bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridging the Gap: Infusing Natural Science Classes with Computer Science Concepts and Skills
Authors: Yanakieva Elena , Bieniusa Annette , Becka Thomas , Moser Brian B. , Jerger Dominik , Thyssen Christoph
Published: September 2023

As we venture further into an ever-evolving digital society, it has become imperative for schools to adapt and equip future generations with the required skills. Computational Thinking (CT), specifically its algorithmic thinking aspect, plays a significant role in computer science and other sciences, such as biology, chemistry, and physics. It encourages students to reason at multiple levels of abstraction. This ability is particularly useful in natural science, as scientific experiments require critical skills like conceptualization, problem decomposition, and solving or designing structured systems. However, due to organizational and curricular restrictions, these concepts and skills are typically taught separately, leaving it to the learners to connect and apply the acquired skills in the respective context.

To bridge this gap, we designed a two-day workshop that embeds CT in a physics and sustainability context, namely energy-efficient housing. In this workshop, we employ the Calliope Mini, a micro-controller explicitly designed for educational purposes, to teach essential algorithmic thinking and data processing. We carried out the workshop twice in a primary school in Germany, each with 20 children in 4th grade (ages 9–10). In this experience report, we present the multi-disciplinary workshop idea and discuss the outcome and observations from its execution. Overall, our study demonstrates the potential of such a workshop design as a practical tool for teaching CT concepts to children. Finally, we critically examine the challenges of this approach and highlight the importance of proper technical and educational prerequisites for a successful implementation.
All Green: How Different Age Groups Solved the Same Bebras Task
Authors: Bellettini Carlo , Lonati Violetta , Monga Mattia , Morpurgo Anna
Published: September 2023

In this report we investigate how pupils tackle an interactive problem-solving task recently proposed in the Bebras Challenge. The task comes across as fun and simple and we proposed it to all pupils from fourth grade up. We analyzed the data collected, produced by 18,486 participating teams while interacting with the local Bebras platform. The quantitative data were supplemented by interviews conducted after the challenge, in which students were asked to solve the question while thinking aloud. Regardless of their age, all the participants found a good challenge in the task and they spent a lot of time interacting with it. Almost all teams attempted a naive approach to the solution, misled by the superficial characteristics of the problem, and many insisted on attempting the naive approach without ever abandoning it; this behaviour clearly decreases with increasing age.
The Function of Note-Taking in Problem Solving in the Computer Science Escape Game Room-X
Authors: Hacke Alexander , Dittert Nadine
Published: September 2023

The competence to solve problems is of fundamental importance in software engineering and the broader field of computer science. The escape game Room-X provides participating students aged between 13 and 19 years with an opportunity to tackle such a problem using computer science knowledge and general problem-solving skills. The problem-solving task presented in the game is representative of those encountered in professional computer science practice, and thus affords a valuable opportunity to examine the problem-solving processes of learners in this domain. This study focuses on the role of note-taking in the problem-solving process of the participants. Following an analysis of the relevant literature, we conduct a structuring content analysis of the notes taken during the game and examine how these notes are integrated into the problem-solving process. The findings suggest that note-taking is often employed as a simple memory aid and sees only limited use as a tool for organizing the problem-solving process. The study underscores the importance of developing effective note-taking strategies in computer science education to address the challenge of effectively organizing the problem-solving process, given the central role of problem solving in this domain. These findings are contextualized within the framework of computer science education and are discussed in relation to their broader implications for general education.
An Exploratory Investigation on High-School Students’ Understanding of Threads
Authors: Scapin Emanuele , Dalla Pozza Nicola , Mirolo Claudio
Published: September 2023

Students’ difficulties to learn concurrent programming are well known amongst Computer Science instructors. While in the International Computing Education community it is still up to debate the extent to which such topic should be included in pre-university curricula, based on our country’s Ministerial guidelines for technical high schools with a specialization in Computer Science, students are expected to acquire key concurrent programming skills. With the aim of getting insights about the nature of students’ difficulties, as well as to identify possible pedagogical approaches to be adopted by teachers, we have undertaken an investigation on students’ perception, proficiency and self-confidence when dealing with concurrency and synchronization tasks. We then present the results of a preliminary study carried out by submitting a survey in a couple of representative high schools of our area. The survey includes subjective perception questions as well as small program comprehension tasks addressing students’ understanding of thread synchronization. Moreover, we also analyze students’ self-confidence in connection with their actual performance in such tasks. A total of 68 high school students were engaged in the survey. Our findings indicate that students’ perception of self-confidence tends to weakly correlate to their actual performance, although more in general they express a low self-confidence level in relation to the topic. In particular, the results clearly show that the concept of thread synchronization is especially difficult to master for a large majority of them.
KulturSchule und Fortbildung im Urteil der Fortgebildeten
Authors: Ackermann Heike
Published: September 2023

Wenn Lehrkräfte mit ihrem Beruf zufrieden sind und sich an ihrer Schule richtig fühlen, kann dies als günstig für eine Innovationsbereitschaft angesehen werden. Auf ein Untersuchungssample von fünf Kollegien von KulturSchulen scheint dieser Befund zuzutreffen. Eine Befragung zur Akzeptanz des KulturSchul-Profils, der verabredeten Zielsetzungen, zur Wahrnehmung der allgemeinen Unterrichtsentwicklung und den Zielsetzungen der Lehrkräfte im Unterricht ergibt Unterschiede in der Wahrnehmung zwischen Fortgebildeten und den (noch) nicht Fortgebildeten. Diese Unterschiede sind oftmals statistisch relevant, sodass sich die Frage stellt, was dafür ursächlich ist. Vermutet wird, dass Fortgebildete sich in der Fortbildung als selbstwirksam und gestützt durch ihre Gruppe erleben konnten. Dies könnte, wie auch die Fortbildner annehmen, eine günstige Voraussetzung dafür sein, dass die intendierte Unterrichts- und Schulentwicklung eine Bereitschaft findet, sie mitzutragen.
Evaluationsdesign
Authors: Ackermann Heike
Published: September 2023

