bluuebunny/crossref_metadata_2025 huggingface dataset:
An mm-sized biomimetic directional microphone array for sound source localization in three dimensions
Authors: Rahaman Ashiqur , Kim Byungki
Published: June 2022

FlyOrmia ochraceaears have been well-studied and mimicked to achieve subwavelength directional sensing, but their efficacy in sound source localization in three dimensions, utilizing sound from theX-,Y-, andZ-axes, has been less explored. This paper focuses on a mm-sized array of threeOrmia ochraceaear-inspired piezoelectric MEMS directional microphones, where their in-plane directionality is considered a cue to demonstrate sound source localization in three dimensions. In the array, biomimetic MEMS directional microphones are positioned in a 120° angular rotation; as a result, six diaphragms out of three directional microphones keep a normal-axis relative to the sound source at six different angles in the azimuth plane starting from 0° to 360° in intervals of ±30°. In addition, the cosine-dependent horizontal component of the applied sound gives cues forZ-axis directional sensing. The whole array is first analytically simulated and then experimentally measured in an anechoic chamber. Both results are found to be compliant, and the angular resolution of sound source localization in three dimensions is found to be ±2° at the normal axis. The resolution at the azimuth plane is found to be ±1.28°, and the same array shows a ± 4.28° resolution when sound is varied from the elevation plane. Looking at the scope within this area combined with the presented results, this work provides a clear understanding of sound source localization in three dimensions.
Distributed genetic architecture across the hippocampal formation implies common neuropathology across brain disorders
Authors: Bahrami Shahram , Nordengen Kaja , Shadrin Alexey A. , Frei Oleksandr , van der Meer Dennis , Dale Anders M. , Westlye Lars T. , Andreassen Ole A. , Kaufmann Tobias
Published: June 2022

Despite its major role in complex human functions across the lifespan, most notably navigation, learning and memory, much of the genetic architecture of the hippocampal formation is currently unexplored. Here, through multivariate genome-wide association analysis in volumetric data from 35,411 white British individuals, we reveal 177 unique genetic loci with distributed associations across the hippocampal formation. We identify genetic overlap with eight brain disorders with typical onset at different stages of life, where common genes suggest partly age- and disorder-independent mechanisms underlying hippocampal pathology.
Anethole rich Clausena heptaphylla (Roxb.) Wight & Arn., essential oil pharmacology and genotoxic efficiencies
Authors: Lal Mohan , Begum Twahira , Gogoi Roktim , Sarma Neelav , Munda Sunita , Pandey Sudin Kumar , Baruah Joyashree , Tamang Raghu , Saikia Samarjit
Published: June 2022

Anethole, a widely used industrial flavoring agent is majorly sourced from anise and star anise. The present study is aimed to the in-depth pharmacological analysis i.e. anti-diabetic, skin whitening, neurodegenerative disorder inhibitory activities of anethole-rich Clausena heptaphylla leaf essential oil (ARCHEO) (88.59%) as revealed by the Gas Chromatography/Mass Spectrometry (GC/MS) analysis and further confirmed by proton nuclear magnetic resonance 1H-NMR as well as to compare with standard compound anethole. ARCHEO (ABTS EC50 6.97 ± 0.004 µg/mL; Protease assay 4.51 ± 0.004 µg/mL) outperformed the standard compound anethole (ABTS EC50 9.48 ± 0.048 µg/mL; Protease assay EC50 22.64 ± 0.016 µg/mL) in antioxidant and anti-inflammatory experiments. ARCHEO was also shown to be more effective than the reference compound anethole in terms of anti-diabetic activity (EC50 22.35 ± 0.121 µg/mL), tyrosinase inhibitory activity (EC50 16.45 ± 0.012 µg/mL), and anti-cholinesterase activity (EC50 22.32 ± 0.016 µg/mL). However, ARCHEO exhibited lower antimicrobial activity towards all the tested microbes compared to standard compound anethole and as for the MIC, ARCHEO was effective only towards Salmonella typhimurium (60 µg/mL), Streptococcus mutans (20 µg/mL), and Aspergillus fumigatus (75 µg/mL). ARCHEO (11.11%) and anethole (12.33%) showed no genotoxic effect based on Allium cepa assay mitotic index value. Thus, ARCHEO could be a commercially viable and widely available cheaper source of anethole, which has buoyant demand in the field of food flavoring, fragrance, and pharmaceutical industries.
Identification of a novel prognostic signature for HCC and analysis of costimulatory molecule-related lncRNA AC099850.3
Authors: Wang Qi , Fang Qiong , Huang Yanping , Zhou Jin , Liu Meimei
Published: June 2022

