bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of a conversational recommender system in education
Authors: Valtolina Stefano , Matamoros Ricardo Anibal , Epifania Francesco
Published: June 2024

In recent years, we have seen a significant proliferation of e-learning platforms. E-learning platforms allow teachers to create digital courses in a more effective and time-saving way, but several flaws hinder their actual success. One main problem is that teachers have difficulties finding and combining open-access learning materials that match their specific needs precisely when there are so many to choose from. This paper proposes a new strategy for creating digital courses that use learning objects (LOs) as primary elements. The idea consists of using an intelligent chatbot to assist teachers in their activities. Defined using RASA technology, the chatbot asks for information about the course the teacher has to create based on her/his profile and needs. It suggests the best LOs and how to combine them according to their prerequisites and outcomes. A chatbot-based recommendation system provides suggestions through BERT, a machine-learning model based on Transformers, to define the semantic similarity between the entered data and the LOs metadata. In addition, the chatbot also suggests how to combine the LOs into a final learning path. Finally, the paper presents some preliminary results about tests carried out by teachers in creating their digital courses.
Large-scale evaluation of cold-start mitigation in adaptive fact learning: Knowing “what” matters more than knowing “who”
Authors: van der Velde Maarten , Sense Florian , Borst Jelmer P. , Rijn Hedderik van
Published: June 2024

Adaptive learning systems offer a personalised digital environment that continually adjusts to the learner and the material, with the goal of maximising learning gains. Whenever such a system encounters a new learner, or when a returning learner starts studying new material, the system first has to determine the difficulty of the material for that specific learner. Failing to address this “cold-start” problem leads to suboptimal learning and potential disengagement from the system, as the system may present problems of an inappropriate difficulty or provide unhelpful feedback. In a simulation study conducted on a large educational data set from an adaptive fact learning system (about 100 million trials from almost 140 thousand learners), we predicted individual learning parameters from response data. Using these predicted parameters as starting estimates for the adaptive learning system yielded a more accurate model of learners’ memory performance than using default values. We found that predictions based on the difficulty of the fact (“what”) generally outperformed predictions based on the ability of the learner (“who”), though both contributed to better model estimates. This work extends a previous smaller-scale laboratory-based experiment in which using fact-specific predictions in a cold-start scenario improved learning outcomes. The current findings suggest that similar cold-start alleviation may be possible in real-world educational settings. The improved predictions can be harnessed to increase the efficiency of the learning system, mitigate the negative effects of a cold start, and potentially improve learning outcomes.
Strangers in a Strange Land: Legitimacy Formation by Polish Multinationals Venturing into Sub-Saharan Africa
Authors: Wąsowska Aleksandra , Obłój Krzysztof , Kopiński Dominik
Published: June 2024

Our paper revisits one of the fundamental questions of International Business (IB) scholarship, investigating the ways through which multinational enterprises (MNEs) establish legitimacy when entering a foreign market. We address this question in a novel context of Central and Eastern European (CEE) firms venturing into Sub-Saharan Africa (SSA), employing a multiple case study approach. We investigate the process of legitimacy formation by Polish firms entering SSA for market-seeking reasons. We find that the firms studied use their initial liabilities of foreignness, outsidership, and origin as starting points for pragmatic, moral, and cognitive legitimacy-building by developing narratives that neutralize the distance between themselves and important local stakeholders. Our findings contribute to an understanding of the contingent nature of ‘liabilities’ in IB literature and shed light on the role of narratives in the internationalization process.
Effect of the curing agent DETA and its interaction with a rare earth carboxylate as corrosion inhibitor in a hybrid silica-epoxy formulation
Authors: Suárez-Vega Ana , Agustín-Sáenz Cecilia , O’Dell Luke A. , Brusciotti Fabiola , Somers Anthony , Forsyth Maria
Published: June 2024

Sol–gel based coatings are used to protect metals from corrosion. They offer a barrier to the electrolyte penetration, but they do not provide active corrosion protection. Therefore, corrosion inhibitors are often added to sol–gel formulations to improve the overall corrosion behavior. Sol–gel-based coatings typically require relatively high temperatures to be properly cured, which supposes high energy consumptions and might damage some of the precursors of the formulation, including corrosion inhibitors incorporated to improve the coating’s properties. In this study, the effect of diethylenetriamine (DETA) as a curing agent, and yttrium 4-hydroxy cinnamate [Y-(4OHCin)3] as corrosion inhibitor, on the chemistry and corrosion performance of a hybrid silica-epoxy formulation are investigated. Solid nuclear magnetic resonance and attenuated total reflectance Fourier transform infrared spectroscopy are carried out to analyze the influence of the curing agent and the corrosion inhibitor on the chemical structure of the coating. The corrosion performance is assessed by means of electrochemical impedance spectroscopy, and the results are evaluated considering the chemical study and the interaction between the different compounds.
Exploring barriers and facilitators to increase the engagement with a digital app (OLIO) for food/non-food sustainable consumption in citizens from Bogotá, Colombia
Authors: Gómez Ceballos Angela Milena , Antonopoulou Vivi
Published: June 2024

