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Abstract The primary purpose of this paper is to investigate whether text mining of the outpatient narrative notes for patients with severe and persistent mental illness (SPMI) can strengthen the predictions concerning the probability of an upcoming hospital readmission. A five-year study of all clinical notes for SPMI patients at the outpatient clinic of a tertiary hospital was conducted. The clinical notes were studied using ensemble classification i.e., entity recognition. Confounding variables pertaining to the patient’s health status were extracted by text mining. A mixed effects logistic regression model was used for estimating the re-hospitalization risk during a clinic visit. The factors included frequency and continuity of outpatient visits, alterations in medication prescriptions, the usage of long-acting anti-psychotic injections (LAIs), the presence or absence of a legal compulsory treatment order (CTO) and the hospitalizations. The appearance of certain words in the outpatient clinical notes has a statistically significant impact on the risk of an upcoming hospitalization. This study also reconfirms that the risk of a re-hospitalization of an SPMI patient is reduced by the presence of a CTO and the utilization of LAIs, whereas it is increased by the patient dropping out of outpatient care. Our findings pertaining to the risk of re-hospitalization could facilitate preventive interventions for SPMI patients with higher risk.

This study seeks to establish the influence of the Big Five personality traits, which include Openness, Neuroticism, Conscientiousness, Agreeableness, and Extraversion, on growers’ willingness to embrace crop insurance schemes. Furthermore, it explores the role of Attitude, Subjective Norms, and Perceived Behavioral Control, as proposed in the Theory of Planned Behavior (TPB), on this relationship. Using a structured questionnaire, data were collected from 412 growers of arecanut and pepper. The data were analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM) via Smart-PLS 3.3. The analysis revealed that Perceived Behavioral Control (β = 0.462**), Subjective Norms (β = 0.260**), and Attitude (β = 0.115**) positively influenced growers’ behavioral intentions. Interestingly, the Big Five personality traits themselves did not have a direct effect on these intentions. Further mediation analysis demonstrated that Attitude and Subjective Norms fully mediated the effects of Extraversion (α = 0.026**, β = 0.069), Neuroticism (α = 0.019**, β = –0.016), and Openness (α = 0.024**, β = 0.069) on Behavioral Intention. However, these variables did not mediate the relationship between Agreeableness (α = 0.011, β = 0.058), Conscientiousness (α = –0.017, β = –0.080), and Behavioral Intention. Additionally, perceived behavioral control mediated the link between personality traits and intention, though this was not the case for Conscientiousness. This study contributes to the application of the TPB by incorporating the Big Five personality traits and exploring their interaction with the TPB dimensions.

Objective This study aims to map the literature on screening, diagnosis, treatment and outcomes of developmental dysplasia of the hip (DDH) in the Brazilian population aged 0–18 years, to describe regional variations in its presentation and management.Design Scoping review.Data sources PubMed/MEDLINE, Web of Science, Scopus, “Biblioteca Virtual em Saúde” and “Biblioteca Digital Brasileira de Teses e Dissertações”. The journals, Revista Brasileira Ortopedia and Acta Ortopédica Brasileira, were manually searched for non-indexed issues. Databases were searched from their inception to February 2024.Eligibility criteria This scoping review included studies on Brazilian patients aged 0–18 years diagnosed with or being assessed for DDH. No language or date restrictions were applied.Data extraction and synthesis Studies were assessed based on title, authors, publication year, study design, sample size, level of evidence, region of Brazil and healthcare setting (public or private). The articles were then analysed across four categories: screening, diagnosis, treatment and outcomes.Results 52 studies, published between 1951 and 2023, were included. Reported prevalence rates ranged from 0.75 to 56.4 cases per 1000 children. No study examined the effectiveness of specific screening programmes or compared their outcomes. The most common diagnostic methods were the Ortolani manoeuvre and ultrasonography using the Graf method. Of the 27 articles on treatment, 17 focused exclusively on surgical interventions, with the Salter osteotomy being the most frequent procedure.Conclusions There should be a greater focus on understanding the prevalence of DDH in Brazil, the availability of ultrasound devices and trained operators, and the follow-up of conservative treatments. More information on DDH in Brazil is essential for designing and implementing effective screening and treatment programmes. Future research should be done to understand the prevalence of the disease, optimal forms of screening and early treatment.

