bluuebunny/crossref_metadata_2025 huggingface dataset:
Community Emergence of Cefixime-Resistant Escherichia coli Belonging to ST12 with Chromosomal AmpC Hyperproduction
Authors: Zaragoza Gloria , Pérez-Vázquez María , Villar-Gómara Laura , González-Prieto Andrea , Oteo-Iglesias Jesús , Alós Juan-Ignacio
Published: February 2024

Escherichia coli isolates that are resistant to cefixime and amoxicillin/clavulanic acid, but apparently susceptible to cefuroxime, with no ESBL identified, were initially detected in Madrid from urine samples in 2019. Throughout 2020 and 2021, all cases of community UTI by E. coli from six health areas in Madrid were studied. A representative sample of 23 cases was selected for further studies. The broth microdilution method and the agar diffusion method were performed to determine the antibiotic susceptibility. WGS was carried out for phylogeny, resistome and virulome analysis. Community consumption of third-generation oral cephalosporins in Madrid (2017–2021) was analyzed. A total of 582 (1.3%) E. coli isolates had the mentioned resistance profile. The mutation at position –32 (T > A) of the AmpC promoter was found in 21 isolates. No plasmid AmpC- or ESBL-encoding genes were detected. A cluster of 20 ST12 isolates was detected by cgMLST. A 6.2% increase in the consumption of third-generation oral cephalosporins, especially cefixime, was observed in Madrid. Chromosomal AmpC-hyperproducing ST12 E. coli isolates could be implicated in the increase in community UTI cases by cefixime-resistant isolates, which correlates with an increasing trend of cefixime consumption.
Relationship between Target Time above Minimum Inhibitory Concentration Achievement Rate of Meropenem Using Monte Carlo Simulation and In-Hospital Survival in Patients with Pseudomonas aeruginosa Bacteremia
Authors: Nakashima Hajime , Miyazaki Motoyasu , Kuwamura Tsuneo , Oda Kazutaka , Haga Yumi , Imakyure Osamu
Published: February 2024

Pseudomonas aeruginosa bacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration (fT>MIC) of MEPM and its therapeutic efficacy in P. aeruginosa bacteremia has not been explored. This study aimed to investigate this relationship by defining the target % fT>MIC of MEPM as 75%. The retrospective study spanned 14 years and included hospitalized patients treated with MEPM for P. aeruginosa bacteremia. Monte Carlo simulation was used to calculate the probability of target attainment (PTA) for each patient, and the threshold for a PTA of 75% fT>MIC associated with in-hospital survival was determined using receiver operating characteristic (ROC) curves. The ROC curve-derived PTA associated with improved in-hospital survival was 65.0%, a significant finding in multivariate logistic regression analysis adjusted for patient background factors (odds ratio: 20.49, 95% confidence interval: 3.02–245.23, p = 0.005). This result suggests a dosing regimen that achieves a PTA of at least 65% when the target fT>MIC of MEPM for treating P. aeruginosa bacteremia is defined as 75%.
WavLoadNet: Dynamic Load Identification for Aeronautical Structures Based on Convolution Neural Network and Wavelet Transform
Authors: Zhang Xiaoqiang , He Wenbo , Cui Qiang , Bai Ting , Li Baoqing , Li Junjie , Li Xinmin
Published: February 2024

The accurate identification of dynamic load is important for the optimal design and fault diagnosis of aeronautical structures. Aiming at the identification of dynamic loads on complex or unknown aeronautical structures, a deep convolution neural network (CNN) in the transform domain-based method is proposed. It takes decomposed signals from wavelet transform of several vibration signals as input. A CNN is used for feature extraction, and fully connected layers are used for predicting the decomposed loads in the transform domain. After synthesizing the predicted decomposed components, the loads in the time domain can be obtained. The proposed method could avoid the explicit modeling of the system or transfer functions with complex or unknown structures. Using the data collected on a GARTEUR model, the proposed model is trained and verified. Extensive experimental results with qualitative and quantitative evaluations show the accuracy of this method and the robustness to measurement noise and other unknown load disturbances.
Charactering Human-Caused Fires Using GIS-Based Dimensionality Reduction Techniques in Keelung City, Taiwan
Authors: Ku Cheng-Yu , Lu Hsueh-Chuan , Tu Yi-Tse , Liu Chih-Yu
Published: February 2024

Fires resulting from human activities, encompassing arson, electrical problems, smoking, cooking mishaps, and industrial accidents, necessitate understanding to facilitate effective prevention. This study investigates human-caused fires in Keelung City, Taiwan, employing geographic information system (GIS)-based dimensionality reduction techniques. By analyzing eleven diverse factors, including fire incident density, population-related, building-related and economic-related features, valuable insights are gained for enhancing fire prevention. Utilizing principal component analysis (PCA), factor analysis (FA), and out-of-bag (OOB) predictor importance, our algorithm identifies key factors explaining dataset variance. Results from three approaches reveal a significant link between fire incidents and the elderly population, buildings over 40 years old, and the tertiary sector in the economy, contributing to developing effective measures for mitigating and managing fire occurrences.
Extracellular Matrix Tunes the Regenerative Potential of Fetal Stem Cells
Authors: Pei Yixuan Amy , Patel Jhanvee , Pei Ming
Published: February 2024