Engaging in sustainable behaviours is a key priority for environmental sustainability. Behavioural changes such as recycling, and food sharing are needed to achieve a zero-emissions society. Digital technologies can support engagement with these behaviours through publicly accessible digital platforms such as mobile apps which connect those with surplus items to those who need or wish to consume these items. However, very little research has examined the factors influencing engagement with mobile apps, particularly in the context of developing countries. This exploratory sequential mixed methods study used behavioural science models to identify factors influencing engagement with the Olio app, a mobile application for food and non-food items sharing in Bogota, Colombia. Influencing factors were analyzed and categorized as barriers or enablers using the Capability (C), Opportunity (O), and Motivation (M) model of behaviour (B) change (COM-B). Regarding barriers, two were strong influencers “perceived difficulty to use a mobile app” for donating items (physical opportunity, β = -.25, p < .001), and “lack of time to collect a used item in others’ location” (physical opportunity, β = -.18, p < .01). As to the enablers, the strongest predictor for collecting was “finding mobile apps to share used items to be widely disseminated on social media channels” (physical opportunity, β = .27, p < .001) and for donating “Knowing how to use mobile apps” (psychological capability, β = .19, p < .01). Findings are discussed along with implementation strategies that could potentially increase engagement with the Olio app to support sustainable consumption.
Robot-Mediated Intergenerational Childcare: Experimental Study Based on Health-Screening Task in Nursery School
Authors: Nakanishi Junya , Baba Jun , Chang Wei-Chuan , Nakae Aya , Sumioka Hidenobu , Ishiguro Hiroshi
Published: June 2024

Intergenerational interactions between children and older adults are gaining broader recognition because of their mutual benefits. However, such interactions face practical limitations owing to potential disease transmission and the poor health of older adults for face-to-face interactions. This study explores robot-mediated interactions as a potential solution to address these issues. In this study, older adults remotely controlled a social robot to perform a health-screening task for nursery school children, thereby overcoming the problems associated with face-to-face interactions while engaging in physical interactions. The results of this study suggested that the children responded favorably to the robot, and the rate of positive response increased over time. Older adults also found the task generally manageable and experienced a significant positive shift in their attitude toward children. These findings suggest that robot-mediated interactions can effectively facilitate intergenerational engagement and provide psychosocial benefits to both the parties to the engagement. This study provides valuable insights into the potential of robot-mediated interactions in childcare and other similar settings.
A N–CoSe/CoSe2–C@Cu hierarchical architecture as a current collector-integrated anode for potassium-ion batteries
Authors: Mu Zi-Jie , Gao Yan-Jun , Dong Wen-Shuai , Li Zong-You , Song Qing-Yi , Huang Han-Jiao , Xing Li-Dong , Zhang Jian-Guo , Wang Wei , Yu Qi-Yao
Published: June 2024

The highly reversible insertion/extraction of large-radius K+ into electrode materials remains a tough goal, especially for conversion-type materials. Herein, we design a current collector-integrated electrode (N–CoSe/CoSe2–C@Cu) as an advanced anode for potassium-ion battery (PIBs). The conductive CoSe/CoSe2 heterojunction with rich Se vacancy defects, conductive sp2 N-doped carbon layer, and the elastic copper foil matrix can greatly accelerate the electron transfer and enhance the structural stability. Consequently, the well-designed N–CoSe/CoSe2–C@Cu current collector-integrated electrode displays enhanced potassium storage performance with regard to a high capacity (325.1 mAh·g−1 at 0.1 A·g−1 after 200 cycles), an exceptional rate capability (223.5 mAh·g−1 at 2000 mA·g−1), and an extraordinary long-term cycle stability (a capacity fading of only 0.019% per cycle over 1200 cycles at 2000 mA·g−1). Impressively, ex situ scanning electron microscopy (SEM) characterizations prove that the elastic structure of copper foil is merged into the cleverly designed N–CoSe/CoSe2–C@Cu heterostructure, which buffers the deformation of structure and volume and greatly promotes the cycle life during the potassium/depotassium process.

Graphical abstract
Von der Idee einer mathematikdidaktischen Normenforschung
Authors: Lensing Felix
Published: June 2024

Die Mathematikdidaktik ist nicht nur Wissenschaft von der mathematischen Bildungspraxis, sondern sie ist auch Wissenschaft für sie. Sie will die mathematische Bildungspraxis nicht nur in ihren vielfältigen Arten, Formen und Ausprägungen theoretisch erkennen, sondern sie will sie auch praktisch normieren, gestalten und verbessern. Und so steht die Mathematikdidaktik in ihren Forschungsbemühungen vor der Frage, wie sie dieser doppelten Aufgabe gerecht werden kann: Wie kann sie methodisch vorgehen, wenn sie sowohl theoretisch erkennen will, was in der mathematischen Bildungspraxis vor sich geht, als auch praktische Vorschläge dafür ausarbeiten möchte, was in ihr vor sich gehen sollte? Es ist dieses methodologische Problem, mit dem ich mich in diesem Beitrag am Beispiel der Erforschung von Normen in mathematischen Bildungspraxen auseinandersetzen möchte. Dabei wird sich Schritt für Schritt die Idee einer mathematikdidaktischen Normenforschung abzeichnen, welche die theoretische und praktische Forschungsrichtung der Mathematikdidaktik in einem einzigen Forschungsprogramm vereint.
Radiofrequency echographic multi spectrometry (REMS) in the diagnosis and management of osteoporosis: state of the art
Authors: Fuggle Nicholas R , Reginster Jean-Yves , Al-Daghri Nasser , Bruyere Olivier , Burlet Nansa , Campusano Claudia , Cooper Cyrus , Perez Adolfo Diez , Halbout Philippe , Ghi Tullio , Kaufman Jean-Marc , Kurt Andreas , Matijevic Radmila , Radermecker Regis P , Tuzun Sansin , Veronese Nicola , Rizzoli Rene , Harvey Nicholas C , Brandi Maria Luisa , Brandi Maria-Luisa
Published: June 2024

Radiofrequency Echographic Multi Spectrometry (REMS) is a radiation-free, portable technology, which can be used for the assessment and monitoring of osteoporosis at the lumbar spine and femoral neck and may facilitate wider access to axial BMD measurement compared with standard dual-energy x-ray absorptiometry (DXA).

