bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stellabody: A novel hexamer‐promoting mutation for improved IgG potency
Authors: Whitehead Clarissa A. , Wines Bruce D. , Davies Anna M. , McDonnell James M. , Trist Halina M. , Esparon Sandra E. , Hogarth P. Mark 
Published: October 2024

SummaryAdvances in antibody engineering are being directed at the development of next generation immunotherapeutics with improved potency. Hexamerisation of IgG is a normal physiological aspect of IgG biology and recently described mutations that facilitate this process have a substantial impact upon monoclonal antibody behavior resulting in the elicitation of dramatically enhanced complement‐dependent cytotoxicity, Fc receptor function, and enhanced antigen binding effects, such as targeted receptor agonism or microbe neutralization. Whereas the discovery of IgG hexamerisation enhancing mutations has largely focused on residues with exposure at the surface of the Fc‐Fc and CH2‐CH3 interfaces, our unique approach is the engineering of the mostly buried residue H429 in the CH3 domain. Selective substitution at position 429 forms the basis of Stellabody technology, where the choice of amino acid results in distinct hexamerisation outcomes. H429F results in monomeric IgG that hexamerises after target binding, so called “on‐target” hexamerisation, while the H429Y mutant forms pH‐sensitive hexamers in‐solution prior to antigen binding. Moreover, Stellabody technologies are broadly applicable across the family of antibody‐based biologic therapeutics, including conventional mAbs, bispecific mAbs, and Ig‐like biologics such as Fc‐fusions, with applications in diverse diseases.
The importance of IgG glycosylation—What did we learn after analyzing over 100,000 individuals
Authors: Krištić Jasminka , Lauc Gordan 
Published: October 2024

SummaryAll four subclasses of immunoglobulin G (IgG) antibodies have glycan structures attached to the protein part of the IgG molecules. Glycans linked to the Fc portion of IgG are found in all IgG antibodies, while about one‐fifth of IgG antibodies in plasma also have glycans attached to the Fab portion of IgG. The IgG3 subclass is characterized by more complex glycosylation compared to other IgG subclasses. In this review, we discuss the significant influence that glycans exert on the structural and functional properties of IgG. We provide a comprehensive overview of how the composition of these glycans can affect IgG's effector functions by modulating its interactions with Fcγ receptors and other molecules such as the C1q component of complement, which in turn influence various immune responses triggered by IgG, including antibody‐dependent cell‐mediated cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC). In addition, the importance of glycans for the efficacy of therapeutics like monoclonal antibodies and intravenous immunoglobulin (IVIg) therapy is discussed. Moreover, we offer insights into IgG glycosylation characteristics and roles derived from general population, disease‐specific, and interventional studies. These studies indicate that IgG glycans are important biomarkers and functional effectors in health and disease.
On the Brink of Change? Environmental Drivers of Voluntary Thermal Maximum in South American Pitvipers
Authors: Diaz‐Ricaurte Juan C. , Serrano Filipe C. , Camacho Agustín , Nogueira Cristiano de C. , Travaglia‐Cardoso Silvia Regina , Martins Marcio 
Published: October 2024

ABSTRACTAimWe test the relationship between the voluntary thermal maximum (VTMax; the temperature at which an individual actively retreats to a colder site) and geographical/environmental features in the distribution of South American pitvipers. Additionally, we explore the evolution of environmental temperatures and VTMax in species' ranges.LocationSouth America.TaxonSouth American pitvipers of the genera Bothrops and Bothrocophias.MethodsWe experimentally measured the VTMax of 15 species of South American pitvipers. We explored the relationship between VTMax and geographical/environmental features (e.g., latitude, topographic complexity and temperature) with PGLS regressions. Additionally, we explored the evolution of maximum (TMax) and minimum (TMin) environmental temperatures, as well as the Thermal Niche Breadth (TNB) and VTMax, using ancestral state reconstruction and testing for phylogenetic signal.ResultsMean VTMax values for South American pitvipers clustered primarily within the 34°C–36°C range, exhibiting little variation among species or clades. No significant correlations were found between VTMax and climatic or geographic variables. Furthermore, our analysis revealed that these snakes are absent from regions where maximum temperatures surpass their preferred thermal tolerances. Ancestral state reconstruction indicated divergent evolutionary pathways for thermal limits among species, independent of phylogenetic relationships.Main ConclusionsSouth American pitvipers unexpectedly exhibit similar voluntary thermal maximum values across a wide range of habitats and despite distinct phylogenetic relationships. Our results indicate that there is no strong climatic niche conservatism for South American pitvipers, with a likely weak selective pressure of VTMax.
Using peer feedback to improve critical thinking in computer‐supported collaborative argumentation: An exploratory study
Authors: Chen Wenli , Hu Hua , Lyu Qianru , Zheng Lishan 
Published: October 2024

