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Abstract The phase diagram for the quasi-binary Tl2Se–Bi2Te3 system has been established based on the results of phase studies by differential thermal analysis (DTA) and X-ray diffraction (XRD). The diagram for the title system presented in this paper has been compared with that previously published by other authors. As a result of the research, a significant correction of the former phase diagram was made, because it was found that the components of the studied system formed three new chemical compounds. Obtained phase diagram has been compared with other thallium(I)–bismuth(III) chalcogenide systems.

Universities should increasingly collaborate with industries and international counterparts to meet the needs of students, businesses and other stakeholders. However, the literature has not provided a comprehensive response to these aspects of curriculum development. This study has two objectives: to propose a method of curriculum content development in higher education according to the stakeholder-centered quality assurance model and to verify this method based on a case study of a course on the green and digital transformation of small- and medium-sized enterprises (SMEs), as a new development trend. Based on the collaboration of institutions from five EU countries, including faculties and students from four universities, representatives of SMEs, non-governmental organizations and quality assurance institutions, a curriculum development process is proposed, and tested, and then, its implications are discussed. Including the perspectives of different international stakeholders, and integrating qualitative and quantitative methods, the process of curriculum content development is created. It consists of three stages: (1) the initial content proposition, (2) the initial modules and unit proposals, and (3) the final curriculum content. This process benefits from considering the viewpoints of diverse educational stakeholders and ensuring international consistency in curriculum content. While testing this process, the program content in the field of green and digital transformation of SMEs is created, and divided into four education modules, each consisting of three units, with all together 29 topics. Both the process of developing new curriculum content and the program for the green and digital transformation of SMEs can be implemented in the business higher education context.

Extreme weather events are recognized as major drivers of crop yield losses, which threaten food security and farmers’ incomes. Given the increasing frequency and intensity of extreme weather under climate change, it is crucial to quantify the related future yield damages of important crops to inform prospective climate change adaptation planning. In this study, we present a statistical modeling approach to project the changes in crop yields under climate change for eight majorly cultivated field crops in Germany, estimating the impacts of nine types of extreme weather events. To select the most relevant predictors, we apply the least absolute shrinkage and selection operator (LASSO) regression to district-level yield data.The LASSO models select, on average, 62% of the features, which align with well-known biophysical impacts on crops, suggesting that different extremes at various growth stages are relevant for yield prediction. We project on average 2.5-times more severe impacts on summer crops than on winter crops. Under RCP8.5, crop yields experience a mean change from −2.53% to −8.63% in the far future (2069–98) for summer crops and from −0.80% to −2.88% for winter crops, without accounting for CO2 fertilization effects. Heat impacts are identified as the primary driver of yield losses across all crops for 2069–98, while shifting precipitation patterns exacerbate winter and spring waterlogging, and summer and fall drought.Our findings underscore the utility of LASSO regression in identifying relevant drivers for projecting changes in crop yields across multiple crops, crucial for guiding agricultural adaptation. While the present analysis can identify empirical relationships, replicating these findings in biophysical models could provide new insights into the underlying processes.

It has become quite popular to question accepted scientific evidence, particularly as it pertains to the validity of various aspects of sport science. Recently, the concept of periodization has been questioned as to its usefulness and even its existence being described as “Myth.” It is the intent of the authors in this informed perspective to combat this idea through both a philosophical discussion on scientific theory as well as pointing out problems with their claim.

With the amendment to the German Climate Change Act in 2021, the Federal Government of Germany has set the target to become greenhouse gas neutral by 2045. Reaching this ambitious target requires multisectoral efforts, which in turn calls for interdisciplinary collaboration: the Net-Zero-2050 project of the Helmholtz Climate Initiative serves as an example of successful, interdisciplinary collaboration with the aim of producing valuable recommendations for action to achieve net-zero CO2 emissions in Germany. To this end, we applied an interdisciplinary approach to combining comprehensive research results from ten German national research centers in the context of carbon neutrality in Germany. In this paper, we present our approach and the method behind the interdisciplinary storylines development, which enabled us to create a common framework between different carbon dioxide removal and avoidance methods and the bigger carbon neutrality context. Thus, the research findings are aggregated into narratives: the two complementary storylines focus on technologies for net-zero CO2 emissions and on different framing conditions for implementing net-zero CO2 measures. Moreover, we outline the Net-Zero-2050 results emerging from the two storylines by presenting the resulting narratives in the context of carbon neutrality in Germany. Aiming at creating insights into how complementary and related expertise can be combined in teams across disciplines, we conclude with the project’s lessons learned. This paper sheds light on how to facilitate cooperation between different science disciplines with the purpose of preparing joint research results that can be communicated to a specific audience. Additionally, it provides further evidence that interdisciplinary and diverse research teams are an essential factor for defining solution spaces for complex, interdisciplinary problems.