Die vorliegende Studie basiert auf einem Auftrag des Hessischen Kultusministeriums zur Evaluation von Fortbildungen, die Lehrkräfte und auch schulische Führungskräfte im und für das KulturSchulprogramm des Landes qualifizieren sollen. Das Interesse lag in der Untersuchung der besonderen Qualität der neu etablierten Fachforen und deren Beitrag zur ästhetischen Praxis an KulturSchulen. Das Kapitel thematisiert die Bereiche der Untersuchung und die Fragestellungen und erläutert die methodischen Entscheidungen im Evaluationsvorgehen.
Fachforen
Authors: Ackermann Heike
Published: September 2023

Unter den vier Fortbildungsformaten zur Lehrkräfte- und Schulleitungsqualifizierung, die rekonstruiert worden sind, sind die Fachforen die zeitlich gesehen jüngste Entwicklung. An der Resonanz, die sie bei den Teilnehmern haben, wird deutlich, inwiefern die didaktischen Zielsetzungen der Programmakteure und Fortbildenden bei den Teilnehmern ankommen. Eine teilnehmende Beobachtung der Fachforen als demzeitlich längsten Fortbildungsformat ermöglicht eine vertiefende Beschreibung und Analyse dieses neuartigen Workshops, der dem pädagogischen Personal an KulturSchulen ästhetische Erfahrung zugänglich macht.
Mutation Induction in Coffea arabica L. Using in Vivo Grafting and Cuttings
Authors: Wu Weihuai , Bai Xuehui , Yi Kexian , Huang Xing , He Chunping , Li Jinhong , Zhang Hongbo , Zhou Hua , Gbokie Thomas , Guo Tieying , Xi Jingen
Published: September 2023

Coffee leaf rust (CLR) caused by the obligate parasite, the biotrophic Hemileia vastatrix Berk. & Broome (Basidiomycetes: Pucciniales), is the most devastating disease of Coffea arabica L. Breeding resistant varieties is one of the most economic and environment friendly means to control the disease. However, this is challenged by the loss of resistance after a short period in commercial production. Catimor CIFC7963, an elite, leaf rust resistant Coffea arabica L. variety, has been cultivated in China for decades, which has resulted in the breakdown of its disease resistance. Due to the lengthy breeding process of coffee, the development of new resistant varieties is arduous. Physical and chemical mutagenesis offers an alternative means to more rapidly create novel and beneficial genetic variations. Bud grafting is a propagation technique frequently used for woody plants whereby a bud of one plant is attached to the rootstock of another plant. Likewise, cutting is a frequently used propagation technique. In coffee, physical irradiation of the bud followed by grafting or cutting can accelerate the mutation breeding process, as cutting or grafting increases the growth rate without affecting the major traits of the background varieties. Here, we present protocols to induce mutations on buds of the C. arabica variety Catimor CIFC7963 by gamma-ray irradiation and their subsequent propagation through cutting or bud grafting.
Use of Open-Source Tools for Imaging and Recording Phenotypic Traits of a Coffee (Coffea arabica L.) Mutant Population
Authors: Nkurunziza Radisras , Jankowicz-Cieslak Joanna , Werbrouck Stefaan P. O. , Ingelbrecht Ivan L. W.
Published: September 2023

Mutation breeding in Coffea arabica offers a powerful tool to induce novel genetic variability for breeding and genetic studies. The success of a mutation breeding program depends largely on the ability to screen large populations for target traits. There is also a need to accurately record induced mutant traits at the individual plant level. Comprehensive phenotyping requires measuring and tracking traits of interest during the crop growth cycle and subsequent generations. Therefore, efficient and accurate data collection and recording of traits is essential, both at the individual plant level and populations. In recent years, various high-throughput plant phenotyping platforms have been developed. However, these are typically proprietary, and/or require costly infrastructures. In this chapter we illustrate the use of Field Book and ImageJ, two public domain software tools, for phenotyping and documenting growth and yield traits of a greenhouse-grown Arabica coffee mutant population. Example data of M1 and M2 mutant phenotypes induced through EMS and gamma-ray mutagenesis are presented. We further demonstrate the use of these tools for quantifying the canopy of mutants and non-mutagenized controls. These tools can be more widely applied to other visual phenotypes including plant or tissue responses to biotic or abiotic stresses. The use of free, open-access tools for integrating electronic data recording with image processing can greatly improve the efficiency, precision and speed of data collection for screening large mutant populations and is especially useful in resource-limiting settings.
Screening for Resistance to Coffee Leaf Rust
Authors: Várzea Vítor , Pereira Ana Paula , Silva Maria do Céu Lavado da
Published: September 2023

Coffee leaf rust (CLR), caused by Hemileia vastatrix (Hv), is one of the main limiting factors of Arabica coffee production worldwide. Breeding for rust resistance is the most appropriate and sustainable strategy to control CLR. The characterization of coffee resistance to Hv, initiated in the 1930s in India, expanded with the creation of Coffee Rusts Research Center (CIFC) in 1955, in Portugal. Since then, the screening of coffee resistance to Hv races, from different geographical origins, has been carried out assisting breeding programmes of coffee growing countries and originating over 90% of the resistant varieties cultivated worldwide. However, the high adaptability of Hv has resulted in the gradual loss of resistance of some varieties. Thus, the characterization of new sources of resistance is crucial, also to face the recent epidemic resurgence of CLR across Latin America and the Caribbean.

