bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing and Evaluating Large Language Model–Generated Emergency Medicine Handoff Notes
Authors: Hartman Vince , Zhang Xinyuan , Poddar Ritika , McCarty Matthew , Fortenko Alexander , Sholle Evan , Sharma Rahul , Campion Thomas , Steel Peter A. D.
Published: December 2024

Importance

An emergency medicine (EM) handoff note generated by a large language model (LLM) has the potential to reduce physician documentation burden without compromising the safety of EM-to-inpatient (IP) handoffs.

Objective

To develop LLM-generated EM-to-IP handoff notes and evaluate their accuracy and safety compared with physician-written notes.

Design, Setting, and Participants

This cohort study used EM patient medical records with acute hospital admissions that occurred in 2023 at NewYork-Presbyterian/Weill Cornell Medical Center. A customized clinical LLM pipeline was trained, tested, and evaluated to generate templated EM-to-IP handoff notes. Using both conventional automated methods (ie, recall-oriented understudy for gisting evaluation [ROUGE], bidirectional encoder representations from transformers score [BERTScore], and source chunking approach for large-scale inconsistency evaluation [SCALE]) and a novel patient safety-focused framework, LLM-generated handoff notes vs physician-written notes were compared. Data were analyzed from October 2023 to March 2024.

Exposure

LLM-generated EM handoff notes.

Main Outcomes and Measures

LLM-generated handoff notes were evaluated for (1) lexical similarity with respect to physician-written notes using ROUGE and BERTScore; (2) fidelity with respect to source notes using SCALE; and (3) readability, completeness, curation, correctness, usefulness, and implications for patient safety using a novel framework.

Results

In this study of 1600 EM patient records (832 [52%] female and mean [SD] age of 59.9 [18.9] years), LLM-generated handoff notes, compared with physician-written ones, had higher ROUGE (0.322 vs 0.088), BERTScore (0.859 vs 0.796), and SCALE scores (0.691 vs 0.456), indicating the LLM-generated summaries exhibited greater similarity and more detail. As reviewed by 3 board-certified EM physicians, a subsample of 50 LLM-generated summaries had a mean (SD) usefulness score of 4.04 (0.86) out of 5 (compared with 4.36 [0.71] for physician-written) and mean (SD) patient safety scores of 4.06 (0.86) out of 5 (compared with 4.50 [0.56] for physician-written). None of the LLM-generated summaries were classified as a critical patient safety risk.

Conclusions and Relevance

In this cohort study of 1600 EM patient medical records, LLM-generated EM-to-IP handoff notes were determined superior compared with physician-written summaries via conventional automated evaluation methods, but marginally inferior in usefulness and safety via a novel evaluation framework. This study suggests the importance of a physician-in-loop implementation design for this model and demonstrates an effective strategy to measure preimplementation patient safety of LLM models.
Using a flipped classroom teaching and learning approach to promote scientific literacy skill development and retention
Authors: Brendel Elaina B. K. , Alzubi Ala , Rai Shrujan , Mariathasan Christine , Snook Laelie A. , Monk Jennifer M.
Published: December 2024

The development of scientific literacy (SL) skills is critical in the life sciences. A flipped classroom reverses traditional learning spaces such that foundational knowledge is acquired by students independently through recorded lectures and/or readings in advance of the lecture period and knowledge is consolidated through active learning activities in the classroom. A flipped classroom learning environment can promote critical skill development and knowledge application, and therefore, could enhance SL skill development. The objectives here were to (a) determine the effect of a flipped classroom learning environment on SL skill development in second‐year kinesiology students enrolled in a research methods course and (b) reassess SL skills 4 months later. SL skills were assessed using the validated test of scientific literacy skills (TOSLS) questionnaire at the start and end of the semester (n = 57) and reassessed 4 months later after the summer semester break (n = 46). During the flipped classroom semester, practical SL skills (TOSLS scores) were increased by 16.3% and TOSLS scores were positively correlated with the students' final grade (r = 0.526, P < 0.001). Four months later, average TOSLS scores significantly decreased compared to the levels at the end of the flipped classroom learning experience. Importantly, retention of SL skills (i.e., 4 months later TOSLS scores) were related to learning approach scores and were positively correlated with deep learning approach scores (r = 0.298, P = 0.044) and negatively correlated with surface learning approach scores (r = −0.314, P = 0.034). Therefore, SL skill retention was higher in students utilizing a deep learning approach (e.g., engaged, self‐regulation in learning, and seeking a deeper understanding of concepts) and lower in students utilizing a surface learning approach (e.g., limited engagement, rote memorization of concepts). Collectively, the results demonstrate the value of a flipped classroom in promoting SL skills while highlighting the role of students' learning approach in critical skill retention.
Superior Capacitive Energy Storage Enabled by Molecularly Interpenetrating Interfaces in Layered Polymers
Authors: Sun Liang , Zhang Fengyuan , Li Li , Liang Jiajie , Dong Jiufeng , Pan Zizhao , Niu Yujuan , Chen Jiaxin , Liu Yuqi , Lu Yani , Wu Kai , Li Qi , Li Jiangyu , Wang Qing , Wang Hong
Published: December 2024

