120 days, the likelihood of remaining on RAASi therapy was 86%-87% for SZC treatment durations exceeding 90 days, versus 82% for shorter SZC treatment durations (1-30 days) (P < 0.05). The CCW analyses were not deemed feasible in the Spanish dataset due to the smaller initial sample size and few patients having a relatively short SZC treatment duration., Conclusions: Patients with longer SZC treatment experience sustained protection against RAASi discontinuation, and the risk of RAASi discontinuation resumes once SZC is discontinued., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Miscarriage is a common experience, affecting 15% of recognized pregnancies, but societal ignorance and taboos often downplay the mental distress and personal impact following a miscarriage. Emerging stories on social media in which women express their miscarriage grief are breaking such taboos. Research in the area of online health communities is increasingly focused on studying how people share their health experiences on social media. However, a clear understanding on the social support involved in this type of sharing of health experiences is lacking., Objective: This study explored the use of Instagram in sharing miscarriage experiences, guided by the following research question: How is social community support given to women who share their miscarriage experiences on social media? Considering that social media is increasingly used as a source of social support, in this study, we chose Instagram as the social media platform. The purpose of this research was to create a better understanding of how social media provides support in expressing personal miscarriage experiences and how people engage with such posts., Methods: This study used a qualitative inductive research method in which a phenomenological strategy and thematic analysis were followed to create a comprehensive understanding of the social community support phenomenon. The dataset was established from a sample of 258 Instagram posts and 736 comments collected over a period of 6 months after initial posts and from 6 different women. These data were categorized and clustered through a thematic analysis., Results: Three themes were identified: (1) storytelling of emotional turmoil and grief after miscarriage, (2) sharing positivity amidst miscarriage grief, and (3) mentioning personal medical information about miscarriage. Theme 1 represents the emotional experience of women who have had a miscarriage. It encompasses the initial posts that included miscarriage storytelling that express deep grief and mental distress and the emotional impact on both the posters and the commenters. Theme 2 highlights the importance of finding moments of joy and positivity in the midst of mental distress and pain. The posts shared with the online community convey a sense of moving forward and a refusal to let grief become the defining aspect of one's life. Theme 3 focuses on sharing medical and practical advice. This theme includes posts and comments about medications, in vitro fertilization procedures, hospital experiences, and personal physical symptoms., Conclusions: As an overarching theme for this social support phenomenon, we introduce the term communal load sharing to describe the therapeutic role of social media in helping women cope with miscarriage by providing a platform for sharing similar experiences, breaking social taboos, and fostering load sharing., (©Julia Dubbelman, Jonelle Ooms, Laura Havgry, Lianne Simonse. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 10.12.2024.)

Research funding systems fundamentally influence how science operates. This paper aims to analyze the allocation of competitive research funding from different perspectives: How reliable are decision processes for funding? What are the economic costs of competitive funding? How does competition for funds affect doing risky research? How do competitive funding environments affect scientists themselves, and which ethical issues must be considered? We attempt to identify gaps in our knowledge of research funding systems; we propose recommendations for policymakers and funding agencies, including empirical experiments of decision processes and the collection of data on these processes. With our recommendations, we hope to contribute to developing improved ways of organizing research funding., Competing Interests: Competing interests statement:The authors declare no competing interest.

In-depth exploration of the coupling relationship between agricultural emission reduction and carbon sequestration (ERCS) and food security provides an important basis for promoting sustainable low-carbon development in agriculture. This research investigates the coupling mechanisms and the current state of coordinated development of agricultural ERCS and food security using provincial panel data from 2001 to 2022 in China. The agricultural ERCS level shows an upward trend, with higher levels in the north and lower in the south; externalities are positive in the north but negative in the south. Significant dynamic interactions and spatial correlations between the agricultural ERCS and food security exist, with a local spatial agglomeration pattern of "north-south opposition". Areas of high-high agglomeration are mainly concentrated in the north, while low-low agglomeration areas are primarily in the south. High-high agglomeration areas drive growth in transitional and low-growth areas through diffusion effects. The average coupling coordination degree of provinces increased from 0.432 to 0.473, indicating more coordinated development, and with a decreasing polarization trend. The spatial distributions of the coupling coordination degree and the relative development index are higher in the north and lower in the south, with many areas showing high adjustment, low adjustment, and high antagonism, particularly in the south where the number of high antagonistic areas has decreased. Implementing differentiated development strategies between the north and the south, using spatial agglomeration characteristics to optimize regional policies, focusing on the diffusion effects of high-coupling coordination areas to drive the development of low-growth and transitional areas, and enhancing the lagged terms can promote sustainable coordinated agricultural development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: To explore the prevalence of vitamin C deficiency, 'undetectable' vitamin C status, and scurvy features, in adult hospitalised patients with protein-energy malnutrition diagnosed using validated malnutrition screening and assessment tools commonly used in clinical practice., Methods: This study included adult inpatients from four acute hospitals within a single Australian tertiary health service, over a 3.5-year period. A medical file review activity retrospectively determined malnutrition risk and diagnosis, via Malnutrition Screening Tool, Malnutrition Universal Screening Tool, Subjective Global Assessment and Global Leadership Initiative on Malnutrition criteria. Prevalence of vitamin C deficiency and scurvy features was examined in adult patients with plasma vitamin C levels <11.4 μmol/L and <5 μmol/L ('undetectable'), respectively., Results: In the final cohort (n = 364), prevalence of vitamin C deficiency was 30.2%. Malnutrition was present in 76.1% and 79.8% of patients via Subjective Global Assessment (n = 310) and Global Leadership Initiative on Malnutrition criteria (n = 342) respectively. Patients with high nutrition risk and those diagnosed with severe malnutrition had the highest prevalence of vitamin C deficiency, reported as 32.8% for malnutrition detected via Malnutrition Screening Tool (n = 244), 32.9% via Malnutrition Universal Screening Tool (n = 222), 35.8% via Subjective Global Assessment (n = 106), and 34.2% via Global Leadership Initiative on Malnutrition (n = 152). Scurvy features were associated with severe malnutrition in patients with 'undetectable' vitamin C status., Conclusions: Severely malnourished adult hospital patients have a high prevalence of vitamin C deficiency, and scurvy features in those with 'undetectable' vitamin C status. Leveraging existing malnutrition screening and assessment practices may support early identification of patients with vitamin C deficiency during hospitalisation., (© 2024 Dietitians Australia.)

