bluuebunny/crossref_metadata_2025 huggingface dataset:
FGF-2 enhances fibrogenetic changes in TGF-β2 treated human conjunctival fibroblasts
Authors: Tsugeno Yuri , Furuhashi Masato , Sato Tatsuya , Watanabe Megumi , Umetsu Araya , Suzuki Soma , Ida Yosuke , Hikage Fumihito , Ohguro Hiroshi
Published: September 2022

The objective of the current study was to examine the effects of fibroblast growth factor-2 (FGF-2) on conjunctival fibrogenesis that was induced by the presence of transforming growth factor-β2 (TGF-β2). Two-dimension (2D) and three-dimension (3D) cultured human conjunctival fibroblasts (HconF) were used for this purpose. The 2D and 3D cultured HconF were characterized by transendothelial electrical resistance (TEER) and FITC dextran permeability measurements (2D), real-time metabolic analyses (2D), size and stiffness measurements (3D), and the mRNA expression of extracellular matrix molecules, their modulators, Tissue inhibitor of metalloproteinases and matrix metalloproteinases and ER-stress related genes (2D and 3D). FGF-2 significantly increased planar proliferation, as evidenced by TEER values and FITC dextran permeability, and shifted glucose metabolism to the energetic phenotype of 2D HconF cells, and the stiffness of the 3D spheroids, and these effects were further enhanced in the presence of TGF-β2. Analyses of the expression of possible candidate molecules involved in cell architecture and stress indicated that some additive effects caused by both factors were also recognized in some of these molecules. The findings reported herein indicate that the FGF-2, either along or additively with TGF- β2 increased the fibrogenetic changes on the plane as well as in the spatial space of HconF cells.
Identification of the effects of COVID-19 on patients with pulmonary fibrosis and lung cancer: a bioinformatics analysis and literature review
Authors: Li Yang , Niu Lipeng
Published: September 2022

Coronavirus disease 2019 (COVID-19) poses a serious threat to human health and life. The effective prevention and treatment of COVID-19 complications have become crucial to saving patients’ lives. During the phase of mass spread of the epidemic, a large number of patients with pulmonary fibrosis and lung cancers were inevitably infected with the SARS-CoV-2 virus. Lung cancers have the highest tumor morbidity and mortality rates worldwide, and pulmonary fibrosis itself is one of the complications of COVID-19. Idiopathic lung fibrosis (IPF) and various lung cancers (primary and metastatic) become risk factors for complications of COVID-19 and significantly increase mortality in patients. Therefore, we applied bioinformatics and systems biology approaches to identify molecular biomarkers and common pathways in COVID-19, IPF, colorectal cancer (CRC) lung metastasis, SCLC and NSCLC. We identified 79 DEGs between COVID-19, IPF, CRC lung metastasis, SCLC and NSCLC. Meanwhile, based on the transcriptome features of DSigDB and common DEGs, we identified 10 drug candidates. In this study, 79 DEGs are the common core genes of the 5 diseases. The 10 drugs were found to have positive effects in treating COVID-19 and lung cancer, potentially reducing the risk of pulmonary fibrosis.
Health behavior changes and mortality among South Korean cancer survivors
Authors: Jeong Wonjeong , Park Eun-Cheol , Nam Chung Mo , Park Sohee , Nam Jin Young , Jang Sung-In
Published: September 2022

Considering the rapid growth in the number of cancer survivors, the successful management of their health behaviors requires further attention. However, there are lack of information about cancer survivors’ health behaviors and the risk of mortality using Korean cohort data. This study aimed to examine the effects of health behavior changes on mortality among cancer survivors and to develop a validated nomogram. This cohort study was conducted using claims data. Data from adult cancer survivors from the National Health Insurance Service–National Sample Cohort, conducted between 2002 and 2015, were included. Individuals who were alive for five years after their cancer diagnosis were defined as cancer survivors. Cox proportional-hazards regression was used to estimate the target associations. Discrimination (Harrell’s C-index) and calibration (Hosmer–Lemeshow test) were employed to validate the nomogram. Data from 9300 cancer survivors were used for analysis. Compared to non-smokers, those who started or quit smoking had a higher risk of all-cause mortality. Those who were physically inactive had a higher risk of all-cause mortality than those who were continuously active. In the nomogram, the C-index value was 0.79 in the training data and 0.81 in the testing data. Hosmer–Lemeshow test was not significant, demonstrating a good fit. We found that individuals with unhealthy behaviors had a higher risk of mortality, thereby highlighting the importance of managing health behaviors among cancer survivors. The development of a validated nomogram may provide useful insights regarding official policies and existing practices in healthcare systems, which would benefit cancer survivors. Our study could provide the evidence to inform the priority of guideline for managing the health behavior among cancer survivors.
Synthesis of patient-specific multipoint 4D flow MRI data of turbulent aortic flow downstream of stenotic valves
Authors: Dirix Pietro , Buoso Stefano , Peper Eva S. , Kozerke Sebastian
Published: September 2022