Here, we provide a protocol for the screening of coffee resistance to Hv using different methods of inoculation on attached and detached leaves and on leaf disks. Information on environmental and pathogenicity factors that may affect the assessment of coffee resistance is also presented. This protocol allows the characterization of rust resistance on coffee mutants at laboratories, greenhouses, and field conditions.
Inoculation and Evaluation of Hemileia vastatrix Under Laboratory Conditions
Authors: Barquero-Miranda Miguel , Cordero-Vega María José , Ureña-Ureña Kimberly
Published: September 2023

The coffee leaf rust, a disease caused by the biotrophic fungusHemileia vastatrix, is one of the main limitations in coffee production today as it causes significant economic losses to the coffee production sector. Genetic improvement is an option to solve these problems. The Arabica varieties have a very narrow genetic base therefore the induction of mutations, through e.g. physical methods such as gamma rays, could be an efficient tool to increase the genetic diversity of the crop. This would allow to obtain desirable agronomic characteristics such as resistance to pests and diseases. To determine the effect of irradiation on the plants, protocols enabling evaluation of improved traits must be applied. In the case of the assessment of plant resistance to pests and diseases, screening protocols that take into account their biology should be considered. This chapter provides a detailed protocol for the inoculation and evaluation ofHemileia vastatrixunder laboratory conditions.
Evaluation of Coffee (Coffea arabica L. var. Catuaí) Tolerance to Leaf Rust (Hemileia vastatrix) Using Inoculation of Leaf Discs Under Controlled Conditions
Authors: Rojas-Chacón José Andrés , Echeverría-Beirute Fabián , Gatica-Arias Andrés
Published: September 2023

Coffee leaf rust (CLR), caused by the obligate biotrophic fungus Hemileia vastatrix, is considered one of the most devastating diseases of Arabica coffee. The use of leaf rust resistant or tolerant coffee varieties is a critical component for effective management of this disease at the farm level. Conventional breeding of Arabica coffee for leaf rust resistance requires many years of breeding and field-testing. Induced mutagenesis is an effective tool to increase genetic variability and generate new alleles with potential benefit for addressing abiotic and biotic stresses such as leaf rust in Arabica coffee. Efficient screening methods are required to evaluate coffee germplasm or mutant populations for resistance to H. vastatrix. Here, we present a screening method that uses inoculation of leaf discs in a controlled environment. The method was evaluated using M1V1 and M2 plants derived from chemically mutagenized Arabica coffee cell suspensions. In this method, the first rust symptoms appear on the leaf discs approximately 29 days after inoculation while the disease severity and incidence can be scored about 47 days after inoculation. Our results show that the methodology is simple, efficient and suitable to rapidly screen large mutant populations in a small area.
Targeted Sequencing in Coffee with the Daicel Arbor Biosciences Exome Capture Kit
Authors: Warthmann Norman
Published: September 2023

Exome Capture is a molecular biology technique that, in combination with Next Generation DNA sequencing technologies (NGS), allows for selectively sequencing the predicted genes of an organism. Such capture sequencing provides a compromise between genome coverage and sequencing cost. The capture reaction is an additional step in an otherwise standard sequencing protocol and exome capture effectively enriches the sequencing library for DNA molecules that overlap with predicted genes (the exome). This enables genome-wide assessments while focusing on the gene space. Capture sequencing is particularly attractive in species with large genomes, where whole genome sequencing in larger numbers of samples would be cost-prohibitive at present prices. Plant Breeding and Genetics Laboratory (PBGL) developed an Exome Capture Kit for Coffea arabica in collaboration with Daicel Arbor Biosciences (Ann Arbor, MI, USA). Use of the kit achieves eightfold enrichment, and hence approx. eightfold reduction in sequencing cost for a whole genome assessment of Coffee arabica plants. The kit is available as a regular product from Daicel Arbor Biosciences and this protocol describes the kit and gives detailed instructions on how to perform the capture reaction.
Coffee Leaf Rust Resistance: An Overview
Authors: Guerra-Guimarães Leonor , Diniz Inês , Azinheira Helena Gil , Loureiro Andreia , Pereira Ana Paula , Tavares Sílvia , Batista Dora , Várzea Vítor , Silva Maria do Céu Lavado da
Published: September 2023

Coffee is one of the most important cash crops and beverages. Several diseases caused by fungi, bacteria, and viruses can affect coffee plantations and compromise production. Coffee leaf rust (CLR), caused by the biotrophic fungus Hemileia vastatrix is the top fungal disease, representing a permanent threat to sustainable Arabica coffee production for more than a century. This review provides a comprehensive survey of the most common coffee diseases, their importance, and geographic distribution, with an emphasis on coffee leaf rust. Summing up the progress obtained so far from different research fields on the coffee–H. vastatrix interaction, we revisited the pathogen genetic diversity and population dynamics, and the complex mechanisms underlying plant resistance/immunity. We also highlight how new advanced technologies can provide avenues for a deeper understanding of this pathosystem, which is crucial for devising more reliable and long-term strategies for disease control.
Protocols for Chromosome Preparations: Molecular Cytogenetics and Studying Genome Organization in Coffee
Authors: Li Le , Schwarzacher Trude , Tomaszewska Paulina , Liu Qing , Li Xiaoyu Zoe , Yi Kexian , Wu Weihuai , Pat Heslop-Harrison J. S.
Published: September 2023