There is a growing literature demonstrating a strong correlation between DXA and REMS measures of BMD and further work supporting 5-year prediction of fracture using the REMS Fragility Score, which provides a measure of bone quality (in addition to the quantitative measure of BMD).

The non-ionising radiation emitted by REMS allows it to be used in previously underserved populations including pregnant women and children and may facilitate more frequent measurement of BMD.

The portability of the device means that it can be deployed to measure BMD for frail patients at the bedside (avoiding the complications in transfer and positioning which can occur with DXA), in primary care, the emergency department, low-resource settings and even at home.

The current evidence base supports the technology as a useful tool in the management of osteoporosis as an alternative to DXA.
Investigating the creep resistance of E-glass/polyester composite for automotive structural components
Authors: Marye Sisay Asmare , Jamir T. Moansunep , Desalegn Yiene Molla
Published: June 2024

This study was focused on investigating the influence of fiber-to-matrix weight ratios on the creep behavior of a composite material made from E-glass fiber and polyester resin. The aim was to assess the practical applicability of the composites for aircraft and vehicle structural parts by checking creep strength. The test specimens were prepared using the hand layup method, combining E-glass fiber and polyester resin. Three different fiber-to-matrix weight ratios (65/35, 55/45, and 35/65) were selected and the test specimens were manufactured according to the ASTM D2990 standard. The tests were conducted on each weight ratio using creep loads of 20, 30, and 40 N., and finite element analysis (FEA) was performed to substantiate the experimental results. Based on the experimental and simulation results, it was observed that the composite with a fiber weight ratio of 65/35 has 62.43 Mpa stress and 7.59 mm deformation. This exhibited favorable creep behavior and higher deformation resistance compared to the other compositions. The finite element analysis results were in good agreement with the experimental findings. This suggests that this weight composition could be preferred for vehicle structural parts. The agreement between the experimental and finite element analysis results further validates the practical applicability of the composite material.
Maternal Uterine Artery Adenoviral Vascular Endothelial Growth Factor (Ad.VEGF-A165) Gene Therapy Normalises Fetal Brain Growth and Microglial Activation in Nutrient Restricted Pregnant Guinea Pigs
Authors: Hristova M. D. , Krishnan T. , Rossi C. A. , Nouza J. , White A. , Peebles D. M. , Sebire N. J. , Zachary I. C. , David A. L. , Vaughan O. R.
Published: June 2024

Fetal growth restriction (FGR) is associated with uteroplacental insufficiency, and neurodevelopmental and structural brain deficits in the infant. It is currently untreatable. We hypothesised that treating the maternal uterine artery with vascular endothelial growth factor adenoviral gene therapy (Ad.VEGF-A165) normalises offspring brain weight and prevents brain injury in a guinea pig model of FGR. Pregnant guinea pigs were fed a restricted diet before and after conception and received Ad.VEGF-A165 (1 × 1010 viral particles, n = 18) or vehicle (n = 18), delivered to the external surface of the uterine arteries, in mid-pregnancy. Pregnant, ad libitum-fed controls received vehicle only (n = 10). Offspring brain weight and histological indices of brain injury were assessed at term and 5-months postnatally. At term, maternal nutrient restriction reduced fetal brain weight and increased microglial ramification in all brain regions but did not alter indices of cell death, astrogliosis or myelination. Ad.VEGF-A165 increased brain weight and reduced microglial ramification in fetuses of nutrient restricted dams. In adult offspring, maternal nutrient restriction did not alter brain weight or markers of brain injury, whilst Ad.VEGF-A165 increased microglial ramification and astrogliosis in the hippocampus and thalamus, respectively. Ad.VEGF-A165 did not affect cell death or myelination in the fetal or offspring brain. Ad.VEGF-A165 normalises brain growth and markers of brain injury in guinea pig fetuses exposed to maternal nutrient restriction and may be a potential intervention to improve childhood neurodevelopmental outcomes in pregnancies complicated by FGR.
Differing Contributions of Anthropogenic Aerosols and Greenhouse Gases on Precipitation Intensity Percentiles Over the Middle and Lower Reaches of the Yangtze River
Authors: Luo Fu , Wang Shanshan , Wang Hao , Shu Xinya , Huang Jianping
Published: June 2024

In June–July 2020, the middle and lower reaches of the Yangtze River (MLYR) were hit by a Meiyu event characterized by a long duration, abundant precipitation, and frequent heavy rainfall, resulting in destructive flooding. We found that the extreme cumulative precipitation in 2020 was mainly contributed by more moderate to heavy daily precipitation rather than extreme daily events. Although some previous studies have been conducted to attribute the 2020 Meiyu event in the MLYR, most of them focused on the cumulative precipitation amount. This attribution case study complements previous attribution analyses and reveals many new features. Our results show that anthropogenic climate change—primarily driven by greenhouse gas (GHG) forcing, anthropogenic aerosol (AA) forcing, and land‐use—has led to a decrease in the number of light to heavy precipitation days, while concurrently increasing the number of extreme precipitation days in the MLYR. Specifically, GHG and AA forcings decreased the frequency of light and moderate precipitation, but only GHG increased the frequency of extreme precipitation. An increasing trend in very heavy precipitation days has been observed. The competitive effects of GHG and AA forcings make it challenging to detect the signal of human activities, which could be intermingled with effects from natural variability. Under the SSP5‐8.5 scenario, the probability of experiencing both light and extreme precipitation events will significantly increase in the MLYR. By 2050–2100, these events are projected to be nearly 4 times more frequent compared to the current climate, which poses significant challenges to water security and economic development decision makers.
Evaluating Aerosol Optical Depth Retrieved From VIIRS Using Global Scale, Multi‐Seasonal Airborne Observations
Authors: Wang Siyuan , Brock Charles , Kondragunta Shobha , Laszlo Istvan , McDonald Brian
Published: June 2024