We propose to synthesize patient-specific 4D flow MRI datasets of turbulent flow paired with ground truth flow data to support training of inference methods. Turbulent blood flow is computed based on the Navier–Stokes equations with moving domains using realistic boundary conditions for aortic shapes, wall displacements and inlet velocities obtained from patient data. From the simulated flow, synthetic multipoint 4D flow MRI data is generated with user-defined spatiotemporal resolutions and reconstructed with a Bayesian approach to compute time-varying velocity and turbulence maps. For MRI data synthesis, a fixed hypothetical scan time budget is assumed and accordingly, changes to spatial resolution and time averaging result in corresponding scaling of signal-to-noise ratios (SNR). In this work, we focused on aortic stenotic flow and quantification of turbulent kinetic energy (TKE). Our results show that for spatial resolutions of 1.5 and 2.5 mm and time averaging of 5 ms as encountered in 4D flow MRI in practice, peak total turbulent kinetic energy downstream of a 50, 75 and 90% stenosis is overestimated by as much as 23, 15 and 14% (1.5 mm) and 38, 24 and 23% (2.5 mm), demonstrating the importance of paired ground truth and 4D flow MRI data for assessing accuracy and precision of turbulent flow inference using 4D flow MRI exams.
Semisynthetic teicoplanin derivatives with dual antimicrobial activity against SARS-CoV-2 and multiresistant bacteria
Authors: Bereczki Ilona , Vimberg Vladimir , Lőrincz Eszter , Papp Henrietta , Nagy Lajos , Kéki Sándor , Batta Gyula , Mitrović Ana , Kos Janko , Zsigmond Áron , Hajdú István , Lőrincz Zsolt , Bajusz Dávid , Petri László , Hodek Jan , Jakab Ferenc , Keserű György M. , Weber Jan , Naesens Lieve , Herczegh Pál , Borbás Anikó
Published: September 2022

Patients infected with SARS-CoV-2 risk co-infection with Gram-positive bacteria, which severely affects their prognosis. Antimicrobial drugs with dual antiviral and antibacterial activity would be very useful in this setting. Although glycopeptide antibiotics are well-known as strong antibacterial drugs, some of them are also active against RNA viruses like SARS-CoV-2. It has been shown that the antiviral and antibacterial efficacy can be enhanced by synthetic modifications. We here report the synthesis and biological evaluation of seven derivatives of teicoplanin bearing hydrophobic or superbasic side chain. All but one teicoplanin derivatives were effective in inhibiting SARS-CoV-2 replication in VeroE6 cells. One lipophilic and three perfluoroalkyl conjugates showed activity against SARS-CoV-2 in human Calu-3 cells and against HCoV-229E, an endemic human coronavirus, in HEL cells. Pseudovirus entry and enzyme inhibition assays established that the teicoplanin derivatives efficiently prevent the cathepsin-mediated endosomal entry of SARS-CoV-2, with some compounds inhibiting also the TMPRSS2-mediated surface entry route. The teicoplanin derivatives showed good to excellent activity against Gram-positive bacteria resistant to all approved glycopeptide antibiotics, due to their ability to dually bind to the bacterial membrane and cell-wall. To conclude, we identified three perfluoralkyl and one monoguanidine analog of teicoplanin as dual inhibitors of Gram-positive bacteria and SARS-CoV-2.
Effect of Cosmos, Crotalaria, Foeniculum, and Canavalia species, single-cropped or mixes, on the community of predatory arthropods
Authors: Barros Adamastor Pereira , de Carvalho Silva Alessandra , de Souza Abboud Antonio Carlos , Ricalde Marcelo Perrone , Ataide Julielson Oliveira
Published: September 2022

Some plants can attract natural enemy by offering resources such as alternative food and refuge. However, studies need to be conducted before agricultural landscape diversification is implement. Our objective was to determine the best floristic compositions of cosmos (Cosmos sulphureus—Asteraceae), showy rattlepod (Crotalaria spectabilis—Fabaceae), fennel (Foeniculum vulgare—Apiaceae), and jack bean (Canavalia ensiformis—Fabaceae) to attract and maintain predatory arthropods, and know the potential of these treatments for future use in diversifying agricultural systems. The experimental design consisted in seven treatments of four species in single-crop, intercrops in three densities called mix1, mix2, and mix3, and the control (weeds). For the arthropod families classified as very frequent and constant, population dynamics in intercropping treatments was plotted according to the plant phenology. We conclude that all plants cultivated in single-cropping and intercropping treatments showed high predator richness and can potentially be used to diversify cultivated areas. Sulfur cosmos as a single crop and three mixes attracts higher numbers and greater family richness. Spider families—Oxyopidae, Araneidae and Thomisidae—and insects—Chrysopidae and Coccinellidae are more frequents. The dynamics of the predator populations varied according to the mixes treatment.
Exceptionally robust magnetism and structure of SrFeO$$_2$$ above 100 GPa
Authors: Balédent V. , Nataf L. , Rueff J.-P.
Published: September 2022

We report the exceptional structural and magnetic stability of SrFeO$$_2$$

2

under pressure by X-Ray Magnetic Circular Dichroism (XMCD) and X-ray Diffraction (XRD) up to the Mbar range. The XMCD data confirm the onset of ferromagnetism above 30 GPa and its stability up to 102 GPa while XRD shows that SrFeO$$_2$$

