bluuebunny/crossref_metadata_2025 huggingface dataset:
Blocking D2/D3 dopamine receptors in male participants increases volatility of beliefs when learning to trust others
Authors: Mikus Nace , Eisenegger Christoph , Mathys Christoph , Clark Luke , Müller Ulrich , Robbins Trevor W. , Lamm Claus , Naef Michael
Published: July 2023

The ability to learn about other people is crucial for human social functioning. Dopamine has been proposed to regulate the precision of beliefs, but direct behavioural evidence of this is lacking. In this study, we investigate how a high dose of the D2/D3 dopamine receptor antagonist sulpiride impacts learning about other people’s prosocial attitudes in a repeated Trust game. Using a Bayesian model of belief updating, we show that in a sample of 76 male participants sulpiride increases the volatility of beliefs, which leads to higher precision weights on prediction errors. This effect is driven by participants with genetically conferred higher dopamine availability (Taq1a polymorphism) and remains even after controlling for working memory performance. Higher precision weights are reflected in higher reciprocal behaviour in the repeated Trust game but not in single-round Trust games. Our data provide evidence that the D2 receptors are pivotal in regulating prediction error-driven belief updating in a social context.
Large depth-of-field ultra-compact microscope by progressive optimization and deep learning
Authors: Zhang Yuanlong , Song Xiaofei , Xie Jiachen , Hu Jing , Chen Jiawei , Li Xiang , Zhang Haiyu , Zhou Qiqun , Yuan Lekang , Kong Chui , Shen Yibing , Wu Jiamin , Fang Lu , Dai Qionghai
Published: July 2023

The optical microscope is customarily an instrument of substantial size and expense but limited performance. Here we report an integrated microscope that achieves optical performance beyond a commercial microscope with a 5×, NA 0.1 objective but only at 0.15 cm3 and 0.5 g, whose size is five orders of magnitude smaller than that of a conventional microscope. To achieve this, a progressive optimization pipeline is proposed which systematically optimizes both aspherical lenses and diffractive optical elements with over 30 times memory reduction compared to the end-to-end optimization. By designing a simulation-supervision deep neural network for spatially varying deconvolution during optical design, we accomplish over 10 times improvement in the depth-of-field compared to traditional microscopes with great generalization in a wide variety of samples. To show the unique advantages, the integrated microscope is equipped in a cell phone without any accessories for the application of portable diagnostics. We believe our method provides a new framework for the design of miniaturized high-performance imaging systems by integrating aspherical optics, computational optics, and deep learning.
Leveraging spatial transcriptomics data to recover cell locations in single-cell RNA-seq with CeLEry
Authors: Zhang Qihuang , Jiang Shunzhou , Schroeder Amelia , Hu Jian , Li Kejie , Zhang Baohong , Dai David , Lee Edward B. , Xiao Rui , Li Mingyao
Published: July 2023

Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity in health and disease. However, the lack of physical relationships among dissociated cells has limited its applications. To address this issue, we present CeLEry (Cell Location recovEry), a supervised deep learning algorithm that leverages gene expression and spatial location relationships learned from spatial transcriptomics to recover the spatial origins of cells in scRNA-seq. CeLEry has an optional data augmentation procedure via a variational autoencoder, which improves the method’s robustness and allows it to overcome noise in scRNA-seq data. We show that CeLEry can infer the spatial origins of cells in scRNA-seq at multiple levels, including 2D location and spatial domain of a cell, while also providing uncertainty estimates for the recovered locations. Our comprehensive benchmarking evaluations on multiple datasets generated from brain and cancer tissues using Visium, MERSCOPE, MERFISH, and Xenium demonstrate that CeLEry can reliably recover the spatial location information for cells using scRNA-seq data.
Pilot-scale drinking water distribution system to study water quality changes during transport
Authors: García-Timermans Cristina , Malfroot Bram , Dierendonck Cameron , Mol Zoë , Pluym Thomas , Waegenaar Fien , Arends Jan B. A. , Demeestere Kristof , Walgraeve Christophe , Boon Nico , De Gusseme Bart
Published: July 2023

Drinking water (DW) quality can change during distribution, leading to taste and odor events and microbial regrowth. Pilot plants mimicking distribution networks are crucial for understanding these changes. We present a new pilot plant design, including piping material, sensors, and instrumentation. The three independent loops (100 m each) of the pilot exhibit identical behavior, allowing simultaneous testing of three conditions. Monitoring includes taste and odor compound formation, microorganism regrowth, and dissolved organic carbon changes. Real-time measurements enable continuous monitoring, and inner pipe biofilm sampling is feasible. The pilot’s modularity facilitates studying climate change effects, different piping materials, and source waters on DW quality in the distribution network.
De novo design of protein structure and function with RFdiffusion
Authors: Watson Joseph L. , Juergens David , Bennett Nathaniel R. , Trippe Brian L. , Yim Jason , Eisenach Helen E. , Ahern Woody , Borst Andrew J. , Ragotte Robert J. , Milles Lukas F. , Wicky Basile I. M. , Hanikel Nikita , Pellock Samuel J. , Courbet Alexis , Sheffler William , Wang Jue , Venkatesh Preetham , Sappington Isaac , Torres Susana Vázquez , Lauko Anna , De Bortoli Valentin , Mathieu Emile , Ovchinnikov Sergey , Barzilay Regina , Jaakkola Tommi S. , DiMaio Frank , Baek Minkyung , Baker David
Published: July 2023