Adult mesenchymal stem cells (MSCs) are a promising cell source for tissue regeneration. However, ex vivo expansion results in cell senescence; cells lose their proliferation and differentiation capacity. Fetal MSCs can offer an alternative due to their robust proliferation and differentiation capacities, as well as their immune privilege properties. Given the rejuvenation effect of the decellularized extracellular matrix (dECM) on adult MSCs, it remains unknown whether dECM influences the regenerative potential of fetal stem cells. In this study, passage five fetal nucleus pulposus cells (fNPCs) and fetal synovium-derived stem cells (fSDSCs) were expanded on dECMs deposited by fNPCs (NECM) and fSDSCs (SECM) for one passage, with expansion on tissue culture plastic (Plastic) as a control. We found that dECM-expanded fNPCs and fSDSCs exhibited both similarities and differences in the expression of stemness genes and surface markers. Expanded fNPCs yielded more differentiated pellets after chondrogenic induction but exhibited no adipogenic differentiation following adipogenic induction in both the Plastic and dECM groups than the corresponding fSDSC group. Despite a significant increase in fNPCs, the dECM-expanded fSDSCs exhibited no increase in chondrogenic potential; however, compared to the Plastic group, dECM-expanded fSDSCs exhibited a small increase in osteogenic potential and a great increase in adipogenic potential. These results suggest that fNPCs are more sensitive to NECM rejuvenation for cartilage tissue engineering and regeneration; in contrast, the dECMs exhibited limited effects on fSDSC rejuvenation in a chondrogenic capacity, except for enhanced adipogenic capacity following expansion on SECM.
Investigation of Heat and Moisture Transfer during the Drying of Packed-Bed Porous Media in Soybeans
Authors: Niu Zhuang , Lu Xiangyou , Li Zhiqiang
Published: February 2024

The research aims to examine the distribution of porosity and the combined heat and moisture movement while grains are being dried. This research concerns the porosity and flow of soybeans with different particle size ratios and the drying of soybeans with varying particle temperatures. Due to the similarity in shape between soybeans and balls, this article adopts a ball shape to study the heat and moisture transfer of soybean particles, which can also be used for the study of grains with similar shapes, such as mung beans and red beans. Random models of soybeans with varying proportions were created using modeling software Edem and UG. UDF programming was added to the preprocessing software Fluent to analyze the porosity, airstream allocation, and the interaction of temperature and moisture transfer in packed beds with various cylinder-to-particle size ratios and particle temperatures. A packed bed of soybeans was created, and the study examined the impact of cylinder-to-particle size ratios of 4.44, 5.6, and 6.25 on porosity. The results show that the radial porosity in the packed bed displays a fluctuating profile, with partial porosity increasing as the cylinder-to-particle size ratio increases. Increasing the ratio of cylinder size to particle size exacerbated the tortuosity of the flow paths within the packed bed. Simultaneously, the particle temperature increases, leading to a rise in the instantaneous heat transfer during the drying process, strengthening the ratio of moisture transfer within the packed bed. The method effectively models during convective heat and mass transfer in the liquid facies, as well as thermal and mass spread in the solid facies. The results of this study have been validated on physical models. The air temperature of 273 K is considered during the simulation process
Antimicrobial Peptide Screening from Microbial Genomes in Sludge Based on Deep Learning
Authors: Liu Yin-Xuan , Jin Xue-Bo , Xu Chun-Ming , Ma Hui-Jun , Wu Qi , Liu Hao-Si , Li Zi-Meng
Published: February 2024

As the issue of traditional antibiotic resistance continues to worsen, exploring new antimicrobial substances has become crucial to addressing this challenge. Antimicrobial peptides (AMPs), recognized for their low resistance levels and minimal bacterial mutation frequencies, have garnered significant attention from researchers. However, traditional screening methods for AMPs are inefficient and costly. This study proposes a combined AMP screening model based on long short-term memory (LSTM) neural networks with an attention mechanism. By analyzing the characteristics of peptide segments, which are simulated enzymatic hydrolysis products of proteins expressed in sludge microbial genomes, the model accurately identifies peptide segments with potential antimicrobial activity. Molecular docking and dynamic simulation results validate three potential antimicrobial peptide candidates: LLPRLLARRY, GVREIHGLNPGGCLHTVRLVCR, and FRTTLAPHVLTRLLAPCW. These candidates exhibit high binding stability and affinity with target proteins, confirming the efficiency of the proposed AMP screening model.
Photovoltaic Tiles for the Wavelength-Selective Greenhouse: Exploring Yellow and Green Dye-Sensitized Solar Cells in Outdoor Conditions
Authors: Bularka Szilard , Vajda Melinda , Ilies Elisei , Ricman Radu , Marinca Magdalena , Miclau Marinela , Gontean Aurel , Ursu Daniel
Published: February 2024