Influenza viruses cause 3-5 million severe cases and 300,000-600,000 deaths worldwide. Most of the disease burden is in Low- and Middle-Income Countries (LMICs) owing to factors such as high population density, infrastructure challenges, poor quality healthcare, lack of consistent recommendations, less prioritization of all high-risk groups, and prevalent use of trivalent influenza vaccines. Although influenza vaccines are effective in reducing the annual influenza disease burden, existing vaccines have several limitations. In this narrative review, we address the unmet needs of existing influenza vaccines in LMICs in Africa, Asia Pacific, Latin America and the Middle East and discuss the characteristics of novel vaccines in clinical development. We also describe features of a successful vaccination program that LMICs could emulate to improve their current vaccination coverage and reduce the public health burden of influenza., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

The Social Systems Citations Theory (SSCT) is the most recent theory of citations integrating previous theories. It focuses on communications in science that are formally manifested as publications and citations in scientific communication networks. These networks can be observed and empirically studied by using science maps. Science maps typically visualize networks of communication elements such as key words, cited references, and subject areas. In this study, a procedure to create global overlay maps using OpenAlex is proposed. It is an important advantage of OpenAlex publication and citation data that they are freely available. Overlay maps visualize how the overlaid data (e.g., research of an institution) are positioned in the whole science system (the base map). Six different base maps are provided to the user for their own applications. Using one of these base maps, example overlay maps for two individuals (the authors of this paper) and four research institutions are shown and discussed. A method for normalizing the overlay data is also proposed that can be used for the comparison of two different overlaid units. Overlay maps using raw overlay data display general concepts more pronounced than specific concepts. It is the other way around with their counterparts using normalized overlay data. Advantages and limitations of the proposed overlay approach based on OpenAlex are discussed., Competing Interests: “Both authors currently serve as academic editors for PLOS ONE. This does not alter our adherence to PLOS ONE policies on sharing data and materials.”, (Copyright: © 2024 Haunschild, Bornmann. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study reevaluates criticism of the Korean government's R&D investment strategy, which was considered an 'R&D cartel' and was cited as a reason for the Korean government's R&D cuts in 2023, through an advanced framework of quantum game theory. By modeling the interaction between the government and researchers as a quantum information strategy game, it redefines the dynamics of R&D investment as a quantum game involving two key players: the R&D manager (Alice) and the research performer (Bob). This quantum game, akin to the Prisoner's Dilemma but focused on responsibility and sincerity, allows for the exploration of strategic complexities and decision-making dynamics not possible in classical models. It introduces quantum entanglement and superposition as innovative strategies to shift the paradigm of R&D investment, suggesting that terms like 'R&D bureaucracy' and 'R&D monopoly' more accurately describe the moral hazards in this sector than 'R&D cartel'. Through simulations, the paper demonstrates how quantum strategies can significantly alter outcomes, providing fresh insights and policy alternatives for R&D innovation. This research not only challenges conventional investment frameworks but also proposes a novel approach for achieving Pareto optimal outcomes in government R&D investments, emphasizing the transformative potential of quantum game theory in strategic decision-making and policy development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Won et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Although primary care is central to healthcare provision, inconsistent methods and data sources mean that relatively little is known about long-term trends in general practice consultation rates. We aimed to explore long-term trends in English general practice consultation rates using two electronic health records databases, Clinical Practice Research Datalink Gold and Aurum, from 1995 to 2021., Methods: Consultations were identified and classified using a set of rules and code lists. Consultation rates were calculated as the ratio of the count of consultations and the registration duration. We used negative binomial regression to model the relationship between the number of consultations and the patient's age, sex and year from each database. These models are then used to estimate annual crude consultation rates for England., Results: The number of general practices in the Gold database decreased from 346 (1995) to 41 (2021), while in Aurum, it increased from 555 (1995) to 1347 (2021). In Gold, the average number of consultations per person-year increased from 2.91 in 1995 to 5.12 in 2012, then fell to 4.59 in 2019 and to 4.12 in 2021. In Aurum, average consultations per person-year rose from 2.17 (1995) to 4.89 (2012), then fell to 4.76 (2019) and rose again to 5.40 (2021). Half of the total increase in consultations from Aurum was due to a new consultation code, for 'AccurX consultations', an electronic messaging system for communication with patients., Conclusion: Trends in general practice consultation showed three distinct epochs: rising from 1995 to 2012, falling from 2012 to 2019 and rising in Aurum but falling in Gold from 2019 to 2021. Consultation rates in Gold were higher than Aurum until the inclusion of a new consultation code in Aurum in 2019, which underscores the need for operational definitions of a consultation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mineral resources are essential for reaching net-zero ambitions by 2050. There is a rising diversity of metals in electricity generation and storage technologies, as well as for mobility technologies. However, little is known about the future supply of minor elements historically mined in low volumes such as indium, tellurium, germanium, or tantalum. Those minor elements are found in lower concentrations in the ores of major elements and therefore rarely form economic deposits on their own. Such elements are often produced as byproducts of a host (or "target commodity", which underpins the bulk of a mine's profitability) in ore, e.g., in porphyry ore, tellurium is a byproduct where copper is the host. As a result, the primary supply of those minor elements depends on the supply of the major elements. Such dependency has not been accounted for in scenarios of the mineral supply. To address this gap, we developed a methodology to harmonize scattered data of mineral resource estimates and to calculate the mass ratio between the byproduct and the host in ores and concentrates, called the byproduct-to-host (BtH) ratio. We collected crude ore tonnage and element grades, among other key data, from the state-of-the-art literature and publicly available mining company reports. Our data set covers 3422 deposits across 141 countries providing 22 275 BtH ratios. The future supply of minor elements can be derived by multiplying the primary production of host elements by the developed BtH ratios, noting the limitations of data representativity. The open-access nature of this work facilitates the enrichment and update of this data set in the coming years.

Two-dimensional (2D) nanomaterials have garnered extensive attention owing to their unique properties and versatile application. Here, a family of 2D rare-earth metal phosphides (M 2 P, M = Sc, Y, La) and their derivatives M 2 POT (T = F, OH) is developed to find their topological and electronic properties on the basis of density functional theory simulations. We show that the 2D M 2 P compounds are most possibly obtained from thermodynamically stable M 2 InP by chemical exfoliation. The In with a substantial atomic radius of 156 pm exhibits weak polarization ability, resulting in homogeneity of the electron cloud and a weakening of the M-In bond relative to the M-P bond. Upon exfoliation of the In layer, the M 2 2+ P 3- : e - emerges as an electride with surface electrons, which is attributed to the larger ion radius and lower electronegativity of M 2+ ions in M 2 P. The metallic M 2 P is found to be a Weyl semimetal derived from the contribution of surface electrons. Further, by leveraging the high reactivity of surface electrons, surface functionalization can produce M 2 POT compounds with the increased valence state of M 3+ , which results in their semiconducting properties characterized by high carrier mobilities and strong built-in electronic fields. These distinct topological and electronic characteristics position the 2D M 2 P and M 2 POT as promising candidates for a wide range of applications.