ObjectivePreclinical models of seizures and epilepsy in rodents contributed substantially to the discovery of currently available antiseizure medications. These were also broadly used for investigation of processes of epileptogenesis. Nevertheless, rodent models pose some limitations, thus, new models using alternative species are in high demand. The aim of this study was to describe a new model of seizures/epilepsy induced by the cholinomimetic agent, pilocarpine (PILO), in larval zebrafish.MethodsLocal field potential (LFP) recordings were conducted to analyze electroencephalographic discharges and correlate it with larval behavior. Hematoxylin and eosin (H&E) staining, as well as TUNEL staining were performed to analyze morphology and apoptosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) was undertaken for gene expression analysis.ResultsAcute exposure to PILO, in a concentration-dependent manner, induces electroencephalographic discharges in larval zebrafish, which behaviorally manifest as decreased locomotion and moving time, but enhanced movement velocity. The PILO-induced seizure-like activity is behaviorally distinct from this induced by the application of chemoconvulsant pentylenetetrazole (PTZ). Zebrafish larvae previously exposed to PILO (2 h), after a washing out period, exhibit spontaneous, unprovoked discharges and apoptotic changes in their brains.SignificanceHere, we comprehensively investigated a new model of PILO-induced seizures/epilepsy in larval zebrafish. We propose that this model may be used to study epileptogenesis and for antiseizure drug screening purposes.

Abstract Background Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs. Methods Here, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs. Results scDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensive in vitro, in vivo, and in silico studies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn’s disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn’s disease patients. The analysis showed great variations in drug predictions between patients, for example, assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment. Conclusions We propose a computational framework, scDrugPrio, for drug prioritisation based on scRNA-seq of IMID disease. Application to individual patients indicates scDrugPrio’s potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package ( https://github.com/SDTC-CPMed/scDrugPrio ).

The main objective of this study was to evaluate the effects of different ischemic pressures applied during rest intervals on bar velocity during the bench press exercise. 10 resistance trained males (age = 23.2±2.7 years; body mass = 83.9±9 kg; body height = 181±5.2 cm; bench press 1 repetition maximum (1RM) = 125±16.4 kg; training experience = 5.4±3.4 years) participated in the study. During 4 experimental sessions, following a randomized crossover design, the subjects performed 5 sets of 3 repetitions of the bench press exercise with a load of 60% 1RM under conditions: with ischemia (50% or 80% of arterial occlusion pressure), with SHAM ischemia (20 mmHg) and without ischemia (control condition). For the ischemic conditions cuffs were applied before each set for 6.5 min and released 30 s before the start of the set as reperfusion (6.5 min ischemia + 0.5 min reperfusion). In the control condition, ischemia was not applied. The two-way repeated measures ANOVA showed no significant condition×set interaction for mean bar velocity (MV; p = 0.17) and peak bar velocity (PV; p = 0.66). There was also no main effect of condition for MV ( p = 0.58) and PV ( p = 0.61). The results indicate that ischemic or SHAM treatment (6.5 minutes ischemia or SHAM + 30 s reperfusion) does not affect mean and peak bar velocity during the bench press exercise regardless of the applied pressure.

The increase in the variety of nano-based tools offers new possibilities to approach the therapy of poorly treatable tumors, which includes glioblastoma multiforme (GBM; a primary brain tumor). The available nanocomplexes exhibit great potential as vehicles for the targeted delivery of anti-GBM compounds, including chemotherapeutics, nucleic acids, and inhibitors. The main advantages of nanoparticles (NPs) include improved drug stability, increased penetration of the blood–brain barrier, and better precision of tumor targeting. Importantly, alongside their drug-delivery ability, NPs may also present theranostic properties, including applications for targeted imaging or photothermal therapy of malignant brain cells. The available NPs can be classified into two categories according to their core, which can be metal or non-metal based. Among non-metal NPs, the most studied in regard to GBM treatment are exosomes, liposomes, cubosomes, polymeric NPs, micelles, dendrimers, nanogels, carbon nanotubes, and silica- and selenium-based NPs. They are characterized by satisfactory stability and biocompatibility, limited toxicity, and high accumulation in the targeted tumor tissue. Moreover, they can be easily functionalized for the improved delivery of their cargo to GBM cells. Therefore, the non-metal NPs discussed here, offer a promising approach to improving the treatment outcomes of aggressive GBM tumors.

Pro-environmental intentions encourage individuals to make conscious decisions that help protect the environment, reduce waste, conserve resources, and preserve natural habitats. This study aims to assess the predictive power of environmental concern, perceived behavioral control and social norms in determining the pro-environmental intentions in the Theory of Planned Behavior (TPB) framework. Methodologically we rely on Structural Equation Modelling (SEM), applied to the survey study among 2,702 university students majoring in economics, finance, management, or marketing from Croatia, the Czech Republic, Hungary, Poland, Slovakia, and Spain. The results show that the model explained 51% of the total variance of pro-environmental intentions, with the predictive power of environmental concern and perceived behavioral control at 42% and 45%, respectively, and social norms at only 6% (out of total 51% of explanatory power). The implications of our results suggest a major focus on increasing environmental concern and perceived behavioral control in behavioral interventions to support pro-environmental behavior. The effectiveness of social pressure produced by injunctive social norms proved limited. The cross-country differences were not statistically significant. More research must be done to study the relative effect of injunctive and descriptive social norms on pro-environmental behavior.

