bluuebunny/crossref_metadata_2025 huggingface dataset:
The asset administration shell as enabler for predictive maintenance: a review
Authors: Rahal Jhonny Rodriguez , Schwarz Alexander , Sahelices Benjamín , Weis Ronny , Antón Simon Duque
Published: November 2023

The emergence of the Internet of Things and the interconnection of systems and machines enables the idea of Industry 4.0, a new industrial paradigm with a strong focus on interaction and communication between physical and digital entities, leading to the creation of cyber-physical systems. The digital twin and the standard for the Asset Administration Shell are concepts derived from Industry 4.0 that exploit the advantages of connecting the physical and virtual domains, improving the management and display of the collected data. Furthermore, the increasing availability of data has enabled the implementation of data-driven approaches, such as machine and deep learning models, for predictive maintenance in industrial and automotive applications. This paper provides a two-dimensional review of the Asset Administration Shell and data-driven methods for predictive maintenance, including fault diagnosis and prognostics. Additionally, a digital twin architecture combining the Asset Administration Shell, predictive maintenance and data-driven methods is proposed within the context of the WaVe project.
Centenary Personality: Are There Psychological Resources that Distinguish Centenarians?
Authors: Merino Mª Dolores , Sánchez-Ortega Marta , Elvira-Flores Elvira , Mateo-Rodríguez Inmaculada
Published: November 2023

The number of centenarians is increasing year by year. Considering that happier people are likely to live longer, we asked ourselves whether healthy centenarians share psychological resources or positive personality characteristics that have enabled them to face traumatic situations and the challenges life more successfully. To our knowledge this is an issue that has not been sufficiently researched. Mixed methodology was applied. Qualitative Study 1: Nineteen centenarians participated between 100 and 107 years old of which 16 were women. Semi-structured, in-depth interviews about their life story were done. Quantitative Study 2: The purpose was to control the results of Study 1. Fifteen proxies for the centenarians participated. Results: In Study 1, 35 psychological resources were identified, of which 19 were central or identifying resources of the centenarians, and 16 peripheral or the product of individual differences. The central resources were grouped into six categories: vitality, taking pleasure in interaction, commitment, control, intellectually motivated and positivity, with resilience and intelligence added. The results in Study 2 were completely concordant. In conclusion, analysis of the lives of healthy centenarians provides us with knowledge that could help in achieving a healthy old age. Additionally, the study opens up new lines of research.
Tribological Behaviour of Ti6Al4V Alloy: An Application in Small Joint Implants
Authors: Odehnal Lukáš , Ranuša Matúš , Vrbka Martin , Křupka Ivan , Hartl Martin
Published: November 2023

The presented study deals with the analysis of the tribological behaviour of the Ti6Al4V alloy manufactured conventionally. The study aimed to verify whether the titanium alloy is suitable for use as a contact material in small joint implants, as additive manufacturing of this alloy can in the future provide certain benefits, such as individualization and simplification of the implant construction, or controlled porosity. The tested pair consisted of a pin and a glass plate lubricated with model synovial fluid. The contact area was observed with colorimetric interferometry. Alongside film thickness, friction, and wear scars were measured. From the designed experimental conditions, the titanium alloy was not able to create a sufficiently thick lubrication film to overcome its surface roughness and damage to contact surfaces occurred. Friction was comparable for all the tested configurations. The application of conventionally manufactured titanium alloy as a contact surface in small joint implants seems to not be suitable since its performance fell short when compared to conventional cobaltous alloy. Nevertheless, there are various alternative methods available, such as unconventional manufacturing, polishing, surface texturing, and coating.

Graphical Abstract
New Frontiers in Health Literacy: Using ChatGPT to Simplify Health Information for People in the Community
Authors: Ayre Julie , Mac Olivia , McCaffery Kirsten , McKay Brad R. , Liu Mingyi , Shi Yi , Rezwan Atria , Dunn Adam G.
Published: November 2023

Background

Most health information does not meet the health literacy needs of our communities. Writing health information in plain language is time-consuming but the release of tools like ChatGPT may make it easier to produce reliable plain language health information.

Objective

To investigate the capacity for ChatGPT to produce plain language versions of health texts.

Design

Observational study of 26 health texts from reputable websites.

Methods

ChatGPT was prompted to ‘rewrite the text for people with low literacy’. Researchers captured three revised versions of each original text.

Main Measures

Objective health literacy assessment, including Simple Measure of Gobbledygook (SMOG), proportion of the text that contains complex language (%), number of instances of passive voice and subjective ratings of key messages retained (%).

Key Results

On average, original texts were written at grade 12.8 (SD = 2.2) and revised to grade 11.0 (SD = 1.2), p < 0.001. Original texts were on average 22.8% complex (SD = 7.5%) compared to 14.4% (SD = 5.6%) in revised texts, p < 0.001. Original texts had on average 4.7 instances (SD = 3.2) of passive text compared to 1.7 (SD = 1.2) in revised texts, p < 0.001. On average 80% of key messages were retained (SD = 15.0). The more complex original texts showed more improvements than less complex original texts. For example, when original texts were ≥ grade 13, revised versions improved by an average 3.3 grades (SD = 2.2), p < 0.001. Simpler original texts (< grade 11) improved by an average 0.5 grades (SD = 1.4), p < 0.001.