Cytological preparations from cell nuclei are required to count the number of chromosomes (including determining ploidy or aneuploidy), to investigate their morphology and organization. The results are valuable for genetic and evolutionary studies, and in breeding programs to understand species relationships, polyploidy, and potential introgression of chromosomes in hybrids between different species. Preparation of good chromosome spreads with well-separated metaphase chromosomes is the foundation of cytogenetic research including chromosomal mapping based on FISH (fluorescence in situ hybridization). FISH combined with specific locus probes correlated with molecular markers to specific chromosomes for integrating physical and linkage maps as well as studying the genetic evolution of allopolyploidization, has rarely been applied in Coffea spp. despite being a global high-value crop. Cytogenetic studies of Coffea are limited by the small size and similar morphology of the chromosomes, but FISH can help to map sequences to chromosome arms and identify individual chromosomes. This chapter presents protocols for germinating seeds and growing coffee plants involving pre-treatment and fixation of root-tips where the meristems of actively growing roots have many divisions. Mitotic metaphase chromosome preparation on microscope slides is described, as well as preparing probes of 5S and 18S rDNA to be used for FISH. The FISH experiments involve a two-step protocol with pre-treatments and setting up the hybridization on day 1 and the detection of probe sites on day 2 after overnight hybridization. A final section gives advice about visualization using a fluorescent microscope and capturing images.
Protocol on Mutation Induction in Coffee Using In Vitro Tissue Cultures
Authors: Laimer Margit , Boro Rashmi , Hanzer Veronika , Ogwok Emmanuel , Borroto Fernandez Eduviges G.
Published: September 2023

Pathogens are the major limiting factors in coffee production. Approximately 26% of the global annual coffee production is lost to diseases, threatening the income of approx. 125 million people worldwide. Therefore, reducing coffee yield losses by improving coffee resistance to diseases and insect attacks through breeding can make a major contribution to agricultural sustainability. Mutation breeding in vegetatively propagated and perennial crops is hampered in large part due to bottlenecks in the induction of variation (lack of recombination) and challenges in screening. Tissue culture approaches using alternative types of material were developed. This offers a clear advantage of providing the required sample size for mutation induction and subsequent screening within a reasonable time frame. The protocols developed compare different tissue culture systems for mutation induction involving unicellular and multicellular explants requiring different numbers of subsequent subcultures to reduce the impact of chimerism: (a) axillary shoot culture for the provision of donor material for mutation induction and regeneration; (b) leaf disc cultures for the induction of calli; (c) direct and indirect somatic embryogenesis for the production of somatic embryos; (d) the irradiation of somatic embryos at the globular and cotyledonary stage. Mutagenesis was induced by irradiation with a Cobalt-60 Gamma-source at the FAO/IAEA Laboratories in Seibersdorf, Austria. A comparison of the time required for the regeneration of high numbers (hundreds) of plantlets from irradiated in vitro shoots versus irradiated embryogenic calli is clearly in favor of embryogenic calli, since the plantlets regenerate from individual cells and can be used for genotypic and phenotypic analyses directly. This chapter describes the general methods for mutation induction using gamma irradiation and the procedures that can be used to generate large numbers of induced mutants in different tissues of coffee under in vitro conditions.
Mutation Induction Using Gamma-Ray Irradiation and High Frequency Embryogenic Callus from Coffee (Coffea arabica L.)
Authors: Barquero-Miranda Miguel , Céspedes Reina
Published: September 2023

Mutation induction through chemical or physical mutagenesis has been widely used for crop improvement for more than 70 years. Coffee is one of the most important crops in Latin-America, and, as any other crop, it can be affected by pests and diseases. Coffee leaf rust (CLR), caused by the biotrophic fungus Hemileia vastatrix, is the most important disease affecting Arabica coffee leading to significant losses for growers. As a perennial crop, conventional breeding of Arabica coffee is time-consuming. Plant tissue culture in combination with mutation induction techniques can provide an alternative approach to increase genetic variability of Arabica coffee for breeding applications. The present chapter describes protocols to establish embryogenic callus suspensions from Arabica coffee cv Venecia and for gamma ray irradiation of callus suspension cultures to achieve genetic improvement in the crop.
Chemical Mutagenesis of Embryogenic Cell Suspensions of Coffea arabica L. var. Catuaí Using EMS and NaN3
Authors: Gatica-Arias Andrés , Bolívar-González Alejandro
Published: September 2023