Polymer dielectrics are essential for advanced electronics and electrical power systems, yet they suffer from low energy density (Ue) due to their low dielectric constant (K) and the inverse relationship between K and breakdown stength (Eb). Here a scalable approach utilizing the designed molecularly interpenetrating interfaces is presented to achieve all‐organic dielectric polymers with high Ue and charge–dischage efficiency (η). Distinctive intermolecular interactions and microstructural changes, as demonstrated experimentally and theoretically, are introduced by the molecularly interpenetrating interfaces, resulting in simultaneous improvements in dielectric responses and mechanical strength while inhibiting electrical conduction – outcomes unattainable in conventional layered polymers. Consequently, exceptional improvments in both K and Eb are achieved, yielding a very high Ue of 22.89 J cm−3 with η ≥ 90%, outperforming current layered polymer dielectrics. The bilayers can be easily fabricated into large‐area films with high uniformity and outstanding capacitive stability (>500 000 cycles), offering a practical route to scalable high‐Ue polymer dielectrics for electrical energy storage.
Alu‐Mediated Deletion of FANCA in Turkish Families With Fanconi Anemia: Evidence of a Founder Effect
Authors: Durmaz Ceren Damla , Gümrük Fatma , Celkan Tiraje , Unal Sule , Çetinkaya Arda
Published: December 2024

Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome characterized by pancytopenia, increased susceptibility to malignancies, and a spectrum of congenital anomalies. Here, we report on eight affected individuals from six unrelated families with a large Alu‐mediated intragenic deletion encompassing exons 6–31 in the FANCA gene, identified as a founder mutation in the Turkish population through haplotype analysis. This deletion, mediated by Alu repeat sequences, underscores the role of repetitive elements in FA pathogenesis. Clinical data revealed variable phenotypic presentations among affected individuals, highlighting the challenge of establishing genotype–phenotype correlations even in the presence of identical FANCA pathogenic variants. We carried out an easy and effective PCR‐based diagnostic test for detecting this mutation, enabling precise diagnosis and genetic counseling for affected individuals and their families. This study provides valuable insights into the molecular mechanisms underlying FA pathogenesis and offers a practical approach for genetic diagnosis in affected individuals, particularly those of Turkish descent.
Aliphatic Amines Unlocked for Selective Transformations through Diazotization
Authors: Durka Jakub , Zielińska Barbara , Gryko Dorota
Published: December 2024

While aromatic diazonium salts are important reagents in organic synthesis, ‘Diazonium ions generated from ordinary aliphatic primary amines are usually useless for preparative purposes, since they lead to a mixture of products giving not only substitution by any nucleophile present, but also elimination and rearrangements if the substrate permits.’1 In this work, we report that this statement is no longer valid, and it is now possible to control diazotization of aliphatic amines by utilizing isopentyl nitrite in HFIP. This transformation enabled electrophilic aromatic substitution with these highly abundant and commercially available alkyl reagents, as well as transforming them into building blocks typically employed in organic synthesis. The methodology opens an avenue for reactions involving aliphatic amines, even such demanding substrates as amino acids, as a source of carbocations thus expanding the degree of chemical space.
Asymmetric S‐Arylation of Sulfenamides to Access Axially Chiral Sulfilimines Enabled by Anionic Stereogenic‐at‐Cobalt(III) Complexes
Authors: Fang Wei , Meng Yan‐Dong , Ding Shu‐Ying , Wang Ju‐Yan , Pei Zheng‐Hao , Shen Meng‐Lan , Yao Chuan‐Zhi , Li Qiankun , Gu Zhenhua , Yu Jie , Jiang Hua‐Jie
Published: December 2024

An efficient enantioselective coupling reaction between sulfenamides and cyclic diaryliodonium salts is established via adaptive Cu/anionic stereogenic‐at‐Co(III) complex combined catalysis, precisely synthesizing a broad range of axially chiral sulfilimines with excellent enantioselectivities, diastereoselectivities, regioselectivities, and chemoselectivities (67 examples under same conditions, up to 98 % ee). The following thermodynamically controlled pyramidal inversion enables efficient stereodivegent synthesis of all four stereoisomers. Mechanistic studies suggest that anionic stereogenic‐at‐cobalt(III) complexes serve as counteranions of diaryliodonium and anionic ligand of Cu(I) catalyst simultaneously, which could be regarded as an explanation for outstanding selectivities.
The Role of Electron Transfer in Copper‐Mediated C(sp2)−H Trifluoromethylation
Authors: Ball Margaret A. P. , Myers Preston J. , Ritch Grayson D. , Bower Jamey K. , Moore Curtis E. , Szymczak Nathaniel K. , Zhang Shiyu
Published: December 2024

We report copper(II) and copper(III) trifluoromethyl complexes supported by a pyridinedicarboxamide ligand (L) as a platform for investigating the role of electron transfer in C(sp2)−H trifluoromethylation. While the copper(II) trifluoromethyl complex is unreactive towards (hetero)arenes, the formal copper(III) trifluoromethyl complex performs C(sp2)−H trifluoromethylation of a wide range of (hetero)arenes. Mechanistic studies using the copper(III) trifluoromethyl complex suggest that the mechanism of arene trifluoromethylation is substrate‐dependent. When the thermodynamic driving force for electron transfer is high, the reaction proceeds through a previously unidentified single electron transfer (SET) mechanism, where an initial electron transfer occurs between the substrate and oxidant prior to CF3 group transfer. Otherwise, a CF3 radical release/electrophilic aromatic substitution (SEAr) mechanism is followed. These studies provide valuable insights into the role of strong oxidants and potential mechanistic dichotomy in Cu‐mediated C(sp2)−H trifluoromethylation.
Self‐assembled free nanocarrier prodrugs based on camptothecin and dihydroartemisinin exhibit accumulation and improved anticancer efficacy
Authors: Garg Mohan , Rangaswamy Roopashree , Mishra Rahul , Giri Shivangi , Chinnathambi Arunachalam , Alahmadi Tahani Awad , Arulselvan Palanisamy , Thangavelu Indumathi
Published: December 2024