There has been considerable recent progress in designing new proteins using deep-learning methods1–9. Despite this progress, a general deep-learning framework for protein design that enables solution of a wide range of design challenges, including de novo binder design and design of higher-order symmetric architectures, has yet to be described. Diffusion models10,11 have had considerable success in image and language generative modelling but limited success when applied to protein modelling, probably due to the complexity of protein backbone geometry and sequence–structure relationships. Here we show that by fine-tuning the RoseTTAFold structure prediction network on protein structure denoising tasks, we obtain a generative model of protein backbones that achieves outstanding performance on unconditional and topology-constrained protein monomer design, protein binder design, symmetric oligomer design, enzyme active site scaffolding and symmetric motif scaffolding for therapeutic and metal-binding protein design. We demonstrate the power and generality of the method, called RoseTTAFold diffusion (RFdiffusion), by experimentally characterizing the structures and functions of hundreds of designed symmetric assemblies, metal-binding proteins and protein binders. The accuracy of RFdiffusion is confirmed by the cryogenic electron microscopy structure of a designed binder in complex with influenza haemagglutinin that is nearly identical to the design model. In a manner analogous to networks that produce images from user-specified inputs, RFdiffusion enables the design of diverse functional proteins from simple molecular specifications.
The European Tertiary Education Register, the reference dataset on European Higher Education Institutions
Authors: Lepori Benedetto , Lambrechts Agata A. , Wagner-Schuster Daniel , Zahradnik Georg
Published: July 2023

The European Tertiary Education Register (ETER) is the reference dataset on European Higher Education Institutions (HEIs). ETER provides data on nearly 3,500 HEIs in about 40 European countries, including descriptive information, geographical information, students and graduates (with various breakdowns), revenues and expenditures, personnel, and research activities; as of March 2023, data cover the years from 2011–2020. ETER complies with OECD-UNESCO-EUROSTAT standards for educational statistics; most data are collected from National Statistical Authorities (NSAs) or ministries of participating countries and are subject to extensive checks and harmonization. The development of ETER has been funded by the European Commission and is part of the current efforts to establish a European Higher Education Sector Observatory; it is closely connected to the establishment of a broader data infrastructure in the field of science and innovation studies (RISIS). The ETER dataset is widely used in the scholarly literature on higher education and science policy, as well as for policy reports and analyses.
Arteriovenous malformation Map2k1 mutation affects vasculogenesis
Authors: Sudduth Christopher L. , Smits Patrick J. , Vivero Matthew P. , Cheng Yu Sheng , Ad Michal , Konczyk Dennis J. , Bischoff Joyce , Warman Matthew L. , Greene Arin K.
Published: July 2023

Somatic activating MAP2K1 mutations in endothelial cells (ECs) cause extracranial arteriovenous malformation (AVM). We previously reported the generation of a mouse line allowing inducible expression of constitutively active MAP2K1 (p.K57N) from the Rosa locus (R26GT-Map2k1-GFP/+) and showed, using Tg-Cdh5CreER, that EC expression of mutant MAP2K1 is sufficient for the development of vascular malformations in the brain, ear, and intestines. To gain further insight into the mechanism by which mutant MAP2K1 drives AVM development, we induced MAP2K1 (p.K57N) expression in ECs of postnatal-day-1 pups (P1) and investigated the changes in gene expression in P9 brain ECs by RNA-seq. We found that over-expression of MAP2K1 altered the transcript abundance of > 1600 genes. Several genes had > 20-fold changes between MAP2K1 expressing and wild-type ECs; the highest were Col15a1 (39-fold) and Itgb3 (24-fold). Increased expression of COL15A1 in R26GT-Map2k1-GFP/+; Tg-Cdh5CreER+/− brain ECs was validated by immunostaining. Ontology showed that differentially expressed genes were involved in processes important for vasculogenesis (e.g., cell migration, adhesion, extracellular matrix organization, tube formation, angiogenesis). Understanding how these genes and pathways contribute to AVM formation will help identify targets for therapeutic intervention.
A wideband and compact Quasi-Yagi antenna based on spoof surface plasmon polaritons
Authors: Arghandeh Farshad , Abbasi-Arand Bijan , Hesari-Shermeh Maryam
Published: July 2023

In this paper, a novel wideband end-fire antenna, based on a spoof surface plasmon polaritons (SSPP) transmission line, is proposed. Periodically modulated corrugated metal strips are used as a transmission line for quasi-TEM conversion in the microstrip line to the state of SSPP and the best impedance matching. Due to the strong confinement of the field in the SSPP waveguide and its high transmission performance, it has been used as a transmission line. The antenna consists of SSPP waveguides for the transmission line, a metal plate on the ground as the reflector of the antenna, a metal strip director, and two half-rings to realize the radiation, reaching a wide bandwidth in the range of 4.1 to 8.1 GHz. The simulation results show that this antenna achieves a gain of 6.5 dBi, a bandwidth of 65%, and an efficiency of 97% across a wide operating frequency band, from 4.1 to 8.1 GHz. The proposed end-fire antenna has been fabricated, and the measured results agree well with the simulated results. The end-fire antenna implemented on a dielectric layer also has the advantages of high efficiency, good directivity, high gain, a wide bandwidth, easy fabrication, and a compact size.
A novel neural network model with distributed evolutionary approach for big data classification
Authors: Haritha K. , Shailesh S. , Judy M. V. , Ravichandran K. S. , Krishankumar Raghunathan , Gandomi Amir H.
Published: July 2023