Conclusions

This study used multiple objective assessments of health literacy to demonstrate that ChatGPT can simplify health information while retaining most key messages. However, the revised texts typically did not meet health literacy targets for grade reading score, and improvements were marginal for texts that were already relatively simple.
UAV-mounted Ground Penetrating Radar: an example for the stability analysis of a mountain rock debris slope
Authors: Salvini Riccardo , Beltramone Luisa , De Lucia Vivien , Ermini Andrea , Vanneschi Claudio , Zei Caterina , Silvestri Daniele , Rindinella Andrea
Published: November 2023

This paper describes scientific research conducted to highlight the potential of an integrated GPR-UAV system in engineering-geological applications. The analysis focused on the stability of a natural scree slope in the Germanasca Valley, in the western Italian Alps. As a consequence of its steep shape and the related geological hazard, the study used different remote sensed methodologies such as UAV photogrammetry and geophysics survey by a GPR-drone integrated system. Furthermore, conventional in-situ surveys led to the collection of geological and geomorphological data. The use of the UAV-mounted GPR allowed us to investigate the bedrock depth under the detrital slope deposit, using a non-invasive technique able to conduct surveys on inaccessible areas prone to hazardous conditions for operators. The collected evidence and the results of the analysis highlighted the stability of the slope with Factors of Safety, verified in static conditions (i.e., natural static condition and static condition with snow cover), slightly above the stability limit value of 1. On the contrary, the dynamic loading conditions (i.e., seismic action applied) showed a Factor of Safety below the stability limit value. The UAV-mounted GPR represented an essential contribution to the surveys allowing the definition of the interface debris deposit-bedrock, which are useful to design the slope model and to evaluate the scree slope stability in different conditions.
Diverse Sexual Definitions and Their Predictors Among Adolescents: A Multilevel Analysis in Hungary
Authors: Eörsi Daniel , Major David , Arva Dorottya , Bikas Luca , Nagy Norbert , Fazekas-Pongor Vince , Horváth Ferenc , Terebessy András
Published: November 2023

Introduction

Inconsistency of sexual definitions may lead to misunderstandings when evaluating research data or delivering health education. Diverse sexual definitions are especially common with unidirectional genital contacts (only one participant is involved with their genitals). Our aim was to analyze sexual definitions of adolescents and the role of age, gender, previous sexual experience, anxiety, and body image as possible determinants of unidirectional intimate behavior definitions.

Methods

Pooled cross-sectional survey data of 9th-grade Hungarian students (n = 612, mean age = 16.1 years, range from 15 to 18 years) were used from the baseline assessment (conducted in 2019 and 2020) of the Balassagyarmat Health Education Program. Our questionnaire was based on the Sexual Definitions Survey. The associations of definition of manual and oral stimulation with gender, age, sexual experience, trait anxiety, and body image were further examined in a multilevel logistic regression model.

Results

The rating of different sexual behaviors as sex showed a hierarchy from kissing (10.3%) to vaginal intercourse (98.5%). Manual and oral stimulation was claimed to be sex by 73.4% and 84.3% of students. Girls (OR = 0.40; CI = 0.25–0.62) and older participants (OR = 0.75; CI = 0.59–0.96) were less likely to consider manual stimulation as sex. Conversely, previous sexual experience, anxiety, and body image were not significant predictors.

Conclusions

Our study is the first to investigate sexual definitions among non-English-speaking adolescents. It contributes to the understanding of ambiguity regarding the definitions of oral and manual stimulation in this specific age group.

Policy implications

As adolescents are the primary focus of sexual education, policies should take into consideration the semantic differences in sexual definitions, as these may influence the participants’ interpretation of information and have an effect on their sexual behavior.
Appearance and reality: Einstein and the early debate on the reality of length contraction
Authors: Giovanelli Marco
Published: November 2023

In 1909, Ehrenfest published a note in the Physikalische Zeitschrift showing that a Born rigid cylinder could not be set into rotation without stresses, as elements of the circumference would be contracted but not the radius. Ignatowski and Varićak challenged Ehrenfest’s result in the same journal, arguing that the stresses would emerge if length contraction were a real dynamical effect, as in Lorentz’s theory. However, no stresses are expected to arise, according to Einstein’s theory, where length contraction is only an apparent effect due to an arbitrary choice of clock synchronization. Ehrenfest and Einstein considered this line of reasoning dangerously misleading and took a public stance in the Physikalische Zeitschrift, countering that relativistic length contraction is both apparent and real. It is apparent since it disappears for the comoving observer, but it is also real since it can be experimentally verified. By drawing on his lesser-known private correspondence with Varićak, this paper shows how Einstein used the Ehrenfest paradox as a tool for an ‘Einsteinian pedagogy’. Einstein’s argumentative stance is contrasted with Bell’s use of the Dewan-Beran thread-between-spaceships paradox to advocate for a ‘Lorentzian pedagogy’. The paper concludes that the disagreement between the two ways of ‘teaching special relativity’ stems from divergent interpretations of philosophical categories such as ‘reality’ and ‘appearance’.
Assessing the energy trap of industrial agriculture in North America and Europe: 82 balances from 1830 to 2012
Authors: Tello Enric , Sacristán Vera , Olarieta José R. , Cattaneo Claudio , Marull Joan , Pons Manel , Gingrich Simone , Krausmann Fridolin , Galán Elena , Marco Inés , Padró Roc , Guzmán Gloria I. , González de Molina Manuel , Cunfer Geoff , Watson Andrew , MacFadyen Joshua , Fraňková Eva , Aguilera Eduardo , Infante-Amate Juan , Urrego-Mesa Alexander , Soto David , Parcerisas Lluis , Dupras Jérôme , Díez-Sanjuán Lucía , Caravaca Jonathan , Gómez Laura , Fullana Onofre , Murray Ivan , Jover Gabriel , Cussó Xavier , Garrabou Ramon
Published: November 2023

