bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative size-resolved characterization of mRNA nanoparticles by in-line coupling of asymmetrical-flow field-flow fractionation with small angle X-ray scattering
Authors: Graewert Melissa A. , Wilhelmy Christoph , Bacic Tijana , Schumacher Jens , Blanchet Clement , Meier Florian , Drexel Roland , Welz Roland , Kolb Bastian , Bartels Kim , Nawroth Thomas , Klein Thorsten , Svergun Dmitri , Langguth Peter , Haas Heinrich 
Published: September 2023

AbstractWe present a generically applicable approach to determine an extensive set of size-dependent critical quality attributes inside nanoparticulate pharmaceutical products. By coupling asymmetrical-flow field-flow fractionation (AF4) measurements directly in-line with solution small angle X-ray scattering (SAXS), vital information such as (i) quantitative, absolute size distribution profiles, (ii) drug loading, (iii) size-dependent internal structures, and (iv) quantitative information on free drug is obtained. Here the validity of the method was demonstrated by characterizing complex mRNA-based lipid nanoparticle products. The approach is particularly applicable to particles in the size range of 100 nm and below, which is highly relevant for pharmaceutical products—both biologics and nanoparticles. The method can be applied as well in other fields, including structural biology and environmental sciences.
An Innovative AI-based primer design tool for precise and accurate detection of SARS-CoV-2 variants of concern
Authors: Perez-Romero Carmina Angelica , Mendoza-Maldonado Lucero , Tonda Alberto , Coz Etienne , Tabeling Patrick , Vanhomwegen Jessica , MacSharry John , Szafran Joanna , Bobadilla-Morales Lucina , Corona-Rivera Alfredo , Claassen Eric , Garssen Johan , Kraneveld Aletta D. , Lopez-Rincon Alejandro 
Published: September 2023

AbstractAs the COVID-19 pandemic winds down, it leaves behind the serious concern that future, even more disruptive pandemics may eventually surface. One of the crucial steps in handling the SARS-CoV-2 pandemic was being able to detect the presence of the virus in an accurate and timely manner, to then develop policies counteracting the spread. Nevertheless, as the pandemic evolved, new variants with potentially dangerous mutations appeared. Faced by these developments, it becomes clear that there is a need for fast and reliable techniques to create highly specific molecular tests, able to uniquely identify VOCs. Using an automated pipeline built around evolutionary algorithms, we designed primer sets for SARS-CoV-2 (main lineage) and for VOC, B.1.1.7 (Alpha) and B.1.1.529 (Omicron). Starting from sequences openly available in the GISAID repository, our pipeline was able to deliver the primer sets for the main lineage and each variant in a matter of hours. Preliminary in-silico validation showed that the sequences in the primer sets featured high accuracy. A pilot test in a laboratory setting confirmed the results: the developed primers were favorably compared against existing commercial versions for the main lineage, and the specific versions for the VOCs B.1.1.7 and B.1.1.529 were clinically tested successfully.
Evaluating construction parameters of HB and CD methods for super large section tunnel: a case study
Authors: Zhu Ting , Liu Yuanming 
Published: September 2023

AbstractThe double sidewall guide pit and centre cross diagram (CRD) methods are often used for the construction of large-section tunnels through water-rich fault fracture zones due to their long construction time and high construction cost. To shorten the construction period and save costs, the top heading and benching method (HB) and centre diaphragm (CD) can be chosen for construction. The construction parameters of the step and CD methods are optimized to ensure the surrounding rock stability and tunnel safety. By relying on the Tongzi Tunnel, we simulate the excavation of different step heights in the construction of the top heading and benching method (HB) and CD methods through numerical simulation, the laws of tunnel vault settlement, and changes in the surrounding rock stress, initial support axial force, bending moment and safety factor. The study shows that as the height of the upper step increases, the settlement of the vault and the convergence of the periphery increase, the initial support safety factor decreases, and the plastic zone of the surrounding rock increases at 30 m from the target face. The step height for the top heading and benching method (HB) of construction is optimized as follows. The ratios of the upper, middle and lower step heights are 0.45H, 0.35H and 0.2H, respectively. The CD method construction step height is optimized to the left (right) upper and left (right) lower step height ratios of 0.5H and 0.5H, respectively.
Protective effects of a new generation of probiotic Bacteroides fragilis against colitis in vivo and in vitro
Authors: He Qiuyue , Niu Min , Bi Jiandie , Du Na , Liu Shumin , Yang Kai , Li Huanqin , Yao Jing , Du Yan , Duan Yong 
Published: September 2023

