bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of secretome-based strategies to improve cell culture protocols in tissue engineering
Authors: Cases-Perera O. , Blanco-Elices C. , Chato-Astrain J. , Miranda-Fernández C. , Campos F. , Crespo P. V. , Sánchez-Montesinos I. , Alaminos M. , Martín-Piedra M. A. , Garzón I. 
Published: June 2022

AbstractAdvances in skin tissue engineering have promoted the development of artificial skin substitutes to treat large burns and other major skin loss conditions. However, one of the main drawbacks to bioengineered skin is the need to obtain a large amount of viable epithelial cells in short periods of time, making the skin biofabrication process challenging and slow. Enhancing skin epithelial cell cultures by using mesenchymal stem cells secretome can favor the scalability of manufacturing processes for bioengineered skin. The effects of three different types of secretome derived from human mesenchymal stem cells, e.g. hADSC-s (adipose cells), hDPSC-s (dental pulp) and hWJSC-s (umbilical cord), were evaluated on cultured skin epithelial cells during 24, 48, 72 and 120 h to determine the potential of this product to enhance cell proliferation and improve biofabrication strategies for tissue engineering. Then, secretomes were applied in vivo in preliminary analyses carried out on Wistar rats. Results showed that the use of secretomes derived from mesenchymal stem cells enhanced currently available cell culture protocols. Secretome was associated with increased viability, proliferation and migration of human skin epithelial cells, with hDPSC-s and hWJSC-s yielding greater inductive effects than hADSC-s. Animals treated with hWJSC-s and especially, hDPSC-s tended to show enhanced wound healing in vivo with no detectable side effects. Mesenchymal stem cells derived secretomes could be considered as a promising approach to cell-free therapy able to improve skin wound healing and regeneration.
Predisposition of HLA-DRB1*04:01/*15 heterozygous genotypes to Japanese mixed connective tissue disease
Authors: Oka Shomi , Higuchi Takashi , Furukawa Hiroshi , Shimada Kota , Hashimoto Atsushi , Komiya Akiko , Matsui Toshihiro , Fukui Naoshi , Suematsu Eiichi , Ohno Shigeru , Kono Hajime , Katayama Masao , Nagaoka Shouhei , Migita Kiyoshi , Tohma Shigeto 
Published: June 2022

AbstractMixed connective tissue disease (MCTD) is a rare systemic autoimmune disease characterized by the production of anti-U1 ribonucleoprotein antibodies and systemic symptoms similar to those of some other autoimmune diseases. HLA-DRB1 polymorphisms are important genetic risk factors for MCTD, but precise associations of DRB1 genotypes with MCTD have not been reported in Japanese people. Genotyping of HLA-DRB1 and -DQB1 was performed in Japanese MCTD patients (n = 116) and controls (n = 413). Associations of specific allele carriers and genotype frequencies with MCTD were analyzed.The following alleles were found to be associated with predisposition to MCTD: HLA-DRB1*04:01 (P = 8.66 × 10–6, Pc = 0.0003, odds ratio [OR] 7.96, 95% confidence interval [CI] 3.13‒20.24) and DRB1*09:01 (P = 0.0189, Pc = 0.5468, OR 1.73, 95% CI 1.12‒2.67). In contrast, the carrier frequency of the DRB1*13:02 allele (P = 0.0032, Pc = 0.0929, OR 0.28, 95% CI 0.11‒0.72) was lower in MCTD patients than in controls. The frequencies of heterozygosity for HLA-DRB1*04:01/*15 (P = 1.88 × 10–7, OR 81.54, 95% CI 4.74‒1402.63) and DRB1*09:01/*15 (P = 0.0061, OR 2.94, 95% CI 1.38‒6.25) were also higher in MCTD patients. Haplotype and logistic regression analyses suggested a predisposing role for HLA-DRB1*04:01, DQB1*03:03, and a protective role for DRB1*13:02. Increased frequencies of HLA-DRB1*04:01/*15 and DRB1*09:01/*15 heterozygous genotypes were found in Japanese MCTD patients.
Photocatalytic degradation activity of goji berry extract synthesized silver-loaded mesoporous zinc oxide (Ag@ZnO) nanocomposites under simulated solar light irradiation
Authors: Sharwani Abdulrahman Ahmed , Narayanan Kannan Badri , Khan Mohammad Ehtisham , Han Sung Soo 
Published: June 2022