Chemical mutagens, such as ethyl methanesulfonate (EMS) and sodium azide (NaN3), interact with DNA and can primarily induce single base modifications along the genome. Populations derived from chemical mutagenesis experiments are presumed to harbor high density of point mutations in the genome. Therefore, this technique, along with in vitro culture methods such as somatic embryogenesis (SE), can introduce genetic variation in otherwise genetically homogeneous populations. In vitro mutagenesis of embryogenic cell suspension cultures represents an efficient method to quickly develop mutant plantlets of unicellular origin. The development of mutant populations in this important crop represents a fundamental steppingstone in the development of novel varieties and the characterization of candidate genes involved in traits such as disease resistance, grain metabolite content and flowering induction. This chapter describes the protocol for establishment of embryogenic cell suspension cultures as well as methods of mutation induction using EMS and NaN3 on embryogenic cell suspensions of C. arabica, variety Catuaí. Furthermore, this chapter includes a protocol for mutant plant regeneration in in vitro conditions.
Vorbemerkungen zum politischen, institutionellen und historischen Hintergrund
Authors: Möller Ellen Franziska
Published: September 2023

Das Philosophische Seminar der Universität zu Köln unterhält seit 2013 eine forschungsfähige Einheit, die empirisch zu Fragen des Philosophierens mit Kindern forscht. Das Forschungsprojekt Philosophie in der Primarstufe wird zusätzlich auch von zivilgesellschaftlicher Seite, namentlich durch den Kölner Gymnasial- undStiftungsfonds, finanziell unterstützt. Im Rahmen dieses Forschungsprojekts ist auch die vorliegende Studie entstanden. Dieses einleitende Kapitel verschafft einen kurzen Überblick darüber, vor welchem politischen, institutionellen und historischen Hintergrund die vorliegende Studie entwickelt wurde.
Offene Auswertung: Was geschieht…
Authors: Möller Ellen Franziska
Published: September 2023

Die fokussierte Auswertung, die auf dem Analyseinstrument nach Daniel und Gagnon beruht (vgl. Kap. 10), legt insbesondere dar, welcher Stufe des Abstrakten die kindlichen Äußerungen nach Einsatz eines Kürzesttexts zuzuordnen sind. Einen detaillierten Einblick in das tatsächliche Unterrichtsgeschehen liefert diese Auswertung allerdings nicht: Was genau in den Lerngruppen nach Einsatz eines Kürzesttexts geschieht, bildet die fokussierte Auswertung unzureichend ab. Denn durch die Fokussierung auf die Stufen des Abstrakten gehen bedeutsame Informationen verloren, die durch das Analyseinstrument nicht erfasst werden.
Zentrale Herausforderung
Authors: Möller Ellen Franziska
Published: September 2023

An dieser Stelle ist eine Gegenüberstellung des bisher Erörterten angezeigt. Das Philosophieren mit Kindern wird aus zwei Richtungen betrachtet: Es werden Besonderheiten des Philosophierens mit Kindern herausgestellt, indem der Begriff Philosophieren definiert wird als ein Prozess, der ein abstraktes Element enthält (vgl. Kap. 3). Es werden Besonderheiten herausgestellt, die insbesondere für das Philosophieren mit Kindern gelten, indem Kinder dazu neigen, im Anschaulichen zu verharren (vgl. Kap. 4).
Transverse momentum distributions of heavy hadrons and polarized heavy quarks
Authors: von Kuk Rebecca , Michel Johannes K. L. , Sun Zhiquan
Published: September 2023

Abstract

We initiate the study of transverse momentum-dependent (TMD) fragmentation functions for heavy quarks, demonstrate their factorization in terms of novel nonperturbative matrix elements in heavy-quark effective theory (HQET), and prove new TMD sum rules that arise from heavy-quark spin symmetry. We discuss the phenomenology of heavy-quark TMD FFs at B factories and find that the Collins effect, in contrast to claims in the literature, is not parametrically suppressed by the heavy-quark mass. We further calculate all TMD parton distribution functions for the production of heavy quarks from polarized gluons within the nucleon and use our results to demonstrate the potential of the future EIC to resolve TMD heavy-quark fragmentation in semi-inclusive DIS, complementing the planned EIC program to use heavy quarks as probes of gluon distributions.
The osteogenic and mineralogenic potential of the microalgae Skeletonema costatum and Tetraselmis striata CTP4 in fish models
Authors: Carletti Alessio , Rosa Joana T. , Pes Katia , Borges Inês , Santos Tamára , Barreira Luísa , Varela João , Pereira Hugo , Cancela M. Leonor , Gavaia Paulo J. , Laizé Vincent
Published: September 2023

Skeletal disorders are problematic aspects for the aquaculture industry as skeletal deformities, which affect most species of farmed fish, increase production costs and affect fish welfare. Following recent findings that show the presence of osteoactive compounds in marine organisms, we evaluated the osteogenic and mineralogenic potential of commercially available microalgae strains Skeletonema costatum and Tetraselmis striata CTP4 in several fish systems. Ethanolic extracts increased extracellular matrix mineralization in gilthead seabream (Sparus aurata) bone-derived cell cultures and promoted osteoblastic differentiation in zebrafish (Danio rerio) larvae. Long-term dietary exposure to both extracts increased bone mineralization in zebrafish and upregulated the expression of genes involved in bone formation (sp7, col1a1a, oc1, and oc2), bone remodeling (acp5a), and antioxidant defenses (cat, sod1). Extracts also improved the skeletal status of zebrafish juveniles by reducing the incidence of skeletal anomalies. Our results indicate that both strains of microalgae contain osteogenic and mineralogenic compounds, and that ethanolic extracts have the potential for an application in the aquaculture sector as dietary supplements to support fish bone health. Future studies should also identify osteoactive compounds and establish whether they can be used in human health to broaden the therapeutic options for bone erosive disorders such as osteoporosis.
Elevated remnant cholesterol and atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study
Authors: Wadström Benjamin N. , Pedersen Kasper M. , Wulff Anders B. , Nordestgaard Børge G.
Published: September 2023

Aims/hypothesis

Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. This association is not well studied in individuals with diabetes, who are often included in clinical trials of remnant cholesterol-lowering therapy. We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of ASCVD in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol.