Background: Desmoplastic reaction is recognized as a prognostic factor in colorectal cancer. However, its significance in locally advanced rectal cancer following neoadjuvant chemoradiotherapy remains underexplored., Objective: To assess the prognostic value of desmoplastic reaction in specimens from patients with advanced rectal cancer after chemoradiotherapy., Design: This is a retrospective study., Settings: This study was conducted at a single comprehensive cancer center., Patients: The study included 255 patients with advanced rectal cancer who underwent fluoropyrimidine-based chemoradiotherapy followed by total mesorectal excision from 2005 to 2014. Desmoplastic reaction was classified into mature, intermediate, and immature categories based on histological analysis., Main Outcomes: The primary outcomes were recurrence-free survival and overall survival., Results: Desmoplastic reaction was classified as mature (69.0%), intermediate (5.5%), or immature (25.5%). The mature group had a higher percentage of good responders (34.1%) compared with the intermediate (0%) and immature (4.6%) groups (p < 0.0001). The mature group correlated with better outcomes, with a higher 5-year recurrence-free survival (85.4%) and overall survival (93.0%) as compared with intermediate (45.1% and 76.2%, respectively) and immature (65.8% and 88.8%, respectively) groups. In the multivariable analysis, intermediate/immature desmoplastic reaction was significantly associated with poorer recurrence-free survival (p = 0.03). Among poor responders, intermediate/immature desmoplastic reaction was associated with poorer recurrence-free survival (p = 0.03). Adjuvant chemotherapy did not significantly improve the 5-year recurrence-free survival rate for the mature group (adjuvant chemotherapy vs. no chemotherapy, 86.4% vs. 84.8%; p = 0.64), with worse trends observed in the intermediate/immature combined group (55.9% vs. 69.4%, respectively, p = 0.27)., Limitations: The limitations include the subjective nature of desmoplastic reaction assessment and the study's retrospective design., Conclusions: Desmoplastic reaction in surgical specimens post-chemoradiotherapy is associated with responses to chemoradiotherapy and serves as a significant prognostic factor in advanced rectal cancer, particularly for those responding poorly to chemoradiotherapy. See Video Abstract., (Copyright © The ASCRS 2024.)

Background: The project of scaling up noncommunicable disease (NCD) interventions in Southeast Asia aimed to strengthen the prevention and control of hypertension and diabetes, focusing on primary health care and community levels. In Vietnam, health volunteers who were members of the Intergenerational Self-Help Clubs (ISHCs) implemented community-based NCD screening and health promotion activities in communities. The ISHC health volunteers used an app based on District Health Information Software, version 2 (DHIS2) tracker (Society for Health Information Systems Programmes, India) to record details of participants during screening and other health activities., Objective: This study aimed to assess the strengths, barriers, and limitations of the NCD screening app used by the ISHC health volunteers on tablets and to provide recommendations for further scaling up., Methods: A mixed methods observational study with a convergent parallel design was performed. For the quantitative data analysis, 2 rounds of screening data collected from all 59 ISHCs were analyzed on completeness and quality. For the qualitative analysis, 2 rounds of evaluation of the screening app were completed. Focus group discussions with ISHC health volunteers and club management boards and in-depth interviews with members of the Association of the Elderly and Commune Health Station staff were performed., Results: In the quantitative analysis, data completeness of all 6704 screenings (n=3485 individuals) was very high. For anthropomorphic measurements, such as blood pressure, body weight, and abdominal circumference, less than 1% errors were found. The data on NCD risk factors were not adequately recorded in 1908 (29.5%) of the screenings. From the qualitative analysis, the NCD screening app was appreciated by ISHC health volunteers and supervisors, as an easier and more efficient way to report to higher levels, secure data, and strengthen relationships with relevant stakeholders, using tablets to connect to the internet and internet-based platforms to access information for self-learning and sharing to promote a healthy lifestyle as the strengths. The barriers and limitations reported by the respondents were a non-age-friendly app, incomplete translation of parts of the app into Vietnamese, some issues with the tablet's display, lack of sharing of responsibilities among the health volunteers, and suboptimal involvement of the health sector; limited digital literacy among ISHC health volunteers. Recommendations are continuous capacity building, improving app issues, improving tablet issues, and involving relevant stakeholders or younger members in technology adoption to support older people., Conclusions: The implementation of the NCD screening app by ISHC volunteers can be an effective way to improve community-led NCD screening and increase the uptake of NCD prevention and management services at the primary health care level. However, our study has shown that some barriers need to be addressed to maximize the efficient use of the app by ISHC health volunteers to record, report, and manage the screening data., (©Trang Thi Thu Nong, Giang Hoang Nguyen, Alexander Lepe, Thuy Bich Tran, Lan Thi Phuong Nguyen, Jaap A R Koot. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 02.12.2024.)

McLaughlin, Gotlieb, and Mills introduced the concept of problematic news consumption (PNC) in their 2023 study, finding that those classified as having severely problematic news consumption (16.5% of the sample) exhibited significantly greater levels of mental and physical ill-being. These results were the product of a single cross-sectional survey, however. Using a two-wave longitudinal survey, we sought to replicate their findings. In the current study, we found support for the factor structure of the PNC scale and the 4-profile solution, although the severely problematic news consumption profile represented a substantially smaller portion of the sample (7.5%) than in the initial study. Additionally, we found support for greater levels of mental and physical ill-being among those in the severely problematic news consumption profile in the Wave 1 cross-sectional model. However, while we found greater levels of mental ill-being among these participants in the autoregressive model, we did not find greater levels of physical ill-being.

Background: Neonatal intensive care unit admissions of newborns are emotional and stressful for parents, influencing their mental and physical well-being and resulting in high rates of psychological morbidities. Significant research has been undertaken to understand and quantify the burden of a newborn's medical journey on parents' well-being. Simultaneously, an increase has been observed in the development and implementation of telemedicine interventions, defined as the remote delivery of health care. Telemedicine is used as an overarching term for different technological interventions grouped as real-time audio-visual communication, remote patient monitoring, and asynchronous communication. Various telemedicine interventions have been proposed and developed but scarcely with the primary goal of improving parental well-being during their newborn's medical journey., Objective: This study aims to identify telemedicine interventions with the potential to improve parents' well-being and to present the methods used to measure their experience., Methods: A scoping review was conducted, including empirical studies evaluating telemedicine in neonatal care that either measured parental well-being or included parents in the evaluation. Abstract and title screening, full-text screening, and data extraction were performed by three researchers. Two researchers were needed to reach decisions on both the inclusion and extraction of articles., Results: The review included 50 out of 737 screened articles. Telemedicine interventions focused mainly on daily visits at the neonatal intensive care unit and discharge preparedness for parents. Surveys were the primary tool used for outcome measurement (36/50, 72%). Aspects of parents' well-being were evaluated in 62% (31/50) of studies. Telemedicine interventions developed to provide education and support showed a potential to improve self-efficacy and discharge preparedness and decrease anxiety and stress when they included a real-time telemedicine component., Conclusions: This scoping review identified specific telemedicine interventions, such as real-time audio-visual communication and eHealth apps, that have the potential to improve parental well-being by enhancing self-efficacy and discharge preparedness, and reducing anxiety and stress. However, more insights are needed to understand how these interventions affect well-being. Parents should be included in future research in both the development and evaluation stages. It is important to not only measure parents' perceptions but also focus on the impact of a telemedicine intervention on their well-being., (© Josephine Wagenaar, Crystal Mah, Fredrik Bodell, Irwin Reiss, Maaike Kleinsmann, Sylvia Obermann-Borst, H Rob Taal. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org).)