In response to two major global crises, Agriculture 4.0 proposes the use of the same land both for energy production and plant culture. The wavelength-selective greenhouse could be a promising agrivoltaic system if it can provide an optimal balance between the microclimate suitable for plants and increasing energy production, an ambitious future goal being an energy independent and combined fully automated arboretum. The dye-sensitized solar cell has recently been proposed as an ideal candidate due to its easy adaptation to the conditions imposed by the optimal operation of greenhouses. Using laboratory-sized yellow and green dye-sensitized solar cells, the photovoltaic tiles, as the main part of a wavelength-selective greenhouse, were constructed and tested under outdoor conditions on a hot summer day. The values of the temperature coefficient for the maximum power (γ), namely −0.003%/°C for the Si tile, −0.0017%/°C for the yellow tile, and −0.0004%/°C for the green tile have highlighted that the thermal stability of the green and yellow tiles is clearly higher than that of the Si tile. Furthermore, it was experimentally demonstrated that the DSSC based on DN-F15 green dye decreases in temperature by approximately 3 °C compared to the ambient temperature. Thus, in addition to the basic function of energy production, the photovoltaic tile based on green DSSCs is proposed as a smart solution to lower the temperature inside the greenhouse, a small step in the development of a strategy for adapting agriculture to advancing climate change. Therefore, the photovoltaic tile concept based on yellow and green DSSCs has been experimentally validated both from the energy production and greenhouse microclimate perspectives.
Climate Change Impacts on the Energy System of a Climate-Vulnerable Mediterranean Country (Greece)
Authors: Georgopoulou Elena , Mirasgedis Sevastianos , Sarafidis Yannis , Giannakopoulos Christos , Varotsos Konstantinos V. , Gakis Nikos
Published: February 2024

Climate change is expected to significantly affect countries in Southern Europe and the Mediterranean Basin, causing higher-than-average temperature increases, considerable reductions in rainfall and water runoff, and extreme events such as heatwaves. These pose severe threats to local energy systems, requiring a reliable and quantitative risk analysis. A methodological approach is thus proposed which covers both energy supply and demand, utilizing the latest climate projections under different greenhouse gas emissions scenarios and an appropriate scale for each energy form. For energy supply technologies, risks are assessed through statistical regression models and/or mathematical equations correlating climatic parameters with energy productivity. To analyze climate risks for energy demand, bottom–up models were developed, integrating both behavioral and policy aspects which are often considered in a very limited way. The results show that climate change will mainly affect electricity generation from hydroelectric and thermal power plants, with variations depending on the plants’ locations and uncertainties associated with precipitation and runoff changes. The climate risks for solar and wind energy were found to be low. Energy consumption will also be affected, but the range of risks depends on the ambition and the effectiveness of measures for upgrading the thermal performance of buildings and the intensity of climate change.
Revisiting the Characteristics of Super Typhoon Saola (2023) Using GPM, Himawari-9 and FY-4B Satellite Data
Authors: Wang Yuanmou , Xia Baicheng , Chen Yanan , Chen Huan , Xie Jing
Published: February 2024

Typhoon Saola was the ninth typhoon that generated over the Western North Pacific (WNP) in 2023, and it caused severe storm impacts. However, its complex moving track and heavy intensity made it extremely difficult to forecast; therefore, detailed analysis is necessary. In this study, GPM, Himawari-9, and FY-4B satellite data were used to analyze the characteristics of the structure, brightness temperature, and precipitation of the typhoon cloud system. Our results showed that, in the 89 and 183 GHz channels of GPM-1CGMI, the brightness temperature of the typhoon eye was 80–90 K higher than that of the eye wall, and the strong convective areas below 200 K were clearer in these high-frequency channels. GPM-2ADPR estimated heavy rain (over 30 mm/h) area, storm height (5 km), and vertical precipitation rate (30–40 mm/h) more accurately than the GPM-2Aka and GPM-2Aku products. Himawari-9 satellite data showed that the brightness temperature of the eye wall and spiral cloud bands was 180–200 K, the typhoon eye was small and round, and strong convective activities were mostly located in the southwest side of the center. The FY-4B CLP and CLT products showed that, in the mature period of the typhoon, the percentage of supercooled and mixed clouds first stabilized and then rapidly decreased. The trends observed among the three types of ice-phase clouds were characterized by an initial increase, followed by a decrease, and then another increase, with percentages between 10% and 25%, 5% and 15%, and 15% and 30%, respectively.
Occurrence of Polycyclic Aromatic Hydrocarbons and Polychlorinated Biphenyls in Fogwater at Urban, Suburban, and Rural Sites in Northeast France between 2015 and 2021
Authors: Khoury Dani , Millet Maurice , Jabali Yasmine , Delhomme Olivier
Published: February 2024

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) exist in the atmosphere in the vapor and particulate phases, as well as in solubilized form in fog/rain/cloud waters. In the current paper, fogwater samples are collected during 42 events between 2015 and 2021 at four different sites (Strasbourg, Geispolsheim, Erstein, Cronenbourg) in the Alsace region. Organics are extracted using liquid–liquid extraction (LLE) supported on a solid cartridge (XTR Chromabond), and then analyzed by gas chromatography–tandem mass spectrometry (GC-MS/MS). The total PAHs and PCBs concentrations in fog samples vary between 0.58 and 6.7 µg L−1 (average of 2.70 µg L−1), and 0.14 and 15.5 µg L−1 (average of 2.75 µg L−1). Low-molecular-weight (LMW) PAHs are predominant and highly detectable compared to high-molecular-weight (HMW) PAHs, while pentachloro-biphenyls are the dominant PCB congener. The PAHs and PCBs concentrations have increased over the sampling years at all sites, except for a slight decrease in PCBs level at Geispolsheim. A diagnostic ratio (DR) and principal component analysis (PCA) are applied to suggest potential contamination sources at Strasbourg metropolitan. Their results reveal that PAHs derive from a mixture of pyrogenic activities, while PCBs mainly come from industrial activities. The results also reveal, in some cases, inter-site variability for simultaneous and successive fog events.
Energy Levels and Transition Data of Cs VI
Authors: Husain Abid , Kunari Haris , Ahmad Tauheed
Published: February 2024