The considerable improvement of technology produced for various applications has resulted in a growth in data sizes, such as healthcare data, which is renowned for having a large number of variables and data samples. Artificial neural networks (ANN) have demonstrated adaptability and effectiveness in classification, regression, and function approximation tasks. ANN is used extensively in function approximation, prediction, and classification. Irrespective of the task, ANN learns from the data by adjusting the edge weights to minimize the error between the actual and predicted values. Back Propagation is the most frequent learning technique that is used to learn the weights of ANN. However, this approach is prone to the problem of sluggish convergence, which is especially problematic in the case of Big Data. In this paper, we propose a Distributed Genetic Algorithm based ANN Learning Algorithm for addressing challenges associated with ANN learning for Big data. Genetic Algorithm is one of the well-utilized bio-inspired combinatorial optimization methods. Also, it is possible to parallelize it at multiple stages, and this may be done in an extremely effective manner for the distributed learning process. The proposed model is tested with various datasets to evaluate its realizability and efficiency. The results obtained from the experiments show that after a specific volume of data, the proposed learning method outperformed the traditional methods in terms of convergence time and accuracy. The proposed model outperformed the traditional model by almost 80% improvement in computational time.
Field attraction of Eurydema ornata (Hemiptera: Pentatomidae) to allyl isothiocyanate
Authors: Koczor Sándor , Tóth Miklós
Published: July 2023

Several Eurydema species (Hemiptera: Pentatomidae) are considered as pests, however, reports on their chemical ecology are scarce. In the current study we focused on Eurydema ornata (Linnaeus) a pentatomid pest of several brassicaceous crops. Since the species is known to feed preferably on generative parts of plants, a series of floral and green leaf volatiles were tested by electroantennography and compounds eliciting remarkable responses were also tested in the field. Three compounds elicited the most outstanding responses from antennae of E. ornata: allyl isothiocyanate, phenylacetaldehyde and ± linalool. Field experiments were conducted in Hungary between 2017 and 2021 to test the potential attractive effects of the compounds. Three Eurydema species were caught in the experiments E. ornata, E. oleracea (Linnaeus) and E. ventralis Kolenati. In the experiments combinations containing allyl isothiocyanate attracted both males and females of E. ornata. The compound was also attractive on its own, in a positive, dose-dependent manner. When presented alone, neither phenylacetaldehyde nor ± linalool was attractive to the species, furthermore, addition of these compounds to allyl isothiocyanate did not affect attraction considerably. To our knowledge this is the first demonstration of field attration of an Eurydema species to a semiochemical and one of the few reports on trapping of a pentatomid species with a synthetic plant volatile in the field. Perspectives regarding research and potential practical applications are discussed in the paper.
MXene/graphene oxide nanocomposites for friction and wear reduction of rough steel surfaces
Authors: Macknojia Ali Zayaan , Ayyagari Aditya , Shevchenko Elena , Berman Diana
Published: July 2023

Development of solid lubricant materials that render reliable performance in ambient conditions, are amenable to industrial size and design complexities, and work on engineered surfaces is reported. These coatings are composed of Ti3C2Tx-Graphene Oxide blends, spray-coated onto bearing steel surfaces. The tribological assessment was carried out in ambient environmental conditions and high contact pressures in a ball-on-disc experimental set-up. The evaluation yielded that the use of Ti3C2Tx-Graphene-Oxide coatings led to substantial reduction in friction down to 0.065 (at 1 GPa contact pressure and 100 mm/s) in comparison to the uncoated of single-component-coated surfaces, surpassing the state-of-the-art. The coatings also provided excellent protection against wear loss of the substrate and counter-face. The results were explained based on the observations from Raman spectroscopy, scanning electron microscopy, transmission electron microscopy, and nanoindentation measurements. In operando formation of a dense, hard and stiff, dangling-bond-saturated tribolayer was observed to be the reason for the sustained lubricity even at high test loads and sliding speeds. This report presents the holistic exploration and correlation of structure-property-processing pertaining to the advancement of solid lubrication science.
Rapid screening of SARS-CoV-2 variants, a key tool for pandemic surveillance
Authors: Muñoz-Gallego Irene , Meléndez Carmona María Ángeles , Martín Higuera Carmen , Viedma Esther , Delgado Rafael , Folgueira María Dolores
Published: July 2023

The utility of reverse transcription-polymerase chain reaction (RT-PCR) in analysis SARS-COV-2 variants was evaluated. RT-PCR tests were used to analyse the majority of new SARS-CoV-2 cases (n = 9315) in a tertiary hospital (Madrid, Spain) throughout 2021. Subsequently, whole genome sequencing (WGS) was conducted on 10.8% of these samples (n = 1002). Notably, the Delta and Omicron variants emerged rapidly. There were no discrepancies between RT-PCR and WGS results. Continuous surveillance of SARS-CoV-2 variants is essential, and RT-PCR is a highly useful method, specially during periods of high COVID-19 incidence. This feasible technique can be implemented in all SARS-CoV-2 laboratories. However, WGS remains the gold standard method for comprehensive detection of all existing SARS-CoV-2 variants.
Potential use of dry powder of Vossia cuspidata (Roxb.) Griff. rhizomes and leaves in methylene blue dye remediation
Authors: Awad Hossam E. A. , Mohammad Ahmad M. , Farahat Emad A.
Published: July 2023