Abstract To reach their net‐zero targets, countries will have to compensate hard‐to‐abate CO2 emissions through carbon dioxide removal (CDR). Yet, current assessments rarely include socio‐cultural or institutional aspects or fail to contextualize CDR options for implementation. Here we present a context‐specific feasibility assessment of CDR options for the example of Germany. We assess 14 CDR options, including three chemical carbon capture options, six options for bioenergy combined with carbon capture and storage (BECCS), and five options that aim to increase ecosystem carbon uptake. The assessment addresses technological, economic, environmental, institutional, social‐cultural and systemic considerations using a traffic‐light system to evaluate implementation opportunities and hurdles. We find that in Germany CDR options like cover crops or seagrass restoration currently face comparably low implementation hurdles in terms of technological, economic, or environmental feasibility and low institutional or social opposition but show comparably small CO2 removal potentials. In contrast, some BECCS options that show high CDR potentials face significant techno‐economic, societal and institutional hurdles when it comes to the geological storage of CO2. While a combination of CDR options is likely required to meet the net‐zero target in Germany, the current climate protection law includes a limited set of options. Our analysis aims to provide comprehensive information on CDR hurdles and possibilities for Germany for use in further research on CDR options, climate, and energy scenario development, as well as an effective decision support basis for various actors.

The isometric mid-thigh pull (IMTP) is commonly used to measure isometric strength of characteristics of weightlifters. The isometric pull from the start position (IPSP) has not been studied as much as the IMTP but may potentially be a viable option for a weightlifting monitoring program. This study aims to compare isometric force-time characteristics from both the IMTP and IPSP to weightlifting competition performance. Collegiate weightlifters’ performances were compared to isometric peak force (IPF), rate of force development (RFD), and allometrically scaled peak force (IPFa) of both isometric testing protocols by a Pearson’s Correlation Coefficient. Strong correlations between weightlifting performance and force-time characteristics for both protocols were found with IPSP having slightly higher correlations. This suggests that both isometric testing protocols are viable tools for predicting weightlifting performance. It may be useful to include both protocols in a weightlifting monitoring program.

Hacktivism represents a dynamic intersection of technology and activism, where individuals or groups leverage digital tools to advance social or political causes. This text explores the multifaceted nature of hacktivism, encompassing a spectrum of activities from online protests and information dissemination to more disruptive forms of digital direct action.

Kynurenic acid (KYNA) is a metabolite of tryptophan formed on the kynurenine pathway. Its pharmacological effects are relatively well characterized in mammals, whereas its role in fish is poorly understood. Therefore, the aim of the study was to expand the knowledge of KYNA’s presence inside a fish’s body and its impact on fish development and function. The study was performed on zebrafish larvae and adult rainbow trout. We provide evidence that KYNA is present in the embryo, larva and mature fish and that its distribution in organs varies considerably. A study of KYNA’s effect on early larval development suggests that it can accelerate larval maturation, especially under conditions that are suboptimal for fish growth. Moreover, KYNA in concentrations over 1 mM caused morphological impairment and death of larvae. However, long-lasting exposure of larvae to subtoxic concentrations of KYNA does not affect the behavior of 5-day-old larvae kept under standard optimal conditions. We also show that ingestion of KYNA-supplemented feed can lead to KYNA accumulation, particularly in the pyloric caeca of mature trout. These results shed new light on the relevance of KYNA and provide new impulse for further research on the importance of the kynurenine pathway in fish.

Abstract Bivalve mollusc meat—that from mussels, clams, and oysters—offers a highly sustainable and nutritious alternative to meat from other shellfish, fish, or livestock. However, bivalves are an unpopular mass market food relative to these other meat items, limiting our ability to reap potential environmental and health benefits. Hence, this study aimed to assess current barriers to and drivers for bivalve consumption and investigated whether offering bivalves in a highly transformed (i.e., more processed) product format might help to drive consumption. The United Kingdom was used as a case study, and the study was performed via an online survey. Nutrition and quality of ingredients were key drivers, and price and convenience key barriers to bivalve consumption, with views on taste/smell/texture mixed. The more regularly individuals consumed meat, the more willing they were to try bivalves, and those who thought bivalves were healthier or more environmentally friendly than livestock were more likely to substitute bivalves for meat. Importantly, individuals were more willing to substitute highly transformed than minimally transformed (i.e., unprocessed) meats for bivalves. They were also willing to pay more for highly transformed bivalves than any other highly transformed meat product. We suggest that greater publicity regarding the health and environmental benefits of bivalve meat, and industry engagement to develop and pilot a greater range of appealing, affordable, and convenient bivalve products, are key actions that can help drive growth in the bivalve sector for planetary benefit.

