Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation.

Enteroendocrine cells (EECs) secrete serotonin (enterochromaffin [EC] cells) or specific peptide hormones (non-EC cells) that serve vital metabolic functions. The basis for terminal EEC diversity remains obscure. By forcing activity of the transcription factor (TF) NEUROG3 in 2D cultures of human intestinal stem cells, we replicated physiologic EEC differentiation and examined transcriptional and cis-regulatory dynamics that culminate in discrete cell types. Abundant EEC precursors expressed stage-specific genes and TFs. Before expressing pre-terminal NEUROD1, post-mitotic precursors oscillated between transcriptionally distinct ASCL1+ and HES6hi cell states. Loss of either factor accelerated EEC differentiation substantially and disrupted EEC individuality; ASCL1 or NEUROD1 deficiency had opposing consequences on EC and non-EC cell features. These TFs mainly bind cis-elements that are accessible in undifferentiated stem cells, and they tailor subsequent expression of TF combinations that underlie discrete EEC identities. Thus, early TF oscillations retard EEC maturation to enable accurate diversity within a medically important cell lineage.

Sensory, emotional, and appropriateness of plant- and meat-based burgers.

The plant-based meat alternative market is experiencing rapid growth. However, whether this growth extends to mainstream consumers will depend on the sensory profile, emotional profile, and situational appropriateness of these products. This study provides a sensory comparison between two plant-based burgers, one hybrid burger, and a conventional 100% ground beef burger. The sensory evaluation was carried out under blind and informed conditions using a between-subject design. Participants (n = 177) were asked to rate the appearance, flavor, odor, and texture of each product and indicate their overall liking. In addition, 26 sensory terms were evaluated using the rate-all-that-apply technique. The study also measured the emotional profile and the situational appropriateness elicited by each product using the check-all-that-apply technique. The results showed that (a) in the blind condition, there were no significant differences observed in overall liking across the four burgers; (b) the plant-based burger made with pea protein received the lowest overall liking score, and its evaluation was not positively influenced by product information disclosure; (c) providing product information influenced the perceived intensity of the attributes associated with meat; (d) discriminatory ability for emotions was higher in the informed condition; and (e) for the situational appropriateness, when prioritizing healthy eating, participants considered plant-based burgers more suitable than the groundbeef burger. PRACTICAL APPLICATION: Our results demonstrate that product descriptions could have an impact on consumer acceptance of different meat burger alternatives. In order to launch successfull meat alternatives, product developers and communication marketing specialists should consider the extent to which these alternatives resemble regular meat products in terms of their sensory and emotional profiles and context of use.

HoopTransformer: Advancing NBA Offensive Play Recognition with Self-Supervised Learning from Player Trajectories.

BACKGROUND AND OBJECTIVE: Understanding and recognizing basketball offensive set plays, which involve intricate interactions between players, have always been regarded as challenging tasks for untrained humans, not to mention machines. In this study, our objective is to propose an artificial intelligence model that can automatically recognize offensive plays using a novel self-supervised learning approach. METHODS: The dataset was collected by SportVU from 632 games during the 2015-2016 season of the National Basketball Association (NBA), with a total of 90,524 possessions. A multi-agent motion prediction pretraining model was built on the basis of axial-attention transformer and trained with different masking strategies: motion prediction (MP), motion reconstruction (MR), and MP + MR joint strategy. A downstream play-level classification task and similarity search were used to evaluate the models' performance. RESULTS: The results showed that the MP + MR joint masking strategy maximized the ability of the model compared with individual masking strategies. For the classification task, the joint strategy achieved a top-1 accuracy of 81.5% and top-3 accuracy of 97.5%. In the similarity search evaluation, the joint strategy attained a top-5 accuracy of 76% and top-10 accuracy of 59%. Additionally, with the same MP + MR joint masking strategy, our HoopTransformer model outperformed the two baseline models in the classification task and similarity search. CONCLUSION: This study presents a self-supervised learning model and demonstrates the effectiveness and potential of the model in accurately comprehending and capturing player movements and complex interactions during offensive plays.

Adherence to the Mediterranean Diet and its association with sustainable dietary behaviors, sociodemographic factors, and lifestyle: a cross-sectional study in US University students.