Small molecule targeted inhibitor therapies often have several drawbacks, including limited oral bioavailability, quick metabolism, toxic effects that limit dosage, and poor water solubility. This study aims to develop a nanodrug self‐delivery system that does not require a carrier by utilizing the self‐assembly of camptothecin (CPT) and dihydroartemisinin (DHA). CPT/DHA nanoparticles (NPs) with varying diameters can be synthesized without requiring further carrier materials or chemical modifications by changing the CPT‐to‐DHA ratio (10:1, 5:1, 2:1, 1:1). Even more crucially, CPT/DHA NPs generate an AIE impact when they self‐assemble. CPT/DHA NPs are used for cell tracking and bioimaging fluorescent probes. We chose CPT/DHA NPs (2:1) with a size of approximately 140 nm for the anticancer examinations. The A549 cells were used to assess the cytotoxicity, morphological changes by biochemical staining methods and apoptosis by flow cytometric techniques of CPT/DHA NPs. Finally, in vitro anticancer research proved that CPT/DHA NPs are biocompatible and have strong synergistic anticancer properties.
The Multiscale Wisdom of the Body: Collective Intelligence as a Tractable Interface for Next‐Generation Biomedicine
Authors: Levin Michael
Published: December 2024

The dominant paradigm in biomedicine focuses on genetically‐specified components of cells and their biochemical dynamics, emphasizing bottom‐up emergence of complexity. Here, I explore the biomedical implications of a complementary emerging field: diverse intelligence. Using tools from behavioral science and multiscale neuroscience, we can study development, regenerative repair, and cancer suppression as behaviors of a collective intelligence of cells navigating the spaces of possible morphologies and transcriptional and physiological states. A focus on the competencies of living material—from molecular to organismal scales—reveals a new landscape for interventions. Such top‐down approaches take advantage of the memories and homeodynamic goal‐seeking behavior of cells and tissues, offering the same massive advantages in biomedicine and bioengineering that reprogrammable hardware has provided information technologies. The bioelectric networks that bind individual cells toward large‐scale anatomical goals are an especially tractable interface to organ‐level plasticity, and tools to modulate them already exist. This suggests a research program to understand and tame the software of life for therapeutic gain by understanding the many examples of basal cognition that operate throughout living bodies.
Lasia spinosa Stem Aqueous Extract Potentiates Antidiabetic Effects Exhibiting Antioxidant Genes Upregulation and DNA‐Damage Protection
Authors: Sharmen Farjana , Abu Ahmed A. M. , Rahman Md. Atiar
Published: December 2024

This research elucidated the hypoglycemic effect correlated with DNA‐protective and antioxidative activity of Lasia spinosa stem aqueous extract (LSSAE) using streptozotocin‐induced type 2 diabetic rat models. LSSAE, characterized by phytochemical screening, gas chromatography–mass spectroscopy (GC–MS), and FTIR analyses, was investigated for its DNA‐protective activity by exposing PBR322 plasmid DNA to Fenton's reagents. Long Evans rats, treated by LSSAE, were found to be improved for body weight, fasting blood glucose level, and oral glucose load. A 30‐day supplement of LSSAE significantly recovered serum biochemical markers, including hepatic (i.e., ALP, AST, ALT, and TB); renal (i.e., creatinine and uric acid); and lipid profiles (i.e., TC, TG, HDLc, LDLc, and VLDLc). An increased level of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH), and a decreased level of malondialdehyde (MDA) were observed in LSSAE‐treated rat liver. Antioxidant enzyme activities were evaluated by mRNA expression level of antioxidant genes (CAT, SOD2, GPX1, PON1, PFK1, GAPDH, using the 2−ΔΔCT method, normalized with housekeeping gene, ß‐ACTIN) using qRT‐PCR. Additionally, histological examination confirmed the restoration of morphology, and function of pancreatic β‐cell, kidney, liver, and spleen. Results reveal that LSSAE exerts an antidiabetic effect through upregulation of antioxidant genes, DNA protection and modulation of biochemical and histological parameters.
How Does Cloning Change Phenolics, Minerals and Antioxidant Activity in Helichrysum arenarium (L.) Moench (Clone A, Clone B)?
Authors: Saygi Kadriye Ozlem , Erenler Ramazan , Telci Isa
Published: December 2024