Phytoremediation is a promising, cost-effective, and eco-friendly process for wastewater treatment. Herein, the dry biomasses of Vossia cuspidata (Roxb.) Griff. leaves (PL) and rhizomes including aerial stems (PR) were used to effectively remediate methylene blue (MB) dyes. Interestingly, the adsorption uptake and removal efficiency of MB by PR were higher than those of PL; exceeding 97 and 91% in 35 and 25 min for 0.1 and 0.4 g/L MB, respectively. The MB diffusion within the PL and PR was insignificant and the adsorption kinetics was principally controlled by the surface MB–adsorbent interaction, as consistently approved by the pseudo-second order kinetic model. In addition, the adsorption increased rapidly with the plant dosage with high dependence on the initial MB concentration. Moreover, the impact of shaking speed on the adsorption was minor but temperature played a critical role where the highest efficiencies were recorded at 30 and 40 °C on PL (91.9%) and PR (93.3%), respectively. The best removal efficiencies were attained with PR at pH 6, but with PL at pH 8. The Temkin isotherm could perfectly simulate the experimental data (R2 > 0.97); suggesting a linear decrease of the adsorption heat of MB with the plant coverage.
Dog ownership may promote cardiometabolic health in U.S. military veterans
Authors: Woodward Steven H. , Baldassarri Stephen R. , Pietrzak Robert H.
Published: July 2023

Dog ownership has been associated with reduced cardiovascular and all-cause mortality in civilian epidemiological samples. Associations between dog ownership and cardiometabolic disease were examined in the 2019–2020 wave of the National Health and Resilience in Veterans Study. Dog and cat ownership data were obtained from 3078 Veterans and cross-tabulated with self-reported, professionally diagnosed, heart disease, heart attack, stroke, high blood pressure, diabetes, and high cholesterol. In unadjusted tests, dog ownership was associated with lower rates of heart disease, high blood pressure, diabetes, and high cholesterol, while cat ownership was not. Relative to non-owners, dog owners were younger, were more likely to screen positive for posttraumatic stress disorder and/or major depressive disorder, and more active. Binary logistic regression models of associations between dog ownership and cardiometabolic disease were adjusted for age, sex, trauma load, mood disorder, substance abuse, nicotine abuse, and exercise. After adjustment, dog ownership was still associated with lower odds of hypertension and high cholesterol. Dog ownership also interacted with exercise to lower odds of heart disease and attenuated the effect of trauma load on hypertension. Conversely, age interacted with dog ownership such that odds of diabetes and stroke were higher in older Veterans who owned dogs.
Aluminum surface defect detection method based on a lightweight YOLOv4 network
Authors: Li Songsong , Guo Shangrong , Han Zhaolong , Kou Chen , Huang Benchi , Luan Minghui
Published: July 2023

Deep learning is currently being used to automate surface defect detection in aluminum. The common target detection models based on neural networks often have a large number of parameters and a slow detection speed, which is not conducive to real-time detection. Therefore, this paper proposes a lightweight aluminum surface defect detection model, M2-BL-YOLOv4, based on the YOLOv4 algorithm. First, in the YOLOv4 model, the complex CSPDarkNet53 backbone network was modified into an inverted residual structure, which greatly reduced the number of parameters in the model and increased the detection speed. Second, a new feature fusion network, BiFPN-Lite, is designed to improve the fusion ability of the network and further improve its detection accuracy. The final results show that the mean average precision of the improved lightweight YOLOv4 algorithm in the aluminum surface defect test set reaches 93.5%, the number of model parameters is reduced to 60% of the original, and the number of frames per second (FPS) detected is 52.99, which increases the detection speed by 30%. The efficient detection of aluminum surface defects is realized.
Serum RGC-32 in children with systemic lupus erythematosus
Authors: Huang Bingxue , Feng Dan , Niu Xiaoling , Huang Wenyan , Hao Sheng
Published: July 2023

Childhood-onset systemic lupus erythematosus (SLE) can be more severe than adult patients. Early diagnosis and accurate evaluation of the disease are very important for the patients. Response gene to complement-32 (RGC-32) protein is the downstream regulator of C5b-9 complex which is the terminal pathway of complement activation. Complement system plays a very important role in the pathogenesis of SLE. RGC-32 in patients with SLE has not been reported yet. We aimed to examine the clinical value of RGC-32 in children with SLE. A total of 40 children with SLE and another 40 healthy children were enrolled for this study. Clinical data were obtained prospectively. Serum RGC-32 was determined by ELISA. We found that serum RGC-32 was significantly elevated in children with SLE than that in the healthy group. Serum RGC-32 was significantly higher in the children with moderately/severely active SLE than that in the children with no/mildly active SLE. Furthermore, serum RGC-32 level correlated positively with C-reactive protein, erythrocyte sedimentation rate and ferritin and correlated negatively with white blood cell counts and C3. RGC-32 may be involved in the pathogenesis of SLE. RGC-32 might become a good biomarker in the diagnosis and evaluation of SLE.
Bias sputtering of granular L10-FePt films with hexagonal boron nitride grain boundaries
Authors: Xu Chengchao , Varaprasad B. S. D. Ch. S. , Laughlin David E. , Zhu Jian-Gang
Published: July 2023