AbstractBackgroundCritical thinking is one of the 21st Century competencies for students. While previous research acknowledges the potential of peer feedback to enhance critical thinking skills, particularly within computer‐supported collaborative learning (CSCL) environments, there is limited understanding of which specific aspects of critical thinking are improved through peer feedback and how various components of critical thinking are interrelated within a CSCL environment in K‐12 education contexts.ObjectivesThis study aims to investigate how peer feedback affects secondary school students' critical thinking skills within a computer‐supported collaborative argumentation (CSCA) environment. It explores the specific aspects of critical thinking that were enhanced and examines the relationships among different critical thinking indicators using Epistemic Network Analysis (ENA) to provide a deep understanding of these skills' development before and after peer feedback.MethodsThis study adopted a mixed‐method approach. Qualitative content analysis was conducted to explore the effect of peer feedback on students' depth of critical thinking by adopting Newman's framework. Quantitative ethnographic method known as ENA was employed to analyse the co‐occurrence patterns of critical thinking influenced by peer feedback.Results and ConclusionsThis study found that peer feedback was effective in promoting students' critical thinking measured by Newman's framework (Justification, Ambiguities, Importance, Novelty, Relevance, Width of understanding, and Linking ideas, factors, and interpretation). However, the study noted a lack of improvement in the dimensions of Bringing Outside Knowledge/Experience to Bear on the Problem (O), Critical Assessment (C), and Practical Utility (P). Peer feedback significantly influenced the co‐occurrence patterns of critical thinking. Before peer feedback, students’ arguments were characterized by confusion and narrow viewpoints, despite containing important and relevant points. After peer feedback, there was a marked improvement, with students presenting their arguments with greater clarity, breadth of information, and creativity. This suggests that peer feedback helped students refine their argumentation skills, making their points clearer and more comprehensive.
Prevention and control of cardiac arrhythmic by using therapeutic foods: A review
Authors: Wu Xue , Zhi Xiaodong , Liu Kai , Jiang HuGang , Zhao Xinke , Li Yingdong 
Published: October 2024

AbstractIntroductionArrhythmia occurs as a common heart vascular disease. Functional food is a rich source of natural compounds with significant pharmacological, The aim of this paper is to explore its effect on arrhythmia.MethodsBy reviewing the literature and summarising the findings, we described the role of functional foods in the alleviation of cardiac arrhythmias from different perspectives.ResultsOur study shows that functional foods have anti‐arrhythmic effects through modulation of ion channels, oxidative stress, and Calmodulin‐dependent protein kinase II.ConclusionsWe summarize the mechanism of arrhythmia inhibition by the active ingredients of medicinal diets in this review article, intending to provide research ideas for dietary therapy to regulate arrhythmia.
Contrast‐Enhanced Micro‐CT Imaging of Murine Mandibles: A Multi‐Method Approach for Simultaneous Hard and Soft Tissue Analysis
Authors: Hildebrand Torben , Humphris Yolanda , Haugen Håvard Jostein , Nogueira Liebert Parreiras 
Published: October 2024

ABSTRACTAimTo develop and evaluate a novel multi‐method micro‐computed tomography (μCT) imaging protocol for enhanced visualization of both hard and soft tissues in murine mandibles, addressing the limitations of traditional imaging techniques in dental research.Materials and MethodsWe employed a contrast‐enhanced (CE) μCT imaging technique using Lugol's iodine as a contrast agent to visualize the intricate structures of murine mandibles. The protocol involved the combination of conventional μCT imaging as well as CE‐μCT, including decalcification with EDTA, allowing for simultaneous assessment of hard and soft tissues. The method is compared with standard imaging modalities, and the ability to visualize detailed anatomical features is discussed.ResultsThe CE‐μCT imaging technique provided superior visualization of murine mandibular structures, including dental pulp, periodontal ligaments and the surrounding soft tissues, along with conventional μCT imaging of alveolar bone and teeth. This method revealed detailed anatomical features with high specificity and contrast, surpassing traditional imaging approaches.ConclusionOur findings demonstrate the potential of CE‐μCT imaging with Lugol's iodine as a powerful tool for dental research. This technique offers a comprehensive view of the murine mandible, facilitating advanced studies in tissue engineering, dental pathology and the development of dental materials.
Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1‐day withdrawal of direct oral anticoagulants
Authors: Hirata Shoichiro , Hamada Kenta , Iwamuro Masaya , Mouri Hirokazu , Miyahara Koji , Tsuzuki Takao , Yamauchi Kenji , Kobayashi Sayo , Takahashi Sakuma , Takenaka Ryuta , Hori Shinichiro , Inoue Masafumi , Toyokawa Tatsuya , Nishimura Mamoru , Ishiyama Shuhei , Miyaike Jiro , Kato Ryo , Matsubara Minoru , Yunoki Naoko , Kanzaki Hiromitsu , Kawahara Yoshiro , Okada Hiroyuki , Ishikawa Hideki , Otsuka Motoyuki ,   Okayama Gut Study Group
Published: October 2024