Abstract Background Elite swimmers may be predisposed to disturbances in the range of motion (ROM) of hip joints and spinal curvatures, which are a factor that induces body’s compensatory mechanisms that may have an impact on sports training, athletic performance and health. This study aimed to identify compensatory mechanisms in body posture of elite Para and able-bodied swimmers (spinal curvatures, ROM), to indicate the dominant locations of the compensatory mechanisms in the groups of Para and able-bodied athletes, and to identify and compare the prevalence and location of musculoskeletal pain from the last week and the last six months in the context of compensatory mechanisms. Methods Thirty-five (nF = 8; nM = 27; age = 20.51 ± 4.24) elite Para and able-bodied swimmers from the Polish national team took part in the study and were divided into: study group (SG) of Para swimmers and control group (CG) of able-bodied swimmers. Depth of the anteroposterior spinal curvatures and sagittal spinal mobility testing were evaluated with a Medi Mouse device. The prevalence and locations of musculoskeletal pain were assessed with a Nordic Musculoskeletal Questionnaire for the last seven days (NMQ-7) and the last six months (NMQ-6). Results In both groups lumbar hypolordosis, anterior pelvic tilt and pain in the shoulders, lower back and hips/thighs (NMQ-7) were reported the most frequent. In SG several significant relationships were found between duration of sport-specific training experience (years) and depth of angle the lumbar lordosis, the depth of the angle of pelvic inclination the ROM in the lumbar spine and thoracic spine, what was not reported in CG. Conclusions Extrinsic compensatory mechanism was identified in both study groups, however only in SG it occurred as structural (depth of the angle of lumbar lordosis and pelvic inclination) and functional changes (ROM in the thoracic and lumbar spine) in the body posture. Internal compensatory mechanism was identified in SG, however external compensation showed only partially suppressive character regarding to internal compensation. The locations of the musculoskeletal complaints seems to result from both internal compensatory mechanism (SG) and continuous overload of the anatomy trains as a result of swimming training (SG, CG).

This article attends to the intimate contradictions that differentially shape and limit caring capacities and relations in a violent world, and the embodied ethical and political transformations at the heart of learning to care otherwise. From manifestos calling for ‘universal care’ in defiance of the state-sanctioned horrors of the pandemic era, to the abolitionist politics of care developed by BLM organizers through movement building and healing, and the proliferation of mutual-aid infrastructures to meet needs and distribute resources in the face of overwhelming crisis and neglect—these examples and so many others illustrate with undeniable clarity that radical care is finally on the agenda. In what follows, I hope to contribute to this urgent conversation by pointing to how care is shaped in fundamentally contradictory ways under conditions of entrenched structural violence, and the limitations of normative frameworks when confronting this reality. To unambiguously valorize care in ethical and political life is to risk occluding the constitutive violence of existing social structures and norms, its impact on the intimacies of caring relations, and ultimately the ways that communities mobilize alternate economies and practices of care towards healing and social change. While it is crucial to value care and work for a more caring society, I claim that efforts to transform patterns of relational harm and develop new sensibilities should also be highlighted as integral components of radical caring praxis.

Changes in human behaviors, such as reductions of physical contacts and the adoption of preventive measures, impact the transmission of infectious diseases considerably. Behavioral adaptations may be the result of individuals aiming to protect themselves or mere responses to public containment measures, or a combination of both. What drives autonomous and policy-induced adaptation, how they are related and change over time is insufficiently understood. Here, we develop a framework for more precise analysis of behavioral adaptation, focusing on confluence, interactions and time variance of autonomous and policy-induced adaptation. We carry out an empirical analysis of Germany during the fall of 2020 and beyond. Subsequently, we discuss how behavioral adaptation processes can be better represented in behavioral-epidemiological models. We find that our framework is useful to understand the interplay of autonomous and policy-induced adaptation as a "moving target". Our empirical analysis suggests that mobility patterns in Germany changed significantly due to both autonomous and policy-induced adaption, with potentially weaker effects over time due to decreasing risk signals, diminishing risk perceptions and an erosion of trust in the government. We find that while a number of simulation and prediction models have made great efforts to represent behavioral adaptation, the interplay of autonomous and policy-induced adaption needs to be better understood to construct convincing counterfactual scenarios for policy analysis. The insights presented here are of interest to modelers and policy makers aiming to understand and account for behaviors during a pandemic response more accurately.

BackgroundGlobal and national surveillance efforts have tracked COVID-19 incidence and clinical outcomes, but few studies have compared comorbid conditions and clinical outcomes across each wave of the pandemic. We analyzed data from the COVID-19 registry of a large urban healthcare system to determine the associations between presenting comorbidities and clinical outcomes during the pandemic.MethodsWe analyzed registry data for all inpatients and outpatients with COVID-19 from March 2020 through September 2022 (N = 44,499). Clinical outcomes were death, hospitalization, and intensive care unit (ICU) admission. Demographic and clinical outcomes data were analyzed overall and for each wave. Unadjusted and multivariable logistic regressions were performed to explore the associations between age, sex, race, ethnicity, comorbidities, and mortality.ResultsWaves 2 and 3 (Alpha and Delta variants) were associated with greater hospitalizations, ICU admissions, and mortality than other variants. Chronic pulmonary disease was the most common comorbid condition across all age groups and waves. Mortality rates were higher in older patients but decreased across all age groups in later waves. In every wave, mortality was associated with renal disease, congestive heart failure, cerebrovascular disease, diabetes, and chronic pulmonary disease. Multivariable analysis found that liver disease and renal disease were significantly associated with mortality, hospitalization, and ICU admission, and diabetes was significantly associated with hospitalization and ICU admission.ConclusionThe COVID-19 registry is a valuable resource to identify risk factors for clinical outcomes. Our findings may inform risk stratification and care planning for patients with COVID-19 based on age and comorbid conditions.