2

structure remains unchanged from 30 GPa up to 111 GPa without any sign of structural transition. Our results demonstrate the robustness of Fe properties under extreme conditions in the square planar environment.
Striatal D1 and D2 receptor availability are selectively associated with eye-blink rates after methylphenidate treatment
Authors: Demiral Şükrü B. , Manza Peter , Biesecker Erin , Wiers Corinde , Shokri-Kojori Ehsan , McPherson Katherine , Dennis Evan , Johnson Allison , Tomasi Dardo , Wang Gene-Jack , Volkow Nora D.
Published: September 2022

Eye-blink rate has been proposed as a biomarker of the brain dopamine system, however, findings have not been consistent. This study assessed the relationship between blink rates, measured after oral placebo) (PL) and after a challenge with oral methylphenidate (MP; 60 mg) and striatal D1 receptor (D1R) (measured at baseline) and D2 receptor (D2R) availability (measured after PL and after MP) in healthy participants. PET measures of baseline D1R ([11C]NNC112) (BL-D1R) and D2R availability ([11C]raclopride) after PL (PL-D2R) and after MP (MP-D2R) were quantified in the striatum as non-displaceable binding potential. MP reduced the number of blinks and increased the time participants kept their eyes open. Correlations with dopamine receptors were only significant for the eye blink measures obtained after MP; being positive for BL-D1R in putamen and MP-D2R in caudate (PL-D2R were not significant). MP-induced changes in blink rates (PL minus MP) were negatively correlated with BL-D1R in caudate and putamen. Our findings suggest that eye blink measures obtained while stressing the dopamine system might provide a more sensitive behavioral biomarker of striatal D1R or D2R in healthy volunteers than that obtained at baseline or after placebo.
3D stochastic interferometer detects picometer deformations and minute dielectric fluctuations of its optical volume
Authors: Graciani Guillaume , Filoche Marcel , Amblard François
Published: September 2022

Speckle metrology harnesses the interferometric properties of disordered light to achieve remarkable sensitivities. Often relying on time-domain analysis, it is rate-limited by the acquisition of speckle images. In the present work instead, we use a frequency-domain approach which spans 8 to 10 frequency decades up to 100 MHz, and reveals minute changes of speckle decorrelation spectra. We built a 3D stochastic interferometer using a centimeter-sized quartz-powder cavity with arbitrary shape and high Lambertian reflectivity. Filled with a coherent monochromatic photon gas, it creates statistically isotropic and homogeneous 3D interference patterns, whose variations arise from cavity deformations or fluctuations of the dielectric tensor field inside. Speckle decorrelation depends neither on where the perturbation sits nor on where it is measured. With an average 62 m photon transit path and a finesse of 10500, cavity deformations are detected with a power noise floor of 4 × 10−3 pm2, i.e., 2.7 pm at 1 kHz. We also demonstrate a 100-fold sensitivity gain compared to conventional light scattering techniques when probing thermal motions of single and multiply scattering colloids.
Cave opening and fossil accumulation in Naracoorte, Australia, through charcoal and pollen in dated speleothems
Authors: Weij Rieneke , Woodhead Jon D. , Sniderman J. M. Kale , Hellstrom John C. , Reed Elizabeth , Bourne Steven , Drysdale Russell N. , Pollard Timothy J.
Published: September 2022

Caves are important fossil repositories which provide records extending back over million-year timescales. While the physical processes of cave formation are well understood, the timing of initial cave development and opening—a more important parameter to studies of palaeontology, palaeoanthropology and archaeology—has proved more difficult to constrain. Here we investigate speleothems from the Naracoorte Cave Complex in southern Australia, with a rich record of Pleistocene vertebrate fossils (including extinct megafauna) and partly World Heritage-listed, using U-Th-Pb dating and analyses of their charcoal and pollen content. We find that, although speleothem formation began at least 1.34 million years ago, pollen and charcoal only began to be trapped within growing speleothems from 600,000 years ago. We interpret these two ages to represent the timing of initial cave development and the subsequent opening of the caves to the atmosphere respectively. These findings demonstrate the potential of U-Th-Pb dating combined with charcoal and pollen as proxies to assess the potential upper age limit of vertebrate fossil records found within caves.
Drone-based particle monitoring above two harmful algal blooms (HABs) in the USA
Authors: Bilyeu Landon , Bloomfield Bryan , Hanlon Regina , González-Rocha Javier , Jacquemin Stephen J. , Ault Andrew P. , Birbeck Johnna A. , Westrick Judy A. , Foroutan Hosein , Ross Shane D. , Powers Craig W. , Schmale David G.
Published: September 2022

Little is known about the transport and fate of aerosolized particles associated with harmful algal blooms (HABs).
Lipidomic analysis probes lipid coronas on hydrophilic nanoparticles from natural lung surfactant
Authors: Bai Xuan , Lam Sin Man , Nie Pengcheng , Xu Ming , Liu Sijin , Shui Guanghou , Hu Guoqing
Published: September 2022

Liquid chromatography-mass spectrometry and molecular dynamics simulation demonstrate that positive surface charges promote the formation of a complete lipid corona with compositions different from the pristine natural lung surfactant.
Triplet–triplet annihilation upconversion in LAPONITE®/PVP nanocomposites: absolute quantum yields of up to 23.8% in the solid state and application to anti-counterfeiting
Authors: Wei Lingling , Fan Chunying , Rao Ming , Gao Fanrui , He Cheng , Sun Yujiao , Zhu Sijia , He Qiuhui , Yang Cheng , Wu Wanhua
Published: September 2022