Market turmoil caused by COVID-19 has weakened firms’ financial performance, highlighting the prominence of sustainable business practices by incorporating Environmental, Social, and Governance performance and their disclosure. Though past studies investigated COVID-19’s impact on firm performance, there is consensus on the role of firms’ Environmental, Social, and Governance disclosures between firm performance and the pandemic. With this view, the study aims to examine the impact of COVID-19 on firms’ financial performance with the moderating role of Environmental, Social, and Governance performance disclosure. To do so, the study retrieved data of Nifty 500 index companies from the Bloomberg database for a sample period ranging from 2016 to 2022. To this end, the study performed the fixed-effect regression and GMM model. The findings reveal a significant negative impact of the pandemic on Return on Assets (β =-4.812), Return on Equity (β =–.675), and Earnings Per Share (β = –2.875), highlighting the unfavorable effect of the pandemic on firm performance. Further results showed that firms’ Environmental, Social, and Governance performance disclosure positively moderates the connection between COVID-19 and Return on Assets (β = 3.231), Return on Equity (β = 0.032), and Earnings Per Share (β = 1.523), respectively. This indicates that companies actively involved in Environmental, Social, and Governance disclosure are less likely to suffer during the pandemic in terms of financial performance due to their ESG disclosures.

Studying exoplanet atmospheres is essential for assessing their potential to host liquid water and their capacity to support life (their habitability). Each atmosphere uniquely influences the likelihood of surface liquid water, defining the habitable zone (HZ)—the region around a star where liquid water can exist. However, being within the HZ does not guarantee habitability, as life requires more than just liquid water. In this study, we adopted a two-pronged approach. First, we estimated the surface conditions of planets near the HZ’s inner edge under various atmospheric compositions. By utilizing a 3D climate model, we refined the inner boundaries of the HZ for planets with atmospheres dominated by H2 and CO2 for the first time. Second, we investigated microbial survival in these environments, conducting laboratory experiments on the growth and survival of E. coli K-12, focusing on the impact of different gas compositions. This innovative combination of climate modeling and biological experiments bridges theoretical climate predictions with biological outcomes. Our findings indicate that atmospheric composition significantly affects bacterial growth patterns, highlighting the importance of considering diverse atmospheres in evaluating exoplanet habitability and advancing the search for life beyond Earth.

A commercially available 100 kW PEM fuel cell system designed for efficient operation on ground-level was tested at low ambient pressures between 750 mbar and 940 mbar in a low-pressure chamber. The current–voltage characteristics at 940 mbar and 900 mbar showed only small differences, while the system performed worse at lower ambient pressures. To enable operation at these low pressures, an additional current-limiting strategy had to be implemented, as it was found that the compressor could not deliver sufficient mass flow at ambient pressures below 867 mbar to reach the maximum current allowed by the system (420 A). The results show that the fuel cell system, which was designed for ground-level applications, can be operated at lower pressures if the proposed current-limiting strategy is implemented, although at the cost of a lower maximum current output at low ambient pressures. Based on the results, suggestions for further hardware measures to optimise the system for flight conditions are made.

The adoption of financial technology (fintech) has the potential to make banking and financial services more accessible and convenient for all, but there are significant barriers preventing the adoption of fintech by street vendors and hawkers in India. This study aims to identify and analyse the barriers to fintech adoption using interpretive structural modelling (ISM). The research identified nine key barriers to fintech adoption, including perceived risk, lack of trust, lack of perceived benefit, social influence, lack of awareness, cash culture, lack of literacy, perceived ease of use, and lack of financial literacy. The study utilizes ISM to develop a hierarchy of these barriers and their interrelationships. The findings suggest that to promote the adoption of fintech, it is essential to build trust and awareness of fintech services through education and out-reach programs. This research provides a comprehensive understanding of the barriers to fintech adoption among street vendors and hawkers in India and offers insights into how these barriers can be overcomed. The study contributes to the development of strategies that can help promote the adoption of fintech among marginalized populations and advance financial inclusion in India.