In this paper, we present an experimental study of L10-FePt granular films with crystalline boron nitride (BN) grain boundary materials for heat assisted magnetic recording (HAMR). It is found that application of a RF substrate bias (VDC = -15 V) yields the formation of hexagonal boron nitride (h-BN) nanosheets in grain boundaries, facilitating the columnar growth of FePt grains during sputtering at high temperatures. The h-BN monolayers conform to the side surfaces of columnar FePt grains, completely encircling individual FePt grains. The resulting core–shell FePt-(h-BN) nanostructures appear to be highly promising for HAMR application. The high thermal stability of h-BN grain boundaries allows the deposition temperature to be as high as 650℃ such that high order parameters of FePt L10 phase have been obtained. For the fabricated FePt-(h-BN) thin film, excellent granular microstructure with FePt grains of 6.5 nm in diameter and 11.5 nm in height has been achieved along with good magnetic hysteresis properties.
Prediction of habitat complexity using a trait-based approach on coral reefs in Guam
Authors: Ferreira Sofia B. , Burns John H. R. , Pascoe Kailey H. , Kapono Clifford A. , Reyes Andres J. , Fukunaga Atsuko
Published: July 2023

Scleractinian corals are primary contributors to the structural complexity of coral reef ecosystems. The structure derived from their carbonate skeletons underpins the biodiversity and myriad of ecosystem services provided by coral reefs. This study used a trait-based approach to provide new insights into the relationships between habitat complexity and coral morphology. Three-Dimensional (3D) photogrammetry techniques were used to survey 208 study plots on the island of Guam, from which structural complexity metrics were derived and physical traits of corals were quantified. Three traits at the individual colony level (e.g., morphology, size, and genera) and two site-level environmental characteristics (e.g., wave exposure and substratum-habitat type) were examined. Standard taxonomy-based metrics were also included at the reef-plot level (e.g., coral abundance, richness, and diversity). Different traits disproportionately contributed to 3D metrics of habitat complexity. Larger colonies with a columnar morphology have the highest contribution to surface complexity, slope, and vector ruggedness measure, whereas branching and encrusting columnar colonies have the highest contribution to planform and profile curvature. These results highlight the importance of considering colony morphology and size in addition to conventional taxonomic metrics for the understanding and monitoring reef structural complexity. The approach presented here provides a framework for studies in other locations to predict the trajectory of reefs under changing environmental conditions.
Targeted metabolomic profiling as a tool for diagnostics of patients with non-small-cell lung cancer
Authors: Shestakova Ksenia M. , Moskaleva Natalia E. , Boldin Andrey A. , Rezvanov Pavel M. , Shestopalov Alexandr V. , Rumyantsev Sergey A. , Zlatnik Elena Yu. , Novikova Inna A. , Sagakyants Alexander B. , Timofeeva Sofya V. , Simonov Yuriy , Baskhanova Sabina N. , Tobolkina Elena , Rudaz Serge , Appolonova Svetlana A.
Published: July 2023

Lung cancer is referred to as the second most common cancer worldwide and is mainly associated with complex diagnostics and the absence of personalized therapy. Metabolomics may provide significant insights into the improvement of lung cancer diagnostics through identification of the specific biomarkers or biomarker panels that characterize the pathological state of the patient. We performed targeted metabolomic profiling of plasma samples from individuals with non-small cell lung cancer (NSLC, n = 100) and individuals without any cancer or chronic pathologies (n = 100) to identify the relationship between plasma endogenous metabolites and NSLC by means of modern comprehensive bioinformatics tools, including univariate analysis, multivariate analysis, partial correlation network analysis and machine learning. Through the comparison of metabolomic profiles of patients with NSCLC and noncancer individuals, we identified significant alterations in the concentration levels of metabolites mainly related to tryptophan metabolism, the TCA cycle, the urea cycle and lipid metabolism. Additionally, partial correlation network analysis revealed new ratios of the metabolites that significantly distinguished the considered groups of participants. Using the identified significantly altered metabolites and their ratios, we developed a machine learning classification model with an ROC AUC value equal to 0.96. The developed machine learning lung cancer model may serve as a prototype of the approach for the in-time diagnostics of lung cancer that in the future may be introduced in routine clinical use. Overall, we have demonstrated that the combination of metabolomics and up-to-date bioinformatics can be used as a potential tool for proper diagnostics of patients with NSCLC.
Synthesis and pharmacological activity of the epimers of hexahydrocannabinol (HHC)
Authors: Russo Fabiana , Vandelli Maria Angela , Biagini Giuseppe , Schmid Martin , Luongo Livio , Perrone Michela , Ricciardi Federica , Maione Sabatino , Laganà Aldo , Capriotti Anna Laura , Gallo Alfonso , Carbone Luigi , Perrone Elisabetta , Gigli Giuseppe , Cannazza Giuseppe , Citti Cinzia
Published: July 2023

Cannabis is a multifaceted plant with numerous therapeutic properties on one hand, and controversial psychotropic activities on the other hand, which are modulated by CB1 endocannabinoid receptors. Δ9-Tetrahydrocannabinol (Δ9-THC) has been identified as the main component responsible for the psychotropic effects, while its constitutional isomer cannabidiol (CBD) has shown completely different pharmacological properties. Due to its reported beneficial effects, Cannabis has gained global popularity and is openly sold in shops and online. To circumvent legal restrictions, semi-synthetic derivatives of CBD are now frequently added to cannabis products, producing "high" effects similar to those induced by Δ9-THC. The first semi-synthetic cannabinoid to appear in the EU was obtained through cyclization and hydrogenation of CBD, and is known as hexahydrocannabinol (HHC). Currently, there is limited knowledge regarding HHC, its pharmacological properties, and its prevalence, as it is not commonly investigated in routine toxicological assays. In this study, synthetic strategies were explored to obtain an excess of the active epimer of HHC. Furthermore, the two epimers were purified and individually tested for their cannabinomimetic activity. Lastly, a simple and rapid chromatographic method employing a UV detector and a high-resolution mass spectrometer was applied to identify and quantify up to ten major phytocannabinoids, as well as the HHC epimers, in commercial cannabis samples.
Stressed neuronal cells can recover from profound membrane blebbing, nuclear condensation and mitochondrial fragmentation, but not from cytochrome c release
Authors: You Wenting , Zhou Tao , Knoops Kèvin , Berendschot Tos T. J. M. , van Zandvoort Marc A. M. J. , Germeraad Wilfred T. V. , Benedikter Birke , Webers Carroll A. B. , Reutelingsperger Chris P. M. , Gorgels Theo G. M. F.
Published: July 2023

