bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes derived from human adipose mesenchymal stem cells inhibits fibrosis and treats oral submucous fibrosis via the miR-181a-5p/Smad2 axis.
Authors: Shao Zifei , Xu Jinhao , Xu Xiaoyang , Wang Xiang , Zhou Yuxi , Li Yiyang , Li Kun 
Published: February 2023

Abstract
Background: Oral submucous fibrosis (OSF) is a chronic disease with carcinogenic tendency that poses a non-negligible threat to human health. Exosomes derived from human adipose mesenchymal stem cells (ADSC-Exo) reduces visceral and cutaneous fibroses, but theirrole in OSF has received little attention. The aim of this studywas to investigate the effects of ADSC-Exo on OSFand elucidate the mechanism.
Methods: In brief, ADSCs were extracted from adipose tissues and subjected to flow cytometry and induction culture. Fibroblasts were isolated from human buccal mucosa and subjected to immunofluorescence. Myofibroblasts were obtained from fibroblasts induced by arecoline and identified. Immunofluorescence assay confirmed that myofibroblasts could take up ADSC-Exo. The effects of ADSC-Exo on the proliferative and migratory capacities of myofibroblasts were examined using the Cell Counting Kit-8 and scratch assay. Real-time quantitative polymerase chain reaction (qPCR) was performed to evaluate mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad7, collagen type 1 (Col1),Col3, alpha smooth muscle actin (α-SMA), fibronectin, and vimentin. Western blotting was performed to detect phospho (p)-Smad2, Smad2, p-Smad2/3, Smad2/3, Smad7, Col1, Col3, α-SMA, fibronectin, and vimentin. Furthermore, the dual-luciferase reporter assay was performed to prove that miR-181a-5p in ADSC-Exo directly inhibited the expression of Smad2mRNA to regulate the transforming growth factor beta (TGF-β)pathway. We also performed qPCR and western blotting to verify the results.
Results: ADSC-Exo could promote the proliferation and migration of myofibroblasts, reduce the expressions of p-smad2, Smad2, p-smad2/3, Smad2/3, Col1, αSMA, fibronectin, and vimentin and elevated the levels of Smad7 and Col3. In addition, miR-181a-5p was highly expressed in ADSC-Exo and bound to the 3'-untranslated region of Smad2. ADSC-Exo enriched with miR-181a-5p reduced collagen production in myofibroblasts and modulated the TGF-β pathway.
Conclusions: ADSC-Exo promoted the proliferative and migratory capacities of myofibroblasts and inhibited collagen deposition and trans-differentiation of myofibroblasts in vitro. miR-181a-5p in exosomes targets Smad2 to regulate the TGF-β pathway in myofibroblasts. ADSC-Exo perform antifibrotic actions through the miR-181a-5p/Smad2 axis and may be a promising clinical treatment for OSF.
Trial registration: Not applicable
Predicting ‘Brainage’ in the Developmental Period using Structural MRI, Morphometric Similarity, and Machine Learning
Authors: Griffiths-King Daniel J. , Wood Amanda G. , Novak Jan 
Published: February 2023

Abstract
Brain development is regularly studied using structural MRI. Recently, studies have used a combination of statistical learning and large-scale imaging databases of healthy-children to predict an individual’s age from structural MRI. This data-driven, ‘brainage’ typically differs from the subjects chronological age, with this difference a potential measure of individual difference. Few studies have leveraged higher-order or connectomic representations of structural MRI data for this brainage approach. We leveraged morphometric similarity as a network-level approach to structural MRI to generate predictive models of age. We benchmarked these novel brain-age approaches using morphometric similarity against more typical, single feature (i.e. cortical thickness) approaches. We showed that these novel methods did not outperform cortical thickness or cortical volume measures. All models were significantly biased by age, but robust to motion confounds. The main results show that, whilst morphometric similarity mapping may be a novel way to leverage additional information from a T1-weighted structural MRI beyond individual features, in the context of a brain-age framework, morphometric similarity does not explain more variance than individual structural features. Morphometric similarity as a network-level approach to structural MRI may be poorly positioned to study individual differences in brain development in healthy individuals.
Genetic Determinants of Vitamin D Deficiency in the Middle Eastern Qatari Population by a Genome-Wide Association Study
Authors: Nemer Georges , Hindi Nagham , Al-Sarraj Yasser , Umlai Umm-Kulthum , Suhre Karsten , Albagha Omar 
Published: February 2023