Aerosol optical depth (AOD) is a vital parameter in atmospheric research. Using observations of the Visible Infrared Imaging Radiometer Suite (VIIRS), onboard Suomi National Polar‐orbiting Partnership (Suomi‐NPP) and NOAA‐20 satellites, National Oceanic and Atmospheric Administration (NOAA) produces near‐real time AOD product with high pixel resolution (750 m), wide swath width (3,040 km), and a 16‐day repeat cycle. Here we report the evaluation of the NOAA/VIIRS AOD using a comprehensive aerosol data set, derived from a global‐scale, multi‐seasonal airborne mission, the NASA Atmospheric Tomography Mission (ATom). This data set includes rich physical and chemical information, such as size distributions, chemical compositions, optical properties, and hygroscopicities of major aerosol types, including dust, sea salt, smoke, internally mixed sulfate/nitrate/organics particles (non‐smoke), black carbon, etc. Globally, VIIRS AOD (Suomi‐NPP and NOAA‐20) shows good agreement with the ATom AOD in the moderate to high AOD range (>0.3), with respect to measurement uncertainties (orthogonal distance regression fitting slope: 1.5 ± 0.2 for Suomi‐NPP and 1.6 ± 0.5 for NOAA‐20; correlation coefficient: 0.85 for Suomi‐NPP and 0.73 for NOAA‐20). There is a persistent bias in the low AOD range (<0.3) on the order of 0.03, likely reflecting systematic errors on VIIRS and/or the ATom AOD product. Ångström exponent reported by VIIRS shows excellent agreement with ATom results within expected uncertainties. Given the unique insights revealed by the ATom AOD and aerosol property data set, it is desirable to have ATom‐like comprehensive payloads in future airborne satellite validation programs.
Iron Oxyhydroxide‐Rich Hydrothermal Deposits at the High‐Temperature Fåvne Vent Field, Mohns Ridge
Authors: Gini Caroline , Jamieson John W. , Reeves Eoghan P. , Gartman Amy , Barreyre Thibaut , Babechuk Michael G. , Jørgensen Steffen L. , Robert Katleen
Published: June 2024

The recently discovered Fåvne vent field, located at 3,040 m depth on the slow‐spreading Mohns mid‐ocean ridge between Greenland and Norway, is a high‐temperature (≥250°C) vent field that is characterized by Fe oxyhydroxide‐rich and S‐poor chimneys and mounds. The vent field is located on both the hanging wall and footwall of a normal fault with a ∼1.5 km throw that forms the western edge of the ∼20 km wide ridge axial valley. Data collected during exploration of the site using a remotely operated vehicle as well as mineralogical and geochemical analyses of rock samples and sediments are used to characterize the geological setting of the vent field and composition of the hydrothermal deposits. The chimney walls are highly porous and lack defined chalcopyrite lined conduits, typical of high‐temperature chimneys. Overall, abundant Fe oxyhydroxide precipitation at high‐temperature vents at Fåvne reflects an excess of Fe over reduced S in the fluid, leading to precipitation of Fe oxide and oxyhydroxide minerals at high to moderate temperature vents (>100°C), and as microbially mediated and abiotic precipitation of Fe oxyhydroxide minerals at low‐temperature diffuse vents (<100°C). The mounds and chimneys exhibit low base metal and reduced S concentrations relative to globally averaged seafloor deposits and suggest subseafloor mixing of hydrothermal fluid with seawater, causing metal sulfide precipitation. Cobalt enrichment at Fåvne may reflect a subsurface influence of an ultramafic substrate on circulating fluids, although ultramafic rocks are absent on the seafloor and no other elements typical of ultramafic deposits are present.
Probabilistic Determination of the Role of Faults and Intrusions in Helium‐Rich Gas Fields Formation
Authors: Halford D. T. , Karolytė R. , Andreason M. W. , Cathey B. , Cathey M. , Dellenbach J. T. , Cuzella J. J. , Sonnenberg S. A. , Cheng A. , McCaffrey K. J. W. , Gluyas J. G. , Ballentine C. J.
Published: June 2024

Natural gas fields with economic helium (>0.3 He %) require the radioactive decay of crustal uranium (U) and thorium (Th) to generate He and tectonic/structural regimes favorable to releasing and concentrating He. An unknown is determining the role of faults and structural features in focusing deep‐seated He sources on shallow accumulations. We tested the correlation between high‐He wells (n = 94) and structural features using a new high‐resolution aeromagnetic survey in the Four Corners area, USA. A depth‐to‐basement map with basement lineaments/faults, an intrusion map, and a flattened basement structural high map were created using Werner deconvolution algorithms by combining magnetic, gravity, and topography data with magnetic and gravity depth profiles. We show quantitatively (via analysis of variance) that a non‐random process controls the relationship between He (>0.3%) and both basement faults and intrusions: 88% of high‐He wells occur <1 km of basement faults; and 85% of high‐He wells occur <1 km of intrusions. As He % increases, the distance to the structural features decreases. Strong spatial/statistical correlations of He wells to both basement faults and intrusions suggest that advective transport via faults/intrusions facilitates He migration. The role of gas phase buoyancy and structural trapping is confirmed: 88% of high‐He occurs within basement structural highs, and 91% of the remaining wells are <1 km from intrusions (potential structural high). We present a composite figure to illustrate how a probabilistic approach can be used as a predictive model to improve He exploration success by targeting zones of intersection of basement faults and intrusions within basement structural highs.
Radiative Heating of High‐Level Clouds and Its Impacts on Climate
Authors: Haslehner Kerstin , Gasparini Blaž , Voigt Aiko
Published: June 2024