Early energy analyses of agriculture revealed that behind higher labor and land productivity of industrial farming, there was a decrease in energy returns on energy (EROI) invested, in comparison to more traditional organic agricultural systems. Studies on recent trends show that efficiency gains in production and use of inputs have again somewhat improved energy returns. However, most of these agricultural energy studies have focused only on external inputs at the crop level, concealing the important role of internal biomass flows that livestock and forestry recirculate within agroecosystems. Here, we synthesize the results of 82 farm systems in North America and Europe from 1830 to 2012 that for the first time show the changing energy profiles of agroecosystems, including livestock and forestry, with a multi-EROI approach that accounts for the energy returns on external inputs, on internal biomass reuses, and on all inputs invested. With this historical circular bioeconomic approach, we found a general trend towards much lower external returns, little or no increases in internal returns, and almost no improvement in total returns. This “energy trap” was driven by shifts towards a growing dependence of crop production on fossil-fueled external inputs, much more intensive livestock production based on feed grains, less forestry, and a structural disintegration of agroecosystem components by increasingly linear industrial farm managements. We conclude that overcoming the energy trap requires nature-based solutions to reduce current dependence on fossil-fueled external industrial inputs and increase the circularity and complexity of agroecosystems to provide healthier diets with less animal products.
Equipment developed for simplifying routine phototesting in dermatology
Authors: Wulf Hans Christian , Heydenreich Jakob , Philipsen Peter Alshede
Published: November 2023

Some people react abnormally when exposed to sunlight by getting easily burned or develop a rash. When testing a patient’s level of photosensitivity in the clinic, the UVR dose to provoke erythema is determined by the minimal erythema dose (MED) test. Subsequently, a photoprovocation test is performed to detect abnormal skin reactions by daily exposing the skin to UVR for several consecutive days. Associated problems in MED testing include choice of an even skin area for testing, patients keeping still during the test, testing with different UVR doses simultaneously, and securing clear borders of erythema. To address these issues, a MED Test Patch was developed which adheres closely to the skin to ensure sharp erythema borders and provides six irradiation fields with decremental doses of 20%. For MED testing, we constructed a solar simulator and LED lamps with peak emissions at 309 and 370 nm, small enough to be mounted directly on to the MED Test Patch and accommodate patient movements. These lamps and a 415 nm LED can also be used for provocation testing which is best performed on the back where the skin is assumed to have identical UVR sensitivity, and the area is large enough for adjacent MED and provocation test fields. Reading of erythema is still performed by visual and tactile evaluation. The UVA and UVB MED test can be performed in 1 h. The advantage of these developments is an easy-to-use, standardized test method with improved accuracy of the results.

Graphical Abstract
Development and validation of an occurrence-based healthy dietary diversity (ORCHID) score easy to operationalise in dietary prevention interventions in older adults: a French study
Authors: Jacquemot Anne-Fleur , Prat Rosalie , Gazan Rozenn , Dubois Christophe , Darmon Nicole , Feart Catherine , Verger Eric O.
Published: November 2023

Healthy diet and dietary diversity have been associated with healthy ageing. Several scores have been developed to assess dietary diversity or healthy diets in epidemiological studies, but they are not adapted to be used in the context of preventive nutrition interventions. This study aimed to develop an occurrence-based healthy dietary diversity (ORCHID) score easy to implement in the field and to validate it using dietary data from older participants in the latest French food consumption survey (INCA3). The ORCHID score was made of several components representing the consumption occurrences of twenty food groups, in line with French dietary guidelines. The score was then validated using dietary data (namely three 24-h recalls and a food propensity questionnaire) from 696 participants aged 60 years and over in the INCA3 survey. Score validity was evaluated by describing the association of the score with its components, as well as with energy intakes, solid energy density (SED) and the probability of adequate nutrient intakes (assessed by the PANDiet). Higher scores were associated with more points in healthy components such as ‘fruits’ and ‘vegetables’ (r = 0·51, and r = 0·54, respectively). The score was positively associated with the PANDiet (r = 0·43) and inversely associated with SED (r = −0·37), while no significant association was found with energy intakes. The ORCHID score was validated as a good proxy of the nutritional quality of French older adults’ diets. It could therefore be a useful tool for both public health research and nutrition interventions.
Variations in mango fruit quality in response to management factors on a pre- and post-harvest continuum
Authors: Drouillard Antoine , Léchaudel Mathieu , Génard Michel , Doizy Anna , Grechi Isabelle
Published: November 2023