Respite and permanent transition to residential aged care are processes that are designed to support preferences and needs of people living with dementia and their carers as the disease progresses. These services are highly variable in acceptability, accessibility, and availability for the caregiving dyad, often not reflecting a person-centred, co-ordinated and cohesive approach. This study aimed to use a two-phase realist synthesis to explore how respite and permanent transition models of care work in different contexts, through different mechanisms to produce varying outcomes.Phase 1 explored preliminary theories and assumptions of the respite care journey, including (a) identification of systematic reviews and innovative programs, and (b) semi-structured interviews sessions with key stakeholders. Phase 2 involved an iterative scoping review to identify and map the available evidence, with a synthesis designed to unpack underlying program theories of why, for whom and in what circumstances respite/transition models of care works.Phase 1(a) identified ten citations from 126 systematic review abstracts. Fourteen residential care managers participated in a contextual scan - Phase 1(b). Phase 2 expanded this knowledge, identifying a further 13 studies. Three program theories, at the macro, meso and micro level, were elucidated: (1) system-level evidence-based integration, through collaboration and co-ordination; (2) inclusive, quality care, with supportive environmental design; and (3) trust, autonomy, and meaning-making.A novel realist synthesis approach was used to explore respite and permanent transition models of care beyond 'what works'. Importantly, findings at the macro, meso and micro level context, suggest nuance, with a shared decision-making approach, is needed to optimise the ever-changing dementia care journey., Competing Interests: Declarations. Ethics approval and consent to participate: This entire project has been approved by the Bolton Clarke Human Research Ethics Committee (project no. 215), with individual consent not required. Consent for publication: Not applicable as there is no individual person-level data. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Human mesenchymal stem cells (hMSCs) have therapeutic applications and potential for use in regenerative medicine. However, the use of hMSCs in research and clinical medicine is limited by a lack of information pertaining to their donor-specific functional attributes. In this study, we compared the characteristics of same-donor derived placenta (PL) and Wharton's jelly (WJ)-derived hMSCs, we also compared their mechanism of action in a skeletal muscle disease in vitro model. The same-donor-derived hWJ- and hPL-MSCs exhibited typical hMSC characteristics. However, GRO-α was differentially expressed in hWJ- and hPL-MSCs. hWJ-MSCs, which secreted a high amount of GRO-α, displayed a higher ability to inhibit necroptosis in skeletal muscle cells than hPL-MSCs. This demonstrates the anti-necroptotic therapeutic effect of GRO-α in the skeletal muscle cell death model. Furthermore, GRO-α also exhibited the anti-necroptotic effect in a Duchenne muscular dystrophy (DMD) mouse model. Considering their potential to inhibit necroptosis in skeletal muscle cells, hWJ-MSCs and the derived GRO-α are novel treatment options for skeletal muscle diseases such as DMD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A., Methods: This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide. Participants aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 2 or less, with no more than two previous anticancer treatments and no more than one previous chemotherapy regimen, were enrolled in three cohorts. In cohort A, patients must have had progression on or after a CDK4/6 inhibitor plus an aromatase inhibitor as the immediate previous treatment. Patients received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary endpoint was the proportion of patients alive without disease progression at 6 months per local assessment using Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation. This trial is registered with ClinicalTrials.gov, NCT03056755., Findings: Between Aug 14, 2017, and Jul 29, 2022 (data cutoff), 127 patients with at least 18 months' follow-up were enrolled into cohort A. 119 patients had a centrally confirmed PIK3CA mutation. At data cutoff, median follow-up was 21·8 months (IQR 10·8-37·6). 64 (53·8%; 95% CI 44·4-63·0) of 119 patients were alive without disease progression at 6 months. The most frequent grade 3 or worse adverse events were hyperglycaemia (37 [29%] of 127 patients), rash (13 [10%]), and rash maculopapular (11 [9%]). Serious adverse events occurred in 37 (29%) of 127 patients. No treatment-related deaths were reported., Interpretation: BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor., Funding: Novartis Pharmaceuticals., Competing Interests: Declaration of interests HSR reports research support to the University of California San Francisco from Pfizer, Merck, Novartis, Eli Lilly, Genentech, OBI, Odonate, Daiichi, Eisai, Seattle Genetics, MacroGenics, Sermonix, and Immunomedics; a limited consulting role with Samsung; honoraria from Puma and Mylan; and travel support from Daiichi, Mylan, Pfizer, Merck, AstraZeneca, Novartis, and MacroGenics. FL reports consulting for AstraZeneca, Eisai, Genomic Health, and Eli Lilly; and travel support from Eli Lilly, Novartis, Pfizer, Roche, and Laboratories Pierre Fabre. EC reports honoraria, and consulting and paid speakers’ bureaus for Novartis, Pfizer, Eli Lilly, and Roche; and travel support from Roche and Pfizer. PD reports research funding from Roche and Novartis. YHP reports grants from Novartis, during the conduct of the study; personal fees from AstraZeneca, Pfizer, Daiichi Sankyo, and Eli Lilly; grants and personal fees from Merck, AstraZeneca, Eisai, and Novartis; grants and non-financial support from Pfizer; and personal fees and non-financial support from Roche, outside the submitted work. AP reports immediate family member employee of Novartis; personal honoraria from Pfizer, Novartis, Roche, MSD Oncology, Eli Lilly, Daiichi Sankyo, and Amgen; consultant for Amgen, Roche, Novartis, Pfizer, Bristol-Myers Squibb, Boehringer, Puma, Oncolytics Biotech, Daiichi Sankyo, and AbbVie; institutional honorarium from Nanostring Technologies; institutional research funding from Roche, Novartis, Incyte, and Puma; patents on HER2 and chemoendocrine score predictors; travel support from Daiichi Sankyo; an advisory role with Oncolytics and consultancy for Peptomyc; and is the founder of Reveal Genomics. TB reports personal fees and non-financial support from Roche; and grants, personal fees, and non-financial support from Novartis, AstraZeneca, and Pfizer, outside the submitted work. DJ reports personal fees from Novartis, Genentech, Eisai, Ipsen, and EMD Serono, during the conduct of the study. NT reports advisory board honoraria from AstraZeneca, Bristol-Myers Squibb, Lilly, Merck Sharpe & Dohme, Novartis, Pfizer, Roche/Genentech, Bicycle Therapeutics, Taiho, Zeno Pharmaceuticals, Repare Therapeutics; and research funding from AstraZeneca, BioRad, Pfizer, Roche/Genentech, Clovis, Merck Sharpe & Dohme, and Guardant Health. NS reports employment at Novartis. JPZ reports employment at and stock ownership in Novartis. JPZ's wife is employed by Johnson & Johnson. CA and Y-MS report employment at Novartis. ST reports employment at and stock ownership in Novartis. HK and W-CH reports consulting agreements and research funding for the conduct of this study from Novartis. SC reports grants and personal fees from Novartis and Pfizer; and personal fees from Eli Lilly, during the conduct of the study; and grants and personal fees from Hoffmann LaRoche, AstraZeneca, and Genomic Health, outside the submitted work. MR-B and PN declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Patient engagement in research aims to foster meaningful partnerships, integrating patient experiences into the research process. This paper describes the development of a Terms of Reference (ToR) to support these meaningful partnerships. While engagement improves data collection and empowerment, ineffective engagement can lead to negative outcomes. A well-developed ToR promotes a structured, inclusive, and respectful process., Methods: Using an integrated knowledge translation (iKT) approach, we established a panel of youth, caregivers, healthcare providers, and healthcare leaders/decision-makers. Through collaborative discussions, we incorporated key elements into the ToR, including values, roles, decision-making processes, and recognition of contributions., Results: To promote effective engagement the ToR included sections to encourage open, transparent and vulnerable dialogue, evaluation, and accommodations for disabilities. The ToR draft was reviewed and refined by panel members for clarity. Regular reviews and updates will keep the ToR a living document and adaptable to the evolving engagement process., Conclusion: The implementation of our ToR is designed to foster inclusivity, mutual respect, and accountability, avoiding tokenistic partnership, enriching the experience for patients and researchers alike, and ultimately enhancing research quality., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Objective: Recognizing the substantial role of modifiable risk factors such as physical inactivity, unhealthy diets, and substance use in driving global healthcare expenses, this study aims to assess the impact of a lifestyle behaviour change mobile health (mHealth) app on healthcare costs within a real-world setting., Methods: Employing a difference-in-difference approach, this research compared healthcare costs between users of an mHealth app (treatment group) and a propensity score-matched control group of non-users. The study included data from 15,506 participants in the Netherlands, covering healthcare cost records collected from 2015 to 2019., Results: The implementation of the mHealth app was linked to a steady reduction in healthcare costs, achieving a 4.9 % decrease (β=-0.05,95%CI:-0.10to0.00) during the first year following the program's implementation, and a further 5.3 % decrease (β=-0.05,95%CI:-0.10to-0.00) in the second year. This healthcare costs reduction is associated with lower expenses for general practitioner services as well as diminished specialist visits. Additionally, increased app use led to further cost reductions, with frequency of use proving more important than intensity., Conclusions: This study demonstrates that a behaviour change mHealth app is linked to significant reductions in healthcare costs, with more frequent and intense use leading to greater savings. Given their relatively low cost and ability to reach diverse population groups, such apps not only enhance individual health outcomes but can also serve as effective policy tools for large-scale health promotion, supporting broader societal health improvements., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Elena Agachi reports financial support was provided by Menzis. Elena Agachi reports a relationship with Menzis that includes: Funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The environmental impact of large language models (LLMs) in medicine spans carbon emission, water consumption and rare mineral usage. Prior-generation LLMs, such as GPT-3, already have concerning environmental impacts. Next-generation LLMs, such as GPT-4, are more energy intensive and used frequently, posing potentially significant environmental harms. We propose a five-step pathway for clinical researchers to minimise the environmental impact of the natural language algorithms they create., (© 2024 Royal Australasian College of Physicians.)