An organic–inorganic hybrid nanocomposite-based dry gel fabricated by self-assembly of LAPONITE® clay and PVP showed the highest solid-state TTA-UC quantum yield of 23.8% under air which was conveniently applied to anti-counterfeiting.
The benefits of combining 1D and 3D nanofillers in a piezocomposite nanogenerator for biomechanical energy harvesting
Authors: Hanani Zouhair , Izanzar Ilyasse , Merselmiz Soukaina , Amjoud M'barek , Mezzane Daoud , Ghanbaja Jaafar , Saadoune Ismael , Lahcini Mohammed , Spreitzer Matjaž , Vengust Damjan , El Marssi Mimoun , Kutnjak Zdravko , Luk'yanchuk Igor A. , Gouné Mohamed
Published: September 2022

Design of a self-poled, bio-flexible and ultra-sensitive piezoelectric nanogenerator based on HZTO nanowires and BCZT multipods as fillers and PLA as a biopolymer matrix.
Synthesis of fluorinated polycyclic dehydroaltenusin analogs through hypervalent iodine-catalyzed dearomatization
Authors: Cao Jiaqi , Deng Qingfu , Hu Liangzhen , Zhang Xiaohui , Xiong Yan
Published: September 2022

We developed a convenient method to synthesize fluorine-containing dehydroaltenusin analogs under mild conditions, and without expensive reagents.
The effect of Sr doping on the electronic structure and electromagnetic properties of LaCo0.9Fe0.1O3 perovskites
Authors: Wang Fan , Wu Yue , Zhao Yue , Zhou Ming , Tang Shaolong , Ji Guangbin
Published: September 2022

Herein, different La/Sr molar ratios of LSCFO perovskites were prepared via a sol–gel method. The electronic structure of LSCFO perovskites was investigated by the density functional theory and first principles calculation.
2D NbIrTe4 and TaRhTe4 monolayers: two fascinating topological insulators as electrocatalysts for oxygen reduction
Authors: Lv Mingyue , Yu Guangtao , Chen Wei
Published: September 2022

2D topological insulator NbIrTe4 and TaRhTe4 monolayers can be high-efficiency oxygen reduction electrocatalysts with good selectivity of 4e pathway for fuel cells. Topological behavior also plays an important role in their oxygen reduction activity.
Carbon cage isomers and magnetic Dy⋯Dy interactions in Dy2O@C88 and Dy2C2@C88 metallofullerenes
Authors: Yang Wei , Velkos Georgios , Sudarkova Svetlana , Büchner Bernd , Avdoshenko Stanislav M. , Liu Fupin , Popov Alexey A. , Chen Ning
Published: September 2022

Isomers of Dy2O@C88 and Dy2C2@C88 show a strong variation in the type and strength of Dy⋯Dy superexchange interactions and magnetization relaxation rate.
Ba4Ag5(IO3)6(I3O8)3(I4O11)2: a nonlinear optical crystal containing two types of polyiodate anions
Authors: Chen Jin , Chen Qian-Qian , Mao Fei-Fei , Liu Zhen , Li Bing-Xuan , Wu Xiao-Hui , Du Ke-Zhao
Published: September 2022

Herein, a novel metal polyiodate, namely, Ba4Ag5(IO3)6(I3O8)3(I4O11)2, has been prepared by using H3PO4 (≥85 wt% in H2O) as the reaction medium.
Electrospun dual-aeolotropic conductive exceptive Janus membrane and Janus tubule functionalized by up-/down-converting fluorescence and magnetism
Authors: Yang Xiuling , Qi Haina , Jiang Shaohua , Zhang Chunmei , Dong Xiangting
Published: September 2022

Micro- and macro-divisions realized synchronously in the SJM are integrated into Janus tubules to reduce the adverse interactions among the various substances, and realize the triumphant transition from a 2D Janus array membrane to 3D Janus tubules.
In situ oxidative etching-enabled synthesis of hollow Cu2O nanocrystals for efficient CO2RR into C2+ products
Authors: Zhang Haifeng , Qiao Yan , Wang Yingying , Zheng Yiqun , Huang Hongwen
Published: September 2022

The prepared hollow Cu2O nanocrystals via oxidative etching yield C2+ products with a faradaic efficiency of 75.9% and a C2+ partial current density of 0.54 A cm−2 ascribed to their defect-rich sites and abundant stepped facets.
Biobased catalyst-free covalent adaptable networks based on CF3-activated synergistic aza-Michael exchange and transesterification
Authors: Berne Dimitri , Quienne Baptiste , Caillol Sylvain , Leclerc Eric , Ladmiral Vincent
Published: September 2022

This study reports the synthesis and characterization of biobased CANs incorporating CF3-activated aza-Michael bonds and ester groups showing remarkable reprocessing abilities and high activation energy.
In vitro reconstitution of kallikrein-kinin system and progress curve analysis
Authors: Favier Bertrand , Bicout Dominique J. , Baroso Rémi , Paclet Marie-Hélène , Drouet Christian
Published: September 2022

Human kallikrein-kinin system (KKS) is a proteolytic cascade with two serine-protease zymogen couples (Factor XII and prekallikrein (PK) and their activated forms, FXIIa, PKa, respectively), releasing bradykinin by cleavage of native high-molecular-weight kininogen (nHK) into cleaved HK. For KKS investigation in human plasma, this cascade is usually triggered on ice eventually by mixing with purified proteins. It has been established that purified FXIIa, PK, and nHK required a fixed order and timing for mixing protein on ice to ensure reproducibility of testing, we investigated the activation kinetics of both enzymes. The activation process of this in vitro minimal reconstitution of KKS was studied by progress curve analysis, in condition of high enzyme/substrate ratio and by using on natural rather than peptide substrates.