Previously reported atomic data (spectral lines, wavelengths, energy levels, and transition probabilities) were collected and systematically analyzed for Cs VI. The present theoretical analysis was supported by extensive calculations made for Cs VI with a pseudo-relativistic Hartree–Fock (HFR) method together with the superposition of configuration interactions implemented in Cowan’s codes. In this work, all previously reported energy levels and their (allowed) transition assignments were confirmed. A critically evaluated set of optimized energy levels with their uncertainties, observed and Ritz wavelengths along with their uncertainties, and theoretical transition probabilities with their estimated uncertainties were presented in the compilation. In addition to this, we determined the radiative transition parameters for several forbidden lines within the ground configuration 5s25p2 of Cs VI.
Iterative Stability Analysis for Generalized α-Nonexpensive Mappings with Fixed Points
Authors: Iqbal Maryam , Ali Amjad , Sulami Hamid Al , Hussain Aftab
Published: February 2024

This article introduces a novel iterative process, denoted as F★, designed for the class of generalized α-Nonexpensive mappings. The study establishes strong and weak convergence theorems within the context of Banach spaces, supported by carefully chosen assumptions. The convergence results contribute to the theoretical foundation of iterative processes in functional analysis. The presented framework is applied to address nonlinear integral equations, showcasing the versatility and applicability of the proposed F* for the class of generalized iteration process. Additionally, the article includes numerical examples that not only validate the theoretical findings but also provide insights into the practical utility of the developed methodology.
Improving Generalizability of PET DL Algorithms: List-Mode Reconstructions Improve DOTATATE PET Hepatic Lesion Detection Performance
Authors: Yang Xinyi , Silosky Michael , Wehrend Jonathan , Litwiller Daniel V. , Nachiappan Muthiah , Metzler Scott D. , Ghosh Debashis , Xing Fuyong , Chin Bennett B.
Published: February 2024

Deep learning (DL) algorithms used for DOTATATE PET lesion detection typically require large, well-annotated training datasets. These are difficult to obtain due to low incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and the high cost of manual annotation. Furthermore, networks trained and tested with data acquired from site specific PET/CT instrumentation, acquisition and processing protocols have reduced performance when tested with offsite data. This lack of generalizability requires even larger, more diverse training datasets. The objective of this study is to investigate the feasibility of improving DL algorithm performance by better matching the background noise in training datasets to higher noise, out-of-domain testing datasets. 68Ga-DOTATATE PET/CT datasets were obtained from two scanners: Scanner1, a state-of-the-art digital PET/CT (GE DMI PET/CT; n = 83 subjects), and Scanner2, an older-generation analog PET/CT (GE STE; n = 123 subjects). Set1, the data set from Scanner1, was reconstructed with standard clinical parameters (5 min; Q.Clear) and list-mode reconstructions (VPFXS 2, 3, 4, and 5-min). Set2, data from Scanner2 representing out-of-domain clinical scans, used standard iterative reconstruction (5 min; OSEM). A deep neural network was trained with each dataset: Network1 for Scanner1 and Network2 for Scanner2. DL performance (Network1) was tested with out-of-domain test data (Set2). To evaluate the effect of training sample size, we tested DL model performance using a fraction (25%, 50% and 75%) of Set1 for training. Scanner1, list-mode 2-min reconstructed data demonstrated the most similar noise level compared that of Set2, resulting in the best performance (F1 = 0.713). This was not significantly different compared to the highest performance, upper-bound limit using in-domain training for Network2 (F1 = 0.755; p-value = 0.103). Regarding sample size, the F1 score significantly increased from 25% training data (F1 = 0.478) to 100% training data (F1 = 0.713; p < 0.001). List-mode data from modern PET scanners can be reconstructed to better match the noise properties of older scanners. Using existing data and their associated annotations dramatically reduces the cost and effort in generating these datasets and significantly improves the performance of existing DL algorithms. List-mode reconstructions can provide an efficient, low-cost method to improve DL algorithm generalizability.
Motion Artifact Reduction Using U-Net Model with Three-Dimensional Simulation-Based Datasets for Brain Magnetic Resonance Images
Authors: Kang Seong-Hyeon , Lee Youngjin
Published: February 2024