Costimulatory molecules are involved in initiation of anti-tumor immune responses while long non‐coding RNAs (lncRNAs) regulate the development of various cancers. However, the roles of lncRNA in hepatocellular carcinoma (HCC) have not been fully established. In this study, we aimed at identifying lncRNAs-related costimulatory molecules in HCC and to construct a prognostic signature for predicting the clinical outcomes for HCC patients. Data were downloaded from The Cancer Genome Atlas database for bioinformatics analyses. Costimulatory molecules were obtained from published literature. The R software, SPSS, and GraphPad Prism were used for statistical analyses. A risk model that is based on five costimulatory molecule-related lncRNAs was constructed using lasso and Cox regression analyses. Multivariate regression analysis revealed that the risk score could predict the prognostic outcomes for HCC. Samples in high- and low-risk groups exhibited significant differences in gene set enrichment and immune infiltration levels. Through colony formation and CCK8 assays, we found that AC099850.3 was strongly associated with HCC cell proliferation. We identified and validated a novel costimulatory molecule-related survival model. In addition, AC099850.3 was found to be closely associated with clinical stages and proliferation of HCC cells, making it a potential target for HCC treatment.
Identification of aquifer pollution’s point sources with the reciprocity principle
Authors: Bouhlila Rachida , Hariga Nejla T.
Published: June 2022

The principle of reciprocity, called Maxwell–Betti theorem, initially used in mechanics in an elastic structure, establishes a relation of equality between two distinct strains under different loads. In this paper, we extend and apply this principle to flow and solute transport equations in porous media, in order to perform the pollution sources identification in aquifers. We developed general 2D expressions of the reciprocity principle for transient transport problems. This model leads to a linear equations set, with point sources coordinates, concentrations and associated water fluxes as unknowns The proposed model is then applied to the Rocky Mountain Arsenal aquifer (Konikow in Modeling Chloride Movement in the Alluvial Aquifer at the Rocky Mountain Arsenal, Colorado. Technical Report Water-Supply Paper 2044, USGS, 1979), where polluted water is injected into a well in the domain. The used inverse technique successfully recovered the position and the pollutant concentration in addition to the associated water flux. In addition, we developed and implemented the inverse method for different knowledge levels of the degrees of the aquifer contamination, i.e. more or less data available in the field. Multiple pollution point sources and noisy data situations are also developed and tested with high efficiency. The proposed method would be easy and useful to be implemented in the modeling software now widely used by researchers and groundwater managers. It can thus be applied in real case studies, to help authorities and regulators to efficiently identify the polluters and the contamination process, i.e. its location, onset, duration and the associated mass and water fluxes.
Prevention of lymphocele or seroma after mastectomy and axillary lymphadenectomy for breast cancer: systematic review and meta-analysis
Authors: Adrien Crestani , Katia Mahiou , Marie-Lucile Bodet , Alice Roosen , Claire Bonneau , Roman Rouzier
Published: June 2022

Seroma or lymphocele remains the most common complication after mastectomy and lymphadenectomy for breast cancer. Many different techniques are available to prevent this complication: wound drainage, reduction of the dead space by flap fixation, use of various types of energy, external compression dressings, shoulder immobilization or physical activity, as well as numerous drugs and glues. We searched MEDLINE, clinicaltrials.gov, Cochrane Library, and Web of Science databases for publications addressing the issue of prevention of lymphocele or seroma after mastectomy and axillary lymphadenectomy. Quality was assessed using Hawker’s quality assessment tool. Incidence of seroma or lymphocele were collected. Fifteen randomized controlled trials including a total of 1766 patients undergoing radical mastectomy and axillary lymphadenectomy for breast cancer were retrieved. The incidence of lymphocele or seroma in the study population was 24.2% (411/1698): 25.2% (232/920) in the test groups and 23.0% (179/778) in the control groups. Neither modification of surgical technique (RR 0.86; 95% CI [0.72, 1.03]) nor application of a medical treatment (RR 0.96; 95% CI [0.72, 1.29]) was effective in preventing lymphocele. On the contrary, decreasing the drainage time increased the risk of lymphocele (RR 1.88; 95% CI [1.43, 2.48). There was no publication bias but the studies were of medium to low quality. To conclude, despite the heterogeneity of study designs, drainage appears to be the most effective technique, although the overall quality of the data is low.
Immuno-reactive cancer organoid model to assess effects of the microbiome on cancer immunotherapy
Authors: Shelkey Ethan , Oommen David , Stirling Elizabeth R. , Soto-Pantoja David R. , Cook Katherine L. , Lu Yong , Votanopoulos Konstantinos I. , Soker Shay
Published: June 2022