FXIIa and PKa were found five-times less active on ice than at 37°C: kcat = 0.133 ± 0.034 and 0.0119 ± 0.0027 s−1, KM = 672 ± 150 and 115 ± 24 nM, respectively. The progress curve analysis of our in vitro KKS reconstitutions differed from a Michaelis–Menten mathematical simulation by a faster initial rate and a slower late rate. These two features were also observed ex vivo by using dextran sulfate-activated plasma and could reinforce the hypothesis of a maximal local effect (bradykinin release) and a minimal systemic consequence (PK preservation) in KKS activation process.

Analyzing the complete curve of cold KKS activation would provide valuable information for ex vivo investigation of KKS in samples from patients presenting with hereditary angioedema and other inflammatory conditions.
ANGPTL1, Foxo3a-Sox2, and colorectal cancer metastasis
Authors: Jiang Kai , Chen Haiyan , Ding Kefeng
Published: September 2022

In the present commentary, we discuss new observations stating that angiopoietin-like protein 1 (ANGPTL1) attenuates cancer metastasis and stemness through Forkhead box O-3a (Foxo3a)–SRY-related HMG-box-2 (Sox2) axis in colorectal cancer (Clin. Sci. (2022) 136, 657–673, https://doi.org/10.1042/CS20220043). ANGPTL1 has been reported to play a critical role in cancer progression and metastasis. However, the underlying mechanisms remain controversial. Here, we integrate the possible mechanisms for ANGPTL1 inhibiting colorectal cancer liver metastasis and discuss the regulation of ANGPTL1 on the Foxo3a–Sox2 pathway. Although ANGPTL1 showed multifunctional potential, there is still a long way to go for ANGPTL1 to be an effective treatment strategy in the clinic.
Reduction mechanisms for dislocation densities in GaN heteroepitaxy over Si substrate patterned with a serpentine channel structure
Authors: Wang Kejia , Wei Tiantian , Song Yuzi , Xie Yahong , Hu Xiaodong , Cheng Zhiyuan
Published: September 2022

Heteroepitaxial growth of gallium nitride (GaN) over patterned Silicon (Si) substrates using serpentine channel structure was demonstrated and studied with transmission electron microscopy (TEM). Cross‐sectional TEM images showed that the dislocations were filtered out effectively, through two 90° turns in GaN growth front with the unique serpentine channel structure, resulting in high crystal quality GaN materials over the top mask layer. Dislocation behaviours at different parts of the structure were investigated to understand the mechanism of dislocation density reduction.
A boost converter‐based MPPT steady‐state oscillation‐free fast tracking control strategy for photovoltaic power systems
Authors: Li Ning , Zhang Changjie , Wei Deng , Liu Ming , Zhang Yan
Published: September 2022

With the conventional perturbation and observation (P&O) method, photovoltaic (PV) converters have long maximum power point (MPP) tracking times and three‐point oscillations at the steady state that can lead to output power losses and inefficiencies in grid connections. To overcome these drawbacks, a fast tracking and steady‐state‐oscillation‐free control strategy is proposed. The strategy first stores four random duty cycle values on the basis of the duty cycle variation characteristics of the PV panel power adjustment, then calculates the odd and even duty cycle difference and judges the steady state by varying the duty cycle difference threshold. The strategy next obtains the MPP duty cycle using a median filtering algorithm (MFA) to suppress the steady‐state oscillation and improves the tracking speed by resetting the appropriate duty cycle step according to the slope of the PV curve of the PV panel output and the corresponding adaptive coefficients. The proposed algorithm was simulated and experimentally validated under various irradiance conditions, and the results show that the algorithm can improve the PV panel output efficiency compared to both the conventional P&O and the adaptive P&O methods.
EURADWASTE’22 Paper – Host rocks and THMC processes in DGR
Authors: Levasseur Séverine , Sillen Xavier , Marschall Paul , Wendling Jacques , Olin Markus , Grgic Dragan , Svoboda Jiří
Published: September 2022