Abstract
Epidemiological studies have revealed that Middle Eastern countries have the highest incidence of Vitamin D deficiency with severe complications. However, the impact of Vitamin D polymorphisms and the performance of polygenic models have been studied primarily in European with little knowledge of the Middle Eastern. Here, we conducted the first genome-wide association study to identify genetic determinants of Vitamin D levels in Middle Eastern populations using a whole genome sequencing approach in 6,047 discovery subjects. We discovered a novel variant, rs2298850 (P-value = 1.71 × 10-08, effect size (Beta) = -0.1285), in a region of a known locus for the group-specific component gene (GC). We also confirmed the association of Vitamin D to several variants, including rs11723621 (P-value = 1.93 × 10-08, Beta = -0.12574) and rs4588 (P-value = 8.06 × 10-08, Beta = -0.1188) in the GC. A GWAS meta-analysis combining results from our Qatari cohort and previous European data identified novel variants in known loci, including rs67609747 and rs1945603 on chromosome 11. We found a moderately low heritability of Vitamin D (estimated at 18%) compared to Europeans. Finally, a low predictive performance of European ancestry-derived polygenic scores was observed when applied to the Qatari individuals. These results emphasize the diversity in the genetic architecture and its impact on preventive and precision medicine across different populations. Our findings offer novel perspectives on the physiological mechanisms and genetic factors contributing to the variation of Vitamin D levels in the Qatari population.
Depressive symptoms as a predictor of 5-year subsequent work nonparticipation due to long-term sickness absence, unemployment and early retirement in a cohort of 2,413 employees in Germany
Authors: Rose Uwe , Kersten Norbert , Pattloch Dagmar , Burr Hermann 
Published: February 2023

Abstract
Background: We examined the impact of depressive symptoms on events – and duration thereof – of work nonparticipation (long-term sickness absence, unemployment, early retirement).
Methods: We used a 5-year cohort of the Study on Mental Health at Work (S-MGA) based on a random sample of employees subject to social contributions aged 31–60 years in 2012 (N =2413). Depressive symptoms were assessed at baseline through questionnaires, while employment history was recorded in follow-up interviews. Effects of depressive symptoms on work nonparticipation were examined in two-part models, with events analysed by logistic regressions and their duration by generalized linear models (GLMs).
Results: Medium to severe depressive symptoms increased the risk of events of work nonparticipation (males OR=3.22, 95% CI=1.90–5.45; females OR: 1.92, 1.29–2.87), particularly events of long-term sickness absence in both genders and events of unemployment among males. Mild depressive symptoms increased the risk of events of work nonparticipation (males OR=1.59, 1.19–2.11; females OR = 1.42, 1.10–1.84). Among those experiencing one or more events, the duration of total work nonparticipation was twice as high among males [EXP(B) =2.06; 95% CI: 1.53–2.78] and about one third higher [EXP(B) =1.38; 95% CI: 1.05–1.83] among females with medium to severe depressive symptoms.
Conclusions: The present study takes into account the occurrence of work nonparticipation but also its duration, which are both critical for assessing societal consequences of depressive symptoms. It is important to consider mild depressive symptoms and examine several types of work nonparticipation.
FDS_2D: Rethinking magnitude-phase features for DeepFake Detection
Authors: Yang Gaoming , Wei AnXing , Fang Xianjin , Zhang Ji 
Published: February 2023