The intracellular level of podoplanin (PDPN), a transmembrane protein of still unclear function, is frequently altered in metastatic tumors. High expression of PDPN is frequently observed in papillary thyroid cancer (PTC) specimens. Similarly, PTC-derived cell lines (BCPAP and TPC1, harboring the BRAF V600E mutation and RET/PTC1 fusion, respectively), also present enhanced PDPN yield. We previously reported that depletion of PDPN impairs migration of TPC1 cells, but augments metastasis of BCPAP cells. Interestingly, this phenomenon stays in contrast to the migratory pattern observed for wild-type cells, where TPC1 exhibited higher motility than BCPAP cells. Here, we aimed to elucidate the potential role of PDPN in regulation of molecular mechanisms leading to the diverse metastatic features of the studied PTC-derived cells. We consider that this phenomenon may be caused by alternative regulation of signaling pathways due to the presence of the mutated BRAF allele or RET/PTC1 fusion. The high-throughput RNA sequencing (RNA-seq) technique was used to uncover the genes and signaling pathways affected in wild-type and PDPN-depleted TPC1 and BCPAP cells. We found that changes in the expression of various factors of signaling pathways, like RHOA and RAC1 GTPases and their regulators, are linked with both high PDPN levels and presence of the BRAF V600E mutation. We imply that the suppressed motility of wild-type BCPAP cells results from overactivation of RHOA through natively high PDPN expression. This process is accompanied by inhibition of the PI3K kinase and consequently RAC1, due to overactivation of RAS-mediated signaling and the PTEN regulator.

The competitiveness is a multidimensional concept, being analysed at different levels. National and company competitiveness are deeply investigated, however, less attention is given to regional competitiveness. The importance of regional competitiveness arises from the factuality that it creates the quality of local conditions for companies' operations. Following this rational, two main goals of this researchare accepted. First goal is to model the impact of selected determinants on regional competitiveness, using a multiple linear regression model. The second goal is to propose activities that need to be implemented with the aim to improve the competitive performance of the analyzed regions. The model proves the positive impact of international exchange, human resources, and innovation, so future measures and activities at the regional, city and municipal levels need to be focused on strengthening these determinants.

Many animals avoid predation using aposematic displays that pair toxic/dangerous defences with conspicuous achromatic warning patterns, such as high-contrast stripes. To understand how these prey defences work, we need to understand the decision-making of visual predators. Here we gave two species of jumping spiders (Phidippus regius and Habronattus trimaculatus) choice tests using live termites that had their back patterns manipulated using paper capes (solid white, solid black, striped). For P. regius, black and striped termites were quicker to capture attention. Yet despite this increased attention, striped termites were attacked at lower rates than either white or black. This suggests that the termite's contrast with the background elicits attention, but the internal striped body patterning reduces attacks. Results from tests with H. trimaculatus were qualitatively similar but did not meet the threshold for statistical significance. Additional exploratory analyses suggest that attention to and aversion to stripes is at least partially innate and provide further insight into how decision-making played out during trials. Because of their rich diversity (over 6500 species) that includes variation in natural history, toxin susceptibility and degree of colour vision, jumping spiders are well suited to test broad generalizations about how and why aposematic displays work.

The aim of this article is to examine whether the cross-country and gender variations of entrepreneurship can be explained within the institutional framework. The study addresses normative forces to which entrepreneurs are expected to adapt within European welfare states. The normative forces are focused on norm-based factors of governmental quality and value-based factors of governmental generosity, which are both hypothesized to be associated with entrepreneurship at the level of society and furthermore from the gender perspective. To verify our hypotheses, the research was conducted among 28 European countries in the years 2012 to 2018. We adopted the macro-level of analysis and undertook panel data analysis (PDA). We estimated the econometric models with entrepreneurship rates as dependent variables and those with norm-based and value-based factors as independent variables. The results confirm that norm-based factors are associated with entrepreneurship and there are significant differences in the responses of female and male entrepreneurial activities to the quality of government. However, we did not find supporting evidence for the statistically significant impact of governmental generosity on entrepreneurship. The novelty of our research is in implementing institutional theory into the discussion on entrepreneurship from the welfare state perspective, by introducing the concept of norm-based and value-based factors which reflect the quality and generosity of the government. We also distinguish between the impact of governmental quality and generosity on entrepreneurship from the gender perspective to contribute to the discussion on the gender gap in entrepreneurship.