Fruit quality is a key factor – beginning with the producer, continuing through the supply chain, and ending with the consumer. It is described by multiple indicators and varies during the growth and ripening of the fruit. This study focused on two main aspects of Cogshall mango (Mangifera indicaL.) quality: (i) the physical properties of the fruit with fresh mass (FM), pulp dry matter content (DMC), and pulp coloration; and (ii) the chemical properties with pulp sugar content and pulp acidity. These indicators were monitored on on-tree fruit, from about 60 days after bloom until full maturity. The same indicators were also monitored on fruit stored in cold storage rooms during ripening. The effects of leaf-to-fruit ratio (manageable by pruning or fruit thinning), maturity stage of fruit at harvest (manageable by harvest date), and storage temperature on the kinetics of quality traits of on-tree and stored fruit were assessed. In addition, a change-point analysis was applied to the sweetness index kinetics (used as a proxy of fruit ripening) to study fruit ripening induction. The leaf-to-fruit ratio mainly influenced fruit growth in terms of FM and pulp DMC, whereas it had less impact on the evolution of fruit chemical properties. The maturity stage of the fruit at harvest was a key factor in determining the potential quality at the ripe stage. Ripening occurs naturally at the mature green stage for on-tree fruit, but ripening at an earlier stage can be induced by harvesting the fruit. During the ripening phase, a low leaf-to-fruit ratio and a cold storage temperature tended to slow down the daily rate of sweetness increase. The use of cold temperatures during storage slowed down starch degradation and sucrose accumulation, while almost stopping the variation in fruit coloration and acidity.
For King, Country, and Patron: The Despensers and Local Administration, 1321-1322
Authors: Waugh Scott L.
Published: November 2023

As the royal government in England expanded from the twelfth century onward and touched more aspects of the economy and society, landlords tried to control the administration and to protect their interests by retaining royal officers as their private clients. Simultaneously, lords built their own administrations to manage their estates and households. As clients, administrators could move easily between the royal government and baronial administrations and serve two or more masters, thereby compromising their loyalty and impartiality. The problem of “double allegiance,” as it has been called, therefore worried moralists and became an important characteristic of English government and politics in the fourteenth century.
Edward Alford and the Making of Country Radicalism
Authors: Zaller Robert
Published: November 2023

Resentment of monopoly and purveyance, weariness with the burdens of a long war, and the fears and hopes attendant upon the accession of a new and foreign dynasty were all focussed by the meeting of James I's first parliament in 1604. If there was nothing entirely new in these elements, there was novelty and danger in the concurrence of so many grievances at a time when the sense of external crisis which had unified the country for the preceding quarter century was at last relaxed. The new political climate, parochial, isolationist, and hostile to government intrusion whether of church or state, was soon associated with the term “Country.” In one sense, this climate was merely a moderate intensification of perennial English localism, and as such devoid of ideological implication. But allied with the persistent failures of the early Stuart administration, particularly in dealing with parliament, it became a medium in which genuine political opposition began to develop.
Cornwall Politics 1826-1832: Another Face of Reform?
Authors: Jaggard Edwin
Published: November 2023

It is now more than six years since Professors D.C. Moore and R.W. Davis battled it out, toe to toe like a pair of heavyweights, over the “other face of reform” in Buckinghamshire. The controversy began, it will be recalled, when Davis in his book on Bucks electoral politics addressed himself to Moore's conclusions about a country-based reform movement. Moore suggested that it was composed of ultra-Tories and rural Whigs, who eventually influenced the framing of the First Reform Act. Davis labelled Moore's “other face of reform” an “hallucination,” at least so far as Bucks was concerned. Whereupon the latter launched a vigorous counterattack in the pages of this journal. Both scholars defended their conclusions about events in Bucks, as well as the sources upon which they were based. When the final bell rang each stood bloodied but unbowed, still convinced of the validity of his viewpoint. Since then no challengers have come forward to join the battle. The arena has remained empty, the spotlights dimmed, as if mourning a memorable brawl.
Description of Aphelenchoides persicus sp. n. (Nematoda: Aphelenchoididae) from Iran
Authors: Aliramaji F. , Taheri A. , Shokoohi E.
Published: November 2023

During a survey on the soil nematodes, a population of the genus Aphelenchoides was collected around the rhizosphere of persimmon in Guilan Province, Iran. The morphological and molecular characters confirmed the new species, namely A. persicus sp. n. The new species is characterized by a female body length (699–1068 μm), lip region offset from the rest of the body by a slight constriction, lateral fields with six incisures, stylet 12–13.5 μm long, with a clear basal swelling, excretory pore ca 1.5 metacorpal length posterior to base of the metacorpus, post uterine sac elongate, about 4–7 times than the vulval body diameter; conical female tail with a single centrally located mucron with tiny projection close to the tail tip, male body length (663–908 μm), and spicule well developed with rounded condylus, blunt conical rostrum, and a hook-like tip of dorsal limb. The new species belongs to the Group 2 category of Aphelenchoides species and was similar to seven known species with six lateral field incisures, including A. allius, A. chinensis, A. meghalayensis, A. nechaleos, A. paranechaleos, A. parasexlineatus, and A. sexlineatus. The molecular phylogeny based on 28S rDNA revealed that the new species stands close to A. hamospiculatus (MN931591; MN931592) and two unidentified Aphelenchoides (KY769057; LC583315). The measurements, line illustrations, LM photographs, and phylogenetic analysis are given for the new species.
Using active learning and an agent-based system to perform interactive knowledge extraction based on the COVID-19 corpus
Authors: Yao Yao , Liu Junying , Ryan Conor
Published: November 2023