Methods

We included 4569 white Danish individuals with diabetes (58% statin users) nested within the Copenhagen General Population Study (2003–2015). The ASCVDs peripheral artery disease, myocardial infarction and ischaemic stroke were extracted from national Danish health registries without losses to follow-up. Remnant cholesterol was calculated from a standard lipid profile.

Results

During up to 15 years of follow-up, 236 individuals were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischaemic stroke and 498 with any ASCVD. Multivariable adjusted HR (95% CI) per doubling of remnant cholesterol was 1.6 (1.1, 2.3; p=0.01) for peripheral artery disease, 1.8 (1.2, 2.5; p=0.002) for myocardial infarction, 1.5 (1.0, 2.1; p=0.04) for ischaemic stroke, and 1.6 (1.2, 2.0; p=0.0003) for any ASCVD. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischaemic stroke and 1.6-fold for any ASCVD. Excess risk explained by elevated remnant cholesterol and low-grade inflammation was 14% and 8% for peripheral artery disease, 26% and 16% for myocardial infarction, 34% and 34% for ischaemic stroke, and 24% and 18% for any ASCVD, respectively. LDL-cholesterol did not explain excess risk, as it was not higher in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol.

Conclusions/interpretation

Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes. Remnant cholesterol and low-grade inflammation explained substantial excess risk of ASCVD conferred by diabetes. Whether remnant cholesterol should be used as a treatment target remains to be determined in randomised controlled trials.

Graphical Abstract
How do German pharmacologists publish in the non-peer-reviewed science magazine Biospektrum?
Authors: Zöllner Helena , Seifert Roland
Published: September 2023

Publications in peer-reviewed journals are the most important currency in science. But what about publications in non-peer-reviewed magazines? The objective of this study was to analyze the publications of scientists, with a focus on pharmacologists, in the non-peer-reviewed German science magazine Biospektrum from 1999 to 2021. Biospektrum is edited by five scientific societies in Germany including the Society for Experimental and Clinical Society Pharmacology and Toxicology (DGPT) and provides opportunities to researchers to showcase their research to a broad audience. We analyzed 3197 authors of 1326 articles. Compared to the fields of biochemistry, microbiology, and genetics, pharmacology was largely underrepresented. Just three institutions in Germany contributed most papers to Biospektrum. Researchers with a doctoral degree were the largest author group, followed by researchers with a habilitation degree. Among all major fields, women were underrepresented as authors, particularly as senior authors. The Covid pandemic leads to a drop of publications of female first authors but not last authors. Compared to publications in the peer-reviewed journal Naunyn–Schmiedeberg’s Archives of Pharmacology (Zehetbauer et al., Naunyn-Schmiedebergs Arch Pharmacol 395:39–50 (2022)), female pharmacologists were underrepresented in the Biospektrum. Thus, German pharmacologists as a group do not value investing in “social impact” gained by publications in Biospektrum, and this attitude is even more prominent among female pharmacologists. Investing less in “social impact” by female pharmacologists may result in reduced visibility on the academic job market and may contribute to reduced opportunities to achieve high academic positions.
Carbon ion radiotherapy combined with immunotherapy: synergistic anti-tumor efficacy and preliminary investigation of ferroptosis
Authors: Huang Qingting , Hu Jiyi , Chen Li , Lin Wanzun , Yang Jing , Hu Weixu , Gao Jing , Zhang Haojiong , Lu Jiade Jay , Kong Lin
Published: September 2023

Carbon ion radiotherapy (CIRT) may yield satisfactory clinical outcomes for patients who are resistant to radiotherapy. However, the therapeutic impact of carbon ions is still limited in certain recurring or refractory tumors. Therefore, we aimed to evaluate the synergistic anti-tumor effects of immune checkpoint inhibitors (ICIs) in combination with CIRT. We then explored the involvement of ferroptosis in a preliminary investigation. A tumor-bearing mouse model was established, and mice were inoculated subcutaneously with B16-OVA cells into the flanks of both hind legs. Mice were assigned to four groups to receive CIRT, ICIs, or combined treatment. Thereafter, we conducted transcriptome sequencing (RNA-seq), bioinformatics analysis, and various immune-related experiments on the available tumor tissues to investigate differences in the synergistic anticancer effects and potential mechanisms across the groups. The combination therapies significantly improved the survival of mice and inhibited tumor growth, both at local and distant sites. Based on bioinformatics and RNA-seq data, immune-related pathways and genes, immune cell infiltration, and the production of cytokines and chemokines were the most enhanced in the combined treatment group compared to other groups. Finally, we identified a potential role for ferroptosis in the development of local anti-tumor synergy during CIRT combination treatment. In conclusion, this study showed that CIRT and ICIs can enhance the anti-tumor immune effects. We also proposed that ferroptosis may induce anti-tumor effects in CIRT combination therapy, offering a unique perspective on its ability to enhance immunotherapy responses.
Evaluation of simultaneous multi-slice acquisition with advanced processing for free-breathing diffusion-weighted imaging in patients with liver metastasis
Authors: Rata Mihaela , De Paepe Katja N. , Orton Matthew R. , Castagnoli Francesca , d’Arcy James , Winfield Jessica M. , Hughes Julie , Stemmer Alto , Nickel Marcel Dominik , Koh Dow-Mu
Published: September 2023

Objectives

Diffusion-weighted imaging (DWI) with simultaneous multi-slice (SMS) acquisition and advanced processing can accelerate acquisition time and improve MR image quality. This study evaluated the image quality and apparent diffusion coefficient (ADC) measurements of free-breathing DWI acquired from patients with liver metastases using a prototype SMS-DWI acquisition (with/without an advanced processing option) and conventional DWI.