Abstract Aim The Universal Definition of Heart Failure (UDHF) provides a framework for staging risk for HF events. It is not clear whether prognostic biomarkers have different meaning across UDHF stages. We sought to evaluate performance of biomarkers to predict HF events among high‐risk patients undergoing coronary and/or peripheral angiography categorized into UDHF stages. Methods One thousand two hundred thirty‐five individuals underwent coronary and/or peripheral angiography were enrolled. Study participants were categorized into UDHF Stage A (at risk), Stage B (pre‐HF), and Stage C or D (HF, including end stage) and grouped into Stage A/B and C/D. Biomarkers and clinical variables were used to develop prognostic models. Other measures examined included total HF hospitalizations. Results Over a median of 3.67 years of follow‐up, 155 cardiovascular (CV) deaths occurred, and 299 patients were hospitalized with acute HF. In patients with Stage A/B, galectin‐3 (HR = 1.52, P = 0.03), endothelin‐1 (HR = 2.16, P = 0.001), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP; HR = 1.43, P

Background Individuals who experience assaultive firearm injury are at elevated risk for violent reinjury and multiple negative physical and psychological health outcomes. Hospital-based violence intervention programs (HVIPs) may improve patient outcomes through intensive, community-based case management.Methods We conducted a multimethod evaluation of an emerging HVIP at a large trauma center using the RE-AIM framework. We assessed recruitment, violent reinjury outcomes, and service provision from 2020 to 2022. Semistructured, qualitative interviews were performed with HVIP participants and program administrators to elicit experiences with HVIP services. Directed content analysis was used to generate and organize codes from the data. We also conducted clinician surveys to assess awareness and referral patterns.Results Of the 319 HVIP-eligible individuals who presented with non-fatal assaultive firearm injury, 39 individuals (12%) were enrolled in the HVIP. Inpatient admission was independently associated with HVIP enrollment (OR 2.6, 95% CI 1.3 to 5.2; p=0.01). Facilitators of Reach included engaging with credible messengers, personal relationships with HVIP program administrators, and encouragement from family to enroll. Fear of disclosure to police was cited as a key barrier to enrollment. For the Effectiveness domain, enrollment was not associated with reinjury (OR 0.70, 95% CI 0.16 to 3.1). Participants identified key areas of focus where needs were not met including housing and mental health. Limited awareness of HVIP services was a barrier to Adoption. Participants described strengths of Implementation, highlighting the deep relationships built between clients and administrators. For the long-term Maintenance of the program, both clinicians and HVIP clients reported that there is a need for HVIP services for individuals who experience violent injury.Conclusions Credible messengers facilitate engagement with potential participants, whereas concerns around police involvement is an important barrier. Inpatient admission provides an opportunity to engage patients and may facilitate recruitment. HVIPs may benefit from increased program intensity.Level of evidence IV.

Traditionally, selected plant sources have been explored for medicines to treat convulsions. This continues today, especially in countries with low-income rates and poor medical systems. However, in the low-income countries, plant extracts and isolated drugs are in high demand due to their good safety profiles. Preclinical studies on animal models of seizures/epilepsy have revealed the anticonvulsant and/or antiepileptogenic properties of, at least some, herb preparations or plant metabolites. Still, there is a significant number of plants known in traditional medicine that exert anticonvulsant activity but have not been evaluated on animal models. Zebrafish is recognized as a suitable in vivo model of epilepsy research and is increasingly used as a screening platform. In this review, the results of selected preclinical studies are summarized to provide credible information for the future development of effective screening methods for plant-derived antiseizure/antiepileptic therapeutics using zebrafish models. We compared zebrafish vs. rodent data to show the translational value of the former in epilepsy research. We also surveyed caveats in methodology. Finally, we proposed a pipeline for screening new anticonvulsant plant-derived drugs in zebrafish (“from tank to bedside and back again”).

In the human body, the majority of tryptophan is metabolized through the kynurenine pathway. This consists of several metabolites collectively called the kynurenines and includes, among others, kynurenic acid, L-kynurenine, or quinolinic acid. The wealth of metabolites, as well as the associated molecular targets and biological pathways, bring about a situation wherein even a slight imbalance in the kynurenine levels, both in the periphery and central nervous system, have broad consequences regarding general health. Cinnabarinic acid (CA) is the least known trace kynurenine, and its physiological and pathological roles are not widely understood. Some studies, however, indicate that it might be neuroprotective. Information on its hepatoprotective properties have also emerged, although these are pioneering studies and need to be replicated. Therefore, in this review, I aim to present and critically discuss the current knowledge on CA and its role in physiological and pathological settings to guide future studies.

The aim of this article is to review the single photon emission computed tomography (SPECT) segmentation methods used in patient-specific dosimetry of 177Lu molecular therapy. Notably, 177Lu-labelled radiopharmaceuticals are currently used in molecular therapy of metastatic neuroendocrine tumours (ligands for somatostatin receptors) and metastatic prostate adenocarcinomas (PSMA ligands). The proper segmentation of the organs at risk and tumours in targeted radionuclide therapy is an important part of the optimisation process of internal patient dosimetry in this kind of therapy. Because this is the first step in dosimetry assessments, on which further dose calculations are based, it is important to know the level of uncertainty that is associated with this part of the analysis. However, the robust quantification of SPECT images, which would ensure accurate dosimetry assessments, is very hard to achieve due to the intrinsic features of this device. In this article, papers on this topic were collected and reviewed to weigh up the advantages and disadvantages of the segmentation methods used in clinical practice. Degrading factors of SPECT images were also studied to assess their impact on the quantification of 177Lu therapy images. Our review of the recent literature gives an insight into this important topic. However, based on the PubMed and IEEE databases, only a few papers investigating segmentation methods in 177Lumolecular therapy were found. Although segmentation is an important step in internal dose calculations, this subject has been relatively lightly investigated for SPECT systems. This is mostly due to the inner features of SPECT. What is more, even when studies are conducted, they usually utilise the diagnostic radionuclide 99mTc and not a therapeutic one like 177Lu, which could be of concern regarding SPECT camera performance and its overall outcome on dosimetry.