This study aimed to remove motion artifacts from brain magnetic resonance (MR) images using a U-Net model. In addition, a simulation method was proposed to increase the size of the dataset required to train the U-Net model while avoiding the overfitting problem. The volume data were rotated and translated with random intensity and frequency, in three dimensions, and were iterated as the number of slices in the volume data. Then, for every slice, a portion of the motion-free k-space data was replaced with motion k-space data, respectively. In addition, based on the transposed k-space data, we acquired MR images with motion artifacts and residual maps and constructed datasets. For a quantitative evaluation, the root mean square error (RMSE), peak signal-to-noise ratio (PSNR), coefficient of correlation (CC), and universal image quality index (UQI) were measured. The U-Net models for motion artifact reduction with the residual map-based dataset showed the best performance across all evaluation factors. In particular, the RMSE, PSNR, CC, and UQI improved by approximately 5.35×, 1.51×, 1.12×, and 1.01×, respectively, and the U-Net model with the residual map-based dataset was compared with the direct images. In conclusion, our simulation-based dataset demonstrates that U-Net models can be effectively trained for motion artifact reduction.
Environmental Effects during Early Life-History Stages and Seed Development on Seed Functional Traits of an Australian Native Legume Species
Authors: Beveridge Fernanda C. , Williams Alwyn , Cave Robyn , Kalaipandian Sundaravelpandian , Haque Mirza M. , Adkins Steve W.
Published: February 2024

Understanding how seed functional traits interact with environmental factors to determine seedling recruitment is critical to assess the impact of climate change on ecosystem restoration. This study focused on the effects of environmental factors on the mother plant during early plant life history stages and during seed development. Desmodium brachypodum A. Gray (large tick trefoil, Fabaceae) was used as a model species. Firstly, this study analyzed seed germination traits in response to temperature and moisture stress. Secondly, it investigated how seed burial depth interacts with temperature and soil moisture to influence seedling emergence traits. Finally, it determined if contrasting levels of post-anthesis soil moisture could result in changes in D. brachypodum reproductive biology and seed and seedling functional traits. The results showed that elevated temperature and moisture stress interacted to significantly reduce the seed germination and seedling emergence (each by >50%), while the seed burial improved the seedling emergence. Post-anthesis soil moisture stress negatively impacted the plant traits, reducing the duration of the reproductive phenology stage (by 9 days) and seed production (by almost 50%). Unexpectedly, soil moisture stress did not affect most seed or seedling traits. In conclusion, elevated temperatures combined with low soil moisture caused significant declines in seed germination and seedling emergence. On the other hand, the reproductive output of D. brachypodum had low seed variability under soil moisture stress, which might be useful when sourcing seeds from climates with high variability. Even so, a reduction in seed quantity under maternal moisture stress can impact the long-term survival of restored plant populations.
Chromatin’s Influence on Pre-Replication Complex Assembly and Function
Authors: Ahmad Hina , Chetlangia Neha , Prasanth Supriya G.
Published: February 2024

In all eukaryotes, the initiation of DNA replication requires a stepwise assembly of factors onto the origins of DNA replication. This is pioneered by the Origin Recognition Complex, which recruits Cdc6. Together, they bring Cdt1, which shepherds MCM2-7 to form the OCCM complex. Sequentially, a second Cdt1-bound hexamer of MCM2-7 is recruited by ORC-Cdc6 to form an MCM double hexamer, which forms a part of the pre-RC. Although the mechanism of ORC binding to DNA varies across eukaryotes, how ORC is recruited to replication origins in human cells remains an area of intense investigation. This review discusses how the chromatin environment influences pre-RC assembly, function, and, eventually, origin activity.
Correction: Chen et al. Multifunctional Injectable Hydrogel Loaded with Cerium-Containing Bioactive Glass Nanoparticles for Diabetic Wound Healing. Biomolecules 2021, 11, 702
Authors: Chen Yue-Hua , Rao Zhou-Feng , Liu Yu-Jie , Liu Xiang-Sheng , Liu Yu-Fei , Xu Lan-Ju , Wang Ze-Qi , Guo Jing-Yue , Zhang Lin , Dong Yun-Sheng , Qi Chun-Xiao , Yang Chao , Wang Shu-Fang
Published: February 2024

The authors would like to replace Figure 4A of the following published paper [...]
Bis-Indole Derivatives as Dual Nuclear Receptor 4A1 (NR4A1) and NR4A2 Ligands
Authors: Upadhyay Srijana , Hailemariam Amanuel Esayas , Mariyam Fuada , Hafiz Zahin , Martin Gregory , Kothari Jainish , Farkas Evan , Sivaram Gargi , Bell Logan , Tjalkens Ronald , Safe Stephen
Published: February 2024