BACKGROUND: Promoting healthy and sustainable diets is increasingly important and the Mediterranean Diet (MD) has been recognized as an appropriate example that can be adapted to different countries. Considering that the college years are the time when US young adults are most likely to adopt unhealthy eating habits, the present study assessed adherence to the MD and the sustainability of dietary behaviors in a nationally representative sample of US university students, aiming to identify crucial levers for improving their eating behaviors. METHODS: MD adherence and the adoption of healthy and sustainable dietary patterns were assessed through the KIDMED and the Sustainable-HEalthy-Diet (SHED Index questionnaires, respectively, administered through an online survey that also included sociodemographic and behavioral questions. Non-parametric and logistic regression analyses were performed. RESULTS: A sample of 1485 participants (median (IQR) age 21.0 (19.0-22.0); 59% women) correctly completed the survey. A medium adherence to the MD was the most prevalent (47%). According to multivariate logistic regression analysis, the likelihood of being more compliant with the MD increased when meeting physical activity recommendations, having a high SHED Index score, having the willingness to purchase and eat healthy and sustainable dishes, eating ultra-processed plant-based meat alternatives foods daily, and regularly attending the university canteen. CONCLUSIONS: Encouraging dietary patterns rich in plant-based foods and with a moderate intake of animal products is crucial to increasing the adoption of healthy and sustainable diets, and university dining services represent a suitable setting to build a supportive environment that educates students on human and planetary health.

Analysis of Madrid Primary Health-Care staff for the implementation of exercise prescription.

OBJECTIVE: To assess the self-perception of nurses and general practitioners (GPs) toward Physical Activity on Prescription (PAP) in Madrid Primary Health-Care (PHC). DESIGN: A survey-cohort study. SITE: Nurses and GPs of Madrid PHC System. PARTICIPANTS: A total of 319 GPs and 285 nurses' responders. MEASUREMENTS: Data were analyzed under a classification tree analysis by four predictor variables: (i) Health professional (Nurses/GPs); (ii) Exercise prescription collaboration with all health professionals: physicians, nurses, psychologists, physical therapists, sports medicine physicians, sports scientists, nutritionists, and teachers (Yes/No); (iii) PA promotion collaboration with Sports Scientists (Yes/No); and (iv) The stage of change of PHC staff to PA promotion (0-4 Likert scale). RESULTS: Regarding the predictor variable (i), responders without PA guidelines knowledge and positive attitude to collaborate with nurses in PA promotion are more GPs of female sex (nurses n=33 and GPs n=175) than male sex (nurses n=3 and GPs n=59) (p<.001). For the predictor variable (ii) only 9.30% of PHC staff with a positive attitude to collaborate with all health professionals in PA promotion and exercise prescription. For the predictor variable (iii) was shown low collaboration with sports physicians and sports scientists under a multidisciplinary PAP approach (26.50% responders). Finally, in the predictor variable (iv) Staff maintaining PAP for at least 6 months, self-considered active, and with PAP knowledge want to collaborate with Sports scientists (Yes=233; No=133). CONCLUSIONS: Nurses and GPs are conscious of health-related PA benefits despite the lack of PAP knowledge and lack of willingness to collaborate with other health personnel, exercise professionals, and community resources available.

Development of a robotic cluster for automated and scalable cell therapy manufacturing.

BACKGROUND AIMS: The production of commercial autologous cell therapies such as chimeric antigen receptor T cells requires complex manual manufacturing processes. Skilled labor costs and challenges in manufacturing scale-out have contributed to high prices for these products. METHODS: We present a robotic system that uses industry-standard cell therapy manufacturing equipment to automate the steps involved in cell therapy manufacturing. The robotic cluster consists of a robotic arm and customized modules, allowing the robot to manipulate a variety of standard cell therapy instruments and materials such as incubators, bioreactors, and reagent bags. This system enables existing manual manufacturing processes to be rapidly adapted to robotic manufacturing, without having to adopt a completely new technology platform. Proof-of-concept for the robotic cluster's expansion module was demonstrated by expanding human CD8+ T cells. RESULTS: The robotic cultures showed comparable cell yields, viability, and identity to those manually performed. In addition, the robotic system was able to maintain culture sterility. CONCLUSIONS: Such modular robotic solutions may support scale-up and scale-out of cell therapies that are developed using classical manual methods in academic laboratories and biotechnology companies. This approach offers a pathway for overcoming manufacturing challenges associated with manual processes, ultimately contributing to the broader accessibility and affordability for personalized immunotherapies.

Examining the Role of Fan Support on Home Advantage and Home Win Percentage in Professional Women's Basketball.