Methods

Four DWI schemes were compared in a pilot 5-patient cohort; three DWI schemes were further assessed in a 24-patient cohort. Two readers scored image quality of all b-value images and ADC maps across the three methods. ADC measurements were performed, for all three methods, in left and right liver parenchyma, spleen, and liver metastases. The Friedman non-parametric test (post-hoc Wilcoxon test with Bonferroni correction) was used to compare image quality scoring; t-test was used for ADC comparisons.

Results

SMS-DWI was faster (by 24%) than conventional DWI. Both readers scored the SMS-DWI with advanced processing as having the best image quality for highest b-value images (b750) and ADC maps; Cohen’s kappa inter-reader agreement was 0.6 for b750 image and 0.56 for ADC maps. The prototype SMS-DWI sequence with advanced processing allowed a better visualization of the left lobe of the liver. ADC measured in liver parenchyma, spleen, and liver metastases using the SMS-DWI with advanced processing option showed lower values than those derived from the SMS-DWI method alone (t-test, p < 0.0001; p < 0.0001; p = 0.002).

Conclusions

Free-breathing SMS-DWI with advanced processing was faster and demonstrated better image quality versus a conventional DWI protocol in liver patients.

Clinical relevance statement

Free-breathing simultaneous multi-slice- diffusion-weighted imaging (DWI) with advanced processing was faster and demonstrated better image quality versus a conventional DWI protocol in liver patients.

Key Points

• Diffusion-weighted imaging (DWI) with simultaneous multi-slice (SMS) can accelerate acquisition time and improve image quality.

• Apparent diffusion coefficients (ADC) measured in liver parenchyma, spleen, and liver metastases using the simultaneous multi-slice DWI with advanced processing were significantly lower than those derived from the simultaneous multi-slice DWI method alone.

• Simultaneous multi-slice DWI sequence with inline advanced processing was faster and demonstrated better image quality in liver patients.
Intraoperative neurophysiology in pediatric neurosurgery: a historical perspective
Authors: Sala Francesco
Published: September 2023

Introduction

Intraoperative neurophysiology (ION) has been established over the past three decades as a valuable discipline to improve the safety of neurosurgical procedures with the main goal of reducing neurological morbidity. Neurosurgeons have substantially contributed to the development of this field not only by implementing the use and refinement of ION in the operating room but also by introducing novel techniques for both mapping and monitoring of neural pathways.

Methods

This review provides a personal perspective on the evolution of ION in a variety of pediatric neurosurgical procedures: from brain tumor to brainstem surgery, from spinal cord tumor to tethered cord surgery.

Results and discussion

The contribution of pediatric neurosurgeons is highlighted showing how our discipline has played a crucial role in promoting ION at the turn of the century. Finally, a view on novel ION techniques and their potential implications for pediatric neurosurgery will provide insights into the future of ION, further supporting the view of a functional, rather than merely anatomical, approach to pediatric neurosurgery.
Comparison of the optimal and suboptimal quantity of mitotype libraries using next-generation sequencing
Authors: Obal Marcel , Zupanc Tomaž , Zupanič Pajnič Irena
Published: September 2023

Optimizing analysis parameters and sample input is crucial in forensic genetics methods to generate reliable results, and even more so when working with muti-copy mitochondrial DNA (mtDNA) and low-quality samples. This study compared mitotypes based on next-generation sequencing (NGS) results derived from the same samples at two different sequencing library concentrations—30 pM and 0.3 pM. Thirty femur samples from the Second World War were used as a model for poorly preserved DNA. Quantitative PCR (qPCR) method targeting 113 bp long fragment was employed to assess the quantity of mitogenomes. HID Ion Chef™ Instrument with Precision ID mtDNA Control Region Panel was used for library preparation and templating. Sequencing was performed with Ion GeneStudio™ S5 System. Reference haplotypes were determined from sequencing samples at 30 pM library input. Haplotypes were compared between optimal (30 pM) and suboptimal (0.3 pM) library inputs. Often the difference in haplotypes was length heteroplasmy, which in line with other studies shows that this type of variant is not reliable for interpretation in forensics. Excluding length variants at positions 573, 309, and 16,193, 56.7% of the samples matched, and in two samples, no sequence was obtained at suboptimal library input. The rest of the samples differed between optimal and suboptimal library input. To conclude, genotyping and analyzing low-quantity libraries derived from low-quality aged skeletonized human remains therefore must be done with caution in forensic genetics casework.
A nonlocal free boundary problem with Wasserstein distance
Authors: Karakhanyan Aram L.
Published: September 2023

We study the probability measures $$\rho \in \mathcal M(\mathbb R^{2})$$

ρ
∈
M
(

R
2

)

minimizing the functional $$\begin{aligned} J[\rho ]=\iint \log \frac{1}{|x-y|}d\rho (x)d\rho (y)+d^2(\rho , \rho _0), \end{aligned}$$

J

[
ρ
]