Abstract
The detection method based on the frequency domain is one of the essential methods to reduce the harm of forged information. This method mostly uses spectra as clues to identify fake content. However, the current methods tend to use only one of the magnitude and phase spectra for learning. In this paper, we notice that the magnitude and phase spectrum contain different image information. Only one spectrum is easily disturbed by noise, and the robustness of the method is difficult to guarantee. Therefore, we propose the Frequency Domain Separable DeepFake Detection (FDS_2D) to use a multi-branch network to obtain features in different frequency spectra. In FDS_2D, the spectral information is divided into three categories: the magnitude spectrum, the phase spectrum, and the relationship between the two spectra. According to their characteristics, we design independent methods for feature extraction from them. Moreover, to improve the utilization efficiency of multi-features, we propose a multi-input multi-output attention mechanism for information interaction between branches. The experimental results show that each part of FDS_2D effectively extracts and applies spectral information; The comprehensive performance of our model is verified on FaceForensic++, CelebDF, and DFDC. It proves that the ability of FDS_2D to detect DeepFake is not inferior to existing models.
A Calorimetric Study of Phase Behavior of the Methane-Propane-Nonane System
Authors: Buleiko V. M. , Buleiko D. V. 
Published: February 2023

Abstract
The recent results of the accurate calorimetric measurements of phase equilibria internary mixtures of methane, propane, and nonane have been presented. The heat capacity, internal energy, pressure, and temperature derivative of pressure at constant volume were measured in the range 160 – 340 K, up to 30 MPa. The phase transitions were localized by the finite discontinuities in temperature derivatives of the thermodynamic potentials. The phase diagrams for ternary mixtures of methane, propane, and nonane have been plotted based on the experimental data. These data are supplemented with the earlier measurements of two ternary hydrocarbon systems for the low concentration of octane and decane. Our investigations show that hydrocarbon mixture for the low concentration of nonane as well as the hydrocarbon mixtures for the low concentration of octane and decane split into two phases, the nonane-lean macrophase and the microphase formed by nonane. Besides, nonane provokes a split of the liquid part of a ternary mixture into two liquid phases, the nonane-rich phase and the nonane-lean phase.
Inhibition of multipotent ILC2s by JAK3 inhibitor attenuates steroid-resistant asthma
Authors: Kim Hye-Young , Kim Jihyun , Ham Jongho , Kang Hye Ryun , Bae Yong-Soo , Kim Tasesoo 
Published: February 2023

Abstract
The standard treatment for allergic-airway inflammation, which is the dominant asthma endotype, is a steroid. However, steroid-refractory asthma is a significant problem. Innate-lymphoid cells (ILCs) produce type-2 cytokines as Th2 cells and play critical roles in asthma pathogenesis. Limited evidence from the asthma-mouse models and human studies suggests that ILC2s may participate in steroid-resistant asthma. Here, we showed that lung ILC2s, but not Th2 cells, can develop steroid resistance that maintains their survival, cytokine production, and pathogenic activities during steroid treatment. Such steroid-resistant ILC2s are associated with the presence of multiple ILC2-stimulating cytokines and the emergence of multipotent IL-5+IL-13+IL-17A+ ILC2s, and the Janus-kinase (JAK) 3/signal-transducer-and-activator-of-transcription (STAT) 3,5, and 6 pathway participates in the acquisition of steroid-resistant ILC2s. JAK3-inhibitor treatment significantly reduced the survival, proliferation, and cytokine production of multipotent ILC2s in vitro ameliorated ILC2-dependent Alternaria-induced asthma. Moreover, JAK3-inhibitor combined with a steroid strongly inhibited steroid-resistant asthma. Therefore, sustained asthmatic conditions may induce multipotent ILC2s that promote steroid-resistant asthma, and combining JAK3-inhibitor with steroid may be a treatment option for steroid-refractory asthma.
Improving recycling sorting behaviour with human eye nudges
Authors: Lotti Lorenzo , Barile Lory , Manfredi Giovanni 
Published: February 2023