Introduction: Hospitalizations during the coronavirus 2019 (COVID-19) pandemic peaked in New York in March–April 2020. In the months following, emergency department (ED) volumes declined. Our objective in this study was to examine the effect of this decline on the procedural experience of emergency medicine (EM) residents compared to the pre-pandemic period. Methods: We conducted this multicenter, retrospective cohort study of patients seen and key procedures performed by EM residents at hospitals spanning three Accreditation Committee for Graduate Medical Education-approved EM residencies in New York City and Nassau County, NY. We obtained numbers of procedures performed during May–July 2020 and compared them to the same time period for 2019 and 2018. We a priori classified critical care procedures—cardioversion, central lines, chest tubes, procedural sedation, and endotracheal intubation. We also studied “fast-track” procedures—fracture/joint reduction, incision and drainage (I&D), laceration repairs, and splints. Results: Total number of critical care procedures in the months following the COVID-19 peak decreased from 694 to 606 (−12.7%, 95% confidence interval [CI] 10.3–15.4%), compared to an increase from 642 to 694 (+8.1%, 95% CI 6.1–10.5%) the previous year (difference −9.3%). Total number of fast-track procedures decreased from 5,253 to 3,369 (−35.9%, 95% CI 34.6–37.2%), compared to a decrease from 5,333 to 5,253 (−1.5%, 95% CI 1.2–1.9%) the year before (difference −36.3%). Specific critical care procedures performed in 2020 compared to the mean of 2019 and 2018 as follows: cardioversion −33.3%; central lines +19.0%; chest tubes −27.9%; procedural sedation −30.8%; endotracheal intubation −13.8%. Specific fast-track procedures: reductions +33.3%; I&D −48.6%; laceration repair −17.3%; and splint application −49.8%. Conclusion: Emergency medicine residents’ critical and fast-track procedural experience at five hospitals was reduced during the months following the COVID-19 peak in comparison to a similar period in the two years prior. Training programs may consider increasing simulation-lab and cadaver-lab experiences, as well as ED and critical care rotations for their residents to offset this trend.

Abstract Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKLS132P in biological membranes and MLKLS132P overriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalent Mlkl S131P mutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells. In vivo, Mlkl S131P homozygosity reduces the capacity to clear Salmonella from major organs and retards recovery of hematopoietic stem cells. Thus, by dysregulating necroptosis, the S131P substitution impairs the return to homeostasis after systemic challenge. Present day carriers of the MLKL S132P polymorphism may be the key to understanding how MLKL and necroptosis modulate the progression of complex polygenic human disease.

Nowadays, cars are an essential part of daily life, and failures, especially of the engine, need to be avoided. Here, we used the determination of the battery voltage as a reference measurement to determine possible malfunctions. Thereby, we compared the use of a digital oscilloscope with the direct measurement of the battery voltage via the electronic control unit. The two devices were evaluated based on criteria such as price, sampling rate, parallel measurements, simplicity, and technical understanding required. Results showed that the oscilloscope (Picoscope 3204D MSO) is more suitable for complex measurements due to its higher sampling rate, accuracy, and versatility. The on-board diagnostics (VCDS HEX-V2) is more accessible to non-professionals, but it is limited in its capabilities. We found that the use of an oscilloscope, specifically the Picoscope, is preferable to measure battery voltage during the engine start-up process, as it provides more accurate and reliable results. However, further investigation is required to analyse numerous influences on the cranking process and the final decision for the appropriate measurement device is case specific.

ZRANB1 (human Trabid) missense mutations have been identified in children diagnosed with a range of congenital disorders including reduced brain size, but how Trabid regulates neurodevelopment is not understood. We have characterized these patient mutations in cells and mice to identify a key role for Trabid in the regulation of neurite growth. One of the patient mutations flanked the catalytic cysteine of Trabid and its deubiquitylating (DUB) activity was abrogated. The second variant retained DUB activity, but failed to bind STRIPAK, a large multiprotein assembly implicated in cytoskeleton organization and neural development. Zranb1 knock-in mice harboring either of these patient mutations exhibited reduced neuronal and glial cell densities in the brain and a motor deficit consistent with fewer dopaminergic neurons and projections. Mechanistically, both DUB-impaired and STRIPAK-binding-deficient Trabid variants impeded the trafficking of adenomatous polyposis coli (APC) to microtubule plus-ends. Consequently, the formation of neuronal growth cones and the trajectory of neurite outgrowth from mutant midbrain progenitors were severely compromised. We propose that STRIPAK recruits Trabid to deubiquitylate APC, and that in cells with mutant Trabid, APC becomes hyperubiquitylated and mislocalized causing impaired organization of the cytoskeleton that underlie the neuronal and developmental phenotypes.