Competing Interests: Declaration of interests JSJ reports grants and non-financial support from WHO, outside the submitted work. MW reports grants from the Wellcome Trust during the conduct of the study. All other authors declare no competing interests.

Competing Interests: Conflicts of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B Sebben, J Stone, K Mallie and S Barnett are cofounders of IPAT (Indigenous Psychedelic Assisted Therapies), a private company that has developed a model of psychedelic-assisted therapy based on Indigenous ways of knowing, being and doing and offers cultural consultation services. J Sarris and D Perkins helped fund IPAT and are also co-CEOs of Psychae Therapeutics, a commercial company developing psychedelic therapies. SGD Ruffell works for the not-for-profit arm of the aforementioned company. He is also the co-founder of a not-for-profit organisation conducting research into traditional plant medicines. VL Beesley has received unrelated funding from Woke Pharmaceuticals for a psilocybin-assisted therapy trial.

Objective: Given the high prevalence of maternal morbidity and mortality, it is imperative that maternal health interventions are comprehensively evaluated, so they can be scaled with fidelity. Community-based care management models focused on perinatal health care are a priority for health care systems and payers. Alternative care management delivery modalities, such as video visits, are needed to expand program reach amidst growing system-level challenges. This evaluation explores the feasibility, acceptability, and impact of video versus telephonic care in perinatal care management., Methods: Using a mixed methods approach, we implemented a quality improvement project to learn about the integration and impact of video-enabled care into the UPMC Health Plan "Pregnancy Clinical Support" (PCS) care management delivery model. Focus groups were conducted with PCS care managers (CMs) to explore their perspectives on video-visit integration. Video-only members were propensity scores matched to telephonic-only members; statistical comparisons were conducted to assess between-group differences in engagement., Results: PCS CMs discussed ways to structure effective video-visit onboarding, strengths, and drawbacks of video-enabled care, workflow integration challenges, and best practices for introducing video visits to members. Video-only members had significantly (P < 0.0001) more clinical sessions (2.56 ± 1.57 vs 2.05 ± 1.52) and longer case duration measured in calendar days (209 ± 80 vs 169 ± 94) during the 17-month project period than telephonic-only members., Conclusion: Evidence generated provides direct guidance on successfully integrating video visits into workflows of community-based CMs while improving engagement in care across diverse member populations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: As the available treatments for moderate-to-severe atopic dermatitis (AD) expand, understanding patient and physician preferences becomes crucial for informed decision-making., Objective: To quantify patient and physician preferences for biologics and oral systemic AD treatment attributes., Materials and methods: We conducted a cross-sectional, online discrete choice experiment (DCE) involving 306 AD patients and 206 physicians throughout the United Kingdom and Germany. Qualitative interviews identified the key attributes for inclusion in the DCE. Each choice task comprised two hypothetical patient profiles. Data were analyzed using a random-parameters logit model., Results: Results indicated a significant emphasis on efficacy, with reducing sleep disturbance and itch ranking first and second among patients, and the reverse for physicians. Time to itch relief was the third most important efficacy attribute for both groups, but relatively more important for patients than for physicians. For both groups, the risk of eye problems was the most important safety concern of those included. Mode of administration was not of great importance compared to efficacy and safety attributes., Conclusions: Our findings suggest patients prioritize sleep disturbance, an attribute not captured in prior preference studies in AD, time to itch relief and itch. These findings emphasize the importance of addressing sleep-related issues, whilst also targeting fast itch control, to enhance patients' well-being.

Introduction: In Japan, patients with chronic obstructive pulmonary disease (COPD) can be escalated to treatment with inhaled triple therapy. Two single-inhaler triple therapies combining an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β 2 -agonist (ICS/LAMA/LABA) are approved maintenance therapies for patients with COPD, and multiple-inhaler triple therapies (MITTs) are also available. There is limited evidence regarding real-life treatment patterns and characteristics of patients with COPD initiating triple therapies., Methods: This observational, retrospective cohort study identified patients with COPD in Japan from an administrative claims database (May 2018-December 2021). Demographics, clinical characteristics, and healthcare resource utilization (HCRU) were assessed in four cohorts initiating a triple therapy: budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) early adopters (initiated ≤ 12 months after market approval [September 1, 2019]), contemporary BGF users (initiated > 12 months after market approval), fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) users, and any MITT users., Results: A total of 636 patients were BGF early adopters, 2558 were contemporary BGF users, 11,187 used FF/UMEC/VI, and 5931 used MITT. The percentage of patients with concomitant asthma in each cohort was 73.0%, BGF early adopter; 74.2%, contemporary BGF; 75.7%, FF/UMEC/VI; and 84.5%, MITT. During the 12-month baseline period, the frequency of patients with ≥ 1 moderate/severe exacerbation was 18.2%, BGF early adopter; 14.3%, contemporary BGF; 13.1%, FF/UMEC/VI; and 14.0%, MITT. ICS/LABA treatment during baseline was the most frequent pathway to triple therapy, ranging from 38.2% to 51.7% across cohorts. HCRU was relatively high across cohorts (range of hospital outpatient visits/patient during the 12-month baseline period, 11.0-14.1). Multimorbidity was observed in > 80% of patients in all cohorts; cardiovascular diseases were among the most common., Conclusion: Many patients initiating triple therapy for COPD had concomitant asthma and had previously received ICS/LABA maintenance therapy. Patients prescribed BGF in the initial post-launch period were more likely to have a previous exacerbation history versus other cohorts, indicating more severe disease., (© 2024. The Author(s).)