Deep geological disposal aims to contain and isolate radioactive waste from the biosphere. Repository systems are made of multiple barriers working together, typically comprising the natural geological barrier provided by the repository host rock and its surroundings and an engineered barrier system. Due to their excellent properties for the confinement of contaminants, including low permeability, high sorption capacity, and swelling/self-sealing capacity, clayey materials are considered as engineered and/or natural barriers in most repository designs under development in Europe. During the lifetime of the repository, clay barriers will be exposed to perturbations, among which those are resulting from gas and heat production within the system. It is important to verify that these perturbations will not be detrimental to the good functioning of these barriers. In this paper, it is shown how the two EURAD R&D work packages, GAS and HITEC use a combination of experimental and modelling approaches to increase the understanding and predictability of the impact on clay barriers of the fundamental processes and their couplings related to gas and heat transport respectively, providing building blocks to support the evaluation of the robustness of the repository concepts.
The Space-Time Meshless Methods for the Solution of One-Dimensional Klein-Gordon Equations
Authors: ZHANG Zhiqiang , WANG Fuzhang , ZHANG Juan
Published: September 2022

A simple direct space-time meshless scheme, based on the radial or non-radial basis function, is proposed for the one-dimensional Klein-Gordon equations. Since these equations are time-dependent, it is worthwhile to present two schemes for the basis functions from radial and non-radial aspects. The first scheme is fulfilled by considering time variable as normal space variable, to construct an "isotropic" space-time radial basis function. The other scheme considered a realistic relationship between space variable and time variable which is not radial. The time-dependent variable is treated regularly during the whole solution process and the Klein-Gordon equations can be solved in a direct way. Numerical results show that the proposed meshless schemes are simple, accurate, stable, easy-to-program and efficient for the Klein-Gordon equations.
Mechanisms of the Traditional Chinese Herb Atractylodes lancea against COVID-19 Based on Network Pharmacology and Molecular Docking
Authors: LEI Jiachuan , TU Yijun , XU Jie , YU Jianqing
Published: September 2022

Atractylodes lancea (Thunb.) DC. (AL) has been proven to be effective in the treatment of coronavirus disease 2019 (COVID-19). In this study, TCMSP, TCMID, OMIM, GeneCards, PharmMapper and SwissTargetPrediction were used to collect potential targets for AL against COVID-19. The online STRING analysis platform and Cytoscape were used for generating a (protein-protein interaction) PPI network. The Cytoscape and Autodock software were used for determining hub genes and key compounds. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via DAVID database. A total of 84 common targets were obtained. The antiviral pathways were main pathways in traetment. 10 hub genes and key compounds were screened by CytoHubba. We found that AL2, AL6 and AL38 had lower binding energy with key proteins. Our study demonstrated that AL might be used to treat COVID-19 by improving the "cytokine storm", regulating some antiviral pathways, and inhibiting the key protein through which the SARS-CoV-2 invades the host cell. These findings give a pharmacological basis and support for treating COVID-19 with AL.
Transabdominal Ultrasound and Magnetic Resonance Enterography in
Inflammatory Bowel Disease: Results of an Observational Retrospective
Single-Center Study
Authors: Calavrezos Lenika , Bannas Peter , Warncke Malte , Wiegard Christiane , Huber Samuel , Manthey Carolin
Published: September 2022

Purpose Transabdominal ultrasound (US) and magnetic resonance enterography
(MRE) are used to assess disease activity and extent in IBD, but their impact on
therapeutic decisions is unclear. Therefore, our study has two goals: to compare
the usefulness of US and MRE in assessing disease extent and activity in the
small and large bowel, and to determine the relevance for clinical decisions in
IBD.

Materials and Methods We included 54 IBD patients who had undergone both
MRE and US within three months. We used the construct reference standard model
to compare MRE and US for detecting inflammation and examined the impact on
clinical decisions in IBD patients.

Results In 54 IBD patients (44 patients Crohn’s disease (CD), 5
ulcerative colitis (UC), 5 indeterminate colitis (IC)), 42 patients
(77.8%) showed inflammation either in the small or large bowel. Small
bowel disease was present in 34 patients (77.3%). Complications were
found in 19 patients (35.2%). MRE and US both showed high sensitivity
(90.5 and 88.1%) and moderate specificity (50% in MRE and US)
for detecting inflammation. MRE revealed higher sensitivity than US for
detecting conglomerate tumors without statistical significance (85.7 vs.
71.4%, p=1.0) and equal specificity (97.9 vs 97.7,
p=1.0). Therapeutic decisions included steroids in 20 patients
(47.6%) and surgery/percutaneous drainage in six patients
(14.3%), these decisions were triggered by results of US or MRE in equal
distribution.

Conclusion US and MRE have comparable sensitivity and specificity for
detecting intestinal inflammation and complications in IBD patients. Therefore,
both methods are sufficient for making clinical decisions.
Stärkende und entlastende Ernährung bei Krebs
– Erfahrungen aus der Praxis
Authors: Pork Sabine
Published: September 2022

In der supportiven Ernährungstherapie gewinnt eine vollwertige,
nachhaltigere Ernährung zunehmend an Bedeutung. Charakteristisch
für diese pflanzenbasierte Kost ist ein höherer Gehalt an
wertgebenden Inhaltsstoffen, kombiniert mit einem niedrigeren Gehalt an
wertmindernden Substanzen
(Schadstoffe/Rückstände/umstrittene
Zusatzstoffe). Die bestmögliche Versorgung mit Mikro- und
Makronährstoffen stärkt den Gesamtorganismus und
unterstützt sowohl das Nebenwirkungs- als auch das Gewichtsmanagement.
Gleichzeitig empowert ein „Gewusst wie“ die PatientInnen
hinsichtlich ihres Gesundheitsverhaltens und ihrer Selbstfürsorge.
Dieser Artikel gibt eine Übersicht über die häufigsten
Themen und beschreibt, was sich in der Praxis bewährt hat.
Langes progressionsfreies Überleben durch medizinischen
Fortschritt
Authors: Holzhauer Peter
Published: September 2022