AbstractBacteroides fragilis, one of the potential next-generation probiotics, but its protective mechanism is not yet known. We aimed to characterize the anti-inflammatory effect of B. fragilisATCC25285 and to elucidate its mechanism through in vivo and in vitro experiments. An in vitro model of inflammation by induction of colonic cells with TNF-a, and co-cultured with B. fragilis to detect cell viability, apoptosis and invasive capacity. Furthermore, critical proteins of the TLR/NF-κB pathway and the inflammatory cytokines were measured. For animal trials, C57BL/6 J male mice were orally administered B. fragilis or PBS once daily for 21 days. Colitis was induced by drinking 2.5% DSS from days 0 to 7. The mice were weighed daily and rectal bleeding, stool condition and blood in the stool were recorded. We found that B. fragilis treatment alone was harmless and had no effect on cell viability or apoptosis. While predictably TNF-α decreased cell viability and increased apoptosis, B. fragilis attenuated this deterioration. The NF-κB pathway and inflammatory cytokines IL-6 and IL-1β activated by TNF-α were also blocked by B. fragilis. Notably, the metabolic supernatant of B. fragilis also has an anti-inflammatory effect. Animal studies showed that live B. fragilis rather than dead strain ameliorated DSS-induced colitis, as evidenced by weight loss, shortened colon length and enhanced barrier function. The colonic tissue levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) were decreased and IL-10 was increased as a result of B. fragilis administration. In conclusion, B. fragilis ATCC25285 exhibited anti-inflammatory effects whether in vivo or in vitro, and it may be a potential probiotic agent for improving colitis.
A comparative analysis of 2D and 3D experimental data for the identification of the parameters of computational models
Authors: Cortesi Marilisa , Liu Dongli , Yee Christine , Marsh Deborah J. , Ford Caroline E. 
Published: September 2023

AbstractComputational models are becoming an increasingly valuable tool in biomedical research. Their accuracy and effectiveness, however, rely on the identification of suitable parameters and on appropriate validation of the in-silico framework. Both these steps are highly dependent on the experimental model used as a reference to acquire the data. Selecting the most appropriate experimental framework thus becomes key, together with the analysis of the effect of combining results from different experimental models, a common practice often necessary due to limited data availability. In this work, the same in-silico model of ovarian cancer cell growth and metastasis, was calibrated with datasets acquired from traditional 2D monolayers, 3D cell culture models or a combination of the two. The comparison between the parameters sets obtained in the different conditions, together with the corresponding simulated behaviours, is presented. It provides a framework for the study of the effect of the different experimental models on the development of computational systems. This work also provides a set of general guidelines for the comparative testing and selection of experimental models and protocols to be used for parameter optimization in computational models.
Modelling antimicrobial resistance transmission to guide personalized antimicrobial stewardship interventions and infection control policies in healthcare setting: a pilot study
Authors: Durazzi Francesco , Pezzani Maria Diletta , Arieti Fabiana , Simonetti Omar , Canziani Lorenzo Maria , Carrara Elena , Barbato Lorenzo , Onorati Francesco , Remondini Daniel , Tacconelli Evelina 
Published: September 2023