Our main aim in this study was to analyze any differences in Win Percentages at Home (HW) that might represent a Home-Court Advantage (HA) in women's professional basketball. A secondary objective was to analyze how team ability might modify the HA effect by comparing any interaction effect between HW and team ability in games played with and without fans. We collected data from first Spanish female basketball divisions, using a linear mixed model (LMM) for repeated measures to identify differences between time periods (games with fans vs. games without fans) for HA and HW. When comparing games with and without fans, we found no significant HA and HW differences (p = .283 and p = .872, respectively). In fact, interestingly, we observed higher win values when fans were absent. Additionally, during the COVID-19 shut down stage, HA increased; but it returned to pre-pandemic levels afterward, with no significant differences between these periods (p = .482). Similarly, while HW seemed to increase during the COVID-19 shut down period and continued improving in the post-pandemic phase, there were actually no statistically significant differences (p = .772). Higher HA and HW were evident without fans during the pandemic compared to the pre-pandemic period when fans were present in women's professional basketball. During the post-pandemic period, HA decreased upon fans' return, while HW continued increasing. We discuss possible bases for these unexpected findings.

Hotspots of biogeochemical activity linked to aridity and plant traits across global drylands.

Perennial plants create productive and biodiverse hotspots, known as fertile islands, beneath their canopies. These hotspots largely determine the structure and functioning of drylands worldwide. Despite their ubiquity, the factors controlling fertile islands under conditions of contrasting grazing by livestock, the most prevalent land use in drylands, remain virtually unknown. Here we evaluated the relative importance of grazing pressure and herbivore type, climate and plant functional traits on 24 soil physical and chemical attributes that represent proxies of key ecosystem services related to decomposition, soil fertility, and soil and water conservation. To do this, we conducted a standardized global survey of 288 plots at 88 sites in 25 countries worldwide. We show that aridity and plant traits are the major factors associated with the magnitude of plant effects on fertile islands in grazed drylands worldwide. Grazing pressure had little influence on the capacity of plants to support fertile islands. Taller and wider shrubs and grasses supported stronger island effects. Stable and functional soils tended to be linked to species-rich sites with taller plants. Together, our findings dispel the notion that grazing pressure or herbivore type are linked to the formation or intensification of fertile islands in drylands. Rather, our study suggests that changes in aridity, and processes that alter island identity and therefore plant traits, will have marked effects on how perennial plants support and maintain the functioning of drylands in a more arid and grazed world.

Early response to Tezepelumab in type-2 severe asthma patients non-responders to other biological treatments: a real-life study.

BACKGROUND: Biologic therapies play a crucial role in the treatment of severe asthma. Tezepelumab, a human monoclonal antibody (mAb), inhibits thymic stromal lymphopoietin, a pivotal factor in the pathophysiology of asthma. Although randomized clinical trials have demonstrated the efficacy of Tezepelumab, evidence gaps remain in real-world scenarios. OBJECTIVE: We sought investigate Tezepelumab's response in a clinical setting, focusing on patients who previously failed to other asthma mAbs. METHODS: Real-life study with severe uncontrolled asthma patients despite mAb treatment, requiring a switch to Tezepelumab. Follow-up was done four to six months after initiation of Tezepelumab. The primary endpoint was to evaluate the response in patients with poor response or intolerance to other mAbs. RESULTS: Nine patients were followed up during 7 months. Patients were predominantly middle-aged females with eosinophilic or eosinophilic-allergic phenotypes. Patients had a median failure rate of 2 mAbs (IQR 2-3), with an uncontrolled asthma (median of 2 severe exacerbations the previous year, airflow obstruction and 78% corticosteroid dependence). Tezepelumab demonstrated after 4 to 6 months of treatment reduce corticosteroid dependence (complete withdrawal in 2/7 patients), no exacerbations in 6/9, symptoms control improvement (Asthma Control Test score improved in 5/9) and modulate lung function (improving in 3/9 patients). These findings align with clinical trial results, suggesting Tezepelumab's potential in real-world settings. CONCLUSION: In real-world scenarios, despite the study's limitations, our results underscore Tezepelumab's promise as a therapeutic option for uncontrolled severe asthma, and may be useful for non-responders to other mAbs. Further studies are needed to corroborate these findings.

RNA Expression of MMP12 Is Strongly Associated with Inflammatory Bowel Disease and Is Regulated by Metabolic Pathways in RAW 264.7 Macrophages.