Determining the extent of pollution in the marine environment remains challenging. Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and metals can, during dredging operations, be transported from a port or harbour into the open sea, where they may exert a harmful effect on the marine ecosystem. To fully understand the impact of these chemicals, monitoring programs should not only focus on sediment concentrations, but should also take into account the bioaccumulated concentration in the tissue of multiple target organisms. In this study, the concentration of primary contaminants is determined in common starfish (Asterias rubens), flying crab (Liocarcinus holsatus), and brown shrimp (Crangon crangon) and the difference in the concentration of contamination between different dredge disposal sites at open sea is investigated. Different factors such as lipid weight, dry weight, grain size, and total organic carbon were measured and used to understand the difference between the observed bioaccumulation and the measured sediment concentrations. KEY MESSAGE: Different contaminants are detected in biota such as common starfish, flying crab and brown shrimp. These contaminants can be linked to dredging activities, with disposal sites associated with industrial ports showing higher contamination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To explore variation in rates of acute care utilization for mental health conditions, including hospitalizations and emergency department (ED) visits, across high-income countries before and during the COVID-19 pandemic., Data Sources and Study Setting: Administrative patient-level data between 2017 and 2020 of eight high-income countries: Canada, England, Finland, France, New Zealand, Spain, Switzerland, and the United States (US)., Study Design: Multi-country retrospective observational study using a federated data approach that evaluated age-sex standardized rates of hospitalizations and ED visits for mental health conditions., Principal Findings: There was significant variation in rates of acute mental health care utilization across countries. Among the subset of four countries with both hospitalization and ED data, the US had the highest pre-COVID-19 combined average annual acute care rate of 1613 episodes/100,000 people (95% CI: 1428, 1797). Finland had the lowest rate of 776 (686, 866). When examining hospitalization rates only, France had the highest rate of inpatient hospitalizations of 988/100,000 (95% CI 858, 1118) while Spain had the lowest at 87/100,000 (95% CI 76, 99). For ED rates for mental health conditions, the US had the highest rate of 958/100,000 (95% CI 861, 1055) while France had the lowest rate with 241/100,000 (95% CI 216, 265). Notable shifts coinciding with the onset of the COVID-19 pandemic were observed including a substitution of care setting in the US from ED to inpatient care, and overall declines in acute care utilization in Canada and France., Conclusion: The study underscores the importance of understanding and addressing variation in acute care utilization for mental health conditions, including the differential effect of COVID-19, across different health care systems. Further research is needed to elucidate the extent to which factors such as workforce capacity, access barriers, financial incentives, COVID-19 preparedness, and community-based care may contribute to these variations., What Is Known on This Topic: Approximately one billion people globally live with a mental health condition, with significant consequences for individuals and societies. Rates of mental health diagnoses vary across high-income countries, with substantial differences in access to effective care. The COVID-19 pandemic has exacerbated mental health challenges globally, with varying impacts across countries., What This Study Adds: This study provides a comprehensive international comparison of hospitalization and emergency department visit rates for mental health conditions across eight high-income countries. It highlights significant variations in acute care utilization patterns, particularly in countries that are more likely to care for people with mental health conditions in emergency departments rather than inpatient facilities The study identifies temporal and cross-country differences in acute care management of mental health conditions coinciding with the onset of the COVID-19 pandemic., (© 2024 The Author(s). Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

Exfoliation from quaternary hexagonal MAB (h-MAB) phases has been suggested as a method for producing 2D in-plane ordered MBenes (i-MBenes) with the general formula (M' 2/3 M″ 1/3 ) 2 AB 2 . However, experimental realization of defect-free i-MBenes has not been achieved yet due to the absence of a suitable parent quaternary h-MAB phase. In this study, a machine learning (ML) model is used to predict the stability of 15771 quaternary h-MAB phases generated by considering 33 transition metals for the M site and 16 p-block elements for the A site. Out of these compounds, only 195 are identified as potentially stable. Subsequent high-precision first-principles calculations confirm that 47 of them exhibit both thermodynamic and dynamic stability. Their potential for exfoliation into bimetallic i-MBenes is investigated by bonding analysis. Leveraging these theoretical insights, a bimetallic i-MBene is successfully synthesized, namely 2D Mo 2 ErB 3 T 2.5 (T = F, Cl and O). Further experimental scrutiny reveals its excellent performance for the hydrogen evolution reaction (HER), highlighting the application potential of bimetallic i-MBenes., (© 2024 Wiley‐VCH GmbH.)