Tissue culture and cloning are valuable techniques in plant biology research as they enable the production of genetically identical plants, which may be utilized for many purposes, such as crop enhancement, plant breeding, and genetic manipulation. Helichrysum arenarium (L.) Moench, also known as immortelle or strawflower (Asteraceae), is a species of flowering plant in the sunflower family. In this study, the aerial part of two Clones (Clone A, Clone B) of H. arenarium were used to consider the effect of Clones on the phenolics, minerals, and antioxidant activities. The methanol extracts were analyzed and compared for phenolic compounds and antioxidant activities. Inductively coupled plasma‐optical emission spectroscopy is a widely used method for the determination of a wide range of elements in plant materials, including macro and microelements. Calcium and potassium are the major mineral elements. The phenolics were identified and quantified using high‐performance liquid chromatography combined with tandem mass spectrometry. The highest caffeic acid was determined in the methanolic extract, followed by protocatechuic aldehyde and protocatechuic acid.
Diverse Multinuclear Alkali Metallated (Li, Na, K, Rb, Cs) Family of the 1,3,5‐tris‐2‐aminopyridyl‐2,4,6‐triethylbenzene Framework
Authors: Lynch Jennifer R. , Navarro Marta , Kennedy Alan R. , Robertson Stuart D. , Mulvey Robert E. , Hernán‐Gómez Alberto
Published: December 2024

Literature on Group One organoelement chemistry is dominated by lithium, though sodium and potassium also feature prominently, whereas rubidium and caesium are rarely mentioned. With recent breakthroughs hinting that organoelement compounds of these two heavier metals can perform better than their lighter congeners in particular applications, important advantages could be missed unless complete sets of alkali metals are included in studies. Here, we report the synthesis and characterisation of a complete set of multi‐alkali‐metallated molecular compounds of the 1,3,5‐tris[(4,6‐dimethylpyridin‐2‐yl)aminomethyl]‐2,4,6‐triethylbenzene framework. Made by deprotonating the framework N−H bonds by a suitable base, the set comprises six THF‐solvated compounds, four of which are homometallic, either containing Li in a trinuclear structure or Na, K, and Rb in hexanuclear structures. Since deprotonation was incomplete with Cs, its homometallic compound is tetranuclear containing two un‐metallated N−H bonds. A heterobimetallic trilithium‐tricaesium hexanuclear compound was also obtained by using a bimetallic Li−Cs base for deprotonation. Such alkali‐metallated frameworks are often precursors to other multimetallic frameworks with unique properties across different fields of science.
Probing TCR Specificity Using Artificial In Vivo Diversification of CDR3 Regions
Authors: Giorgetti Orlando B. , Haas‐Assenbaum Annette , Boehm Thomas
Published: December 2024

The T‐cell receptor sequences expressed on cells recognizing a specific peptide in the context of a given MHC molecule can be explored for common features that might explain their antigen specificity. However, despite the development of numerous experimental and bioinformatic strategies, the specificity problem remains unresolved. To address the need for additional experimental paradigms, we report here on an in vivo experimental strategy designed to artificially diversify a transgenic TCR by CRISPR/Cas9‐mediated mutagenesis of Tcra and Tcrb chain genes. In this system, an initially monoclonal repertoire of known specificity is converted into an oligoclonal pool of TCRs of altered antigen reactivity. Tracking the fate of individual clonotypes during the intrathymic differentiation process illuminates the strong selective pressures that shape the repertoire of naïve T cells. Sequence analyses of the artificially diversified repertoires identify key amino acid residues in the CDR3 regions required for antigen recognition, indicating that artificial diversification of well‐characterized TCR transgene sequences helps to reduce the complexities of learning the rules of antigen recognition.
Understanding Structural Dynamics in Flexible Rare‐Earth Metal‐Organic Frameworks
Authors: Loukopoulos Edward , Trikalitis Pantelis N.
Published: December 2024

Flexible Metal‐Organic Frameworks (FL‐MOFs) are emerging advanced materials with the ability to respond to various stimuli by adapting their structure and pore. In particular, FL‐MOFs based on rare‐earth (RE) elements offer a unique and sophisticated approach towards truly novel responsive materials and properties. This Concept article provides an overview of the main principles and factors that affect structural features in RE‐FL‐MOFs, identifying trends and exploring potential rational design strategies. Common challenges and possible future research directions are also discussed.
Systemic hypoxia has a larger effect on reducing the external load at lower exercise intensity during heart rate clamped cycling
Authors: Li Siu Nam , Peeling Peter , Scott Brendan R. , Peiffer Jeremiah J. , Shaykevich Alex , Girard Olivier
Published: December 2024

The effects of acute hypoxic exposure on mechanical output and internal responses during cycling with heart rate (HR) clamped at lactate thresholds 1 and 2 (LT1 and LT2, respectively) were investigated. On separate days, 12 trained males cycled for 15 min at a clamped HR corresponding to LT1 and LT2 under normoxic or hypoxic conditions (simulated altitude of ∼3500 m and inspired oxygen fraction of 13.6%). Power output (PO), arterial oxygen saturation, ventilatory and perceptual responses were measured every 3 min, with metabolic response assessed pre‐ and post‐exercise. At LT1, PO was consistently lower in hypoxia compared to normoxia (p < 0.01). At LT2, PO was not different between normoxia and hypoxia at 3 and 6 min (both p > 0.42) but was significantly lower in hypoxia at 9, 12 and 15 min (all p < 0.04). Overall, hypoxia induced a greater decrease in PO at LT1 (−33.3% ± 11.3%) than at LT2 (−18.0 ± 14.7%) compared to normoxia. Ventilatory, perceptual and metabolic responses were influenced by exercise intensity (all p < 0.01) but not environmental conditions (all p > 0.17). A simulated altitude of ∼3500 m is more effective in reducing cycling PO at LT1 than LT2 during HR clamped cycling while maintaining other internal loads. Therefore, normobaric hypoxia provides a greater benefit via a larger decrease in the mechanical constraints of exercise at lower exercise intensities.
Germanic Rampart or Roman Encampment?—New Geoarchaeological Evidence at the Roman Conflict Site at Kalkriese (NW‐Germany)
Authors: Härtling Joachim W. , Stele Andreas , Ortisi Salvatore , Jepsen Andre , Rappe Marc , Bussmann Jens , Fülling Alexander
Published: December 2024