Bis-indole derived compounds such as 1,1-bis(3′-indolyl)-1-(3,5-disubstitutedphenyl) methane (DIM-3,5) and the corresponding 4-hydroxyl analogs (DIM8-3,5) are NR4A1 ligands that act as inverse NR4A1 agonists and are potent inhibitors of tumor growth. The high potency of several DIM-3,5 analogs (IC50 < 1 mg/kg/day), coupled with the >60% similarity of the ligand-binding domains (LBDs) of NR4A1 and NR4A2 and the pro-oncogenic activities of both receptors lead us to hypothesize that these compounds may act as dual NR4A1 and NR4A2 ligands. Using a fluorescence binding assay, it was shown that 22 synthetic DIM8-3,5 and DIM-3,5 analogs bound the LBD of NR4A1 and NR4A2 with most KD values in the low µM range. Moreover, the DIM-3,5 and DIM8-3,5 analogs also decreased NR4A1- and NR4A2-dependent transactivation in U87G glioblastoma cells transfected with GAL4-NR4A1 or GAL4-NR4A2 chimeras and a UAS-luciferase reporter gene construct. The DIM-3,5 and DIM8-3,5 analogs were cytotoxic to U87 glioblastoma and RKO colon cancer cells and the DIM-3,5 compounds were more cytotoxic than the DIM8-3,5 compounds. These studies show that both DIM-3,5 and DIM8-3,5 compounds previously identified as NR4A1 ligands bind both NR4A1 and NR4A2 and are dual NR4A1/2 ligands.
Revisiting Multi-Omics Data to Unravel Galectins as Prognostic Factors in Head and Neck Squamous Cell Carcinoma
Authors: Barros Oriana , D’Agostino Vito Giuseppe , Santos Lucio , Ferreira Rita , Vitorino Rui
Published: February 2024

Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignant cancer with a poor prognosis. Galectins (Gal) have been the subject of intensive research, but the comparative prognostic value of each Gal type is not yet understood. Therefore, a literature search for evaluating galectins as prognostic biomarkers in HNSCC was conducted. The relationship between Gal expression in HNSCC with HPV and TP53 mutational status was assessed using the UALCAN database. The impact of these biomarkers on prognosis was analyzed using ToPP and CPPA web tools. The expression of galectins in the tumor microenvironment and the impact on prognosis depending on the cancer immune subtype were analyzed using single-cell RNA sequencing. Gal-1 and Gal-3BP were shown to be promising biomarkers with a triple function for the prediction of HPV and TP53 mutational status, stratification of the HNSCC prognosis, and prediction of the response to treatment. In addition, these two galectins have been shown to be most influenced by the tumor microenvironment of HNSCC. Gal-1 and Gal-3BP are the most promising galectins in HNSCC. Furthermore, this study highlights the need for further studies to evaluate galectins in HNSCC and clarify the role of individual Gals in the patient’s stratification.
Antiphospholipid Antibodies Are Major Risk Factors for Non-Thrombotic Cardiac Complications in Systemic Lupus Erythematosus
Authors: Nagy Nikolett , Bói Bernadett , Papp Gábor , Fiák Edit , Gáspár-Kiss Eszter , Perge Bianka , Farmasi Nikolett , Tarr Tünde
Published: February 2024

In systemic lupus erythematosus (SLE), cardiovascular complications are among the leading causes of death. Cardiovascular risk in SLE is even higher in the presence of antiphospholipid antibodies or secondary antiphospholipid syndrome (APS). The aim of this retrospective, single-center study was to investigate the occurrence of antiphospholipid antibodies and non-thrombotic cardiac manifestations in 369 SLE patients. We also assessed the clinical and laboratory characteristics of the patients to reveal the risk factors for cardiac manifestations. Patients were divided into two groups based on the presence of antiphospholipid antibodies (APA); 258 (69.9%) patients were APA positive, and 111 (30.1%) patients were APA negative. Mitral and tricuspid insufficiency, aortic stenosis and pulmonary arterial hypertension were more common in APA-positive patients. Anticardiolipin IgG showed the strongest correlation with any non-thrombotic cardiac manifestations. Based on our results, the adjusted global antiphospholipid syndrome score (aGAPSS) above 8.5 is predictive of valvulopathies and ischemic heart disease, while aGAPSS above 9.5 is predictive of cardiomyopathies. The presence of antiphospholipid antibodies may affect the development of cardiac manifestations in SLE. Periodic cardiological and echocardiographic screening of patients without cardiac complaints, as well as regular monitoring of antiphospholipid antibodies, have great importance during the treatment of SLE patients.
Long-Term Tracking of the Effects of Colostrum-Derived Lacticaseibacillus rhamnosus Probio-M9 on Gut Microbiota in Mice with Colitis-Associated Tumorigenesis
Authors: Zhao Feiyan , Hiraishi Keizo , Li Xiaodong , Hu Yaopeng , Kojima Daibo , Sun Zhihong , Zhang Heping , Kurahara Lin-Hai
Published: February 2024

Intestinal bacteria play important roles in the progression of colitis-associated carcinogenesis. Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown a protective effect in a colitis-associated cancer (CAC) model, but detailed metagenomic analysis had not been performed. Here, we investigated the preventive effects of the probiotic Probio-M9 on CAC-model mice, tracking the microbiota. Feces were obtained at four time points for evaluation of gut microbiota. The effect of Probio-M9 on tight junction protein expression was evaluated in co-cultured Caco-2 cells. Probio-M9 treatment decreased the number of tumors as well as stool consistency score, spleen weight, inflammatory score, and macrophage expression in the CAC model. Probio-M9 accelerated the recovery of the structure, composition, and function of the intestinal microbiota destroyed by azoxymethane (AOM)/dextran sulfate sodium (DSS) by regulating key bacteria (including Lactobacillus murinus, Muribaculaceae bacterium DSM 103720, Muribaculum intestinale, and Lachnospiraceae bacterium A4) and pathways from immediately after administration until the end of the experiment. Probio-M9 co-culture protected against lipopolysaccharide-induced impairment of tight junctions in Caco-2 cells. This study provides valuable insight into the role of Probio-M9 in correcting gut microbiota defects associated with inflammatory bowel disease carcinogenesis and may have clinical application in the treatment of inflammatory carcinogenesis.
100 Years since the Discovery of Insulin, from Its Discovery to the Insulins of the Future
Authors: Lambert Carmen , Delgado Elias
Published: February 2024