Background: Multidisciplinary team meetings (MTMs) are considered a pillar of cancer care; however, evidence of the independent benefit of MTMs on survival in rectal cancer is controversial., Methods: This population-based cohort analysis included patients undergoing surgery for primary rectal cancer with curative intent. We drew data derived from three clinical audits conducted in Catalonia from 2011 to 2020. The primary outcome was 2-year survival. Multivariable Cox regression analysis was used to assess the hazard ratio for death in patients whose cases were versus were not discussed in a preoperative MTM., Results: A total of 5249 patients were included (66.1 % male, 58.3 % aged 60-79 years, 63.2 % receiving anterior resection): 4096 cases were discussed in a preoperative MTM, and 1153 were not. Multivariable Cox proportional hazards regression analysis showed that the MTM group had better survival than those with no preoperative MTM (hazard ratio 1.22, 95 % confidence interval 1.02-1.48), after adjusting for potential confounders., Conclusions: Preoperative MTM may be associated with improved survival in patients with rectal cancer in Catalonia. Efforts to ensure universal access to MTMs for all newly diagnosed patients should be supported., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To explore how clinicians understand coaching and their clinician-coach practice in emergency medicine., Methods: Participants were surveyed about the value of coaching and their beliefs about the enablers of, and barriers to, being a clinician-coach., Results: Three themes were developed for the value of coaching: empowerment and growth; enhanced interpersonal dynamics; and reflective transformation. Key enablers were supportive infrastructure, self-driven development and recognition of value. Key barriers were time constraints and scheduling conflicts, cultural challenges and financial and structural obstacles., Conclusions: Fostering a supportive environment for coaching could significantly enhance clinician competence and well-being, healthcare delivery and professional development., (© 2024 The Author(s). Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Pathogens in coastal waters cause infectious diseases and endanger public sanitation safety in humans and animals worldwide. To avoid these risks, timely detection of human-associated pathogens in waters is crucial. In this study, the decay kinetics of the molecular markers for human-associated pathogens, including enteric bacteria (Escherichia coli, Enterococcus, and Bacteroides), non-enteric bacteria (Staphylococcus aureus), crAssphage, and polyomavirus, were monitored over time at different temperatures and background microbes in seawater microcosms. The results indicated that temperature and native marine microbes were the main influential factors in attenuating bacterial pathogens. Remarkably, the effect of native microorganisms was more evidentially striking. Furthermore, Enterococcus was a more reliable and suitable fecal indicator bacterium than E. coli for the marine environment. The decay of crAssphage was like that of polyomavirus, indicating that it may be a good indicator of enterovirus in seawater. More importantly, the 16S amplicon sequencing data highlighted the decay kinetics of multiple bacterial pathogens in parallel with the dynamic changes of the whole bacterial communities. This study provides valuable information for public health risk management and a new approach to understanding the fate of bacteria in the coastal environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Large quantities of chlordecone-based insecticides were produced and used throughout the world. One of its most important uses was to control the damage caused by Cosmopolites sordidus in banana-growing regions. In the islands of Martinique and Guadeloupe, 18,000 ha of farmland are potentially contaminated. Despite the key role played by soil macrofauna in agroecosystems, there are currently no data on their contamination. The aim of this study was to explore the fate of chlordecone (CLD) and its transfer to different organisms of the soil food web. Seven species of invertebrates representing different taxonomic groups and trophic levels of the soil communities of Martinique were targeted and collected in six experimental banana fields, with a level of contamination within a range of values classically observed. Soil samples and macrofauna from the study sites were analysed for CLD and chlordecol (CLDOH) its main transformation product. The contamination of the soil fauna were related to δ 15 N (trophic level), proportion of soil ingestion (diet) and types of epidermis (mucus or exoskeleton) in order to study the different mechanisms of macrofauna contamination. Presence of CLD and CLDOH could be quantified in all the soil organisms from contaminated fields. Results showed a significant relationship between the CLD contamination of detritivorous and the ash content of their faeces, suggesting that soil ingestion was the main contamination pathway. In contrast, the exoskeleton-bearing diplopod Trigoniulus coralinus and the soft-bodied earthworm Eudrilus eugeniae, both detritivores with a comparable diet, had similar contamination levels, suggesting that the type of tegument has little influence on bioaccumulation. At the scale of the entire trophic network, a significant relationship was uncovered between δ 15 N values and CLD contamination of the fauna, therefore providing some in situ evidence for a bioamplification process along the soil food chain., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Mathieu coulis reports financial support was provided by the BANABIO project funding obtained under DEPHY EXPE program of the Ecophyto II plan. Julien PARINET reports financial support was provided by French National Research Agency (ANR-19-CE21-0002). Lai Ting pak reports financial support was provided by The French Ministry of the Overseas for this study that was part of the Territoires Durables project carried out in Martinique. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Older adults living in elderly caring social organizations (SOs) are prone to suffer from depression. Many studies have found correlations between environmental and quality-of-life factors and depression; however, evidence from elderly caring SOs is rare, particularly in China., Methods: A cross-sectional study was conducted among service recipients in elderly caring SOs in Anhui and Chongqing, China. Data on demographic and health-related characteristics, living environment factors, and service quality satisfaction factors in 2171 older adults were used for analysis. The binary logistic regression model was conducted to estimate the association between living environment and service quality satisfaction factors and depression., Results: Our results indicated that living environment factors in terms of exposure to suitable temperature and humidity (OR = 0.655; 95 % CI: 0.446, 0.963), green coverage >30 % (OR = 0.432; 95 % CI: 0.337, 0.553) were associated with lower odds of developing depression. Also, an opposite relationship was found in the noise factor (OR = 1.985; 95 % CI: 1.395, 2.823). Higher satisfaction with admission and discharge services, dietary services, entertainment services, and psychological support services were also found to be associated with a lower risk of depression., Limitations: A cross-sectional design precluded determining whether living environment, service quality satisfaction, and depression are causally related. Measurement of living environment factors and service quality satisfaction factors needs to be further clarified comprehensively., Conclusions: Enhancing the living environment and the quality of the services provided to seniors in the elderly caring SOs is conducive to the reduction of the likelihood of depression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the rapidly evolving digital radiology landscape, a surge in solutions has emerged including more than 500 artificial intelligence applications that have received 510 k clearance by the FDA. Moreover, there is an extensive number of non-regulated applications, specifically designed to enhance workflow efficiency within radiology departments. These efficiency applications offer tremendous opportunities to resolve operational pain points and improve efficiency for radiology practices worldwide. However, selecting the most effective workflow efficiency applications presents a major challenge due to the multitude of available solutions and unclear evaluation criteria. In this article, we share our perspective on how to structure the broad field of workflow efficiency applications and how to objectively assess individual solutions. Along the different stages of the radiology workflow, we highlight 31 key operational pain points that radiology practices face and match them with features of workflow efficiency apps aiming to address them. A framework to guide practices in assessing and curating workflow efficiency applications is introduced, addressing key dimensions, including a solution's pain point coverage, efficiency claim strength, evidence and credibility, ease of integration, and usability. We apply this framework in a large-scale analysis of workflow efficiency applications in the market, differentiating comprehensive workflow efficiency ecosystems seeking to address a multitude of pain points through a unified solution from workflow efficiency niche apps following a targeted approach to address individual pain points. Furthermore, we propose an approach to quantify the financial benefits generated by different types of applications that can be leveraged for return-on-investment calculations., Competing Interests: Declarations. Competing Interests: Prateek Bharadwaj, Steven L. Blumer, and Franziska Lobig are employees of Bayer AG. Michael Berger is an employee of Simon-Kucher & Partners Strategy & Marketing Consultants GmbH, a consulting firm which has received consulting fees from Bayer AG., (© 2024. The Author(s).)