Hereditary tyrosinemia type 1 is an inborn error of amino acid metabolism characterized by deficiency of fumarylacetoacetate hydrolase (FAH). Only limited treatment options (e.g., oral nitisinone) are available. Patients must adhere to a strict diet and face a life-long risk of complications, including liver cancer and progressive neurocognitive decline. There is a tremendous need for innovative therapies that standardize metabolite levels and promise normal development. Here, we describe an mRNA-based therapeutic approach that rescues Fah-deficient mice, a well-established tyrosinemia model. Repeated intravenous or intramuscular administration of lipid nanoparticle-formulated human FAH mRNA resulted in FAH protein synthesis in deficient mouse livers, stabilized body weight, normalized pathologic increases in metabolites after nitisinone withdrawal, and prevented early death. Dose reduction and extended injection intervals proved therapeutically effective. These results provide proof of concept for an mRNA-based therapeutic approach to treating hereditary tyrosinemia type 1 that is superior to the standard of care.

Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency in functional phenylalanine hydroxylase (PAH), resulting in accumulation of phenylalanine (Phe) in patients’ blood and organs. Affected patients encounter severe developmental delay, neurological deficits, and behavioral abnormalities when not treated. Early diagnosis and treatment are extremely important; newborn screening programs have been implemented in most countries to ensure early identification of patients with PKU. Despite available treatment options, several challenges remain: life-long adherence to a strict diet, approval of some medications for adults only, and lack of response to these therapies in a subpopulation of patients. Therefore, there is an urgent need for treatment alternatives. An mRNA-based approach tested in PKU mice showed a fast reduction in the accumulation of Phe in serum, liver and brain, the most significant organ affected. Repeated injections of LNP-formulated mouse PAH mRNA rescued PKU mice from the disease phenotype for a prolonged period of time. An mRNA-based approach could improve the quality of life tremendously in PKU patients of all ages by replacing standard-of-care treatments.

Hyperactivation of inflammasome-induced IL-1β can cause immunopathology and is a feature of autoinflammatory diseases. Here, the authors show how ubiquitination of IL-1β limits its activity by targeting it for proteasomal degradation and preventing its cleavage by caspase-1.

Summary: Pathogen recognition and TNF receptors signal via receptor interacting serine/threonine kinase-3 (RIPK3) to cause cell death, including MLKL-mediated necroptosis and caspase-8-dependent apoptosis. However, the post-translational control of RIPK3 is not fully understood. Using mass-spectrometry, we identified that RIPK3 is ubiquitylated on K469. The expression of mutant RIPK3 K469R demonstrated that RIPK3 ubiquitylation can limit both RIPK3-mediated apoptosis and necroptosis. The enhanced cell death of overexpressed RIPK3 K469R and activated endogenous RIPK3 correlated with an overall increase in RIPK3 ubiquitylation. Ripk3K469R/K469R mice challenged with Salmonella displayed enhanced bacterial loads and reduced serum IFNγ. However, Ripk3K469R/K469R macrophages and dermal fibroblasts were not sensitized to RIPK3-mediated apoptotic or necroptotic signaling suggesting that, in these cells, there is functional redundancy with alternate RIPK3 ubiquitin-modified sites. Consistent with this idea, the mutation of other ubiquitylated RIPK3 residues also increased RIPK3 hyper-ubiquitylation and cell death. Therefore, the targeted ubiquitylation of RIPK3 may act as either a brake or accelerator of RIPK3-dependent killing.