Patientinnen mit HER2neu positiver und initial schon metastasierter Erkrankung
haben eine schlechte Prognose. Nur 33% überleben mehr als 5
Jahre und nur 7% mehr als 10 Jahre 1. Deshalb ist es sehr interessant, einen genaueren und in diesem Fall
individuellen Blick auf die kleine Gruppe der außergewöhnlichen
Responder zu werfen. Nachstehend wird detailliert der Fall einer bei
Erstdiagnose jüngeren Patientin vorgestellt, bei der neben der
ausgeprägten ossären Metastasierung nur ein einziges Organsystem
(Pleura) befallen war. Die Behandlung erfolgte bei klinisch sehr schlechtem
Allgemeinzustand mit drohendem Querschnitt durch die Knochenmetastasierung, und
zwar als Kombination von Strahlentherapie, Chemotherapie und
Doppelrezeptorblockade mit den anti-HER2neu Antikörpern Trastuzumab und
Pertuzumab. Die kombinierte Systemtherapie mit Taxan und Antikörpern
wurde dabei nur von 04/2017 bis 10/2017 durchgeführt
2. Die Kombination war sehr effektiv,
sodass sich der Zustand der Patientin eindrucksvoll besserte und dann ab
10/2017 bis heute mit einer Erhaltungstherapie mit den
Antikörpern Trastuzumab/Pertuzumab erfolgreich und stabil weiter
behandelt werden konnte. Alle konventionellen Behandlungsmaßnahmen
wurden kontinuierlich von komplementären Maßnahmen
begleitet.
Accuracy of self-assessment in gastrointestinal endoscopy: a systematic review and meta-analysis
Authors: Scaffidi Michael A. , Li Juana , Genis Shai , Tipton Elizabeth , Khan Rishad , Pattni Chandni , Gimpaya Nikko , Bradley-Ridout Glyneva , Walsh Catharine M. , Grover Samir C.
Published: September 2022

Background Assessment is necessary to ensure both attainment and maintenance of competency in gastrointestinal (GI) endoscopy, and this can be accomplished through self-assessment. We conducted a systematic review with meta-analysis to evaluate the accuracy of self-assessment among GI endoscopists.

Methods This was an individual participant data meta-analysis of studies that investigated self-assessment of endoscopic competency. We performed a systematic search of the following databases: Ovid MEDLINE, Ovid EMBASE, Wiley Cochrane CENTRAL, and ProQuest Education Resources Information Center. We included studies if they were primary investigations of self-assessment accuracy in GI endoscopy that used statistical analyses to determine accuracy. We conducted a meta-analysis of studies using a limits of agreement (LoA) approach to meta-analysis of Bland–Altman studies.

Results After removing duplicate entries, we screened 7138 records. After full-text review, we included 16 studies for qualitative analysis and three for meta-analysis. In the meta-analysis, we found that the LoA were wide (−41.0 % to 34.0 %) and beyond the clinically acceptable difference. Subgroup analyses found that both novice and intermediate endoscopists had wide LoA (−45.0 % to 35.1 % and −54.7 % to 46.5 %, respectively) and expert endoscopists had narrow LoA (−14.2 % to 21.4 %).

Conclusions GI endoscopists are inaccurate in self-assessment of their endoscopic competency. Subgroup analyses demonstrated that novice and intermediate endoscopists were inaccurate, while expert endoscopists have accurate self-assessment. While we advise against the sole use of self-assessment among novice and intermediate endoscopists, expert endoscopists may wish to integrate it into their practice.
Fixed Subluxation of the Distal Radioulnar Joint following Malunion of the Ulnar Styloid Process
Authors: Brackertz Sophie , Reissner Lisa , Fritz Benjamin , Walker Jonas , Nagy Ladislav
Published: September 2022

Purpose Recent literature on significance and treatment of ulnar styloid fractures suggest that the ulnar styloid is not the central problem but the radioulnar ligaments and their impact on joint stability. However, specifically displaced ulnar styloid process fractures that secondarily heal in an ectopic position remain a rare situation for which diagnostics and treatment options remain a topic of discussion.

Methods This case series presents four patients with limited supination due to a fixed dorsal subluxation of the distal radioulnar joint (DRUJ). The reason here fore was a significant malunion of ulnar styloid fracture that was addressed by corrective ulnar styloid osteotomy. Three of these osteotomies used three-dimensional (3D) preoperative planning and patient specific guides.

Results All patients presented with a significant displacement of the malunited ulnar styloid fracture (average 32-degree rotation and 5-mm translation). In all four patients, the fixed subluxation of the ulnar head was resolved clinically and radiographically, and the forearm rotation restored after corrective osteotomy of the ulnar styloid and fixation in an anatomical position.

Conclusion This case series presents a very specific subset of patients with nonanatomically healed ulnar styloid fractures responsible for a chronic DRUJ dislocation and limited prosupination and its treatment.