Background: Insights from mental health stigma research indicate the importance of societal and political views on mental health perceptions. Most studies originate from typical Western neo-liberal settings and focus on generic mental health issues. Our research explores these associations in Hungary, an understudied post-communist context with significant stigma levels, examining a broad range of stigmas related to both general and three specific mental illnesses: schizophrenia, depression, and alcohol use disorder (AUD)., Aims: The study aims to connect a wide array of political dispositions to stigma associated with both general and specific mental illnesses, exploring both attitudes and behavioral intentions., Methods: We surveyed 492 participants (147 males, 342 females) on their political dispositions, including Right-Wing Authoritarianism (RWA), Social Dominance Orientation (SDO), general and economic system justification, and conservative political ideology, and their attitudes toward general and specific mental illnesses. Regression analyses identified key political dispositions influencing stigma., Results: RWA was significantly linked to most stigma outcomes, while conservative political ideology showed a selective impact. Other predictors had minimal influence on stigma outcomes., Conclusion: Our findings suggest that perceptions of danger, threat, and unconventionality, as indicated by RWA, are crucial for mental health stigmatization in Hungary. Intervention programs should target these factors, particularly in similar contexts., Competing Interests: Conflict of interestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Emergency medicine (EM) doctors are often required to manage a diverse set of complex challenges; navigating direct patient care, systemic issues and inter-professional interactions. Leadership is well recognised as crucial in optimising both the delivery and the quality of patient care. There is a clear need to gain greater understanding of the reality of EM leadership through exploring doctors' experience and perception of leadership in EM, yet there is a paucity of research focusing on this area. The objective of the present study was to explore the research question: 'What are the experiences and perceptions of leadership by EM doctors?', Methods: This single-site qualitative study was undertaken using semi-structured in-depth individual interviews to collect data. Interviews were audio recorded, transcribed and de-identified. Reflexive thematic analysis was performed by the research team with the aid of DelveTool software., Results: Our sample included nine participants incorporating consultants and registrars. Three major themes were identified: (i) situational tensions, (ii) relational tensions and (iii) leadership style tensions. Each of these was further explored with subthemes discussed separately., Conclusions: Leadership within the ED is complex and multifaceted, with doctors required to navigate many competing tensions. The present study highlighted key areas for future leadership development, including situational awareness, emotional intelligence and a fluid approach to leadership styles. The present study provides an important step towards enhancing the development of targeted leadership training for EM doctors., (© 2024 Australasian College for Emergency Medicine.)

Objective: This study aims to assess outcomes among patients with non-small cell lung cancer (NSCLC) who received treatment with pembrolizumab on a weight-based dose (WBD) or fixed-dose (FD) regimen using a non-inferiority (NI) analysis., Material and Methods: This retrospective cohort study included adult patients with NSCLC weighing under 100 kg who received pembrolizumab between 1 January 2015 and 31 December 2020. Patients were grouped into either WBD or FD cohort based on the initial pembrolizumab dose and dosing regimen. The primary effectiveness outcome was overall survival (OS), analyzed using NI analysis with a lower margin of 10% comparing WBD to FD. Safety outcomes were all-cause emergency room visits or hospitalizations and incidence of selected immune-related adverse events (irAEs) and analyzed using NI analysis with an upper margin of 10%. All patients were followed until the end of health plan membership, death, or 30 June 2022, whichever occurred first., Results: A total of 1413 patients were evaluated. OS was observed in 36.6% of the FD group, and 37.7% in the WBD group (rate difference: 1%, 90% CI: -6%-8%, NI p -value < 0.01). NI was met in all three safety outcomes: proportion of all-cause emergency room visits (rate difference: 1.1%, NI p -value < 0.01); proportion of hospitalizations (rate difference: 2%, NI p -value < 0.01); and composite incidence of irAEs (rate difference: -2.2%, NI p -value = 0.03)., Conclusion: These findings suggest that WBD of pembrolizumab may be as appropriate as FD for the treatment of lung cancer., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Persistent facial erythema represents a significant complication in atopic dermatitis (AD) patients undergoing treatment with dupilumab. Stratifying patients based on the erythema course is crucial for elucidating heterogeneous phenotypes and facilitating advanced drug efficacy predictions., Objectives: This study aimed to identify factors associated with facial erythema severity in dupilumab-treated AD patients and to establish a prediction model for drug response based on the identified factors., Methods: Data from a retrospective study conducted between July 2018 and July 2021 were collected and analysed. Patients were categorized into three groups via hierarchical clustering based on the course of facial erythema: early remission, low remission and persistent residual. LightGBM, a supervised gradient boosting decision tree algorithm, was employed to discern group differences and construct a prediction model. The model incorporated patient demographic and clinical profiles, including pre- and post-treatment examinations. The model's performance was evaluated using accuracy and the area under the receiver operating characteristic curve (AUC)., Results: The binary classification model demonstrated an accuracy of 89.10% and an AUC of 0.862 when distinguishing between early remission and persistent residual patients. The eight prominent factors associated with facial erythema severity included age, sex, lactate dehydrogenase (LDH), immunoglobulin E (IgE), eosinophil count, white blood cell count, Alnus allergy and cedar allergy., Conclusions: This study has two main significances: first, three clusters were identified through unsupervised learning; second, a classification model was constructed that proved more accurate than random prediction. The stratification and identification of crucial factors associated with residual facial erythema in dupilumab-treated AD patients lay the foundation for AI-powered prognostic models. This groundwork provides a substantial basis for enhancing future medical AI support in AD treatment selection, potentially improving personalized treatment approaches and outcomes., (© 2024 European Academy of Dermatology and Venereology.)

Cyanobacteria are excellent autotrophic photosynthetic chassis employed in synthetic biology, and previous studies have suggested that they have alkaline tolerance but low acid tolerance, significantly limiting their productivity as photosynthetic chassis and necessitating investigations into the acid stress resistance mechanism. In this study, differentially expressed genes were obtained by RNA sequencing-based comparative transcriptomic analysis under long-term acidic stress conditions and acidic shock treatment, in the model cyanobacterium Synechococcus elongatus PCC 7942. A pathway enrichment analysis revealed the upregulated and downregulated pathways during long-term acidic and shock stress treatment. The subsequent single gene knockout and phenotype analysis showed that under acidic stress conditions, the strains with chlL, chlN, pex, synpcc7942&#95;2038, synpcc7942&#95;1890, or synpcc7942&#95;2547 knocked out grew worse than the wild type, suggesting their involvement in acid tolerance. This finding was further confirmed by introducing the corresponding genes back into the knockout mutant individually. Moreover, individual overexpression of the chlL and chlN genes in the wild type successfully improved the tolerance of S. elongatus PCC 7942 to acidic stress. This work successfully identified six genes involved in acidic stress responses, and overexpressing chIL or chIN individually successfully improved acid tolerance in S. elongatus PCC 7942, providing valuable information to better understand the acid resistance mechanism in S. elongatus PCC 7942 and novel insights into the robustness and tolerance engineering of cyanobacterial chassis. KEY POINTS: • DEGs were identified by RNA-seq based transcriptomics analysis in response to acidic stress in S. elongatus PCC 7942. • Six genes were identified to be involved in acid tolerance in S. elongatus PCC 7942. • Overexpression of chIL or chIN individually successfully improved the acid tolerance of S. elongatus PCC 7942., (© 2024. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome and remains a major global health burden. The increased prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide has contributed to the rising incidence of NAFLD. It is widely believed that atherosclerotic cardiovascular disease (ASCVD) is associated with NAFLD. In the past decade, the clinical implications of NAFLD have gone beyond liver-related morbidity and mortality, with a majority of patient deaths attributed to malignancy, coronary heart disease (CHD), and other cardiovascular (CVD) complications. To better define fatty liver disease associated with metabolic disorders, experts proposed a new term in 2020 - metabolic dysfunction associated with fatty liver disease (MAFLD). Along with this new designation, updated diagnostic criteria were introduced, resulting in some differentiation between NAFLD and MAFLD patient populations, although there is overlap. The aim of this review is to explore the relationship between MAFLD and ASCVD based on the new definitions and diagnostic criteria, while briefly discussing potential mechanisms underlying cardiovascular disease in patients with MAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)