AbstractInfection control programs and antimicrobial stewardship have been proven effective in reducing the burden of diseases due to multidrug-resistant organisms, but quantifying the effect of each intervention is an open issue. For this aim, we propose a model to characterize the effect of interventions at single ward level. We adapted the Ross-Macdonald model to describe hospital cross-transmission dynamics of carbapenem resistant Klebsiella pneumoniae (CRKP), considering healthcare workers as the vectors transmitting susceptible and resistant pathogens among admitted patients. The model parameters were estimated from a literature review, further adjusted to reproduce observed clinical outcomes, and validated using real life data from a 2-year study in a university hospital. The model has been further explored through extensive sensitivity analysis, in order to assess the relevance of single interventions as well as their synergistic effects. Our model has been shown to be an effective tool to describe and predict the impact of interventions in reducing the prevalence of CRKP colonisation and infection, and can be extended to other specific hospital and pathological scenarios to produce tailored estimates of the most effective strategies.
Harmonic dependence of thermal magnetic particle imaging
Authors: Bui Thinh Q. , Henn Mark-Alexander , Tew Weston L. , Catterton Megan A. , Woods Solomon I. 
Published: September 2023

AbstractAdvances in instrumentation and tracer materials are still required to enable sensitive, accurate, and localized in situ 3D temperature monitoring by magnetic particle imaging (MPI). We have developed a high-resolution magnetic particle imaging instrument and implemented a low-noise multi-harmonic lock-in detection method to observe and quantify temperature variations in iron oxide nanoparticle tracers using the harmonic ratio method for determining temperature. Using isolated harmonics for MPI and temperature imaging revealed an apparent dependence of imaging resolution on harmonic number. Thus, we present experimental and simulation studies to quantify the imaging resolution dependence on temperature and harmonic number, and directly validate the fundamental origin of MPI imaging resolution on harmonic number based on the concept of a harmonic point-spread-function.
Computational evidence for multi-layer crosstalk between the cadherin-11 and PDGFR pathways
Authors: Karagöz Zeynep , Passanha Fiona R. , Robeerst Lars , van Griensven Martijn , LaPointe Vanessa L. S. , Carlier Aurélie 
Published: September 2023

AbstractVarious cell surface receptors play an important role in the differentiation and self-renewal of human mesenchymal stem cells (hMSCs). One example of such receptors are the cadherins, which maintain cell–cell adhesion and mechanically couple cells together. Recently, cadherin-11, which is a member of the type II classical cadherin family, has been shown to be involved in the fate commitment of hMSCs. Interestingly, cadherin-11 has no known intrinsic signaling activity and is thought to affect cell behavior via interactions with other cell surface receptors. Members of the platelet-derived growth factor receptor (PDGFR) family are hypothesized to be one of the interaction partners of cadherin-11. Experiments confirmed that PDGFR-α binding to extracellular cadherin-11 regions increases the PDGFR-α activity, whereas the interaction between PDGFR-β and cadherin-11 suppresses the activity of the growth factor receptor. Cadherin-11 knockdown experiments also decreased cell proliferation. These interactions between cadherin-11 and PDGFRs indicate a crosstalk between these receptors and their downstream signaling activities but the nature of this crosstalk is not entirely known. In this study, we used a computational model to represent the experimentally proven interactions between cadherin-11 and the two PDGFRs and we inspected whether the crosstalk also exists downstream of the signaling initiated by the two receptor families. The computational framework allowed us to monitor the relative activity levels of each protein in the network. We performed model simulations to mimic the conditions of previous cadherin-11 knockdown experiments and to predict the effect of crosstalk on cell proliferation. Overall, our predictions suggest the existence of another layer of crosstalk, namely between β-catenin (downstream to cadherin-11) and an ERK inhibitor protein (e.g. DUSP1), different than the crosstalk at the receptor level between cadherin-11 and PDGFR-α and -β. By investigating the multi-level crosstalk between cadherin and PDGFRs computationally, this study contributes to an improved understanding of the effect of cell surface receptors on hMSCs proliferation.
Reduced effects of social feedback on learning in Turner syndrome
Authors: Björlin Avdic Hanna , Strannegård Claes , Engberg Hedvig , Willfors Charlotte , Nordgren Ida , Frisén Louise , Hirschberg Angelica Lindén , Guath Mona , Nordgren Ann , Kleberg Johan Lundin 
Published: September 2023