The interactions of clouds with radiation influence climate. Many of these impacts appear to be related to the radiative heating and cooling from high‐level clouds, but few studies have explicitly tested this. Here, we use simulations with the ICON‐ESM model to understand how high‐level clouds, through their radiative heating and cooling, influence the large‐scale atmospheric circulation and precipitation in the present‐day climate. We introduce a new method to diagnose the radiative heating of high‐level clouds: instead of defining high‐level clouds as all clouds at temperatures colder than −35°C, we define them as all clouds with a cloud top at temperatures colder than −35°C. The inclusion of the lower cloud parts at temperatures warmer than −35°C circumvents the creation of artificial cloud boundaries and strong artificial radiative heating at the temperature threshold. To isolate the impact of high‐level clouds, we analyze simulations with active cloud‐radiative heating, with the radiative heating from high‐level clouds set to zero, and with the radiative heating from all clouds set to zero. We show that the radiative interactions of high‐level clouds warm the troposphere and strengthen the eddy‐driven jet streams, but have no impact on the Hadley circulation strength and the latitude of the Intertropical Convergence Zone. Consistent with their positive radiative heating and energetic arguments, high‐level clouds reduce precipitation throughout the tropics and lower midlatitudes. Overall, our results confirm that the radiative interactions of high‐level clouds have important impacts on climate and highlight the need for better representing their radiative interactions in models.
QL1209 (pertuzumab biosimilar) versus reference pertuzumab plus trastuzumab and docetaxel in neoadjuvant treatment for HER2-positive, ER/PR-negative, early or locally advanced breast cancer: A multicenter, randomized, double-blinded, parallel-controlled, phase III equivalence trial
Authors: Zuo Wenjia , Wang Zhonghua , Qian Jun , Ma Xiaopeng , Niu Zhaofeng , Ou Jianghua , Mo Qinguo , Sun Jing , Li Xinzheng , Wang Qitang , Yao Yongzhong , Yu Guohua , Li Hongsheng , Chen Dedian , Zhang Hao , Geng Cuizhi , Qiao Guangdong , Zhao Mengmeng , Zhang Baihui , Kang Xiaoyan , Zhang Jin , Shao Zhimin
Published: June 2024

Background

This randomized, parallel-controlled, double-blinded, phase III equivalence study evaluated the equivalence of a proposed pertuzumab biosimilar QL1209 to the pertuzumab (Perjeta®) each with trastuzumab and docetaxel in neoadjuvant treatment of early or locally advanced breast cancer patients with HER2-positive, ER/PR-negative.

Methods

Eligible patients were randomly (1:1) assigned to receive 4 cycles of neoadjuvant QL1209 or pertuzumab each with trastuzumab and docetaxel, and adjuvant treatment. The primary endpoint was total pathologic complete response (tpCR), with equivalence margins of 0.76 to 1.32.

Results

Among the 585 patients enrolled, 257 and 259 patients were assigned to the QL1209 and pertuzumab groups, respectively. The tpCR rates were comparable in the QL1209 (109/255, 42.75%; 90% CI 37.65 to 47.84) and pertuzumab (117/259, 45.17%; 90% CI 40.09 to 50.26) groups. The tpCR risk ratio was 0.95 (90% CI, 0.80 to 1.11), and the 90% CI fell within the predefined equivalence margin. The most common grade ≥3 treatment-related adverse event was decreased neutrophil count (10. 9% vs. 12.7%) in the QL1209 and pertuzumab groups.

Conclusions

QL1209 demonstrated equivalent efficacy and comparable safety profile to the reference pertuzumab in neoadjuvant treatment of HER2-positive, ER/PR-negative, early, or locally advanced breast cancer.

Trial registration

Chinadrugtrials.org CTR20201073; ClinicalTrials.gov NCT04629846.
Limitations in next-generation sequencing-based genotyping of breast cancer polygenic risk score loci
Authors: Baumann Alexandra , Ruckert Christian , Meier Christoph , Hutschenreiter Tim , Remy Robert , Schnur Benedikt , Döbel Marvin , Fankep Rudel Christian Nkouamedjo , Skowronek Dariush , Kutz Oliver , Arnold Norbert , Katzke Anna-Lena , Forster Michael , Kobiela Anna-Lena , Thiedig Katharina , Zimmer Andreas , Ritter Julia , Weber Bernhard H. F. , Honisch Ellen , Hackmann Karl ,   Bioinformatics Working Group of the German Consortium for Hereditary Breast & Ovarian Cancer, Drukewitz Stephan , Engel Christoph , Frommolt Peter , Groß Eva , Helmuth Johannes , Kowalzyk Zarah , Radtke Maximilian , Ramser Juliane , Uebe Steffen , Wang-Gohrke Shan , Schmidt Gunnar , Sturm Marc , Ernst Corinna
Published: June 2024