Kalkriese, near Osnabrueck (NW Germany), is considered the location of the ‘Battle of Varus’, where a coalition of Germanic tribes, under the leadership of Arminius, defeated three Legions under the command of Varus in 9 ad. Roman coinage and remains of military equipment prove that the Oberesch site at Kalkriese saw military operations between Germanic tribes and the Roman legions during Early Imperial times, but the sequence and magnitude of the military operations still remain unclear. In this study, we present for the first time absolute dates from the Oberesch site to decipher the general sequence of the Holocene landscape development at Kalkriese, identify the antique surface, and evaluate the ‘Germanic Rampart Theory’ and the ‘Roman Encampment Theory’. The geoprofile encompasses the entire stratigraphic sequence from the Pleistocene base, indicating intensive agricultural use of the area since the Early Neolithic. A fossil topsoil of late Pre‐Roman Iron Age to Roman Imperial Age was identified, which probably represents the antique surface of the Roman conflict site. Our results do not support either the ‘Germanic Rampart Theory’ or the ‘Roman Encampment Theory’, as both linear structures seem to be of High Middle Age origin.
Magnetohydrodynamic Natural Convection in a Circular Dome‐Shaped Enclosure
Authors: Venkatadri K.
Published: December 2024

The design of flow structures plays a crucial role in enhancing natural convective heat transfer within enclosures. By optimizing the geometry of enclosures to influence flow structures, we can significantly improve their natural convective heat transfer performance. Specifically, the dome‐shaped wall can alter flow direction, improving flow circulation and natural convection. The current study conducts a numerical investigation of the laminar flow and natural convective heat transfer of air within a dome‐shaped enclosure, while also considering the impact of a magnetic field. The analysis encompasses the interaction between magnetic field and buoyancy‐driven flow. Governing equations for momentum, energy, and angular momentum are formulated, integrating the influence of the Lorentz force. The working fluid Pr = 0.71 is considered in this study. The equations are transformed into dimensionless form using key parameters, such as the buoyancy number (Ra) and Hartmann number (Ha). The modeled partial differential equations were carried out with a vorticity‐stream function algorithm to explore the influence of magnetic field strength on the flow and thermal characteristics. Results indicate significant alterations in flow patterns and temperature distribution behavior under varying magnetic field and Rayleigh number. The interaction between buoyancy and magnetic fields plays a critical role in determining the heat transfer characteristics of an incompressible fluid, with Ra enhancing, and Ha suppressing, convective efficiency. Heat transfer enhancement of 82.84% is noticed for a Rayleigh number ranging from 103 to 104, while a 48.316% decrement is found for a Hartmann number ranging from 0 to 10 with Ra = 105. The transition from a magnetically dominated regime (high Ha) to a thermally driven regime (low Ha) leads to a shift from a uniform temperature field to one with more complex thermal layering and mixing, which is reflected in the varying shapes and amplitudes of the Nusselt number distributions. At higher Ha values, magnetic forces dominate, significantly suppressing buoyancy‐driven convection, and reducing the intensity of thermal mixing.
Nonpuerperal uterine inversion complicating a huge prolapsed submucous myoma: A case report
Authors: Abasiattai Aniekan Monday , James Robert , Atat Bless , Edemekong Victor , Etuknwa Utibe
Published: December 2024

Synopsis

Nonpuerperal uterine inversion complicating a huge submucous fundal myoma.
Skin Sensitization Potency Prediction Based on Read‐Across (RAx) Incorporating RhE‐Based Testing Strategy (RTSv1)–Defined Approach: RTSv1‐Based RAx
Authors: Suzuki Sho , Mizumachi Hideyuki , Miyazawa Masaaki
Published: December 2024

In recent years, nonanimal approaches for skin sensitization have been developed in response to political, regulatory, and ethical demands. The reconstructed human epidermis (RhE)–based testing strategy (RTS)v1–defined approach (DA) is used to categorize skin sensitization potency. However, the RTSv1 DA alone cannot be used to predict potency based on EC3 values [the estimated concentration that produces a stimulation index of 3 in the local lymph node assay (LLNA)], and underpredictions have been reported. Read‐across (RAx) can complement DA data and improve prediction confidence. Although case studies combining new approach methodology/DA data with RAx have been reported, they focus on a single target chemical and lack a comprehensive and robust strategy with well‐examined reliability. This study developed a strategy incorporating the RTSv1 DA into RAx (RTSv1‐based RAx) to predict skin sensitization potency, applying it to 43 chemicals. The predictive performance of RTSv1‐based RAx was evaluated by comparing its predicted potency category and EC3 outcomes with those of RTSv1 DA and the LLNA. RTSv1‐based RAx accurately predicted the Globally Harmonized System of Classification (GHS) subcategorization for 38 chemicals and determined the predicted EC3 values for 17 sensitizers within a fourfold range of LLNA‐derived EC3 values. This study demonstrates that RTSv1‐based RAx offers robust predictivity for both GHS subcategorization and predicted EC3 values, making it useful for quantitative risk assessment.
The effect of early weaning on feeding behavior parameters in rodents: A systematic review
Authors: Alves Swane Miranda , de Oliveira Elifrances Galdino , Araújo Eulália Rebeca Da Silva , Silva Paula Brielle Pontes , de Castro Raul Manhães , de Souza Sandra Lopes
Published: December 2024