Abstract
This paper aims to test whether visual nudges help improving attention towards existing instructions to increase waste sorting accuracy. The study was conducted in a quasi-experimental setting over a period of 8 weeks in two buildings of a large UK university campus. Two treatments were tested against a control group: one considered the impact of visual nudges in the form of human eyes on recycling behaviour; the other one combined human eye with pre-existing sorting instructions. Results show that the combination of visual and information nudges decreased sorting errors by 7 percentage points. By contrast, visual nudges alone increased sorting error by 4.5 percentage points. These findings prove that, when combined, information and a visual nudge are cost-effective tools to improve sorting behaviour with strong efficacy, bringing new evidence to experiments based on neuroscientific theories.
Behavioural Economics, Recycling, Neuroscience, Nudges
Effects of cardiac glycoside digoxin on dendritic spines and motor learning performance in mice
Authors: Hashimoto Junichi , Fujita Erika , Tanimoto Keisuke , Kondo Suzuo , Matsumoto-Miyai Kazumasa 
Published: February 2023

Abstract
Synapse formation following the generation of postsynaptic dendritic spines is essential for motor learning and functional recovery after brain injury. The C -terminal fragment of agrin cleaved by neurotrypsin induces dendritic spine formation in the adult hippocampus. Since the α3 subunit of sodium-potassium ATPase (Na/K ATPase) is a neuronal receptor for agrin in the central nervous system, cardiac glycosides might facilitate dendritic spine formation and subsequent improvements in learning. This study investigated the effects of the cardiac glycoside digoxin on dendritic spine turnover and learning performance in mice. Golgi-Cox staining revealed that intraperitoneal injection of digoxin less than its IC50 in brain significantly increased the density of long spines (≥2 µm) in cerebral cortex and hippocampus in wild-type mice and neurotrypsin-knockout (NT-KO) mice showing impairment of activity-dependent spine formation. Whereas motor learning performance of NT-KO mice showed significantly lower than control wild-type mice under the control condition, low dose of digoxin enhanced performance to a similar degree in both strains. In NT-KO mice, lower doses of digoxin equivalent to clinical doses also significantly improved performance. These data suggest that lower doses of digoxin could modify dendritic spine formation or recycling and facilitate motor learning in compensation for the neurotrypsin-agrin pathway.
Is it up there? - an MR spectroscopy study of frontal lobes and non-primary-auditory temporal areas in subjective bilateral and unilateral tinnitus
Authors: Wójcik Joanna , Kochański Bartosz , Cieśla Katarzyna , Lewandowska Monika , Karpiesz Lucyna , Niedziałek Iwona , Raj-Koziak Danuta , Skarżyński Piotr Henryk , Wolak Tomasz 
Published: February 2023

Abstract
Subjective tinnitus is a prevalent, though heterogeneous, condition whose pathophysiological mechanisms are still under investigation. Based on animal models, changes in neurotransmission along the auditory pathway have been suggested as co-occurring with tinnitus. It has not, however, been studied whether such effects can also be found in other sites beyond the auditory cortex. Our MR spectroscopy study is the first one to measure composite levels of glutamate and glutamine (Glx; and other central nervous system metabolites) in bilateral medial frontal and non-primary auditory temporal brain areas in tinnitus. We studied two groups of participants with unilateral and bilateral tinnitus and a control group without tinnitus, all three with a similar hearing profile. We found no metabolite level changes as related to tinnitus status in neither region of interest, except for a tendency of an increased concentration of Glx in the left frontal lobe in people with bilateral vs unilateral tinnitus. Slightly elevated depressive and anxiety symptoms are also shown in participants with tinnitus, as compared to healthy individuals, with the bilateral tinnitus group marginally more affected by the condition. We discuss the null effect in the temporal lobes, as well as the role of frontal brain areas in chronic tinnitus, with respect to hearing loss, attention mechanisms and psychological well-being. We furthermore elaborate on the design-related and technical obstacles when using MR spectroscopy to elucidate the role of neurometabolites in tinnitus.
Influence of species invasion, seasonality, and connectivity on fish functional and taxonomic beta-diversity in a Neotropical floodplain
Authors: Aleixo Matheus Henrique Ferreira , Florêncio Fernanda Moreira , Lansac-Toha Fernando Miranda , Quirino Barbara Angélio , Fugi Rosemara 
Published: February 2023