Efficient knowledge extraction from Big Data is quite a challenging topic. Recognizing relevant concepts from unannotated data while considering both context and domain knowledge is critical to implementing successful knowledge extraction. In this research, we provide a novel platform we call Active Learning Integrated with Knowledge Extraction (ALIKE) that overcomes the challenges of context awareness and concept extraction, which have impeded knowledge extraction in Big Data. We propose a method to extract related concepts from unorganized data with different contexts using multiple agents, synergy, reinforcement learning, and active learning.

We test ALIKE on the datasets of the COVID-19 Open Research Dataset Challenge. The experiment result suggests that the ALIKE platform can more efficiently distinguish inherent concepts from different papers than a non-agent-based method (without active learning) and that our proposed approach has a better chance to address the challenges of knowledge extraction with heterogeneous datasets. Moreover, the techniques used in ALIKE are transferable across any domain with multidisciplinary activity.
Healthy Aging: Insights for Research and Policy
Authors: Payne B. , Dawe J. , Evans R. , Marshall V. , Clarke P. , Norris D. , Hagey J. , Shapiro E. , Wilkins R. , Havens B.
Published: November 2023

In times of health reform, fiscal restraint and population aging, it becomes increasingly imperative to understand what must be done to better link research and policy in the health area. In this paper, the major determinants of healthy aging are discussed in terms of current conceptual frameworks of health, measurement, methodologies, and data sources. In order to maximize the benefit for the health of current and future Canadian seniors, policy recommendations are made to Statistics Canada, Health Canada, and the Seniors Independence Research Program (SIRP) which cover a range of issues related to measurement and data sources, health services, health status, economic status, and education.
Testing the Effect of Information on Discerning the Veracity of News in Real Time
Authors: Aslett Kevin , Sanderson Zeve , Godel William , Persily Nathaniel , Nagler Jonathan , Bonneau Richard , Tucker Joshua A.
Published: November 2023

Despite broad adoption of digital media literacy interventions that provide online users with more information when consuming news, relatively little is known about the effect of this additional information on the discernment of news veracity in real time. Gaining a comprehensive understanding of how information impacts discernment of news veracity has been hindered by challenges of external and ecological validity. Using a series of pre-registered experiments, we measure this effect in real time. Access to the full article relative to solely the headline/lede and access to source information improves an individual's ability to correctly discern the veracity of news. We also find that encouraging individuals to search online increases belief in both false/misleading and true news. Taken together, we provide a generalizable method for measuring the effect of information on news discernment, as well as crucial evidence for practitioners developing strategies for improving the public's digital media literacy.
Emerging and re-emerging pediatric viral diseases: a continuing global challenge
Authors: Hoffman Seth A. , Maldonado Yvonne A.
Published: November 2023

The twenty-first century has been marked by a surge in viral epidemics and pandemics, highlighting the global health challenge posed by emerging and re-emerging pediatric viral diseases. This review article explores the complex dynamics contributing to this challenge, including climate change, globalization, socio-economic interconnectedness, geopolitical tensions, vaccine hesitancy, misinformation, and disparities in access to healthcare resources. Understanding the interactions between the environment, socioeconomics, and health is crucial for effectively addressing current and future outbreaks. This scoping review focuses on emerging and re-emerging viral infectious diseases, with an emphasis on pediatric vulnerability. It highlights the urgent need for prevention, preparedness, and response efforts, particularly in resource-limited communities disproportionately affected by climate change and spillover events. Adopting a One Health/Planetary Health approach, which integrates human, animal, and ecosystem health, can enhance equity and resilience in global communities.

Impact

We provide a scoping review of emerging and re-emerging viral threats to global pediatric populations

This review provides an update on current pediatric viral threats in the context of the COVID-19 pandemic

This review aims to sensitize clinicians, epidemiologists, public health practitioners, and policy stakeholders/decision-makers to the role these viral diseases have in persistent pediatric morbidity and mortality
Beneficial glycaemic effects of high-amylose barley bread compared to wheat bread in type 2 diabetes
Authors: Bohl Mette , Gregersen Søren , Zhong Yuyue , Hebelstrup Kim Henrik , Hermansen Kjeld
Published: November 2023

Background

Cereals foods with a high content of dietary fibres or amylose have potential to lower postprandial glucose levels. Optimisation of cereal foods may improve management of type 2 diabetes (T2D).