=
∬
log

1

|
x
-
y
|

d
ρ

(
x
)

d
ρ

(
y
)

+

d
2

(
ρ
,

ρ
0

)

,

where $$\rho _0$$

ρ
0

is a given probability measure and $$d(\rho , \rho _0)$$

d
(
ρ
,

ρ
0

)

is the 2-Wasserstein distance of $$\rho $$
ρ
and $$\rho _0$$

ρ
0

. $$J[\rho ]$$

J
[
ρ
]

appears in aggregation models when the movement of particles is advanced by the potential $$-\log |x|*\rho $$

-
log
|
x
|

∗
ρ

. We prove the existence of minimizers $$\rho $$
ρ
and show that the potential $$U^\rho =-\log |x|*\rho $$

U
ρ

=
-
log

|
x
|

∗
ρ

solves a degenerate obstacle problem, the obstacle being the transport potential. Every minimizer $$\rho $$
ρ
is absolutely continuous with respect to the Lebesgue measure. The singular set of the free boundary of the obstacle problem is contained in a rectifiable set, and its Hausdorff dimension is $$< n-1$$

<
n
-
1

.Moreover, $$U^\rho $$

U
ρ

solves a nonlocal Monge–Ampère equation, which after linearization leads to the equation $$\rho _t={\text {div}}(\rho \nabla U^\rho )$$

ρ
t

=
div

(
ρ
∇

U
ρ

)

. The methods we develop use Fourier transform techniques. They work equally well in high dimensions $$n\ge 2$$

n
≥
2

for the energy $$\begin{aligned} J[\rho ]=\iint |x-y|^{2-n}d\rho (x)d\rho (y)+d^2(\rho , \rho _0). \end{aligned}$$

J

[
ρ
]

=

∬
|
x
-
y
|

2
-
n

d
ρ

(
x
)

d
ρ

(
y
)

+

d
2

(
ρ
,

ρ
0

)

.
Ten-year outcomes of anterior cruciate ligament reconstruction with hamstring tendon autograft and femoral fixation with a cortico-cancellous screw suspension device
Authors: Senigagliesi Elisa , Farinelli Luca , Aquili Alberto , Canè Pier Paolo , Fravisini Marco , Gigante Antonio Pompilio
Published: September 2023

Purpose

To evaluate the clinical and radiographic outcomes of anterior cruciate (ACL) reconstruction at minimum 10-year follow-up.

Methods

Ninety-three patients who underwent primary unilateral ACL reconstruction with hamstring tendon autograft, transtibial technique and femoral cortico-cancellous screw suspension device (Athrax, Leader Medica s.r.l) between 2010 and 2012 were retrospectively reviewed. Mean follow-up was 136 months. Evaluation was performed using the International Knee Documentation Committee score (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score and Tegner Activity Level Scale. Incidence of OA was determined by comparing standard anteroposterior and lateral weightbearing radiographs of the ACL-reconstructed and contralateral knee. Osteoarthritis severity was graded according to the Kellgren–Lawrence (KL) score.

Results

Median Tegner activity level was 6 (5–7). Lysholm and IKDC scores were 100 (95–100) and 90 (86–95), respectively, KOOS was 98 (95–100). Of ACL-reconstructed knees, 41 (50%) had radiographic OA, of which 6 (7.3%) had severe OA (KL III). Of the contralateral healthy knees, 28 (34.1%) had radiographic evidence of OA. Of these 22 (26.8%) and 6 (7.3%) patients had, respectively, KL-I and KL-II. 11 patients (11.8%) underwent subsequent knee surgery: 5 (5.4%) revisions, 3 (3.2%) meniscal surgeries, 2 (2.2%) other surgeries, 1 (1.1%) contralateral ACL reconstruction.

Conclusions

The study demonstrates that ACL reconstruction with HT autograft and cortico-cancellous screw suspension device determines satisfying clinical results after 10 years of follow-up. From our cohort, a low rate of graft failure has been reported, even though almost 50% of patients present a knee OA greater or equal to grade II KL.
Viscous and thermal velocity slip coefficients via the linearized Boltzmann equation with ab initio potential
Authors: Basdanis Thanasis , Valougeorgis Dimitris , Sharipov Felix
Published: September 2023

The viscous and thermal velocity slip coefficients of various monatomic gases are computed via the linearized classical Boltzmann equation, with ab initio potential, subject to Maxwell and Cercignani–Lampis boundary conditions. Both classical and quantum interatomic interactions are considered. Comparisons with hard sphere and Lennard–Jones potentials, as well as the linearized Shakhov model are performed. The produced database is dense, covers the whole range of the accommodation coefficients and is of high accuracy. Using symbolic regression, very accurate closed form expressions of the slip coefficients, easily implemented in the future computational and experimental works, are deduced. The thermal slip coefficient depends, much more than the viscous one, on the intermolecular potential. For example, in the case of diffuse scattering, the relative differences in the viscous slip coefficient data between HS and AI potentials are less than 4%, whilst the corresponding ones in the thermal slip coefficient data are about 6% for He, reaching 15% for Xe. Quantum effects are considered for He, at temperatures 1–104 K to deduce that deviations from the classical behaviour are not important in the viscous slip coefficient, but they become important in the thermal slip coefficient, where the differences between the classical and quantum approaches reach 15% at 1 K. The computational effort of solving the linearized Boltzmann equation with ab initio and Lennard–Jones potentials is the same. Since ab initio potentials do not contain any adjustable parameters, it is recommended to use them at any temperature.