AbstractBackground and AimThe 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method.MethodsThis retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs.ResultsAmong the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported.ConclusionsContinuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge.
Assessing older adult physical activity levels in clinical settings: The modified PAVS for older adults
Authors: Stoutenberg Mark , Rogers Michael , Denison Paige , Schlicht Jeff , Weitzel Kelsey , Ory Marcia , Kellar Garrett , Summers Louisa , Wingood Mariana 
Published: October 2024

AbstractBackgroundParticipating in recommended levels of physical activity (PA) is critical for preventing functional decline, falls, and frailty, making it essential to identify older adults not meeting national PA guidelines. However, guidance on assessing older adult PA levels, particularly in clinical settings, is lacking. This article presents an overview of clinically feasible PA assessment tools for older adults, identifies gaps in current tools, and provides recommendations on addressing these gaps.MethodsWe conducted a literature review on clinically feasible PA assessment tools, suggested modifications to an existing PA assessment for older adult patients, and highlighted opportunities for integrating the modified PA assessment tool in clinical settings.ResultsWe identified 16 PA assessment tools used in clinical settings. The most widely used tool is the Physical Activity Vital Sign (PAVS), which has been successfully integrated into several electronic health records (EHR) and clinical practices. Most tools, including the PAVS, primarily focus on aerobic activities, with limited consideration for strength and balance. We recommend the use of a Modified PAVS for Older Adults that includes items on muscle‐strengthening and balance activities to better align with national PA guidelines. We then identified several existing opportunities for broad implementation of the Modified PAVS for Older Adults within clinical settings.ConclusionsWidespread integration of the Modified PAVS for Older Adults will better support healthcare providers in identifying individuals not meeting national PA recommendations, assisting them in prescribing tailored PA prescriptions and better connecting their patients to appropriate resources and professionals for further support.
Reading m6A marks in mRNA: A potent mechanism of gene regulation in plants
Authors: Nguyen Thi Kim Hang , Kang Hunseung 
Published: October 2024

ABSTRACTModifications to RNA have recently been recognized as a pivotal regulator of gene expression in living organisms. More than 170 chemical modifications have been identified in RNAs, with N6‐methyladenosine (m6A) being the most abundant modification in eukaryotic mRNAs. The addition and removal of m6A marks are catalyzed by methyltransferases (referred to as “writers”) and demethylases (referred to as “erasers”), respectively. In addition, the m6A marks in mRNAs are recognized and interpreted by m6A‐binding proteins (referred to as “readers”), which regulate the fate of mRNAs, including stability, splicing, transport, and translation. Therefore, exploring the mechanism underlying the m6A reader‐mediated modulation of RNA metabolism is essential for a much deeper understanding of the epigenetic role of RNA modification in plants. Recent discoveries have improved our understanding of the functions of m6A readers in plant growth and development, stress response, and disease resistance. This review highlights the latest developments in m6A reader research, emphasizing the diverse RNA‐binding domains crucial for m6A reader function and the biological and cellular roles of m6A readers in the plant response to developmental and environmental signals. Moreover, we propose and discuss the potential future research directions and challenges in identifying novel m6A readers and elucidating the cellular and mechanistic role of m6A readers in plants.
Rising trend of dentist‐prescribed antibiotics in Brazil: 2011–2021
Authors: Cruz Alex Junio Silva , Martins Maria Auxiliadora Parreiras , Batista Victor Santos , Santos Jacqueline Silva , Santos Thiago Rezende dos , de Castilho Lia Silva , Sohn Woosung , Abreu Mauro Henrique Nogueira Guimarães 
Published: October 2024