Aim: For paediatric patients and families, resuscitation can be an extremely stressful experience with significant medical and psychological consequences. Psychological sequelae may be reduced when healthcare teams apply patient- and family-centered care and trauma-informed care, yet there are few specific instructions for effective family-centered or trauma-informed behaviours that are observable and teachable. We aimed to develop a framework and tools to address this gap. Methods: We reviewed relevant policy statements, guidelines, and research to define core domains of family-centered and trauma-informed care, and identified observable evidence-based practices in each domain. We refined this list of practices via review of provider/team behaviours in simulated paediatric resuscitation scenarios, then developed and piloted an observational checklist. Results: Six domains were identified: (1) Sharing information with patient and family; (2) Promoting family involvement in care and decisions; (3) Addressing family needs and distress; (4) Addressing child distress; (5) Promoting effective emotional support for child; (6) Practicing developmental and cultural competence. A 71-item observational checklist assessing these domains was feasible for use during video review of paediatric resuscitation. Conclusion: This framework can guide future research and provide tools for training and implementation efforts to improve patient outcomes through patient- and family-centered and trauma-informed care.

Initial investigations on oxidation behaviour and phase transformations of equimolar AlCoCrCuNi high entropy alloy with and without 1 at.% silicon addition during 24-hr exposure to air atmosphere at 1273 K was carried out in this work. After determining the oxidation kinetics of the samples by means of thermogravimetric analysis, the morphology, chemical and phase compositions of the oxidized alloys were determined by means of scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction analysis. Additional cross-section studies were performed using transmission electron microscopy combined with energy dispersive X-ray spectroscopy and selected area electron diffraction. From all these investigations, it can be concluded that minor silicon addition improves the oxidation kinetics and hinders the formation of an additional FCC structure near the surface of the material.

Background: Acromioclavicular (AC) joint separation is a common cause of shoulder injury among athletes. High-grade injuries may require operative fixation, and comprehensive return-to-play guidelines have not yet been established. The purpose of this study was to summarize criteria for return to play after operative management of AC joint separation. Methods: A systematic review of the literature was performed from January 1999 to April 2020 to evaluate clinical evidence regarding criteria for return to play after operative management of isolated AC joint separation. Results: Sixty-three studies with at least 1 explicitly stated return-to-play criterion were identified out of an initial database search of 1253 published articles. Eight separate categories of return-to-play criteria were identified, the most common of which was time from surgery (95.2%). Return-to-play timelines ranged from 2 to 12 months, the most common timeline being 6 months (37.8%). Only 4 (6.3%) studies used conditional criteria to guide return to play, which included range of motion, strength, clinical stability, radiographic stability, functional assessment, safety assessment, and hardware removal. Conclusion: Most published studies use only time-based criteria for return to play after surgery for AC joint separation, and only a small number of studies use additional subjective or objective criteria. While this systematic review helps provide a foundation for developing a comprehensive return-to-play checklist, further investigation is needed to establish safe and effective guidelines that will enable athletes to safely return to sport and minimize the recurrence of injury.

Abstract Background Medical digital twins are computational disease models for drug discovery and treatment. Unresolved problems include how to organize and prioritize between disease-associated changes in digital twins, on cellulome- and genome-wide scales. We present a dynamic framework that can be used to model such changes and thereby prioritize upstream regulators (URs) for biomarker- and drug discovery. Methods We started with seasonal allergic rhinitis (SAR) as a disease model, by analyses of in vitro allergen-stimulated peripheral blood mononuclear cells (PBMC) from SAR patients. Time-series a single-cell RNA-sequencing (scRNA-seq) data of these cells were used to construct multicellular network models (MNMs) at each time point of molecular interactions between cell types. We hypothesized that predicted molecular interactions between cell types in the MNMs could be traced to find an UR gene, at an early time point. We performed bioinformatic and functional studies of the MNMs to develop a scalable framework to prioritize UR genes. This framework was tested on a single-cell and bulk-profiling data from SAR and other inflammatory diseases. Results Our scRNA-seq-based time-series MNMs of SAR showed thousands of differentially expressed genes (DEGs) across multiple cell types, which varied between time points. Instead of a single-UR gene in each MNM, we found multiple URs dispersed across the cell types. Thus, at each time point, the MNMs formed multi-directional networks. The absence of linear hierarchies and time-dependent variations in MNMs complicated the prioritization of URs. For example, the expression and functions of Th2 cytokines, which are approved drug targets in allergies, varied across cell types, and time points. Our analyses of bulk- and single-cell data from other inflammatory diseases also revealed multi-directional networks that showed stage-dependent variations. We therefore developed a quantitative approach to prioritize URs: we ranked the URs based on their predicted effects on downstream target cells. Experimental and bioinformatic analyses supported that this kind of ranking is a tractable approach for prioritizing URs. Conclusions We present a scalable framework for modeling dynamic changes in digital twins, on cellulome- and genome-wide scales, to prioritize UR genes for biomarker and drug discovery.