Immune checkpoint blockade (ICB) therapy has demonstrated good efficacy in many cancer types. In cancers such as non-resectable advanced or metastatic triple-negative breast cancer (TNBC), it has recently been approved as a promising treatment. However, clinical data shows overall response rates (ORRs) from ~ 3–40% in breast cancer patients, depending on subtype, previous treatments, and mutation status. Composition of the host-microbiome has a significant role in cancer development and therapeutic responsiveness. Some bacterial families are conducive to oncogenesis and progression, while others aid innate and therapeutically induced anti-tumor immunity. Modeling microbiome effects on anti-tumor immunity in ex vivo systems is challenging, forcing the use of in vivo models, making it difficult to dissect direct effects on immune cells from combined effects on tumor and immune cells. We developed a novel immune-enhanced tumor organoid (iTO) system to study factors affecting ICB response. Using the 4T1 TNBC murine cell line and matched splenocytes, we demonstrated ICB-induced response. Further administration of bacterial-derived metabolites from species found in the immunomodulatory host-microbiome significantly increased ICB-induced apoptosis of tumor cells and altered immune cell receptor expression. These outcomes represent a method to isolate individual factors that alter ICB response and streamline the study of microbiome effects on ICB efficacy.
Compact resonant systems for perfect and broadband sound absorption in wide waveguides in transmission problems
Authors: Boulvert Jean , Gabard Gwénaël , Romero-García Vicente , Groby Jean-Philippe
Published: June 2022

This work deals with wave absorption in reciprocal asymmetric scattering problem by addressing the acoustic problem of compact absorbers for perfect unidirectional absorption, flush mounted to the walls of wide ducts. These absorbers are composed of several side-by-side resonators that are usually of different geometry and thus detuned to yield an asymmetric acoustic response. A simple lumped-element model analysis is performed to link the dependence of the optimal resonators surface impedance, resonance frequency, and losses to the duct cross-sectional area and resonator spacing. This analysis unifies those of several specific configurations into a unique problem. In addition, the impact of the potential evanescent coupling between the resonators, which is usually neglected, is carefully studied. This coupling can have a strong impact especially on the behavior of compact absorbers lining wide ducts. To reduce the evanescent coupling, the resonators should be relatively small and therefore their resonances should be damped, and not arranged by order of increasing or decreasing resonant frequency. Finally, such an absorber is designed and optimized for perfect unidirectional absorption to prove the relevance of the analysis. The absorber is 30 cm long and 5 cm thick and covers a single side of a 14.8 × 15 cm2 rectangular duct. A mean absorption coefficient of 99% is obtained experimentally between 700 and 800 Hz.
Identification of useful genes from multiple microarrays for ulcerative colitis diagnosis based on machine learning methods
Authors: Zhang Lin , Mao Rui , Lau Chung Tai , Chung Wai Chak , Chan Jacky C. P. , Liang Feng , Zhao Chenchen , Zhang Xuan , Bian Zhaoxiang
Published: June 2022