Breastfeeding is essential for somatic development, especially neurodevelopment. The abrupt termination of the mother–child bond, early weaning, is a stressful event during the neonatal period. This has lifelong consequences. The impact on neural plasticity will be reflected in behavioral expression, including feeding behavior. This behavior is modulated by encephalic and peripheral structures, such as the serotonergic and dopaminergic neurotransmission systems, as well as hormonal signaling, leptin, and ghrelin. The central nervous system, particularly the hypothalamus, receives information from the gastrointestinal tract to regulate hunger and satiety. Early weaning alters these mechanisms that control feeding behavior. The alterations most commonly reported in the literature are hyperphagia, increased body mass, and molecular alterations related to the control of feeding behavior. Studies have attempted to identify the factors involved in the changes in feeding behavior control caused by early weaning. Furthermore, pharmacological interventions, herbal medicines, calcium supplementation, and physical activity have been investigated as potential means of reversing these changes. Consequently, the objective of this literature review was to analyze the effects of early weaning on the modulation of parameters that act to control feeding behavior.
Fabrication of cis‐1,4 polyisoprene composites reinforced with well‐dispersed silica/carbon black promoted by silica‐rubber hydrogen‐bonding
Authors: Sun Shurui , Tang Fuming , Gong Dirong
Published: December 2024

Silica is known to be an indispensable ingredient for fuel‐saving tires; however, it has a high tendency to aggregate when compounded with rubber due to component incompatibility. Incorporating hydrophilic groups into hydrophobic rubber would be a promising approach. In the present work, hydroxyl‐modified polyisoprene with high cis‐1,4 regularity (95.3%–97.1%) and controlled functional fraction (0.5 mol‐%‐28.4 mol‐%) was synthesized via neodymium‐catalyzed coordination‐insertion copolymerization of hydroxyl myrcene with isoprene. Polyisoprene composites reinforced with a hybrid filler of silica and black carbon were then fabricated. Intrinsically promoted filler dispersion in the rubber was enabled through the formation of hydrogen‐bonding between the filler and rubber, verified by variable‐temperature FT‐IR, atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic mechanical analysis (DMA). This interaction is critical to achieving superior integrated properties similar to natural rubber, including stronger tensile strength (25.0 MPa), improved toughness (elongation at break of 1343%), enhanced wet‐skid resistance (tan δ of 0.18), increased rebound resilience, and reduced heat buildup and abrasion. The developed fabrication route offers a feasible solution for constructing well‐dispersed silica‐reinforced composites applicable to energy‐saving green tires.

Highlights

Hydroxyl‐functionalized essential cis‐1,4 polyisoprene was synthesized.

Hydroxyl functionality reached up to 28.4 mol‐% incorporation.

Well‐dispersed silica/carbon black‐filled rubber composites were fabricated.

Hydrogen‐bonding promoted silica‐rubber compatibility.

The vulcanizates displayed superior integrated mechanical properties.
Expanding the Impact of New Cystic Fibrosis Therapies in Low‐ and Middle‐Income Countries
Authors: Kerem Eitan
Published: December 2024

Background

Cystic fibrosis (CF) primarily affects Caucasian populations, with the highest prevalence in countries like Ireland, the UK, Australia, and Canada. Despite significant improvements in survival, pulmonary insufficiency remains the leading cause of death. Factors such as nutrition, chronic Pseudomonas aeruginosa (PsA) infection, genotype, pancreatic status, and cystic fibrosis‐related diabetes affect pulmonary function across age groups.

Objective

This review examines disparities in CF care and outcomes between high‐income countries (HICs) and low‐income countries (LICs), focusing on the impact of CFTR modulators like Elexacaftor/Tezacaftor/Ivacaftor (ETI) and challenges in accessing care in LICs.

Methods

Data from the European CF Society Patient Registry and studies on CF outcomes across regions were reviewed to assess survival trends, pulmonary function, and infection rates among people with CF (pwCF). The effects of CFTR modulator therapies, particularly for F508del carriers, were also evaluated.

Results

In HICs, improvements in survival rates and pulmonary function have been noted, especially with the use of CFTR modulators like ETI. However, in LICs, challenges like limited access to therapies, delayed diagnosis, poor nutrition, and high PsA infection rates lead to poorer outcomes. In regions with fewer F508del carriers, access to care and medications is further limited, exacerbating disparities.