Considering polygenic risk scores (PRSs) in individual risk prediction is increasingly implemented in genetic testing for hereditary breast cancer (BC) based on next-generation sequencing (NGS). To calculate individual BC risks, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) with the inclusion of the BCAC 313 or the BRIDGES 306 BC PRS is commonly used. The PRS calculation depends on accurately reproducing the variant allele frequencies (AFs) and, consequently, the distribution of PRS values anticipated by the algorithm. Here, the 324 loci of the BCAC 313 and the BRIDGES 306 BC PRS were examined in population-specific database gnomAD and in real-world data sets of five centers of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), to determine whether these expected AFs can be reproduced by NGS-based genotyping. Four PRS loci were non-existent in gnomAD v3.1.2 non-Finnish Europeans, further 24 loci showed noticeably deviating AFs. In real-world data, between 11 and 23 loci were reported with noticeably deviating AFs, and were shown to have effects on final risk prediction. Deviations depended on the sequencing approach, variant caller and calling mode (forced versus unforced) employed. Therefore, this study demonstrates the necessity to apply quality assurance not only in terms of sequencing coverage but also observed AFs in a sufficiently large cohort, when implementing PRSs in a routine diagnostic setting. Furthermore, future PRS design should be guided by the technical reproducibility of expected AFs across commonly used genotyping methods, especially NGS, in addition to the observed effect sizes.
Key informant perspectives on implementing genomic newborn screening: a qualitative study guided by the Action, Actor, Context, Target, Time framework
Authors: Tutty Erin , Archibald Alison D. , Downie Lilian , Gaff Clara , Lunke Sebastian , Vears Danya F. , Stark Zornitza , Best Stephanie
Published: June 2024

Newborn screening (NBS) programmes are highly successful, trusted, public health interventions. Genomic sequencing offers the opportunity to increase the benefits of NBS by screening infants for a greater number and variety of childhood-onset conditions. This study aimed to describe who needs to do what, when, and for whom to deliver genomic newborn screening (gNBS) and capture perceived implementation barriers and enablers. ‘Key informants’ (individuals involved in the delivery of NBS) were interviewed. The Actor, Action, Context, Time and Target framework guided data collection and analysis. Participants (N = 20) identified new Actions required to deliver gNBS (educating healthcare providers, longitudinal psychosocial support), NBS Actions needing modification (obtaining consent) and NBS Actions that could be adopted for gNBS (prompt referral pathways). Obtaining consent in a prenatal Context was a source of some disagreement. The Time to disclose high chance results was raised as a key consideration in gNBS programme design. Genetic counsellors were identified as key Actors in results management, but workforce limitations may be a barrier. Online decision support tools were an enabler to offering gNBS. The implementation of gNBS will require behaviour changes from HCPs delivering NBS. Findings can inform how to deliver gNBS at population-scale.
Anakinra in Sanfilippo syndrome: a phase 1/2 trial
Authors: Polgreen Lynda E. , Chen Agnes H. , Pak Youngju , Luzzi Anna , Morales Garval Adolfo , Acevedo Jonathan , Bitan Gal , Iacovino Michelina , O’Neill Cara , Eisengart Julie B.
Published: June 2024

Sanfilippo syndrome is a fatal childhood neurodegenerative disorder involving neuroinflammation among multiple pathologies. We hypothesized that anakinra, a recombinant interleukin-1 receptor antagonist, could improve neurobehavioral and functional symptoms owing to its capacity to treat neuroinflammation. This phase 1/2 trial aimed to test the safety, tolerability and effects of anakinra on neurobehavioral, functional and quality-of-life outcomes in patients and their caregivers. The primary outcome was the percent of participants requiring a dose increase at week 8 or week 16. Secondary efficacy outcomes included a multi-domain responder index (MDRI). Twenty-three participants (6–26 years of age) were enrolled. Twenty continued treatment to week 8, and 15 (75%) required an increased dose at week 8 or week 16. There was an improvement in at least one domain in the MDRI in 18 of 21 (86%) at week 8 and in 15 of 16 (94%) at week 36. Seven participants withdrew (intolerability of daily injections and lost to follow-up) before week 36. Adverse events occurred in 22 of 23 (96%) participants, most commonly mild injection site reactions. No serious adverse events were related to anakinra. In conclusion, anakinra was safe and associated with improved neurobehavioral and functional outcomes, supporting continued investigation of anakinra in Sanfilippo syndrome and other mucopolysaccharidoses. ClinicalTrials.gov identifier: NCT04018755.
Derivation and transcriptional reprogramming of border-forming wound repair astrocytes after spinal cord injury or stroke in mice
Authors: O’Shea Timothy M. , Ao Yan , Wang Shinong , Ren Yilong , Cheng Amy L. , Kawaguchi Riki , Shi Zechuan , Swarup Vivek , Sofroniew Michael V.
Published: June 2024

Central nervous system (CNS) lesions become surrounded by neuroprotective borders of newly proliferated reactive astrocytes; however, fundamental features of these cells are poorly understood. Here we show that following spinal cord injury or stroke, 90% and 10% of border-forming astrocytes derive, respectively, from proliferating local astrocytes and oligodendrocyte progenitor cells in adult mice of both sexes. Temporal transcriptome analysis, single-nucleus RNA sequencing and immunohistochemistry show that after focal CNS injury, local mature astrocytes dedifferentiate, proliferate and become transcriptionally reprogrammed to permanently altered new states, with persisting downregulation of molecules associated with astrocyte–neuron interactions and upregulation of molecules associated with wound healing, microbial defense and interactions with stromal and immune cells. These wound repair astrocytes share morphologic and transcriptional features with perimeningeal limitans astrocytes and are the predominant source of neuroprotective borders that re-establish CNS integrity around lesions by separating neural parenchyma from stromal and immune cells as occurs throughout the healthy CNS.
A complete reference genome of broomcorn millet
Authors: Wang Haigang , Wang Junjie , Chen Chunhai , Chen Ling , Li Meng , Qin Huibin , Tian Xiang , Hou Sen , Yang Xukui , Jian Jianbo , Gao Peng , Wang Lun , Qiao Zhijun , Mu Zhixin
Published: June 2024