AbstractDifferent approaches have been developed for the synthesis of various nanostructured materials with unique morphologies. This study demonstrated the photocatalytic and antimicrobial abilities of silver-loaded zinc oxide nanocomposites (Ag@ZnO NCs). Initially, ZnO with a unique mesoporous ellipsoidal morphology in the size range of 0.59 ± 0.11 × 0.33 ± 0.09 µm (length × width) was synthesized using aqueous precipitation in a mild hydrothermal condition (80 °C) with the aqueous fruit extract of goji berry (GB) (as an additive) and calcined in air at 200 °C/2 h and 250 °C/3 h. Powder X-ray diffraction (XRD) revealed the formation of a hexagonal phase of the wurtzite (WZ) structure. The average crystallite size of ZnO was 23.74 ± 4.9 nm as calculated using Debye–Scherrer’s equation. It also possesses higher thermal stability with the surface area, pore volume, and pore size of 11.77 m2/g, 0.027 cm3/g, and 9.52 nm, respectively. Furthermore, different mesoporous Ag@ZnO NCs loaded with face-centered cubic (fcc) silver nanoparticles (Ag NPs) in the range of 90–160 nm were synthesized by GB extract as a reducing and capping agent on the surface of ZnO after calcination in air. The immobilization of Ag NPs was confirmed by XRD, X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), FE-transmission electron microscopy (FE-TEM), and energy-dispersive X-ray spectroscopy (EDS). It was found that Ag0.2@ZnO NC (0.2 wt% of Ag) showed excellent photocatalytic degradation of both methylene blue (MB) (cationic) and congo red (CR) (anionic) dyes under simulated solar irradiation. The photocatalytic degradation of 99.3 ± 0.35% MB and 98.5 ± 1.3% CR occurred in 90 and 55 min, respectively, at room temperature by Ag0.2@ZnO NC. Besides, these NCs also showed broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria. The mechanistic concept of generating reactive oxygen species (ROS) by electron and hole charge (e‾/h+) carriers seems to be responsible for the photocatalytic degradation of commercial dyes and antibacterial activities by Ag@ZnO NCs. Thus, these silver-loaded mesoporous ellipsoidal ZnO NCs are promising candidates as photocatalysts for industrial/wastewater treatment as well as in antimicrobial therapeutics.
Coronilla juncea, a native candidate for phytostabilization of potentially toxic elements and restoration of Mediterranean soils
Authors: Heckenroth Alma , Prudent Pascale , Folzer Hélène , Rabier Jacques , Criquet Stéven , Saatkamp Arne , Salducci Marie-Dominique , Vassalo Laurent , Laffont-Schwob Isabelle 
Published: June 2022

AbstractSoil contamination pattern due to industrial activities often leads to high concentrations of potentially toxic elements (PTE) decreasing with depth. This spatial heterogeneity of the soil contamination may have significant consequences on the soil properties and soil living communities. We evaluated the effects of both surface and solum soil contamination heterogeneity on Coronilla juncea L. (Fabaceae) functional traits in field conditions and the phytostabilization potential of this species. Plant and soil samples were collected on 3 sites along a PTE contamination gradient. The correlations between PTE concentration in plant and soil samples at 2 depths, physico-chemical properties of soil, plant biomass and soil microbial activity were tested. Field measurements highlight a decreasing PTE concentration with soil depth in addition to an important surface heterogeneity of As, Cu, Pb, Sb and Zn soil concentrations. Root PTE concentrations in C. juncea did not follow soil PTE concentrations. Concentrations of PTE in the root parts were higher than those of the aerial parts. Low PTE translocation and root symbioses with microorganisms suggest that this native plant species may play a role as engineer species with positive implications for the phytostabilization of Mediterranean PTE contaminated soils and their ecological restoration.
Asymmetry between right and left optical coherence tomography images identified using convolutional neural networks
Authors: Kang Tae Seen , Lee Woohyuk , Park Shin Hyeong , Han Yong Seop 
Published: June 2022