Abstract
Studies that combine functional and taxonomic beta-diversity are essential for explaining some ecological processes, including the process of species invasion. We evaluated whether environmental factors (such as lake connectivity, subsystem and hydrological period) and biological factors (occurrence and richness of non-native and native fish species) affect beta-diversity components (total, richness and replacement) of fish communities living in the Upper Paraná River floodplain in Brazil. For this, a distance-based redundancy analysis (dbRDA) was performed for both taxonomic (BDtax) and functional (BDfunc) approaches. In order to see which variables influence the local contribution to BDtax and BDfunc (LCBD), mixed effects regression models were fitted. Our results indicated a significant influence of environmental and biological factors on the taxonomic patterns of beta diversity and functional beta-diversity of fish between lakes. Environmental factors influenced the replacement component for both taxonomic and functional diversity, while biotic factors (occurrence and richness of non-native species) influenced the richness component. The richness of native and non-native species, the occurrence of non-native species and hidrological period showed significant influence on LCBD values. Although in our study the occurrence and richness of non-native species are related to beta-diversity, in the long term, these species can cause a decrease in functional and taxonomic beta-diversity, altering the ecological multifunctionality of the environment. Our study emphasizes that both changes in environmental factors and species diversity (such as the introduction of a non-native species) can impact the beta-diversity of Neotropical fish.
FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators
Authors: Roopnarine Osha , Yuen Samantha L. , Thompson Andrew R. , Roelike Lauren N. , Rebbeck Robyn T. , Bidwell Phillip A. , Aldrich Courtney C. , Cornea Razvan L. , Thomas David D. 
Published: February 2023

Abstract
We have used FRET-based biosensors in live cells, in a robust high-throughput screening (HTS) platform, to identify small-molecules that alter the structure and activity of the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a). Our primary aim is to discover drug-like small-molecule activators that improve SERCA’s function for the treatment of heart failure. We have previously demonstrated the use of an intramolecular FRET biosensor, based on human SERCA2a, by screening a small validation library using novel microplate readers that can detect the fluorescence lifetime or emission spectrum with high speed, precision, and resolution. Here we report results from a 50,000-compound screen using the same biosensor, with hit compounds functionally evaluated using Ca2+-ATPase and Ca2+-transport assays. We focused on 18 hit compounds, from which we identified eight structurally unique compounds and four compound classes as SERCA modulators, approximately half of which are activators and half are inhibitors. While both activators and inhibitors have therapeutic potential, the activators establish the basis for future testing in heart disease models and lead development, toward pharmaceutical therapy for heart failure.
Essential oil yield and compositions of Dracocephalum moldavica L. in intercropping with fenugreek and inoculation with mycorrhizal fungi and bacteria
Authors: Chelan Zahra Amiriyan , Amini Rouhollah , Nasab Adel Dabbagh Mohammadi 
Published: February 2023

Abstract
Intercropping is one of the most important components of sustainable production of agricultural products. The effects of chemical fertilizer (CF), arbuscular mycorrhizal fungi (AMF) and the combination of AMF and bacteria (AMF + B) in sole Moldavian balm (Mb) (Dracocephalum moldavica L.) and intercropping with fenugreek (F) (Trigonella foenum-graecum L.), was studied on growth characteristics, essential oil yield and compositions of Moldavian balm. The highest dry herbage yield (6132 kg ha− 1) was obtained in Mb:F(4:2) cropping pattern and CF treatment. The highest values of essential oil content were observed in the Mb:F (2:2) cropping pattern (0.261%) and AMF + B treatment (0.259%). After sole-Moldavian balm, the highest essential oil yield (15.28 kg ha− 1) was obtained in Mb:F (4:2) cropping pattern and AMF + B treatment. Geranial, geranyl acetate, geraniol, neral, and nerol were the main chemical constituents of essential oil. In CF and AMF + B treatments the geranial contents in intercropping patterns of Mb:F (1:1), (2:2) and (100:50), were greater than that of sole-Moldavian balm. The highest LERT values were observed in Mb:F (100:50) cropping pattern in 2021 (1.70 and 1.63 for CF and AMF + B treatments). Generally, it can be concluded that Mb:F (100:50) intercropping and use of AMF + B bio-fertilizer could be recommended to medicinal plant growers in sustainable production systems.