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with an increasing incidence and prevalence worldwide. The diagnosis for UC mainly relies on clinical symptoms and laboratory examinations. As some previous studies have revealed that there is an association between gene expression signature and disease severity, we thereby aim to assess whether genes can help to diagnose UC and predict its correlation with immune regulation. A total of ten eligible microarrays (including 387 UC patients and 139 healthy subjects) were included in this study, specifically with six microarrays (GSE48634, GSE6731, GSE114527, GSE13367, GSE36807, and GSE3629) in the training group and four microarrays (GSE53306, GSE87473, GSE74265, and GSE96665) in the testing group. After the data processing, we found 87 differently expressed genes. Furthermore, a total of six machine learning methods, including support vector machine, least absolute shrinkage and selection operator, random forest, gradient boosting machine, principal component analysis, and neural network were adopted to identify potentially useful genes. The synthetic minority oversampling (SMOTE) was used to adjust the imbalanced sample size for two groups (if any). Consequently, six genes were selected for model establishment. According to the receiver operating characteristic, two genes of OLFM4 and C4BPB were finally identified. The average values of area under curve for these two genes are higher than 0.8, either in the original datasets or SMOTE-adjusted datasets. Besides, these two genes also significantly correlated to six immune cells, namely Macrophages M1, Macrophages M2, Mast cells activated, Mast cells resting, Monocytes, and NK cells activated (P  <  0.05). OLFM4 and C4BPB may be conducive to identifying patients with UC. Further verification studies could be conducted.
Decoronation-induced infected alveolar socket defect rat model for ridge preservation
Authors: Fang Chih-Hsiang , Lin Hung-Ying , Sun Chung-Kai , Lin Yi-Wen , Hung Min-Chih , Li Ching-Hung , Lin I-Ping , Chang Hung-Chen , Sun Jui-Sheng , Chang Jenny Zwei-Chieng
Published: June 2022

Current rat alveolar ridge preservation models have not been well standardized. In this study, we proposed decoronation-induced infected alveolar socket model of rat. The bilateral maxillary first molars (M1) of twenty-four rats were decoronized or extracted. After 2, 6, 10, and 14 weeks, bone and soft tissue changes at M1 and periodontal conditions of maxillary second (M2) and third molars (M3) were evaluated by micro-computed tomography and histological analysis. Additional eighteen rats with standardized size defects were grafted with Bio-Oss Collagen to compare with unmanipulated contralateral side. Decoronation preserved greater bone and soft tissue dimensions at M1, provided larger three-dimensional (3D) bone contour volume, but also promoted periodontal breakdown of M2 Histological results showed intense inflammatory cell infiltrations and severe bone resorption within M1 socket and at mesial aspect of M2. The critical dimensions to accommodate largest standardized defect at M1 were 2.2–2.3 mm at vertical bone height and 2.8–3.2 mm at alveolar crestal width. Bio-Oss Collagen could not fully preserve buccal or palatal bone height but could be beneficial in preserving ridge width in large alveolar defects. Collectively, if periodontally-involved alveolar bone defect is preferred, we suggest extracting M1 roots 6 weeks after decoronation to allow periodontitis to occur at M2. If standardized critical dimension defect is preferred, we suggest extracting M1 roots 2 weeks after decoronation, and creating defect in the middle of M1 site with size no larger than 2.7 mm diameter to its full depth.
A novel photosynthetic biologic topical gel for enhanced localized hyperoxygenation augments wound healing in peripheral artery disease
Authors: Zhu Yuanjia , Jung Jinsuh , Anilkumar Shreya , Ethiraj Sidarth , Madira Sarah , Tran Nicholas A. , Mullis Danielle M. , Casey Kerriann M. , Walsh Sabrina K. , Stark Charles J. , Venkatesh Akshay , Boakye Alexander , Wang Hanjay , Woo Y. Joseph
Published: June 2022

Peripheral artery disease and the associated ischemic wounds are substantial causes of global morbidity and mortality, affecting over 200 million people worldwide. Although advancements have been made in preventive, pharmacologic, and surgical strategies to treat this disease, ischemic wounds, a consequence of end-stage peripheral artery disease, remain a significant clinical and economic challenge. Synechococcus elongatus is a cyanobacterium that grows photoautotrophically and converts carbon dioxide and water into oxygen. We present a novel topical biologic gel containing S. elongatus that provides oxygen via photosynthesis to augment wound healing by rescuing ischemic tissues caused by peripheral artery disease. By using light rather than blood as a source of energy, our novel topical therapy significantly accelerated wound healing in two rodent ischemic wound models. This novel topical gel can be directly translated to clinical practice by using a localized, portable light source without interfering with patients’ daily activities, demonstrating potential to generate a paradigm shift in treating ischemic wounds from peripheral artery disease. Its novelty, low production cost, and ease of clinical translatability can potentially impact the clinical care for millions of patients suffering from peripheral arterial disease.
Melting phase relations in Fe–Si–H at high pressure and implications for Earth’s inner core crystallization
Authors: Hikosaka Koutaro , Tagawa Shoh , Hirose Kei , Okuda Yoshiyuki , Oka Kenta , Umemoto Koichiro , Ohishi Yasuo
Published: June 2022