Macrophage metalloelastase or matrix metalloproteinase-12 (MMP12) is a macrophage-specific proteolytic enzyme involved in the physiopathology of many inflammatory diseases, including inflammatory bowel disease. Although previously published data suggested that the modulation of MMP12 in macrophages could be a determinant for the development of intestinal inflammation, scarce information is available on the mechanisms underlying the regulation of MMP12 expression in those phagocytes. Therefore, in this study, we aimed to delineate the association of MMP12 with inflammatory bowel disease and the molecular events leading to the transcriptional control of this metalloproteinase. For that, we used publicly available transcriptional data. Also, we worked with the RAW 264.7 macrophage cell line for functional experiments. Our results showed a strong association of MMP12 expression with the severity of inflammatory bowel disease and the response to relevant biological therapies. In vitro assays revealed that the inhibition of mechanistic target of rapamycin complex 1 (mTORC1) and the stimulation of the AMP-activated protein kinase (AMPK) signaling pathway potentiated the expression of Mmp12. Additionally, AMPK and mTOR required a functional downstream glycolytic pathway to fully engage with Mmp12 expression. Finally, the pharmacological inhibition of MMP12 abolished the expression of the proinflammatory cytokine Interleukin-6 (Il6) in macrophages. Overall, our findings provide a better understanding of the mechanistic regulation of MMP12 in macrophages and its relationship with inflammation.

Using the Mooney Space to Characterize the Non-Affine Behavior of Elastomers.

The formulation of the entropic statistical theory and the related neo-Hookean model has been a major advance in the modeling of rubber-like materials, but the failure to explain some experimental observations such as the slope in Mooney plots resulted in hundreds of micromechanical and phenomenological models. The origin of the difficulties, the reason for the apparent need for the second invariant, and the reason for the relative success of models based on the Valanis-Landel decomposition have been recently explained. From that insight, a new micro-macro chain stretch connection using the stretch tensor (instead of the right Cauchy-Green deformation tensor) has been proposed and supported both theoretically and from experimental data. A simple three-parameter model using this connection has been suggested. The purpose of this work is to provide further insight into the model, to provide an analytical expression for the Gaussian contribution, and to provide a simple procedure to obtain the parameters from a tensile test using the Mooney space or the Mooney-Rivlin constants. From different papers, a wide variety of experimental tests on different materials and loading conditions have been selected to demonstrate that the simple model calibrated only from a tensile test provides accurate predictions for a wide variety of elastomers under different deformation levels and multiaxial patterns.

Predictive, preventive and personalised approach as a conceptual and technological innovation in primary and secondary care of inflammatory bowel disease benefiting affected individuals and populations.

Inflammatory bowel disease (IBD) is a global health burden which carries lifelong morbidity affecting all age groups in populations with the disease-specific peak of the age groups ranging between 15 and 35 years, which are of great economic importance for the society. An accelerating incidence of IBD is reported for newly industrialised countries, whereas stabilising incidence but increasing prevalence is typical for countries with a Westernised lifestyle, such as the European area and the USA. Although the aetiology of IBD is largely unknown, the interplay between the genetic, environmental, immunological, and microbial components is decisive for the disease manifestation, course, severity and individual outcomes. Contextually, the creation of an individualised patient profile is crucial for the cost-effective disease management in primary and secondary care of IBD. The proposed pathomechanisms include intestinal pathoflora and dysbiosis, chronic inflammation and mitochondrial impairments, amongst others, which collectively may reveal individual molecular signatures defining IBD subtypes and leading to clinical phenotypes, patient stratification and cost-effective protection against health-to-disease transition and treatments tailored to individualised patient profiles-all the pillars of an advanced 3PM approach. The paradigm change from reactive medical services to predictive diagnostics, cost-effective targeted prevention and treatments tailored to individualised patient profiles in overall IBD management holds a promise to meet patient needs in primary and secondary care, to increase the life-quality of affected individuals and to improve health economy in the area of IBD management. This article analyses current achievements and provides the roadmap for future developments in the area in the context of 3P medicine benefiting society at large.

COSMIC-dFBA: A novel multi-scale hybrid framework for bioprocess modeling.

Metabolism governs cell performance in biomanufacturing, as it fuels growth and productivity. However, even in well-controlled culture systems, metabolism is dynamic, with shifting objectives and resources, thus limiting the predictive capability of mechanistic models for process design and optimization. Here, we present Cellular Objectives and State Modulation In bioreaCtors (COSMIC)-dFBA, a hybrid multi-scale modeling paradigm that accurately predicts cell density, antibody titer, and bioreactor metabolite concentration profiles. Using machine-learning, COSMIC-dFBA decomposes the instantaneous metabolite uptake and secretion rates in a bioreactor into weighted contributions from each cell state (growth or antibody-producing state) and integrates these with a genome-scale metabolic model. A major strength of COSMIC-dFBA is that it can be parameterized with only metabolite concentrations from spent media, although constraining the metabolic model with other omics data can further improve its capabilities. Using COSMIC-dFBA, we can predict the final cell density and antibody titer to within 10% of the measured data, and compared to a standard dFBA model, we found the framework showed a 90% and 72% improvement in cell density and antibody titer prediction, respectively. Thus, we demonstrate our hybrid modeling framework effectively captures cellular metabolism and expands the applicability of dFBA to model the dynamic conditions in a bioreactor.