Conclusion

Although CF treatment advancements have improved outcomes in many pwCF, these benefits are not evenly distributed globally. Efforts to improve CF care in LICs, such as increasing awareness, ensuring access to therapies, and establishing specialized clinics, are essential to bridging this gap.
Comparison of laser diffractometry and pipetting methods for particle size determination: A pilot study on the implications of result discrepancies on soil classification
Authors: Tomášová Gabriela , Paseka Stanislav , Bajer Aleš
Published: December 2024

In recent decades, the determination of particle size distribution (PSD) using the laser diffraction method (LDM) has become increasingly common, supplanting traditional sedimentation techniques. Advances in everything from sample preparation to software settings have been realized globally, whether through recommendations from laser diffraction (LD) manufacturers or through user experiences. These developments seek to enhance accuracy and diminish the uncertainties associated with new methodologies. Particularly in the determination of PSD using LDM on various LD instruments and in comparison with the sieve–pipette method (SPM), discrepancies in PSD frequently arise. This article aims to mitigate these discrepancies by predefining parameters, specifically through the adjustment of LD software settings and sample preparation (employing a uniform set of dispersed samples in potassium hydroxide) on two widely used LD instruments for soil measurements: Mastersizer 3000 and Analysette 22. Additionally, these samples were analyzed using the traditional SPM (ISO 11277, 1998), with the results from LDM and SPM subsequently compared. The paper also explores the impact, range of user options, and limitations of predefined software settings on both LD instruments. Eighty soil samples were analyzed for PSD, collected from arable land in the cadastral area of Hrušky, district of Břeclav (Czech Republic), in spring 2022, from depths of 0‐ to 10‐cm and 10‐ to 20‐cm. Significant differences in PSD were confirmed, although the trends of the grain size distribution curves were very similar to those of LDM. Results from the Mastersizer underestimated the clay fraction by an average of 17% compared to SPM, at the expense of the sand fraction, whereas the silt fraction was underestimated by a maximum of 4%. Conversely, Analysette 22 overestimated the silt fraction by an average of 37% at the expense of the sand fraction, confirming only a slight difference in the clay fraction: 3%. Moreover, the quantity of sample entering the dispersion unit was identified as a significant issue when comparing LD instruments, despite the obscuration value being nearly identical, that is, 20%–30%. Therefore, it was not possible to achieve the same or similar weight when introducing suspension into circulation. The robustness of the obtained results underscores the importance of understanding input parameters when interpreting results between different methods.
Enhanced Electrostatic Dust Removal from Solar Panels Using Transparent Conductive Nano‐Textured Surfaces
Authors: Dickhardt Fabian J. , Panat Sreedath , Varanasi Kripa K.
Published: December 2024

Dust accumulation on solar panels is a mjor operational challenge faced by the photovoltaic industry. Removing dust using water‐based cleaning is expensive and unsustainable. Dust repulsion via charge induction is an efficient way to clean solar panels and recover power output without consuming any water. However, it is still challenging to remove particles of ≈30 µm and smaller because Van der Waals force of adhesion dominates electrostatic force of repulsion. Here, the study proposes nano‐textured, transparent, electrically conductive glass surfaces to significantly enhance electrostatic dust removal for particles smaller than ≈30 µm. We perform atomic force microscopy pull‐off force experiments and demonstrates that nano‐textured surfaces reduce the force of adhesion of silica micro‐particles by up to 2 orders of magnitude compared to un‐textured surfaces from 460 to 8.6 nN. We show that reduced adhesion on nano‐textured surfaces results in significantly better dust removal of small particles compared to non‐textured or micro‐textured surfaces, reducing the surface coverage from 35% to 10%. We fabricate transparent, electrically conductive, nano‐textured glass that can be retrofitted on solar panel surfaces using copper nano‐mask based scalable nano‐fabrication technique and shows that 90% of lost power output for particles smaller than ≈10 µm can be recovered.
A structured simulation‐based mastery learning curriculum in chest tube insertion results in superior skills compared to traditional training programs
Authors: De Mol Leander , Van Herzeele Isabelle , Van de Voorde Patrick , Vanommeslaeghe Hanne , Konge Lars , Desender Liesbeth , Willaert Wouter
Published: December 2024

Background

Chest tube insertions (CTI) have a high complication rate, warranting a dedicated Simulation‐Based Mastery Learning (SBML) curriculum to acquire technical skills. This randomized controlled trial compares residents' skills in CTI after completing a SBML curriculum with those enrolled in a traditional residency program.

Methods

Junior residents were baseline tested on cognitive and technical skills (Thiel bodies) before randomization into an intervention and control group. The former deliberately trained CTI on a porcine rib model until passing a predefined pass/fail score and were then summatively tested on Thiel bodies. The latter had no additional training opportunities and was evaluated 3 months later.

Results

Seventeen residents were recruited and randomized. Following the per‐protocol principle, a significant interaction effect for Group × Procedure (F(1,14) = 6.2, p = 0.026) was observed. Between baseline and summative assessment, both the control group (28.0 ± 8.2 vs. 43.6 ± 8.1, p < 0.001) and the intervention group (33.2 ± 7.7 vs. 57.6 ± 5.7, p < 0.001) significantly increased their scores. The intervention group outperformed the control group at summative assessment (43.6 ± 8.1 vs. 57.6 ± 5.7, p < 0.001). All participants in the intervention group and one resident in the control group achieved the pass/fail score.