Loss of neurons in chronic neurodegenerative diseases may occur over a period of many years. Once initiated, neuronal cell death is accompanied by distinct phenotypic changes including cell shrinkage, neurite retraction, mitochondrial fragmentation, nuclear condensation, membrane blebbing and phosphatidylserine (PS) exposure at the plasma membrane. It is still poorly understood which events mark the point of no return for dying neurons. Here we analyzed the neuronal cell line SH-SY5Y expressing cytochrome C (Cyto.C)-GFP. Cells were exposed temporarily to ethanol (EtOH) and tracked longitudinally in time by light and fluorescent microscopy. Exposure to EtOH induced elevation of intracellular Ca2+ and reactive oxygen species, cell shrinkage, neurite retraction, mitochondrial fragmentation, nuclear condensation, membrane blebbing, PS exposure and Cyto.C release into the cytosol. Removing EtOH at predetermined time points revealed that all phenomena except Cyto.C release occurred in a phase of neuronal cell death in which full recovery to a neurite-bearing cell was still possible. Our findings underscore a strategy of treating chronic neurodegenerative diseases by removing stressors from neurons and harnessing intracellular targets that delay or prevent trespassing the point of no return.
Bound entanglement is not Lorentz invariant
Authors: Caban Paweł , Hiesmayr Beatrix C.
Published: July 2023

Bound entanglement, in contrast to free entanglement, cannot be distilled into maximally entangled states by two local observers applying measurements and utilizing classical communication. In this paper we ask whether a relativistic observer classifies states according to being separable, bound or free entangled in the same manner as an unboosted observer. Surprisingly, this turns out not to be the case. And that even if the system in a given inertial frame of reference is separable with respect to the partition momenta versus spins. In detail, we show that if the spin state is initially bound entangled, some boosted observers observe their spin states to be either bound entangled, separable or free entangled. This also explains why a general measure of the entanglement property is difficult to find.
Quantification of cartilage and subchondral bone cysts on knee specimens based on a spectral photon-counting computed tomography
Authors: Garcelon Célestin , Abascal Juan , Olivier Cecile , Uk Stéphanie , Si-Mohamed Salim , Ea Hang-Korng , Douek Philippe , Peyrin Francoise , Chappard Christine
Published: July 2023

Spectral photon-counting computed tomography (SPCCT) is a new technique with the capability to provide mono-energetic (monoE) images with high signal to noise ratio. We demonstrate the feasibility of SPCCT to characterize at the same time cartilage and subchondral bone cysts (SBCs) without contrast agent in osteoarthritis (OA). To achieve this goal, 10 human knee specimens (6 normal and 4 with OA) were imaged with a clinical prototype SPCCT. The monoE images at 60 keV with isotropic voxels of 250 × 250 × 250 µm3 were compared with monoE synchrotron radiation CT (SR micro-CT) images at 55 keV with isotropic voxels of 45 × 45 × 45 µm3 used as benchmark for cartilage segmentation. In the two OA knees with SBCs, the volume and density of SBCs were evaluated in SPCCT images. In 25 compartments (lateral tibial (LT), medial tibial, (MT), lateral femoral (LF), medial femoral and patella), the mean bias between SPCCT and SR micro-CT analyses were 101 ± 272 mm3 for cartilage volume and 0.33 mm ± 0.18 for mean cartilage thickness. Between normal and OA knees, mean cartilage thicknesses were found statistically different (0.005 < p < 0.04) for LT, MT and LF compartments. The 2 OA knees displayed different SBCs profiles in terms of volume, density, and distribution according to size and location. SPCCT with fast acquisitions is able to characterize cartilage morphology and SBCs. SPCCT can be used potentially as a new tool in clinical studies in OA.
A comparison of different machine-learning techniques for the selection of a panel of metabolites allowing early detection of brain tumors
Authors: Godlewski Adrian , Czajkowski Marcin , Mojsak Patrycja , Pienkowski Tomasz , Gosk Wioleta , Lyson Tomasz , Mariak Zenon , Reszec Joanna , Kondraciuk Marcin , Kaminski Karol , Kretowski Marek , Moniuszko Marcin , Kretowski Adam , Ciborowski Michal
Published: July 2023