AbstractTurner syndrome is a genetic condition caused by a complete or partial loss of one of the X chromosomes. Previous studies indicate that Turner syndrome is associated with challenges in social skills, but the underlying mechanisms remain largely unexplored. A possible mechanism is a reduced social influence on learning. The current study examined the impact of social and non-social feedback on learning in women with Turner syndrome (n = 35) and a sex- and age-matched control group (n = 37). Participants were instructed to earn points by repeatedly choosing between two stimuli with unequal probabilities of resulting in a reward. Mastering the task therefore required participants to learn through feedback which of the two stimuli was more likely to be rewarded. Data were analyzed using computational modeling and analyses of choice behavior. Social feedback led to a more explorative choice behavior in the control group, resulting in reduced learning compared to non-social feedback. No effects of social feedback on learning were found in Turner syndrome. The current study thus indicates that women with Turner syndrome may be less sensitive to social influences on reinforcement learning, than the general population.
Gait disorders induced by photothrombotic cerebellar stroke in mice
Authors: Inoue Keisuke , Asaka Meiko , Lee Sachiko , Ishikawa Kinya , Yanagihara Dai 
Published: September 2023

AbstractPatients with cerebellar stroke display relatively mild ataxic gaits. These motor deficits often improve dramatically; however, the neural mechanisms of this improvement have yet to be elucidated. Previous studies in mouse models of gait ataxia, such as ho15J mice and cbln1-null mice, have shown that they have a dysfunction of parallel fiber-Purkinje cell synapses in the cerebellum. However, the effects of cerebellar stroke on the locomotor kinematics of wild-type mice are currently unknown. Here, we performed a kinematic analysis of gait ataxia caused by a photothrombotic stroke in the medial, vermal, and intermediate regions of the cerebellum of wild-type mice. We used the data and observations from this analysis to develop a model that will allow locomotive prognosis and indicate potential treatment regimens following a cerebellar stroke. Our analysis showed that mice performed poorly in a ladder rung test after a stroke. During walking on a treadmill, the mice with induced cerebellar stroke had an increased duty ratio of the hindlimb caused by shortened duration of the swing phase. Overall, our findings suggest that photothrombotic cerebellar infarction and kinematic gait analyses will provide a useful model for quantification of different types of acute management of cerebellar stroke in rodents.
Associative memory by virtual oscillator network based on single spin-torque oscillator
Authors: Imai Yusuke , Taniguchi Tomohiro 
Published: September 2023

AbstractA coupled oscillator network may be able to perform an energy-efficient associative memory operation. However, its realization has been difficult because inhomogeneities unavoidably arise among the oscillators during fabrication and lead to an unreliable operation. This issue could be resolved if the oscillator network were able to be formed from a single oscillator. Here, we performed numerical simulations and theoretical analyses on an associative memory operation that uses a virtual oscillator network based on a spin-torque oscillator. The virtual network combines the concept of coupled oscillators with that of feedforward neural networks. Numerical experiments demonstrate successful associations of 60-pixel patterns with various memorized patterns. Moreover, the origin of the associative memory is shown to be forced synchronization driven by feedforward input, where phase differences among oscillators are fixed and correspond to the colors of the pixels in the pattern.
Synthesis and characterization of a novel magnetic chitosan–nickel ferrite nanocomposite for antibacterial and antioxidant properties
Authors: Shokri Samira , Shariatifar Nabi , Molaee-Aghaee Ebrahim , Khaniki Gholamreza Jahed , Sadighara Parisa , Faramarzi Mohammad Ali , Mohammadi Mansoureh , Rezagholizade-shirvan Alieh 
Published: September 2023