Methods

We investigated the impact on 4 h postprandial glucose responses given as incremental area under curve (iAUC) of bread made of either 50% RNAi-based (genetically modified) amylose-only barley flour (AmOn) (and 50% wheat flour), 50% hulless barley flour (and 50% wheat flour) or 75% hulless barley (and 25% wheat flour) in subjects with T2D compared with 100% wheat flour bread.

Design

Twenty adults with T2D were randomly allocated to one of four breads at four separate visits. We measured fasting and 4 h postprandial responses of glucose, insulin, glucagon, triacylglycerol (TG), free fatty acids (FFA), glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP). Mixed model ANOVA was used to examine the differences.

Results

Bread made from 50% AmOn lowered the 4 h postprandial glucose by 34%, 27%, 23% (P < 0.05) compared with 100% wheat, 50% or 75% hulless barley, respectively. Bread made from 75% hulless barley reduced the postprandial glucose response (iAUC) by 11% (P < 0.05) compared to 100% wheat bread.

Postprandial insulin responses (iAUC) were reduced for 50% AmOn compared with 100% wheat and 50% hulless barley and for 75% hulless compared to 50% hulless barley bread (P < 0.05). 4 h postprandial glucagon (tAUC) did not differ between the four bread types (P > 0.05). Lower postprandial GIP (iAUC) was observed after all barley breads compared to 100% wheat (P < 0.05), whereas no difference was seen in postprandial GLP-1. Postprandial TG and FFA (tAUC) were difficult to judge due to differences in fasting values.

Conclusions

Bread made by replacing wheat flour with either 50% high-amylose or 75% hulless barley flour lowered postprandial glucose responses compared to 100% wheat bread indicating a beneficial impact on glucose regulation in T2D subjects.

This trial was registered at clinicaltrials.gov as NCT04646746.
Cell-free biosynthesis combined with deep learning accelerates de novo-development of antimicrobial peptides
Authors: Pandi Amir , Adam David , Zare Amir , Trinh Van Tuan , Schaefer Stefan L. , Burt Marie , Klabunde Björn , Bobkova Elizaveta , Kushwaha Manish , Foroughijabbari Yeganeh , Braun Peter , Spahn Christoph , Preußer Christian , Pogge von Strandmann Elke , Bode Helge B. , von Buttlar Heiner , Bertrams Wilhelm , Jung Anna Lena , Abendroth Frank , Schmeck Bernd , Hummer Gerhard , Vázquez Olalla , Erb Tobias J.
Published: November 2023

Bioactive peptides are key molecules in health and medicine. Deep learning holds a big promise for the discovery and design of bioactive peptides. Yet, suitable experimental approaches are required to validate candidates in high throughput and at low cost. Here, we established a cell-free protein synthesis (CFPS) pipeline for the rapid and inexpensive production of antimicrobial peptides (AMPs) directly from DNA templates. To validate our platform, we used deep learning to design thousands of AMPs de novo. Using computational methods, we prioritized 500 candidates that we produced and screened with our CFPS pipeline. We identified 30 functional AMPs, which we characterized further through molecular dynamics simulations, antimicrobial activity and toxicity. Notably, six de novo-AMPs feature broad-spectrum activity against multidrug-resistant pathogens and do not develop bacterial resistance. Our work demonstrates the potential of CFPS for high throughput and low-cost production and testing of bioactive peptides within less than 24 h.
Improvement of oxygen reduction activity and stability on a perovskite oxide surface by electrochemical potential
Authors: Koohfar Sanaz , Ghasemi Masoud , Hafen Tyler , Dimitrakopoulos Georgios , Kim Dongha , Pike Jenna , Elangovan Singaravelu , Gomez Enrique D. , Yildiz Bilge
Published: November 2023

The instability of the surface chemistry in transition metal oxide perovskites is the main factor hindering the long-term durability of oxygen electrodes in solid oxide electrochemical cells. The instability of surface chemistry is mainly due to the segregation of A-site dopants from the lattice to the surface. Here we report that cathodic potential can remarkably improve the stability in oxygen reduction reaction and electrochemical activity, by decomposing the near-surface region of the perovskite phase in a porous electrode made of La1-xSrxCo1-xFexO3 mixed with Sm0.2Ce0.8O1.9. Our approach combines X-ray photoelectron spectroscopy and secondary ion mass spectrometry for surface and sub-surface analysis. Formation of Ruddlesden-Popper phase is accompanied by suppression of the A-site dopant segregation, and exsolution of catalytically active Co particles onto the surface. These findings reveal the chemical and structural elements that maintain an active surface for oxygen reduction, and the cathodic potential is one way to generate these desirable chemistries.
A standardized metric to enhance clinical trial design and outcome interpretation in type 1 diabetes
Authors: Ylescupidez Alyssa , Bahnson Henry T. , O’Rourke Colin , Lord Sandra , Speake Cate , Greenbaum Carla J.
Published: November 2023