Metabolomics combined with machine learning methods (MLMs), is a powerful tool for searching novel diagnostic panels. This study was intended to use targeted plasma metabolomics and advanced MLMs to develop strategies for diagnosing brain tumors. Measurement of 188 metabolites was performed on plasma samples collected from 95 patients with gliomas (grade I–IV), 70 with meningioma, and 71 healthy individuals as a control group. Four predictive models to diagnose glioma were prepared using 10 MLMs and a conventional approach. Based on the cross-validation results of the created models, the F1-scores were calculated, then obtained values were compared. Subsequently, the best algorithm was applied to perform five comparisons involving gliomas, meningiomas, and controls. The best results were obtained using the newly developed hybrid evolutionary heterogeneous decision tree (EvoHDTree) algorithm, which was validated using Leave-One-Out Cross-Validation, resulting in an F1-score for all comparisons in the range of 0.476–0.948 and the area under the ROC curves ranging from 0.660 to 0.873. Brain tumor diagnostic panels were constructed with unique metabolites, which reduces the likelihood of misdiagnosis. This study proposes a novel interdisciplinary method for brain tumor diagnosis based on metabolomics and EvoHDTree, exhibiting significant predictive coefficients.
A stratified flow of a non-Newtonian Casson fluid comprising microorganisms on a stretching sheet with activation energy
Authors: Lone Showkat Ahmad , Anwar Sadia , Saeed Anwar , Bognár Gabriella
Published: July 2023

A stratified flow may be seen regularly in a number of significant industrial operations. For instance, the stratified flow regime is typically used by gas-condensate pipelines. Clearly, only a limited set of working situations for which this flow arrangement is stable allow for the achievement of the stratified two-phase flow zone. In this paper, the authors are considered the laminar, steady and incompressible magnetohydrodynamic flow of a non-Newtonian Casson fluid flow past a stratified extending sheet. The features of bio-convection, Brownian motion, thermal radiation thermophoresis, heat source, and chemically reactive activation energy have been employed. The set of equations administered flow of fluid is converted into ordinary differential equation by suitable variables. A semi-analytical investigation of the present analysis is performed with homotopy analysis method. Endorsement of the current results with previous results is also investigated. The outcomes showed that the velocity distribution of the fluid flow lessens with higher Casson and magnetic factors. The temperature profiles of fluid flow shrinkage as the Prandtl number and Casson factor increase and enlarges with higher values of thermal radiation, magnetic, and Brownian motion factors. It is found that the growing thermophoretic and Brownian motion factors reduce the rate of thermal flow of the Casson fluid flow. In contrast, the increasing thermal stratification parameter increases the thermal flow rate of fluid.
Utilizing a nomogram to predict the one-year postoperative mortality risk for geriatric patients with a hip fracture
Authors: Wu Cheng-Yi , Tsai Ching-Fang , Yang Hsin-Yi
Published: July 2023

Despite the abundance of research on the risk factors for mortality following hip fracture surgery, there has been a dearth of studies on prediction models in this population. The objective of this research was to explore the influencing factors and construct a clinical nomogram to predict one-year postoperative mortality in patients with hip fracture surgeries. Using the Ditmanson Research Database (DRD), we included 2333 subjects, aged ≥ 50 years who underwent hip fracture surgery between October, 2008 and August, 2021. The endpoint was all-cause mortality. A least absolute shrinkage and selection operator (LASSO) derived Cox regression was performed to select the independent predictors of one-year postoperative mortality. A nomogram was built for predicting one-year postoperative mortality. The prognostic performance of nomogram was evaluated. On the basis of tertiary points in a nomogram, the patients were divided into low, middle and high risk groups, and compared by the Kaplan–Meier analysis. Within 1 year after hip fracture surgery, 274 patients (11.74%) died. Variables retained in the final model comprised age, sex, length of stay, RBC transfusions, hemoglobin, platelet, and eGFR. The AUC for one-year mortality predictions were 0.717 (95% CI = 0.685–0.749). The Kaplan–Meier curves were significantly different among the three risk groups (p < 0.001). The nomogram showed good calibration. In summary, we explored the one-year postoperative mortality risk in geriatric patients with a hip fracture and developed a prediction model that could help clinicians identify patients at high risk of postoperative mortality.
Reverse effect of home-use binaural beats brain stimulation
Authors: Klichowski Michal , Wicher Andrzej , Kruszwicka Agnieszka , Golebiewski Roman
Published: July 2023

Binaural beats brain stimulation is a popular strategy for supporting home-use cognitive tasks. However, such home-use brain stimulation may be neutral to cognitive processes, and any intellectual improvement may be only a placebo effect. Thus, without belief in it, it may bring no benefits. Here we test 1000 individuals at their homes as they perform a two-part fluid intelligence test. Some took the second part listening to binaural beats, while others took it in silence or listening to other sounds. The binaural beats group was divided into three subgroups. The first one was informed that they would listen to sounds that improve the brain's work, the second that neutral sounds, and the third that some sounds the nature of which was not defined. We found that listening to binaural beats was not neutral, as it dramatically deteriorated the score irrespective of the condition. Silence or other sounds had no effect. Thus, home-use binaural beats brain stimulation brings reverse effects to those assumed: instead of supporting the effectiveness of cognitive activities, it may weaken them.
MicroRNA-146a negatively regulates inflammation via the IRAK1/TRAF6/NF-κB signaling pathway in dry eye
Authors: Han Ruifang , Gao Juan , Wang Liming , Hao Peng , Chen Xi , Wang Yuchuan , Jiang Zhixin , Jiang Li , Wang Ting , Zhu Lin , Li Xuan
Published: July 2023