Conclusion

This SBML curriculum enabled quicker and superior skill acquisition. Skills trained on a porcine model are transferred to the highly realistic Thiel bodies and reach expert level, potentially increasing resident skill in clinical practice.
ESA Mission Publications and Their Impact
Authors: De Marchi Guido , Parmar Arvind
Published: December 2024

We examine over 68,000 refereed publications based on data from 25 missions in the ESA Science Programme and 11 additional missions in which ESA is involved as a junior partner. The publications cover the fields of astronomy, planetary science, and heliophysics and are spread over almost 50 years, spanning the period between the year a mission was launched and the end of 2021. We study the number of papers as a function of time and the evolution of several metrics, including citations and other indices. We also investigate the geographical distribution of the authors, and for ESA Member States we correlate the various indices with the level of financial contribution of the individual countries to the ESA Science Programme. We find that in general the involvement of the scientific communities in the various Member States follows the distribution expected from the countries’ gross domestic products, with communities in some fields and countries, both large and small, being particularly effective at turning data into scientific discoveries. We also analyse the differences between papers written by investigators directly involved in the provision of the payloads or in the definition of the scientific projects and those written by other scientists not directly involved in the process. We find that the latter, the so-called “archival papers”, represent more than 50% of the literature based on data from ESA Space Science missions, and have a similar impact on the literature in the respective fields, as judged by the number of citations. This highlights the importance of sharing and preserving the scientific data produced by the missions.
XMM-Newton Observing Time Proposals
Authors: Parmar Arvind , Schartel Norbert , Santos-Lleó Maria
Published: December 2024

We examine the outcomes of the regular announcements of observing opportunities for ESA’s X-ray observatory XMM-Newton issued between 2001 and 2021. We investigate how success rates vary with the lead proposer’s gender, “academic age” and the country where the proposer’s institute is located. The large number of proposals (10,579) and more than 20 years operational lifetime enable the evolution of community proposing for XMM-Newton to be examined. We determine proposal success rates for high-priority and all proposals using both the numbers of accepted proposals and the amounts of awarded observing time. We find that male lead proposers are between 5–15% more successful than their female counterparts in obtaining XMM-Newton observations. The gender balance and the percentage of successful young proposers are comparable to those of HST after the introduction of dual-anonymous reviewing of HST proposals. We investigate potential correlations between the female-led proposal success rates and the amount of female participation in the Time Allocation Committee. We propose additional investigations to better understand the outcomes presented here.
EU Policy Irregularising Migration—Background, General Trends, and Guiding Logics
Authors: Carrera Sergio , Colombi Davide
Published: December 2024

The 1986 Single European Act (SEA) emphasised the objective of effectively implementing an area without internal frontiers and the free movement of persons.
Problematising Irregularised Human Mobility in the Commission
Authors: Carrera Sergio , Colombi Davide
Published: December 2024

There is a complex patchwork of normative approaches delineating irregularised human mobilities, reflected in the intra-institutional settings and DG structuring of the European Commission (synthesised in Fig. 8.1).
The meso- and bathypelagic cephalopod fauna of the Gully submarine canyon
Authors: Shea Elizabeth K. , Kenchington Trevor J.
Published: December 2024

Four midwater-trawl surveys were conducted during the summers of 2007–2009 and the spring of 2010 to document the meso- and bathypelagic biodiversity of the Gully canyon. These surveys collected 3871 cephalopods of at least 38 species in 22 families. The numerically dominant 13 species and one genus together comprised 90% of the total taken in standard survey sets. Each of those taxa uses the Gully in a different way, including within-family differences for the two cranchids and two mastigoteuthids. Oegopsids of note include Brachioteuthis beanii, which was the most abundant species in summer but entirely absent in March. The cirrate octopod Stauroteuthis syrtensis was collected in large numbers (n = 142) and a wide range of sizes (9–185 mm) suggesting it may complete its life cycle within the canyon. These results expand understanding of the trophic structure in the Gully and establish a baseline for future monitoring of ecosystem change.
Multi-physics simulation study of magnetic shielding on hypersonic vehicles
Authors: Greenslade Thomas J. , Chinnappan Arun Kumar , Kim Minkwan
Published: December 2024

The renewed interest in hypersonic flights due to NASA’s Artemis program has brought fresh attention to the physical challenges of reusable thermal protection systems. The need to enhance the reliability of hypersonic and re-entry vehicles has sharply focused on the limitations of our current comprehension of thermo-chemical non-equilibrium flows and our limited predictive capabilities. This paper presents the work carried out by the University of Southampton and our consortium partners within the MEESST collaboration. This project is currently involved in both numerical and experimental research to develop magnetic shielding techniques for atmospheric re-entry vehicles. These techniques aim to offer additional approaches for mitigating both impinging heat loads and communication blackout. Herein, we present the results of multi-physics simulations conducted with the University of Southampton’s HANSA toolkit, along with comparisons, both experimental and numerical, produced by our consortium partners. These encompass simulations of multiple capsules undergoing atmospheric re-entry and simulations of ground-based experimental campaigns. We give particular attention to the effects of thermo-chemical non-equilibrium and MHD modelling. We illustrate the impacts of various mathematical models on the results obtained, with a strong emphasis on mission-critical parameters such as surface heat fluxes and electron densities. We also present conclusions regarding the implications of these results on magnetic shielding designs. Lastly, we offer an overview of current knowledge gaps in areas crucial to MEESST and lay out plans for future simulations and experiments, both within the MEESST project and beyond.