AbstractIn a previous study, we identified biocular asymmetries in fundus photographs, and macula was discriminative area to distinguish left and right fundus images with > 99.9% accuracy. The purposes of this study were to investigate whether optical coherence tomography (OCT) images of the left and right eyes could be discriminated by convolutional neural networks (CNNs) and to support the previous result. We used a total of 129,546 OCT images. CNNs identified right and left horizontal images with high accuracy (99.50%). Even after flipping the left images, all of the CNNs were capable of discriminating them (DenseNet121: 90.33%, ResNet50: 88.20%, VGG19: 92.68%). The classification accuracy results were similar for the right and left flipped images (90.24% vs. 90.33%, respectively; p = 0.756). The CNNs also differentiated right and left vertical images (86.57%). In all cases, the discriminatory ability of the CNNs yielded a significant p value (< 0.001). However, the CNNs could not well-discriminate right horizontal images (50.82%, p = 0.548). There was a significant difference in identification accuracy between right and left horizontal and vertical OCT images and between flipped and non-flipped images. As this could result in bias in machine learning, care should be taken when flipping images.
Development of a robust radiomic biomarker of progression-free survival in advanced non-small cell lung cancer patients treated with first-line immunotherapy
Authors: Singh Apurva , Horng Hannah , Roshkovan Leonid , Weeks Joanna K. , Hershman Michelle , Noël Peter , Luna José Marcio , Cohen Eric A. , Pantalone Lauren , Shinohara Russell T. , Bauml Joshua M. , Thompson Jeffrey C. , Aggarwal Charu , Carpenter Erica L. , Katz Sharyn I. , Kontos Despina 
Published: June 2022

AbstractWe aim to determine the feasibility of a novel radiomic biomarker that can integrate with other established clinical prognostic factors to predict progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) undergoing first-line immunotherapy. Our study includes 107 patients with stage 4 NSCLC treated with pembrolizumab-based therapy (monotherapy: 30%, combination chemotherapy: 70%). The ITK-SNAP software was used for 3D tumor volume segmentation from pre-therapy CT scans. Radiomic features (n = 102) were extracted using the CaPTk software. Impact of heterogeneity introduced by image physical dimensions (voxel spacing parameters) and acquisition parameters (contrast enhancement and CT reconstruction kernel) was mitigated by resampling the images to the minimum voxel spacing parameters and harmonization by a nested ComBat technique. This technique was initialized with radiomic features, clinical factors of age, sex, race, PD-L1 expression, ECOG status, body mass index (BMI), smoking status, recurrence event and months of progression-free survival, and image acquisition parameters as batch variables. Two phenotypes were identified using unsupervised hierarchical clustering of harmonized features. Prognostic factors, including PDL1 expression, ECOG status, BMI and smoking status, were combined with radiomic phenotypes in Cox regression models of PFS and Kaplan Meier (KM) curve-fitting. Cox model based on clinical factors had a c-statistic of 0.57, which increased to 0.63 upon addition of phenotypes derived from harmonized features. There were statistically significant differences in survival outcomes stratified by clinical covariates, as measured by the log-rank test (p = 0.034), which improved upon addition of phenotypes (p = 0.00022). We found that mitigation of heterogeneity by image resampling and nested ComBat harmonization improves prognostic value of phenotypes, resulting in better prediction of PFS when added to other prognostic variables.
Validation of the forced swim test in Drosophila, and its use to demonstrate psilocybin has long-lasting antidepressant-like effects in flies
Authors: Hibicke M. , Nichols C. D. 
Published: June 2022