Inflammation is a key factor in the pathogenesis of dry eye disease (DED). We aimed to investigate the role of microRNA-146a (miR-146a) in regulating corneal inflammation in a mouse model of benzalkonium chloride (BAC)-induced dry eye and the TNF-α-induced NF-κB signaling pathway in human corneal epithelial cells (HCECs). A mouse model of dry eye was established by administering with BAC to BALB/c mice, and the expression of TNF-α, IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) in the corneas of dry eye model mice was significantly increased; this was accompanied by the upregulation of miR-146a and activation of the NF-κB pathway. In vitro, TNF-α induced miR-146a expression in HCECs, while the NF-κB inhibitor SC-514 reduced the expression of miR-146a. Overexpression of miR-146a decreased the expression of IRAK1 and TRAF6, which have been identified as targets of miR-146a. Furthermore, overexpression of miR-146a suppressed NF-κB p65 translocation from the cytoplasm to the nucleus. Moreover, overexpression of miR-146a attenuated the TNF-α-induced expression of IL-6, IL-8, COX2 and intercellular adhesion molecule 1 (ICAM1), while inhibition of miR-146a exerted the opposite effect. Our results suggest that miR-146a mediates the inflammatory response in DED. MiR-146a negatively regulates inflammation in HCECs through the IRAK1/TRAF6/NF-κB pathway, and this may serve as a potential therapeutic approach for the treatment of DED.
Avoidable heat-related mortality in China during the 21st century
Authors: Zhang Guwei , Sun Zhaobin , Han Ling , Iyakaremye Vedaste , Xu Zhiqi , Miao Shiguang , Tong Shilu
Published: July 2023

Using non-accidental mortality records from 195 sites and 11 model simulations from the Coupled Model Intercomparison Project phase 6, we assessed future avoidable heat-related deaths associated with emission mitigation after accounting for population changes in China. Without human-induced climate change in the 21st century, China’s heat-related mortality would drop by 48–72% (95% confidence interval (CI): 40–76%), especially at high latitudes and altitudes (up to 80%). Nationally, 15,576–87,612 (95% CI: 6605–106,736) heat-related deaths per year would potentially be avoided by reducing emissions. For most of China, temperature changes dominate the variation in heat-related deaths, while in Central and South China, population changes will have a greater influence. These not only reinforce the necessity of mitigating emissions but also suggest that adjusting population structure and spatial distribution could be applied in some areas to minimize warming impacts on public health. Notably, given that abatement will hardly bring immediate success within the next twenty years, more healthcare infrastructures are urgently needed to manage potential growing heat risks. Particularly in Northwest and South China, where future heat-related deaths would still be 110–140% of current levels (1995–2014) even without anthropogenic warming. We also found that without historical human-induced emissions, China’s low level of technology (medical and economic) might increase current heat-related mortality by 57%, even though warming could be mitigated. Consequently, we believe that mitigating climate change risks also requires consideration of the economic/medical losses from lowering emissions.
Global within-species phylogenetics of sewage microbes suggest that local adaptation shapes geographical bacterial clustering
Authors: Jespersen Marie Louise , Munk Patrick , Johansen Joachim , Kaas Rolf Sommer , Webel Henry , Vigre Håkan , Nielsen Henrik Bjørn , Rasmussen Simon , Aarestrup Frank M.
Published: July 2023

Most investigations of geographical within-species differences are limited to focusing on a single species. Here, we investigate global differences for multiple bacterial species using a dataset of 757 metagenomics sewage samples from 101 countries worldwide. The within-species variations were determined by performing genome reconstructions, and the analyses were expanded by gene focused approaches. Applying these methods, we recovered 3353 near complete (NC) metagenome assembled genomes (MAGs) encompassing 1439 different MAG species and found that within-species genomic variation was in 36% of the investigated species (12/33) coherent with regional separation. Additionally, we found that variation of organelle genes correlated less with geography compared to metabolic and membrane genes, suggesting that the global differences of these species are caused by regional environmental selection rather than dissemination limitations. From the combination of the large and globally distributed dataset and in-depth analysis, we present a wide investigation of global within-species phylogeny of sewage bacteria. The global differences found here emphasize the need for worldwide data sets when making global conclusions.
Sensitive microscale thermophoresis assay for rapid ochratoxin A detection with fluorescently labeled engineered aptamer
Authors: Yu Hao , Zhao Qiang
Published: July 2023

A one-step aptamer microscale thermophoresis assay for rapid detection of ochratoxin A is achieved by using a FAM-labeled aptamer.
Comparison of recovery efficiency and matrix effect reduction in pesticide residue analysis: QuEChERS with d-SPE, SPE, and FaPEx in apples and Korean cabbage
Authors: Lee Hyosub , Cho Yuran , Jung Geonhee , Kim Hyanghee , Jeong Wontae
Published: July 2023

The method validation of 128 pesticides, employing FaPEx (amine + C17) and QuEChERS with SPE (PSA + C18), yielded a compliance rate over 98%.
A simple and rapid strategy for monitoring vancomycin concentration in serum using a multicolor immunosensor based on the ratio of gold nanobipyramids and a product of cetyltrimethylammonium bromide-blue oxide of 3,3′,5,5′-tetramethylbenzidine interaction
Authors: Fu Yanwei , Yang Chunjing , Liu Congmin , Xu Xiqiao , Shi Zhengyuan , Jiang Dechun , Yan Dan
Published: July 2023

A rapid and simple multicolor immunosensor was developed for monitoring of vancomycin concentration, and the immunosensor presented good color stability, user friendliness and portability.
Metal–organic-framework-based pyroptosis nanotuner with long blood circulation for augmented chemotherapy
Authors: Zhu Weichu , Xu Jian , Yao Xianxian , Mai Shuting , Shu Dan , Yang Wuli
Published: July 2023

The pH- and glutathione-responsive long-circulating nanotuner could release decitabine and doxorubicin to induce pyroptosis for enhanced tumor chemotherapy.