Broomcorn millet (Panicum miliaceum L.), known for its traits of drought resistance, adaptability to poor soil, short growth period, and high photosynthetic efficiency as a C4 plant, represents one of the earliest domesticated crops globally. This study reports the telomere-to-telomere (T2T) gap-free reference genome for broomcorn millet (AJ8) using PacBio high-fidelity (HiFi) long reads, Oxford Nanopore long-read technologies and high-throughput chromosome conformation capture (Hi-C) sequencing data. The size of AJ8 genome was approximately 834.7 Mb, anchored onto 18 pseudo-chromosomes. Notably, 18 centromeres and 36 telomeres were obtained. The assembled genome showed high quality in terms of completeness (BUSCO score: 99.6%, QV: 61.7, LAI value: 20.4). In addition, 63,678 protein-coding genes and 433.8 Mb (~52.0%) repetitive sequences were identified. The complete reference genome for broomcorn millet provides a valuable resource for genetic studies and breeding of this important cereal crop.
Automatic lithology identification in meteorite impact craters using machine learning algorithms
Authors: Yirenkyi Steven , Boateng Cyril D. , Ahene Emmanuel , Danuor Sylvester K.
Published: June 2024

Identifying lithologies in meteorite impact craters is an important task to unlock processes that have shaped the evolution of planetary bodies. Traditional methods for lithology identification rely on time-consuming manual analysis, which is costly and limits the efficiency of rapid decision-making. This paper utilizes different machine learning algorithms namely Random Forest, Decision Tree, K Nearest Neighbors, and Logistic Regression with Grid Search to classify rock lithologies using data from the Bosumtwi impact crater in Ghana. A repeated stratified k-fold cross-validation method is applied to Grid Search to select the best combination of hyperparameters. The findings demonstrate that the Random Forest algorithm achieves the most promising results in classifying lithologies in the meteorite impact crater with an accuracy score of 86.89%, a recall score of 84.88%, a precision score of 87.21%, and an F1 score of 85.48%. The findings also suggest that more high-quality data has the potential to further increase the accuracy scores of the machine learning algorithm. In conclusion, this study demonstrates the significant potential of machine learning techniques to revolutionize lithology identification in meteorite impact craters, thus paving the way for their influential role in future space exploration endeavors.
Maize edible-legumes intercropping systems for enhancing agrobiodiversity and belowground ecosystem services
Authors: Jalloh Abdul A. , Mutyambai Daniel Munyao , Yusuf Abdullahi Ahmed , Subramanian Sevgan , Khamis Fathiya
Published: June 2024

Intensification of staple crops through conventional agricultural practices with chemical synthetic inputs has yielded positive outcomes in food security but with negative environmental impacts. Ecological intensification using cropping systems such as maize edible-legume intercropping (MLI) systems has the potential to enhance soil health, agrobiodiversity and significantly influence crop productivity. However, mechanisms underlying enhancement of biological soil health have not been well studied. This study investigated the shifts in rhizospheric soil and maize-root microbiomes and associated soil physico-chemical parameters in MLI systems of smallholder farms in comparison to maize-monoculture cropping systems (MMC). Maize-root and rhizospheric soil samples were collected from twenty-five farms each conditioned by MLI and MMC systems in eastern Kenya. Soil characteristics were assessed using Black oxidation and Walkley methods. High-throughput amplicon sequencing was employed to analyze fungal and bacterial communities, predicting their functional roles and diversity. The different MLI systems significantly impacted soil and maize-root microbial communities, resulting in distinct microbe sets. Specific fungal and bacterial genera and species were mainly influenced and enriched in the MLI systems (e.g., Bionectria solani, Sarocladium zeae, Fusarium algeriense, and Acremonium persicinum for fungi, and Bradyrhizobium elkanii, Enterobacter roggenkampii, Pantoea dispersa and Mitsuaria chitosanitabida for bacteria), which contribute to nutrient solubilization, decomposition, carbon utilization, plant protection, bio-insecticides/fertilizer production, and nitrogen fixation. Conversely, the MMC systems enriched phytopathogenic microbial species like Sphingomonas leidyi and Alternaria argroxiphii. Each MLI system exhibited a unique composition of fungal and bacterial communities that shape belowground biodiversity, notably affecting soil attributes, plant well-being, disease control, and agroecological services. Indeed, soil physico-chemical properties, including pH, nitrogen, organic carbon, phosphorus, and potassium were enriched in MLI compared to MMC cropping systems. Thus, diversification of agroecosystems with MLI systems enhances soil properties and shifts rhizosphere and maize-root microbiome in favor of ecologically important microbial communities.
Assessing the feasibility of test-and-cull and test-and-segregation approaches for the control of high-prevalence bovine tuberculosis in Ethiopian intensive dairy farms
Authors: Lakew Matios , Tadesse Biniam , Srinivasan Sreenidhi , Aschalew Muluken , Andarge Bekele , Kebede Dirshaye , Etifu Addisu , Alemu Tena , Yalew Bekele , Benti Teferi , Olani Abebe , Abera Shubisa , Bedada Wegene , Fromsa Abebe , Mekonnen Getnet Abie , Almaw Gizat , Ameni Gobena , Ashenafi Hagos , Gumi Balako , Bakker Douwe , Kapur Vivek
Published: June 2024