The use of a standardized outcome metric enhances clinical trial interpretation and cross-trial comparison. If a disease course is predictable, comparing modeled predictions with outcome data affords the precision and confidence needed to accelerate precision medicine. We demonstrate this approach in type 1 diabetes (T1D) trials aiming to preserve endogenous insulin secretion measured by C-peptide. C-peptide is predictable given an individual’s age and baseline value; quantitative response (QR) adjusts for these variables and represents the difference between the observed and predicted outcome. Validated across 13 trials, the QR metric reduces each trial’s variance and increases statistical power. As smaller studies are especially subject to random sampling variability, using QR as the outcome introduces alternative interpretations of previous clinical trial results. QR can provide model-based estimates that quantify whether individuals or groups did better or worse than expected. QR also provides a purer metric to associate with biomarker measurements. Using data from more than 1300 participants, we demonstrate the value of QR in advancing disease-modifying therapy in T1D. QR applies to any disease where outcome is predictable by pre-specified baseline covariates, rendering it useful for defining responders to therapy, comparing therapeutic efficacy, and understanding causal pathways in disease.
Spatial exosome analysis using cellulose nanofiber sheets reveals the location heterogeneity of extracellular vesicles
Authors: Yokoi Akira , Yoshida Kosuke , Koga Hirotaka , Kitagawa Masami , Nagao Yukari , Iida Mikiko , Kawaguchi Shota , Zhang Min , Nakayama Jun , Yamamoto Yusuke , Baba Yoshinobu , Kajiyama Hiroaki , Yasui Takao
Published: November 2023

Extracellular vesicles (EVs), including exosomes, are recognized as promising functional targets involved in disease mechanisms. However, the intravital heterogeneity of EVs remains unclear, and the general limitation for analyzing EVs is the need for a certain volume of biofluids. Here, we present cellulose nanofiber (CNF) sheets to resolve these issues. We show that CNF sheets capture and preserve EVs from ~10 μL of biofluid and enable the analysis of bioactive molecules inside EVs. By attaching CNF sheets to moistened organs, we collect EVs in trace amounts of ascites, which is sufficient to perform small RNA sequence analyses. In an ovarian cancer mouse model, we demonstrate that CNF sheets enable the detection of cancer-associated miRNAs from the very early phase when mice did not have apparent ascites, and that EVs from different locations have unique miRNA profiles. By performing CNF sheet analyses in patients, we identify further location-based differences in EV miRNA profiles, with profiles reflecting disease conditions. We conduct spatial exosome analyses using CNF sheets to reveal that ascites EVs from cancer patients exhibit location-dependent heterogeneity. This technique could provide insights into EV biology and suggests a clinical strategy contributing to cancer diagnosis, staging evaluation, and therapy planning.
replicAnt: a pipeline for generating annotated images of animals in complex environments using Unreal Engine
Authors: Plum Fabian , Bulla René , Beck Hendrik K. , Imirzian Natalie , Labonte David
Published: November 2023

Deep learning-based computer vision methods are transforming animal behavioural research. Transfer learning has enabled work in non-model species, but still requires hand-annotation of example footage, and is only performant in well-defined conditions. To help overcome these limitations, we developedreplicAnt, a configurable pipeline implemented in Unreal Engine 5 and Python, designed to generate large and variable training datasets on consumer-grade hardware.replicAntplaces 3D animal models into complex, procedurally generated environments, from which automatically annotated images can be exported. We demonstrate that synthetic data generated withreplicAntcan significantly reduce the hand-annotation required to achieve benchmark performance in common applications such as animal detection, tracking, pose-estimation, and semantic segmentation. We also show that it increases the subject-specificity and domain-invariance of the trained networks, thereby conferring robustness. In some applications,replicAntmay even remove the need for hand-annotation altogether. It thus represents a significant step towards porting deep learning-based computer vision tools to the field.
Message framing to promote solar panels
Authors: Bär Dominik , Feuerriegel Stefan , Li Ting , Weinmann Markus
Published: November 2023

Green technologies, such as solar panels, foster the use of clean energy, yet often involve large-scale investments. Hence, adoption by retail consumers has been a key barrier. Here, we show that message framing can significantly increase customers’ serious commitment to adopting solar panels by providing empirical evidence in the field from a large-scale randomized controlled trial with a nationwide online retailer in the Netherlands (N = 26,873 participants). We design four messages aimed at promoting the purchase behavior of solar panel installations. Our messages present outcomes for oneself or for the environment and highlight cost savings versus earnings (for oneself) or reducing emissions versus generating green electricity (for the environment). Across all messages, we observe a higher rate of customers committing to solar panels compared to the baseline. However, the framing in terms of financial savings for oneself was by far the most effective, resulting in a 40% higher level of commitment than the baseline and 30% higher than the average of the other three messages, which were not significantly different in effect from each other. Our results show that message framing is cost-efficient and scalable among retail consumers to promote large-scale investments in green technologies and thus clean energy.
Microglia are not protective against cryptococcal meningitis
Authors: Mohamed Sally H. , Fu Man Shun , Hain Sofia , Alselami Alanoud , Vanhoffelen Eliane , Li Yanjian , Bojang Ebrima , Lukande Robert , Ballou Elizabeth R. , May Robin C. , Ding Chen , Velde Greetje Vande , Drummond Rebecca A.
Published: November 2023