Background: Research suggests dyadic interventions can increase physical activity; such interventions are untested within postpartum parent couples. Methods: A three-armed pilot randomized trial addressed this gap and tested which type of dyadic intervention is most effective. Inactive postpartum mothers and a significant other were recruited in Australia (n = 143 assessed for eligibility) and randomised in a single-blinded fashion (i.e. participants were blinded) to 1 of 3 dyadic conditions involving a single face-to-face session with access to web-based group support: a minimal treatment control (n = 34), collaborative planning group (n = 38), or collaborative planning + need supportive communication group (n = 30). Participants were asked to wear their accelerometers for 8 days and completed self-report measures at baseline, end of intervention (week 4), and follow-up (week 12). We expected dyads in the collaborative planning + need supportive communication group would have the greatest increases in Physical Activity (PA), autonomous motivation, and partners’ need supportive behaviours; and decreases in controlled motivation and controlling partner behaviours. Results: Results from 51 dyads using Bayesian actor-partner interdependence models provided some evidence for a small positive effect on total PA at follow-up for postpartum mothers in the collaborative planning group and for partners in the collaborative planning + need supportive communication group. Furthermore, partners in the collaborative planning + need supportive communication group were more likely to engage in some vigorous PA. At follow-up, postpartum mothers in the collaborative planning + need supportive communication group scored lower on personal autonomous reasons. Conclusions: The impact of prior specification mean intervention effects need to be interpreted with caution. Progression to a full trial is warranted.

Mixed lineage kinase domain-like (MLKL) is the terminal protein in the pro-inflammatory necroptotic cell death program. Here the authors show that MLKL trafficking and plasma membrane accumulation are crucial necroptosis checkpoints, and that accumulation of phosphorylated MLKL at intercellular junctions promotes necroptosis.

Acquired resistance limits the efficacy of PARP inhibitors (PARPi) in high grade serous ovarian cancer (HGSOC). Here, the authors show that inhibition of RNA polymerase I transcription using CX-5461 increases the therapeutic efficacy of PARPi and overcomes PARPi resistance in PDX models of HGSOC.

For the optimal high-efficiency operation of a PEM fuel cell system, the temperature, pressure, humidity and mass flow of the supplied air must be tuned to the fuel cell stack requirements. Especially for aircraft applications, this requires a thorough understanding of the fuel cell air supply system behavior and how it changes when the ambient pressure is below 1 bar(a) during flight. This work investigates the influence of low inlet pressures and varying inlet temperatures on the compression map of an electrical turbo charger. This is especially relevant in airborne fuel cell application and not much literature can be found on that topic. Compressor limits are evaluated experimentally and theoretically. The theory of mass flow and speed correction is compared to experimental findings and found to be applicable for the surge and speed limit of the investigated turbo chargers as long as the compressor map is not limited by the power of the electric motor and inverter. Based on this, a prediction of the compressor map for altitudes up to 10,000 m is made with the help of a developed software tool.

In answer to calls for a 21st century reconsideration of traditional procedures of classroom writing, I offer student-created interactive fiction (IF) as a classroom exercise that blends digital literacy, games-based pedagogy, and writing practice. I find walking simulators like Firewatchand The Stanley Parable serveas effective models of IF games. The walking simulator genre shows that by promoting a sense of immersion, exploration, and letting players take their time, a game can reveal advanced narrativity and literariness, as well as a range of rhetorical possibilities. By workshopping IF platforms such as Twine or InkScript, students can learn to create their own textual walking simulators. In this way,they can engage in an accessible, text-based form of worldbuilding and learn to craft explorable, unfolding narratives that represent their research, point of view, or argument. This article explores the pedagogical potential of interactive fiction, discusses some of the literary possibilities found within walking simulators, offers some ideas about leading a composition classroom in reading and analyzing these games, and provides a brief overview of getting started with worldbuilding in Twine or Ink.

Prosthetic technology for people with missing limbs has made great progress in recent decades. However, acceptance rates and user satisfaction are not only dependent on technical aspects, but also to a great extent on social and psychological factors. We propose that these factors should receive greater attention in order to improve prosthetic care and give recommendations how to incorporate the findings from social science in research and development (R&D) and in care practice. Limited access due to high costs of new prosthetic technology combined with rising costs in health care systems in general is a further issue we address. Our legal and ethical analysis of the reimbursement process in Germany shows that this issue requires further empirical investigation, a stakeholder dialogue and maybe even policy changes. Social science knowledge and participatory methods are of high relevance to answer questions about the benefit of prosthetics for users, based on individual needs and preferences, which should be at the core of debates on ethical resource allocation.