AbstractA novel nanomagnet modified with nickel ferrite nanoparticles (NPs) coated with hybrid chitosan (Cs–NiFe2O4) was synthesized using the co-precipitation method. The resulting nanomagnets were characterized using various techniques. The size of the nanomagnetic particles was estimated to be about 40 nm based on the transmission electron microscopy (TEM) image and X-ray diffraction analysis (XRD) pattern (using the Debye–Scherrer equation). Scanning electron microscopy (SEM) images indicated that the surface of Cs–NiFe2O4 NPs is flatter and smoother than the uncoated NiFe2O4 NPs. According to value stream mapping (VSM) analysis, the magnetization value of Cs–NiFe2O4 NPs (17.34 emu/g) was significantly lower than NiFe2O4 NPs (40.67 emu/g). The Cs–NiFe2O4 NPs indicated higher antibacterial properties than NiFe2O4 NPs and Cs. The minimum inhibitory concentrations of Cs–NiFe2O4 NPs against S. aureus and E. coli were 128 and 256 mg/mL, respectively. Antioxidant activity (evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging test) for NiFe2O4 NPs and Cs–NiFe2O4 NPs at the concentration of 100 µg/mL were 35% and 42%, respectively. Consequently, the synthesized Cs–NiFe2O4 NPs can be proposed as a viable material for biomedical applications.
Surfactant supported chitosan for efficient removal of Cr(VI) and anionic food stuff dyes from aquatic solutions
Authors: Akl Magda A. , Mostafa Aya G. , Abdelaal Magdy Y. , Nour Mennat Allah K. 
Published: September 2023

AbstractIn order to develop a novel and cost-effective adsorbent with outstanding adsorption capacity and excellent recyclability for anionic pollutants, the chitosan-modified cetyltrimethylammonium bromide sorbent (CS@CTAB) was fabricated. Fourier-transform infrared spectroscopy, N2 adsorption–desorption isotherm, elemental analysis, Thermogravimetric analysis, X-ray diffraction, and Scanning electron microscopy have been applied to evaluate both raw and surfactant modified chitosan (CS@CTAB). Azorubine, Sunset Yellow, and hexavalent chromium were used to study the adsorption behavior of CS@CTAB under various parameters such as adsorbent dose, initial dye and metal ion concentration, contact time, and temperature. Adsorption equilibrium, kinetics models and thermodynamic parameters were investigated. The adsorption isotherm fitted well with the Langmuir isotherm model, with a maximum adsorption capacity of 492.6 mg/g, 492.6 mg/g, and 490.196 mg/g for Azorubine, Sunset Yellow, and Hexavalent Chromium, respectively. The kinetic studies showed that the pseudo-second-order model provided a better correlation between experimental data. Furthermore, the calculated thermodynamic parameters confirmed that the adsorption of Cr(VI), E110, and E122 by CS@CTAB material is a spontaneous and exothermic process. The fabricated CS@CTAB adsorbent was employed for the efficient elimination of Azorubine, Sunset Yellow, and hexavalent chromium from real water samples, synthetic mixtures, and colored soft drinks, with a percentage of recovery of ~ 96%. The plausible adsorption mechanisms of Azorubine, Sunset Yellow, and hexavalent chromium on the surface of CS@CTAB are elucidated. The adsorption anticipated to be due to electrostatic interaction and hydrogen bond formation for hexavalent chromium; while the adsorption of Azorubine and Sunset Yellow, was assumed to be due to electrostatic interaction, hydrogen bonding, and n-π interaction. Finally, the study demonstrates the efficiency of CS@CTAB for the removal of anionic species from several samples, including natural water and colored beverages.
Comparisons among barley–pea mixed crop combinations in a replacement design as related to N fertilization and soil variation
Authors: Tavoletti Stefano , Cocco Stefania , Corti Giuseppe 
Published: September 2023

AbstractTwo field trials (2017 and 2018) evaluated the performance of barley–pea mixed cropping by comparing different sowing densities (replacement design) and tailoring N fertilization on barley sowing density (split-plot design). High and Low N inputs were applied to whole plots whereas barley and pea, as pure and in mixed crops, were applied to subplots. The 2017 trial suggested the occurrence of an interaction between soil physical properties and N fertilization. Therefore, in 2018 a pedological survey allowed the soil effect to be included in the ANOVA model applied to evaluate crop performance parameters, showing that N fertilization positively affected barley performance only in the soil unit located downslope. A significantly lower presence of weeds was observed in mixed crops rather than in pea pure crops. Overall, increasing pea density and reducing barley density in mixed crops, and tailoring N fertilization were effective approaches to obtain a more balanced mixed grain at harvest. The combination of crop performance evaluation and assessments of soil conditions suggested that more sustainable agricultural systems, based on mixed cropping and a significant reduction of N fertilizers and herbicides, can be achieved with barley–pea mixed cropping as an alternative to pure cropping systems.