AbstractPsilocybin has been shown to be a powerful, long-lasting antidepressant in human clinical trials and in rodent models. Although rodents have commonly been used to model psychiatric disorders, Drosophila have neurotransmitter systems similar to mammals and many comparable brain structures involved in similar behaviors. The forced swim test (FST), which has been used extensively to evaluate compounds for antidepressant efficacy, has recently been adapted for Drosophila. The fly FST has potential to be a cost-effective, high-throughput assay for evaluating potential antidepressants. For this study we pharmacologically validated the fly FST using methamphetamine, DL-α-methyltyrosine, and the antidepressant citalopram. While methamphetamine and DL-α-methyltyrosine altered overall locomotor activity in the Drosophila Activity Monitor System (DAMS), they had no significant impact on measures of immobility in the FST. Conversely, chronic citalopram decreased measures of immobility in the FST in both sexes without increasing DAMS activity. We used the validated FST to evaluate the antidepressant-like effects of high (3.5 mM) and low (0.03 mM) doses of psilocybin. Both doses of psilocybin significantly reduced measures of immobility in male flies, but not females. 0.03 mM had an effect size comparable to chronic citalopram, and 3.5 mM had an effect size approximately twice that of chronic citalopram.
Molecular-docking-guided design, palladium-catalyzed synthesis and anticancer activity of paclitaxel-benzoxazoles hybrids
Authors: Jiang Ting , Cao Ya-Nan , Xu Jin-Bu , Gao Feng , Zheng Ling-Li 
Published: June 2022

AbstractA series of new paclitaxel-benzoxazoles hybrids were designed based on both the molecular docking mode of beta-tubulin with paclitaxel derivatives (7a and 7g), and the activity-structure relationship of C-13 side chain in paclitaxel. Palladium-catalyzed direct Csp2–H arylation of benzoxazoles with different aryl-bromides was used as the key synthetic strategy for the aryl-benzoxazoles moieties in the hybrids. Twenty-six newly synthesized hybrids were screened for their antiproliferative activity against human cancer cell lines such as human breast cancer cells (MDA-MB-231) and liver hepatocellular cells (HepG2) by the MTT assay and results were compared with paclitaxel. Interestingly, most hybrids (7a–7e, 7i, 7k, 7l, 7A, 7B, 7D and 7E) showed significantly active against both cell lines at concentration of 50 µM, which indicated that the hybrid strategy is effective to get structural simplified paclitaxel analogues with high anti-tumor activity.
Old age and multiple comorbidity are associated with delayed diagnosis of Guillain–Barre syndrome
Authors: Kim Sohyeon , Han Hee Jo , Shin Ha Young , Kim Seung Woo 
Published: June 2022

AbstractTo assess whether older age and presence of comorbidities were associated with a delayed diagnosis of Guillain–Barré syndrome (GBS). The medical records of 140 patients diagnosed with GBS at Severance Hospital from March 2011 to December 2020 were retrospectively reviewed. Comorbidity profiles were assessed using the Charlson comorbidity index (CCI). The age-adjusted CCI (ACCI) score was calculated, which further incorporated the effect of age. Patients were classified into the early diagnosis group (diagnosis duration ≤ 14 days) and late diagnosis group (diagnosis duration > 14 days). Clinical features and comorbidity profiles were compared between the two groups. The cumulative incidence of diagnosis was compared between the low and high ACCI groups. Age was significantly higher in the late diagnosis group (61.8 ± 15.0 years) than in the early diagnosis group (49.1 ± 18.4, p = 0.001). The CCI score was higher in the late diagnosis group (≥ 3 in 26.1%) than in the early diagnosis group (≥ 3 in 5.1%, p = 0.01). The ACCI score demonstrated a positive correlation with the diagnosis duration (β = 1.636, p < 0.001), indicating that the diagnosis was delayed in patients with a higher ACCI score. The duration from onset to diagnosis was longer in the high ACCI group than in the low ACCI group (log-rank test, p < 0.001). The diagnosis duration was significantly longer, especially in patients with malignancy and cardiovascular diseases. Delayed diagnosis of GBS is associated with older age and multiple comorbidities. Diagnostic delay was significant in patients with malignancies and cardiovascular diseases. Early suspicion of GBS is required in these patients.
Cryo-SEM and confocal LSM studies of agar gel, nanoparticle hydrocolloid, mineral clays and saline solutions
Authors: Ivashchenko Olena 
Published: June 2022