Abstract Mother’s milk is widely recommended as complete food for the offspring in earliest postnatal time. However, the knowledge about detailed composition and the physiological role of bioactive components of breast milk is incomplete. Therefore, the aim of our study was to determine the content of kynurenine (KYN) in human breast milk during lactation and to explore the effects exerted by intragastric KYN administration from birth to weaning on physical and psychomotor development of adult rats. We found that KYN is consistently present in human milk and its content gradually increased from day 4 to 28 after delivery and that it is present in commercial baby formulas in amounts noticeably exceeding its physiological range. Animal studies showed that KYN supplementation resulted in a marked elevation of absorptive surface of rat intestine and in enhanced expression of both, aryl hydrocarbon receptor and G protein-coupled receptor 35 in the intestinal tissue in rats. Moreover, we discovered that KYN administration from birth to weaning resulted in neurobehavioral changes in adult rats. Therefore, we postulate that further research is required to thoroughly understand the function of KYN in early developmental stages of mammals and to ensure the safety of its presence in baby food products.

Abstract Background This paper describes a unique case—the first case of multiple fractures of the thoracic vertebrae caused by a low-voltage electric shock. Case presentation A 22-year-old male patient was diagnosed with compression fractures of Th2–Th6 caused by a muscle spasm resulting from an electric shock. The patient was treated conservatively using a cervico-thoracic support corset. After rehabilitation, the patient has regained his physiological movement of the spine without any back pain. Conclusions Albeit vertebral fractures caused by electric shock injury are extremely rare, clinicians should always keep in mind this diagnosis, especially when clinical symptoms such as pain and limitation of movement are present.

Implementation of screening modalities has reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy. In this prospective multicenter study, 8 blood-based biomarkers (carcinoembryonic antigen, ferritin, high-sensitivity C-reactive protein, human epididymis protein 4, Cyfra21-1, hepsin, interleukin 8, and osteoprotegerin) were investigated in 1977 FIT-positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on Architect i2000, Architect c8000 (both from Abbott, Chicago, Ill, USA), or Luminex xMAP machines (MilliporeSigma, St. Louis, Mo, USA). FIT analyses and blood-based biomarker data were combined with clinical data (ie, age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity. The cohort included individuals with CRC (n = 240), adenomas (n = 938), or no neoplastic lesions (n = 799). The cross-validated algorithm combining the 8 biomarkers, quantitative FIT result, and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (area under the receiver operating characteristic curve, 0.77 vs 0.67, respectively; P <.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the areas under the receiver operating characteristic curve were 0.68 versus 0.64 for the algorithm and FIT model, respectively. The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenoma detection rates or vice versa. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Early diagnosis of hepatitis C virus (HCV) infection is essential for prompt initiation of treatment and prevention of transmission, yet several logistical barriers continue to limit access to HCV testing. Dried blood spot (DBS) technology involves a simple fingerstick that eliminates the need for trained personnel, and DBS can be stored and transported at room temperature. We evaluated the use of DBS whole blood samples in the modified Abbott ARCHITECT anti-HCV assay, comparing assay performance against the standard assay run using DBS and venous plasma samples. 144 HCV positive and 104 HCV negative matched venous plasma and whole blood specimens were selected from a retrospective study with convenience sampling in Cameroon. Results obtained using a modified volume DBS assay were highly correlated to the results of the standard assay run with plasma on clinical samples and dilution series (R2 = 0.71 and 0.99 respectively). The ARCHITECT Anti-HCV assay with input volume modification more accurately detects HCV antibodies in DBS whole blood samples with 100% sensitivity and specificity, while the standard assay had 90.97% sensitivity. The use of DBS has the potential to expand access to HCV testing to underserved or marginalized populations with limited access to direct HCV care.

Abstract Background With the dynamic development of professional Paralympic sport, the prevalence of musculoskeletal pain and structural and/or functional disturbances in Para athletes constantly increases. The aim of the study was to evaluate the impact of internal compensatory mechanisms on selected aspects of body structure and function in elite sitting volleyball players. Methods The study included eighteen elite sitting volleyball players (male; n = 12, female; n = 6, age; 36.0 ± 6.1, body mass; 76.6 ± 16.1, body height; 179.3 ± 0.1) from the Polish national team. Retrospective and direct participatory observation methods were used in the study. NMQ-7 was used to assess the current prevalence and location of musculoskeletal pain. The evaluation of spinal curvature and pelvic inclination was performed using a non-invasive Medi Mouse method (Idiag M360) in three different trunk positions. All statistical analyses were performed using Statistica 13.3 software package. Results Lumbar hypolordosis was a predominant sagittal deviation of spinal curvature (n = 15;83%). Low back pain (LBP) and neck pain were the most frequent complaints (50%). Statistically significant differences in the values of thoracic kyphosis angle, pelvic inclination, and spine length (SL) in sagittal standing flexion and extension were found. However, there was no statistically significant difference in sagittal standing flexion for the lumbar lordosis angle with a simultaneous significant change in pelvic inclination (66.9°). Moreover, a tendency to interpenetration of relationships between variables that characterize (a) body structure and (b) function of the spine and musculoskeletal pain were observed. Shoulder pain correlated with SL (R = 0.6; p