Bovine tuberculosis (bTB) is endemic and has a substantial impact on the livestock sector in Ethiopia and other low and middle-income countries (LMICs). With a national emphasis on dairy farm intensification to boost milk production and spur economic growth, the incidence of bTB is anticipated to rise. However, Ethiopia, like other LMICs, lacks a comprehensive national bTB control strategy due to the economic and social infeasibility of traditional test-and-cull (TC) approaches. To inform the development of such a strategy, we evaluated the effectiveness and feasibility of TC and test-and-segregation (TSg) strategies for bTB control on Ethiopian dairy farms. A TC approach was used at Farm A [N = 62; comparative cervical test (CCT) > 4 mm, starting prevalence 11.3%] while TSg was implemented at Farm B (N = 45; CCT > 4 mm, prevalence 22.2%), with testing intervals of 2–4 months. Both strategies achieved a reduction in bTB prevalence to 0%, requiring seven rounds of TC over 18 months at Farm A, and five rounds of TSg over 12 months at Farm B’s negative herd. The results show that adopting more sensitive thresholds [CCT > 0 mm or single cervical test (SCT) > 2 mm] during later rounds was pivotal in identifying and managing previously undetected infections, emphasizing the critical need for optimized diagnostic thresholds. Cost analysis revealed that TC was approximately twice as expensive as TSg, primarily due to testing, labor, and cow losses in TC, versus construction of new facilities and additional labor for TSg. This underscores the economic and logistical challenges of bTB management in resource-limited settings. Taken together, our study highlights an urgent need for the exploration of alternative approaches including TSg and or vaccination to mitigate within herd transmission and enable implementation of bTB control in regions where TC is not feasible.
In idiopathic scoliosis distances of spinal cord to thoracic pedicle are within 2 mm in a large region of the thoracic apex
Authors: Burger Joost A. , Becker Luis , Li Zhao , Wang Zhen , Schmidt Hendrik , Pumberger Matthias , Schömig Friederike
Published: June 2024

Despite a 15% misplacement rate of screws in idiopathic scoliosis surgery, little is known about the relationship between pedicles and nerve structures in the entire thoracic curve. This study aimed to explore the spinal cord’s proximity to the pedicle wall at each thoracic vertebra in the entire thoracic curve, while considering different anatomical changes. Spinal cord to medial pedicle distances were measured on magnetic resonance imaging in 73 patients who underwent posterior spinal fusion with pedicle screw instrumentation. Associations with different variables were examined. A total of 51 patients (69.9%) showed a distance within 2 mm at the apex vertebra on the concave side, more than 50% had a distance within 2 mm in the next thoracic vertebra level above and below, and more than 25% two levels above and below. Weak correlations were found between proximity of the spinal cord at the apex vertebra and vertebra’s level and Cobb angle on the concave side (r = − 0.310, P = 0.008, r = 0.380, P = 0.001, respectively). These results emphasize the importance of thorough assessment when placing thoracic pedicle screws in idiopathic scoliosis patients. Further research is warranted to develop surgical strategies aimed at preventing potentially neurological complications resulting from screw misplacement.
Genetic basis of an elite wheat cultivar Guinong 29 with harmonious improvement between multiple diseases resistance and other comprehensive traits
Authors: Xiao Bei , Qie Yanmin , Jin Yuli , Yu Ningning , Sun Nina , Liu Wei , Wang Xiaolu , Wang Jiaojiao , Qian Zejun , Zhao Ya , Yuan Tangyu , Li Linzhi , Wang Fengtao , Liu Cheng , Ma Pengtao
Published: June 2024

Fungal diseases, such as powdery mildew and rusts, significantly affect the quality and yield of wheat. Pyramiding diverse types of resistance genes into cultivars represents the preferred strategy to combat these diseases. Moreover, achieving collaborative improvement between diseases resistance, abiotic stress, quality, and agronomic and yield traits is difficult in genetic breeding. In this study, the wheat cultivar, Guinong 29 (GN29), showed high resistance to powdery mildew and stripe rust at both seedling and adult plant stages, and was susceptible to leaf rust at the seedling stage but slow resistance at the adult-plant stage. Meanwhile, it has elite agronomic and yield traits, indicating promising coordination ability among multiple diseases resistance and other key breeding traits. To determine the genetic basis of these elite traits, GN29 was tested with 113 molecular markers for 98 genes associated with diseases resistance, stress tolerance, quality, and adaptability. The results indicated that two powdery mildew resistance (Pm) genes, Pm2 and Pm21, confirmed the outstanding resistance to powdery mildew through genetic analysis, marker detection, genomic in situ hybridization (GISH), non-denaturing fluorescence in situ hybridization (ND-FISH), and homology-based cloning; the stripe rust resistance (Yr) gene Yr26 and leaf rust resistance (Lr) genes Lr1 and Lr46 conferred the stripe rust and slow leaf rust resistance in GN29, respectively. Meanwhile, GN29 carries dwarfing genes Rht-B1b and Rht-D1a, vernalization genes vrn-A1, vrn-B1, vrn-D1, and vrn-B3, which were consistent with the phenotypic traits in dwarf characteristic and semi-winter property; carries genes Dreb1 and Ta-CRT for stress tolerance to drought, salinity, low temperature, and abscisic acid (ABA), suggesting that GN29 may also have elite stress-tolerance ability; and carries two low-molecular-weight glutenin subunit genes Glu-B3b and Glu-B3bef which contributed to high baking quality. This study not only elucidated the genetic basis of the elite traits in GN29 but also verified the capability for harmonious improvement in both multiple diseases resistance and other comprehensive traits, offering valuable information for breeding breakthrough-resistant cultivars.