AbstractCryogenic electron microscopy became a powerful tool to study biological objects. For non-biological objects (solutions, gels, dispersions, clays), the polemic about interpretation of cryogenic microscopy results is still in progress splitting on two contradictive trends: considering structure as a near-real state of the sample or as freezing artefacts. In this study, a microstructure of a range of stable aqueous solutions and dispersions (agar, kaolin, montmorillonite, nanoparticles) was investigated by means of cryo-SEM and confocal LSM in order to compare cryo-fixed and unfrozen structures. Noticed correlation between these two methods for studied systems (agar, kaolin, montmorillonite, NPs) allowed to state that ordered microstructure is an inherent feature of these systems. Some inconsistencies in microstructure dimensions were discussed and prescribed to the differences in the bulk and interface layers. Supposedly, NaCl solutions also possess dynamic (femtosecond level) microstructure of neat water clusters and solvated Na+ and Cl- ions that may have an impact on electrolyte abnormal properties.
Effects of bioflavonoid-containing mouth rinses on optical properties of tooth-coloured dental restorative materials
Authors: Divnic-Resnik Tihana , Shen Jay Junyang , Nguyen Jim Vinh The , Lu Derek Weidi , Miletic Vesna 
Published: June 2022

AbstractThis study investigated differences in colour (ΔE00) and translucency parameter (ΔTP00) of nanofilled/microhybrid composites and a glass-ionomer cement following immersion in bioflavonoid (Citrox)- or chlorhexidine-based mouth rinses. Sixty disc-shaped specimens (N = 5/group) of Filtek Supreme (3M), Gradia Anterior (GC) and Fuji IX (GC) were exposed to Citrox/0.2%CHX (Perio+0.2, Curaprox), Citrox/0.09%CHX (Perio+0.09, Curaprox), 0.2%CHX (Savacol, Colgate-Palmolive) or distilled water by 2-min agitation daily for 28 days in an orbital shaker at 200 rpm at 37 °C. Colour recordings were performed using a clinical spectrophometer to obtain CIELab coordinates. General linear model, ANOVA, Tukey test (α = 0.05) and Pearson correlation test were used to analyse data. ΔE00 ranged between 0.33 (Gradia_Savacol_T28) and 6.35 (Fuji_Savacol_T28) (p < 0.001). ΔTP00 ranged between 0.36 (Fuji_ Perio+0.2) and 1.73 (Fuji_Savacol) (p < 0.05). Savacol resulted in higher ΔE00 of Filtek and Fuji and ΔTP00 of Filtek than Perio+0.09 and Perio+0.2 (p = 0.005). Perio+0.09 and Perio+0.2 resulted in higher ΔE00 at T7 than T28 (p < 0.05). There was no correlation between ΔTP00 and ΔE00 (r = 0.445, p = 0.147). Generally, Perio+0.2 and Perio+0.09 mouth rinses produced similar or lower ΔE00 and ΔTP00 than Savacol. GIC Fuji showed higher ΔE00 and similar or higher ΔTP00 than composites Filtek and Gradia. ΔE00 in all materials decreased in Perio+0.2 and Perio+0.09 over time.
Asymmetric effects of amphipathic molecules on mechanosensitive channels
Authors: Bavi Omid , Zhou Zijing , Bavi Navid , Mehdi Vaez Allaei S. , Cox Charles D. , Martinac B. 
Published: June 2022