The term diabetes first emerged in the 3rd century BC, in a reference by Demetrius of Apamea, who described the disease as a dropsy in which any liquid ingested is eliminated in the form of urine. However, the great discovery that revolutionized this field came from the Canadian doctor Frederick Banting, who together with his student and assistant Charles Best, managed to isolate insulin and treat a patient with diabetes on 23 January 1922. This patient was Leonard Thompson, and the results obtained from him were surprising. His glycosuria and ketonuria disappeared and his blood glucose returned to normal. He received daily injections and lived 13 more years. Advances in the treatment of diabetes have been numerous in the 100 years since its discovery. In this review, we recapitulate the most important events that have occurred, and where research is progressing today.
How Are Different Perfectionism Traits Related to Mental Health in Students?
Authors: Larionow Paweł
Published: February 2024

Multidimensional models of perfectionism postulate the existence of various perfectionism traits, with different effects on mental health. In order to suggest parsimonious targets in psychological interventions for university students, this study aimed to explore whether, how, and which individual perfectionism traits are uniquely associated with stress and well-being. The participants were 253 students aged 18–30 who completed the Frost Multidimensional Perfectionism Scale, the Perceived Stress Scale, and the Warwick–Edinburgh Mental Well-being Scale. Controlling for the common variance of perfectionism traits in statistical analysis, it was shown that (1) Personal Standards were associated with higher well-being and lower stress, (2) Concern over Mistakes and Doubts about Actions were related to lower well-being and higher stress, (3) Parental Expectations and Parental Criticism were not correlated with stress, and (4) Parental Criticism was associated with lower well-being. In the multi-predictor mediation model, with five perfectionism traits as predictors, perceived stress was a significant mediator between several perfectionism traits (i.e., Personal Standards, Concern over Mistakes, and Doubts about Actions) and well-being. Overall, Personal Standards, Concern over Mistakes, and Doubts about Actions seem to be parsimonious psychological targets, with Personal Standards expressing mental health-promoting effects, whereas Parental Expectations and Parental Criticism seem to be less important psychological targets.
Older Adults Affected by Abuse–What about Their Mental Health and Social Participation? A Mixed Methods Study
Authors: Salminen-Tuomaala Mari , Tiainen Juha , Paavilainen Eija
Published: February 2024

The purpose of the study was to describe what types of abuse of older adults the healthcare providers in hospital emergency departments are currently able to identify. The study aimed at producing new information about the identification of abuse to enable the development of staff skills in the identification of abuse and in optimal interventions. The study is the first on the topic from the perspective of hospital emergency staff in Finland. The 76 participants represent 5 hospitals. The results are based on a statistical analysis of quantitative questions and on an inductive content analysis of participant experiences of suspected abuse. The inductive content analysis revealed that older adults subjected to abuse have narrowed social networks and many of them surrender to loneliness. Based on the relevant literature, the study discusses how the formal and informal social participation and mental health of this group of people could be promoted. Given the current limited resources, it is proposed that the idea of social prescribing might be applied informally, with help of a volunteer link person. Any interventions should be based on the older adults’ conceptions of what is meaningful to them.
A Simple Approach to Prepare a C3N4/MoO3 Heterojunction with Improved Photocatalytic Performance for the Degradation of Methylparaben
Authors: Imgharn Abdelaziz , Sun Tingwei , Nicolle Jimmy , Naciri Yassine , Hsini Abdelghani , Albourine Abdallah , Ania Conchi
Published: February 2024

The adequate optical properties, low cost, and thermal stability of graphitic carbon nitride and molybdenum oxide make them both promising materials for photocatalytic applications. However, they both suffer from strong recombination of their photogenerated charge carriers. Therefore, searching for strategies that enable an efficient charge carrier separation is desirable for improving the photocatalytic performance of both semiconductors. In this work, we have synthesized a g-C3N4/MoO3 heterojunction by a facile solid dispersion approach to the pristine semiconductors that allows a uniform dispersion of the two phases in the heterojunction. The resulting hybrid photocatalyst exhibits light absorption features similar to pristine g-C3N4 and presents an improved separation of the photogenerated charge carriers, likely through a Z-scheme between both semiconductor phases, as inferred by photoelectrochemical measurements. As a result, the g-C3N4/MoO3 heterojunction showed better photocatalytic activity than the individual semiconductors and good cycling stability for the degradation of methylparaben and its reaction intermediates. We drew these conclusions based on total organic carbon (TOC) measurements.
Mitochondria in the Central Nervous System in Health and Disease: The Puzzle of the Therapeutic Potential of Mitochondrial Transplantation
Authors: Tripathi Kuldeep , Ben-Shachar Dorit
Published: February 2024