AbstractObjectivesTo describe the trends in antibiotic prescribing by dental practitioners and to investigate the relationship between these trends and some factors of public oral health services in Minas Gerais (MG), Brazil.MethodsThis was a time‐series analysis of antibiotics prescribed by dental practitioners between January 2011 and December 2021. The outcome variables were number of defined daily doses (DDD) and DDD/1000 population/year in a sample of cities in MG. Covariates were public oral healthcare factors, such as coverage, estimates of dental procedures, and frequency of dental pain. Linear time‐series regression models were used to examine trends and the influence of covariates on antibiotic prescribing.ResultsOverall, the number of prescriptions increased by 334.69% between 2011 and 2021, with amoxicillin being the most commonly prescribed drug (78.53%). The number of DDD for all antibiotics increased from 17,147.13 to 77,346.67 and the average DDD/1000 inhabitants/year was 126.66 (SD: 130.28). The linear time‐series regression model showed that for each one‐year increase, the average log DDD/1000 inhabitants increased by 0.35 (standard error = 0.07, p < 0.001). No covariates were found to be associated with the outcome.ConclusionsIn Minas Gerais, Brazil, a significant upward trend was observed in the number of prescriptions and the number of DDD of antibiotics prescribed by dental practitioners. No influence of factors related to public oral healthcare services on the outcome was observed, thereby emphasizing the need for further research on factors influencing medication use in dental practice.
A custom‐built single‐channel in‐ear electroencephalography sensor for sleep phase detection: an interdependent solution for at‐home sleep studies
Authors: Borges Daniel Filipe , Soares Joana Isabel , Silva Heloísa , Felgueiras João , Batista Carla , Ferreira Simão , Rocha Nuno Barbosa , Leal Alberto 
Published: October 2024

SummarySleep is vital for health. It has regenerative and protective functions. Its disruption reduces the quality of life and increases susceptibility to disease. During sleep, there is a cyclicity of distinct phases that are studied for clinical purposes using polysomnography (PSG), a costly and technically demanding method that compromises the quality of natural sleep. The search for simpler devices for recording biological signals at home addresses some of these issues. We have reworked a single‐channel in‐ear electroencephalography (EEG) sensor grounded to a commercially available memory foam earplug with conductive tape. A total of 14 healthy volunteers underwent a full night of simultaneous PSG, in‐ear EEG and actigraphy recordings. We analysed the performance of the methods in terms of sleep metrics and staging. In another group of 14 patients evaluated for sleep‐related pathologies, PSG and in‐ear EEG were recorded simultaneously, the latter in two different configurations (with and without a contralateral reference on the scalp). In both groups, the in‐ear EEG sensor showed a strong correlation, agreement and reliability with the ‘gold standard’ of PSG and thus supported accurate sleep classification, which is not feasible with actigraphy. Single‐channel in‐ear EEG offers compelling prospects for simplifying sleep parameterisation in both healthy individuals and clinical patients and paves the way for reliable assessments in a broader range of clinical situations, namely by integrating Level 3 polysomnography devices. In addition, addressing the recognised overestimation of the apnea‐hypopnea index, due to the lack of an EEG signal, and the sparse information on sleep metrics could prove fundamental for optimised clinical decision making.
Functional characterization of extracellular and intracellular catalase‐peroxidases involved in virulence of the fungal wheat pathogen Zymoseptoria tritici
Authors: Mirzadi Gohari Amir , Mehrabi Rahim , Kilaru Sreedhar , Schuster Martin , Steinberg Gero , de Wit Pierre P. J. G. M. , Kema Gert H. J. 
Published: October 2024

AbstractUnderstanding how pathogens defend themselves against host defence mechanisms, such as hydrogen peroxide (H2O2) production, is crucial for comprehending fungal infections. H2O2 poses a significant threat to invading fungi due to its potent oxidizing properties. Our research focuses on the hemibiotrophic fungal wheat pathogen Zymoseptoria tritici, enabling us to investigate host–pathogen interactions. We examined two catalase‐peroxidase (CP) genes, ZtCpx1 and ZtCpx2, to elucidate how Z. tritici deals with host‐generated H2O2 during infection. Our analysis revealed that ZtCpx1 was up‐regulated during biotrophic growth and asexual spore formation in vitro, while ZtCpx2 showed increased expression during the transition from biotrophic to necrotrophic growth and in‐vitro vegetative growth. Deleting ZtCpx1 increased the mutant's sensitivity to exogenously added H2O2 and significantly reduced virulence, as evidenced by decreased Septoria tritici blotch symptom severity and fungal biomass production. Reintroducing the wild‐type ZtCpx1 allele with its native promoter into the mutant strain restored the observed phenotypes. While ZtCpx2 was not essential for full virulence, the ZtCpx2 mutants exhibited reduced fungal biomass development during the transition from biotrophic to necrotrophic growth. Moreover, both CP genes act synergistically, as the double knock‐out mutant displayed a more pronounced reduced virulence compared to ΔZtCpx1. Microscopic analysis using fluorescent proteins revealed that ZtCpx1 was localized in the peroxisome, indicating its potential role in managing host‐generated reactive oxygen species during infection. In conclusion, our research sheds light on the crucial roles of CP genes ZtCpx1 and ZtCpx2 in the defence mechanism of Z. tritici against host‐generated hydrogen peroxide.