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation.

Enteroendocrine cells (EECs), which secrete serotonin (enterochromaffin cells, EC) or a dominant peptide hormone, serve vital physiologic functions. As with any adult human lineage, the basis for terminal cell diversity remains obscure. We replicated human EEC differentiation in vitro , mapped transcriptional and chromatin dynamics that culminate in discrete cell types, and studied abundant EEC precursors expressing selected transcription factors (TFs) and gene programs. Before expressing the pre-terminal factor NEUROD1, non-replicating precursors oscillated between epigenetically similar but transcriptionally distinct ASCL1 + and HES6 hi cell states. Loss of either factor substantially accelerated EEC differentiation and disrupted EEC individuality; ASCL1 or NEUROD1 deficiency had opposing consequences on EC and hormone-producing cell features. Expressed late in EEC differentiation, the latter TFs mainly bind cis -elements that are accessible in undifferentiated stem cells and tailor the subsequent expression of TF combinations that specify EEC types. Thus, TF oscillations retard EEC maturation to enable accurate EEC diversification.

Impact of Spectators, League and Team Ability on Home Advantage in Professional European Basketball.

Our aim in this study was to examine the impact of fans (vs. no fans), geographical location of league, and team ability on home winning percentage (HW%) or home advantage (HA) in professional European basketball. Data were collected from five prestigious professional, national basketball leagues within Europe (Spain, Germany, Italy, Greece and Israel) across 16 regular seasons (2005-2006 to 2020-2021). We conducted comparisons between matches with and without fans, location of leagues, team ability (High, Medium, Low), and combinations of these factors via non-parametric tests (e.g., Mann-Whitney tests, Kruskal-Wallis). We found significantly greater HA during matches with fans for leagues in Germany (p = .001), Italy (p = .012) and Spain (p = .002). For matches with fans, HA and HW% were significantly different between several, but not all, leagues for high (p < .05), medium (p < .05) and low (p < .02) team abilities. In conclusion, HA and HW% were enhanced by spectator attendance, with this phenomenon varying by location/region and team ability. Consideration of these multiple contextual factors may assist coaches and sport organizations to develop key strategies for enhanced team success.

Does monitoring pests pay off? a bioeconomic assessment of Drosophila suzukii controls.

BACKGROUND: Drosophila suzukii is a significant invasive pest that has caused high management costs and economic losses for blueberry growers in the United States. The status quo control strategy commonly used by growers is to apply pesticides proactively and frequently to reduce infestation. Recent studies have shown that the calendar-based spraying strategy might be unsustainable in the long term, making the reduction of pesticide reliance a top priority for the berry industry. Incorporating pest monitoring into the control strategy could be an option to improve efficiency while reducing pesticide usage. This study assesses the economic implications of monitoring-based control strategies compared to calendar-based spraying control strategies for organic blueberry production in Oregon. We combine a D. suzukii population model into the economic simulation framework, evaluate two monitoring methods (adult trapping and fruit sampling), and identify the profit-maximizing control strategy under different scenarios. RESULTS: In the baseline scenario, control strategies that incorporate fruit sampling exhibit the highest average profits. Although the status quo control strategy (spraying every 3 days) generates higher average revenue than monitoring-based strategies, the cost from the higher number of pesticide application offsets the returns. CONCLUSION: This study uses a novel bioeconomic simulation framework to show that incorporating fruit sampling can be a promising tool to reduce pesticide reliance while controlling D. suzukii infestation. These findings provide clearer information on the economic viability of using monitoring-based pest control strategies in organic berry production, and the assessment framework sheds light on the economics of pest management. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

A Narrative Review of the Most Demanding Scenarios in Basketball: Current Trends and Future Directions.

Since the analysis of most demanding scenarios (MDS) in basketball has improved the practical knowledge about match demands and possible impacts for the training process, it seems important to summarize the scientific evidence providing useful information and future directions related to MDS. This review assesses the results reflected in the available literature about the MDS in basketball, synthesizing and discussing data from scientific papers, and then providing relevant insights about terminology, sex and sample size, competition category, workload variables recorded, technology used, method of calculation, time windows analyzed, and activities evaluated related to MDS. Therefore, the present narrative review would be of practical use for coaches, scientists, athletes as well as strength and conditioning trainers exploring the current trends and future directions related to MDS in basketball.