Mitochondria, the energy suppliers of the cells, play a central role in a variety of cellular processes essential for survival or leading to cell death. Consequently, mitochondrial dysfunction is implicated in numerous general and CNS disorders. The clinical manifestations of mitochondrial dysfunction include metabolic disorders, dysfunction of the immune system, tumorigenesis, and neuronal and behavioral abnormalities. In this review, we focus on the mitochondrial role in the CNS, which has unique characteristics and is therefore highly dependent on the mitochondria. First, we review the role of mitochondria in neuronal development, synaptogenesis, plasticity, and behavior as well as their adaptation to the intricate connections between the different cell types in the brain. Then, we review the sparse knowledge of the mechanisms of exogenous mitochondrial uptake and describe attempts to determine their half-life and transplantation long-term effects on neuronal sprouting, cellular proteome, and behavior. We further discuss the potential of mitochondrial transplantation to serve as a tool to study the causal link between mitochondria and neuronal activity and behavior. Next, we describe mitochondrial transplantation’s therapeutic potential in various CNS disorders. Finally, we discuss the basic and reverse—translation challenges of this approach that currently hinder the clinical use of mitochondrial transplantation.
The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice: An Ex Vivo and In Vivo Investigation
Authors: Tejedor Sandra , Wågberg Maria , Correia Cláudia , Åvall Karin , Hölttä Mikko , Hultin Leif , Lerche Michael , Davies Nigel , Bergenhem Nils , Snijder Arjan , Marlow Tom , Dönnes Pierre , Fritsche-Danielson Regina , Synnergren Jane , Jennbacken Karin , Hansson Kenny
Published: February 2024

Background: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1). Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination. Results: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth. Conclusion: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.
Nobiletin Ameliorates Aging of Chicken Ovarian Prehierarchical Follicles by Suppressing Oxidative Stress and Promoting Autophagy
Authors: Bai Jingchun , Wang Xinyu , Chen Yiqiu , Yuan Qiongyu , Yang Zhaoyu , Mi Yuling , Zhang Caiqiao
Published: February 2024

With the increase in the age of laying chickens, the aging of follicles is accelerated, and the reproductive ability is decreased. Increased oxidative stress and mitochondrial malfunction are indispensable causes of ovarian aging. In this study, the physiological condition of prehierarchical small white follicles (SWFs) was compared between D280 high-producing chickens and D580 aging chickens, and the effect of a plant-derived flavonoid nobiletin (Nob), a natural antioxidant, on senescence of SWFs granulosa cells (SWF-GCs) was investigated. The results showed that Nob treatment activated cell autophagy by activating the AMP-activated protein kinase (AMPK) and Sirtuin-1 (SIRT1) pathways in D-galactose (D-gal)-generated senescent SWF-GCs, restoring the expression of proliferation-related mRNAs and proteins. In addition, the expression of inflammation-related protein NF-κB was significantly enhanced in aging GCs that were induced by D-gal. Nob supplementation significantly increased the antioxidant capacity and decreased the expression of several genes associated with cell apoptosis. Furthermore, Nob promoted activation of PINK1 and Parkin pathways for mitophagy and alleviated mitochondrial edema. Either the AMPK inhibitor dorsomorphin (Compound C) or SIRT1 inhibitor selisistat (EX-527) attenuated the effect of Nob on mitophagy. The protective effect of Nob on natural aging, GC proliferation, and elimination of the beneficial impact on energy regulation of naturally aging ovaries was diminished by inhibition of Nob-mediated autophagy. These data suggest that Nob treatment increases the expression of mitophagy-related proteins (PINK1 and Parkin) via the AMPK/SIRT1 pathways to prevent ovarian aging in the laying chickens.
Gene Signature of Regulatory T Cells Isolated from Children with Selective IgA Deficiency and Common Variable Immunodeficiency
Authors: Rutkowska-Zapała Magdalena , Grabowska-Gurgul Agnieszka , Lenart Marzena , Szaflarska Anna , Kluczewska Anna , Mach-Tomalska Monika , Baj-Krzyworzeka Monika , Siedlar Maciej
Published: February 2024

Selective IgA deficiency (SIgAD) is the most common form and common variable immunodeficiency (CVID) is the most symptomatic form of predominant antibody deficiency. Despite differences in the clinical picture, a similar genetic background is suggested. A common feature of both disorders is the occurrence of autoimmune conditions. Regulatory T cells (Tregs) are the major immune cell type that maintains autoimmune tolerance. As the different types of abnormalities of Treg cells have been associated with autoimmune disorders in primary immunodeficiency (PID) patients, in our study we aimed to analyze the gene expression profiles of Treg cells in CVID and SIgAD patients compared to age-matched healthy controls. The transcriptome-wide gene profiling was performed by microarray technology. As a result, we analyzed and visualized gene expression patterns of isolated population of Treg cells. We showed the differences at the gene level between patients with and without autoimmunizations. Our findings suggest that the gene signatures of Treg cells isolated from SIgAD and CVID patients differ from age-matched healthy controls and from each other, presenting transcriptional profiles enriched in innate immune or Th response, respectively. The occurrence of autoimmunity in both types of PID is associated with down-regulation of class I IFNs signaling pathways. In summary, our findings improve our understanding of Treg dysfunctions in patients with common PIDs and associated autoimmunity.