AbstractMechanosensitive (MS) ion channels are primary transducers of mechanical force into electrical and/or chemical intracellular signals. Many diverse MS channel families have been shown to respond to membrane forces. As a result of this intimate relationship with the membrane and proximal lipids, amphipathic compounds exert significant effects on the gating of MS channels. Here, we performed all-atom molecular dynamics (MD) simulations and employed patch-clamp recording to investigate the effect of two amphipaths, Fluorouracil (5-FU) a chemotherapy agent, and the anaesthetic trifluoroethanol (TFE) on structurally distinct mechanosensitive channels. We show that these amphipaths have a profound effect on the bilayer order parameter as well as transbilayer pressure profile. We used bacterial mechanosensitive channels (MscL/MscS) and a eukaryotic mechanosensitive channel (TREK-1) as force-from-lipids reporters and showed that these amphipaths have differential effects on these channels depending on the amphipaths’ size and shape as well as which leaflet of the bilayer they incorporate into. 5-FU is more asymmetric in shape and size than TFE and does not penetrate as deep within the bilayer as TFE. Thereby, 5-FU has a more profound effect on the bilayer and channel activity than TFE at much lower concentrations. We postulate that asymmetric effects of amphipathic molecules on mechanosensitive membrane proteins through the bilayer represents a general regulatory mechanism for these proteins.
Placental sex-dependent spermine synthesis regulates trophoblast gene expression through acetyl-coA metabolism and histone acetylation
Authors: Aye Irving L. M. H. , Gong Sungsam , Avellino Giulia , Barbagallo Roberta , Gaccioli Francesca , Jenkins Benjamin J. , Koulman Albert , Murray Andrew J. , Stephen Charnock-Jones D. , Smith Gordon C. S. 
Published: June 2022

AbstractPlacental function and dysfunction differ by sex but the mechanisms are unknown. Here we show that sex differences in polyamine metabolism are associated with escape from X chromosome inactivation of the gene encoding spermine synthase (SMS). Female placental trophoblasts demonstrate biallelic SMS expression, associated with increased SMS mRNA and enzyme activity. Polyamine depletion in primary trophoblasts reduced glycolysis and oxidative phosphorylation resulting in decreased acetyl-coA availability and global histone hypoacetylation in a sex-dependent manner. Chromatin-immunoprecipitation sequencing and RNA-sequencing identifies progesterone biosynthesis as a target of polyamine regulated gene expression, and polyamine depletion reduced progesterone release in male trophoblasts. The effects of polyamine depletion can be attributed to spermine as SMS-silencing recapitulated the effects on energy metabolism, histone acetylation, and progesterone release. In summary, spermine metabolism alters trophoblast gene expression through acetyl-coA biosynthesis and histone acetylation, and SMS escape from X inactivation explains some features of human placental sex differences.
Signatures of discrete time-crystallinity in transport through an open Fermionic chain
Authors: Sarkar Subhajit , Dubi Yonatan 
Published: June 2022

AbstractDiscrete time-crystals are periodically driven quantum many-body systems with broken discrete time translational symmetry, a non-equilibrium steady state representing self-organization of motion of quantum particles. Observations of discrete time-crystalline order are currently limited to magneto-optical experiments and it was never observed in a transport experiment performed on systems connected to external electrodes. Here we demonstrate that both discrete time-crystal and quasi-crystal survive a very general class of environments corresponding to single-particle gain and loss through system-electrode coupling over experimentally relevant timescales. Using dynamical symmetries, we analytically identify the conditions for observing time-crystalline behavior in a periodically driven open Fermi-Hubbard chain attached to electrodes. We show that the spin-polarized transport current directly manifests the existence of a time-crystalline behavior. Our findings are verifiable in present-day experiments with quantum-dot arrays and Fermionic ultra-cold atoms in optical lattices.