Microglia provide protection against a range of brain infections including bacteria, viruses and parasites, but how these glial cells respond to fungal brain infections is poorly understood. We investigated the role of microglia in the context of cryptococcal meningitis, the most common cause of fungal meningitis in humans. Using a series of transgenic- and chemical-based microglia depletion methods we found that, contrary to their protective role during other infections, loss of microglia did not affect control of Cryptococcus neoformans brain infection which was replicated with several fungal strains. At early time points post-infection, we found that microglia depletion lowered fungal brain burdens, which was related to intracellular residence of C. neoformans within microglia. Further examination of extracellular and intracellular fungal populations revealed that C. neoformans residing in microglia were protected from copper starvation, whereas extracellular yeast upregulated copper transporter CTR4. However, the degree of copper starvation did not equate to fungal survival or abundance of metals within different intracellular niches. Taken together, these data show how tissue-resident myeloid cells may influence fungal phenotype in the brain but do not provide protection against this infection, and instead may act as an early infection reservoir.
The alarmin IL33 orchestrates type 2 immune-mediated control of thymus regeneration
Authors: Cosway Emilie J. , James Kieran D. , White Andrea J. , Parnell Sonia M. , Bacon Andrea , McKenzie Andrew N. J. , Jenkinson W. E. , Anderson Graham
Published: November 2023

As the primary site of T-cell development, the thymus dictates immune competency of the host. The rates of thymus function are not constant, and thymus regeneration is essential to restore new T-cell production following tissue damage from environmental factors and therapeutic interventions. Here, we show the alarmin interleukin (IL) 33 is a product of Sca1+ thymic mesenchyme both necessary and sufficient for thymus regeneration via a type 2 innate immune network. IL33 stimulates expansion of IL5-producing type 2 innate lymphoid cells (ILC2), which triggers a cellular switch in the intrathymic availability of IL4. This enables eosinophil production of IL4 to re-establish thymic mesenchyme prior to recovery of thymopoiesis-inducing epithelial compartments. Collectively, we identify a positive feedback mechanism of type 2 innate immunity that regulates the recovery of thymus function following tissue injury.
Revising the global biogeography of annual and perennial plants
Authors: Poppenwimer Tyler , Mayrose Itay , DeMalach Niv
Published: November 2023

There are two main life cycles in plants—annual and perennial1,2. These life cycles are associated with different traits that determine ecosystem function3,4. Although life cycles are textbook examples of plant adaptation to different environments, we lack comprehensive knowledge regarding their global distributional patterns. Here we assembled an extensive database of plant life cycle assignments of 235,000 plant species coupled with millions of georeferenced datapoints to map the worldwide biogeography of these plant species. We found that annual plants are half as common as initially thought5–8, accounting for only 6% of plant species. Our analyses indicate that annuals are favoured in hot and dry regions. However, a more accurate model shows that the prevalence of annual species is driven by temperature and precipitation in the driest quarter (rather than yearly means), explaining, for example, why some Mediterranean systems have more annuals than desert systems. Furthermore, this pattern remains consistent among different families, indicating convergent evolution. Finally, we demonstrate that increasing climate variability and anthropogenic disturbance increase annual favourability. Considering future climate change, we predict an increase in annual prevalence for 69% of the world’s ecoregions by 2060. Overall, our analyses raise concerns for ecosystem services provided by perennial plants, as ongoing changes are leading to a higher proportion of annual plants globally.
Targeting of intracellular oncoproteins with peptide-centric CARs
Authors: Yarmarkovich Mark , Marshall Quinlen F. , Warrington John M. , Premaratne Rasika , Farrel Alvin , Groff David , Li Wei , di Marco Moreno , Runbeck Erin , Truong Hau , Toor Jugmohit S. , Tripathi Sarvind , Nguyen Son , Shen Helena , Noel Tiffany , Church Nicole L. , Weiner Amber , Kendsersky Nathan , Martinez Dan , Weisberg Rebecca , Christie Molly , Eisenlohr Laurence , Bosse Kristopher R. , Dimitrov Dimiter S. , Stevanovic Stefan , Sgourakis Nikolaos G. , Kiefel Ben R. , Maris John M.
Published: November 2023

The majority of oncogenic drivers are intracellular proteins, constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes1. However, most cancers have a modest mutational burden that is insufficient for generating responses using neoantigen-based therapies2,3. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcriptional networks4. Here we show that the neuroblastoma immunopeptidome is enriched with peptides derived from proteins essential for tumorigenesis. We focused on targeting the unmutated peptide QYNPIRTTF discovered on HLA-A*24:02, which is derived from the neuroblastoma-dependency gene and master transcriptional regulator PHOX2B. To target QYNPIRTTF, we developed peptide-centric chimeric antigen receptors (PC-CARs) through a counter panning strategy using predicted potentially cross-reactive peptides. We further proposed that PC-CARs can recognize peptides on additional HLA allotypes when presenting a similar overall molecular surface. Informed by our computational modelling results, we show that PHOX2B PC-CARs also recognize QYNPIRTTF presented by HLA-A*23:01, the most common non-A2 allele in people with African ancestry. Finally, we demonstrate potent and specific killing of neuroblastoma cells expressing these HLAs in vitro and complete tumour regression in mice. These data suggest that PC-CARs have the potential to expand the pool of immunotherapeutic targets to include non-immunogenic intracellular oncoproteins and allow targeting through additional HLA allotypes in a clinical setting.