Hydrogen could be an important light element in planetary cores, but its effect on phase diagrams of iron alloys is not well known because the solubility of H in Fe is minimal at ambient pressure and high-pressure experiments on H-bearing systems have been challenging. Considering that silicon can be another major light element in planetary cores, here we performed melting experiments on the Fe–Si–H system at ~ 50 GPa and obtained the ternary liquidus phase relations and the solid/liquid partition coefficient,Dof Si and H based onin-situhigh-pressure X-ray diffraction measurements andex-situchemical and textural characterizations on recovered samples. Liquid crystallized hexagonal close-packed (hcp) (Fe0.93Si0.07)H0.25, which explains the observed density and velocities of the Earth’s solid inner core. The relatively highDSi = 0.94(4) andDH = 0.70(12) suggest that in addition to Si and H, the liquid outer core includes other light elements such as O, which is least partitioned into solid Fe and can thus explain the density difference between the outer and inner core. H and O, as well as Si, are likely to be major core light elements, supporting the sequestration of a large amount of water in the Earth’s core.
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

Advances 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

Mixed 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

Different 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

Soil 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

In 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

We 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

Psilocybin 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

A 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

To 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

Cryogenic 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

This 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

Mechanosensitive (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

Placental 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

Discrete 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.
Control of amplitude homogeneity in coherent Ising machines with artificial Zeeman terms
Authors: Inui Yoshitaka , Gunathilaka Mastiyage Don Sudeera Hasaranga , Kako Satoshi , Aonishi Toru , Yamamoto Yoshihisa
Published: June 2022

A coherent Ising machine (CIM) is an open-dissipative Ising solver using optical pulses generated from a degenerate optical parametric oscillator as analog magnetizations. When solving real-world optimization problems with CIM, this solver has two difficulties: mutual coupling induced amplitude inhomogeneity and absence of natural way to implement Zeeman terms. For the approximate Gaussian formulation of CIMs with amplitude control feedback, we add artificial Zeemam terms using the target amplitude information. Here we show, for 16-spin CIM with Zeeman terms, the amplitude control increases the performance, particularly when Zeeman terms are competing against mutual coupling coefficients.
Moderation of gut microbiota and bile acid metabolism by chlorogenic acid improves high-fructose-induced salt-sensitive hypertension in mice
Authors: Zhu Qing , Zhu Yeyan , Liu Yuting , Tao Yufeng , Lin Yike , Lai Sijie , Liang Zixing , Chen Yating , Chen Yang , Wang Lei
Published: June 2022

In high-fructose-induced salt-sensitive hypertensive mice, the oral administration of CGA restructures gut microbiota, modulates bile acid metabolism, enriches DCA et al., improves endothelial vasoconstriction and attenuates hypertension.
Enhanced healing process of tooth sockets using strontium-doped TiO2
Authors: Li Jialing , Fan Zilu , Huang Min , Xie Yonglin , Guan Zhenju , Ruan Jianping
Published: June 2022

SPU/Sr-TiO2/MDI nanocomposite adhesive showed satisfactory antibacterial activity and cell nontoxicity, it greatly promoted the formation of new bone tissue in tooth extraction socket when used for healing.
Molecularly-imprinted polymer-base bulk optode for the determination of ivabradine hydrochloride in Procoralan®
Authors: Abdel-Haleem Fatehy M. , Rizk Mahmoud S. , El-Beshlawy Menna M.
Published: June 2022

IVH may be administered orally twice per day for treating heart failure, sinus rhythm, heart-related chest pain and angina pectoris; its overdose may cause problems as blurred vision, uncontrolled blood pressure, prolonged bradycardia, and others.
Self-assembly induction of reduced graphene oxide decorated CdS nanoboxes for photocatalytic hydrogen evolution
Authors: Li Qiancheng , Ma Di , Zhang Xuetao , Lu Qifang , Guo Enyan , Wei Mingzhi , Pang Yingping
Published: June 2022

A highly efficient rGO decorated CdS hollow nanobox photocatalyst, taking advantage of remarkably long-lived reactive charges and built-in electric field, significantly promotes the photocatalytic H2 evolution activity and stability.