Level of evidence This is a Level IV, therapeutic study.
Emergency General Surgery: Predicting Morbidity and Mortality in the Geriatric Population
Authors: Elamin Abubaker , Tsoutsanis Panagiotis , Sinan Laith , Tari Seyedh Paniz Hashemi , Elamin Wafa , Kurihara Hayato
Published: September 2022

Introduction Numerous scoring systems have been created to predict the risk of morbidity and mortality in patients undergoing emergency general surgery (EGS).

In this article, we compared the different scoring systems utilized at Humanitas Research Hospital and analyzed which one performed the best when assessing geriatric patients (>65 years of age). The scoring systems that were utilized were the APACHE II (Acute Physiology and Chronic Health Evaluation II), ASA (American Society of Anesthesiologists), ACS-NSQIP (American College of Surgeons-National Surgical Quality Improvement Program), Clinical Frailty Score, and the Clavien–Dindo classification as control.

Materials and Methods We compiled a database consisting of all patients over the age of 65 who underwent EGS in a consecutive 24-month period between January 1, 2017 and December 31, 2018. We used the biostatistical program “Stata Version 15” to analyze our results.

Results We found 213 patients who matched our inclusion criteria. Regarding death, we found that the ACS-NSQIP death calculator performed the best with an area under the curve of 0.9017 (odds ratio: 1.09; 95% confidence interval: 1.06–1.12). The APACHE II score had the lowest discriminator when predicting death. Considering short-term complications, the Clavien–Dindo classification scored highly, while both the APACHE II score and Clinical Frailty Score produced the lowest results.

Conclusion The results obtained from our research showed that scoring systems and classifications produced different results depending on whether they were used to predict deaths or short-term complications among geriatric patients undergoing EGS.
The lithiation onset of amorphous silicon thin-film electrodes
Authors: Hüger Erwin , Uxa Daniel , Yang Fuqian , Schmidt Harald
Published: September 2022

The lithiation onset of amorphous silicon (a-silicon) films up to 10% state of charge (SOC) is characterized by a Li+-uptake region around 0.5 V vs a Li reference electrode. In the literature, this is commonly attributed to surface processes such as the formation of a solid electrolyte interphase layer and/or the reduction of the surface native oxide, and more seldom to bulk processes such as reduction of oxygen contaminations inside the silicon film and to silicon lithiation. This work presents evidence that this process is associated with the lithiation of elemental silicon using electrochemical and non-electrochemical measurements and including a discussion of literature data. Cyclic voltammetry performed on pre-lithiated a-silicon and a-silicon films with different oxygen concentrations and with different film thicknesses reveals a lithiation process that is not associated with the reduction of oxygen. Elemental depth-profiling with secondary ion mass spectrometry (SIMS) reveals a two-phase lithiation mechanism at the lithiation onset, which sharply delimits non-lithiated silicon from a Li-poor phase of constant Li content (Li0.3Si). The published operando neutron reflectometry data suggest that this is also the case for oxygen-free Si single crystal wafers. SIMS measurements further show that the whole a-silicon thin film is converted into the Li-poor phase. This phase remains stable in the vicinity of the current collector even at 100% SOC, indicating that mechanical stress may play an important role.
Genetic adaptation of skin pigmentation in highland Tibetans
Authors: Yang Zhaohui , Bai Caijuan , Pu Youwei , Kong Qinghong , Guo Yongbo ,   Ouzhuluobu,   Gengdeng, Liu Xuyang , Zhao Qi , Qiu Zhichao , Zheng Wangshan , He Yaoxi , Lin Yihan , Deng Lian , Zhang Chao , Xu Shuhua , Peng Yi , Xiang Kun , Zhang Xiaoming ,   Baimayangji,   Cirenyangji, Cui Chaoying ,   Baimakangzhuo,   Gonggalanzi,   Bianba, Pan Yongyue , Xin Jingxue , Wang Yong , Liu Shiming , Wang Liangbang , Guo Hengliang , Feng Zhenzhen , Wang Shaobo , Shi Hong , Jiang Binghua , Wu Tianyi , Qi Xuebin , Su Bing
Published: September 2022

Strong ultraviolet (UV) radiation at high altitude imposes a serious selective pressure, which may induce skin pigmentation adaptation of indigenous populations. We conducted skin pigmentation phenotyping and genome-wide analysis of Tibetans in order to understand the underlying mechanism of adaptation to UV radiation. We observe that Tibetans have darker baseline skin color compared with lowland Han Chinese, as well as an improved tanning ability, suggesting a two-level adaptation to boost their melanin production. A genome-wide search for the responsible genes identifies
GNPAT
showing strong signals of positive selection in Tibetans. An enhancer mutation (rs75356281) located in
GNPAT
intron 2 is enriched in Tibetans (58%) but rare in other world populations (0 to 18%). The adaptive allele of rs75356281 is associated with darker skin in Tibetans and, under UVB treatment, it displays higher enhancer activities compared with the wild-type allele in in vitro luciferase assays. Transcriptome analyses of gene-edited cells clearly show that with UVB treatment, the adaptive variant of
GNPAT
promotes melanin synthesis, likely through the interactions of
CAT
and
ACAA1
in peroxisomes with other pigmentation genes, and they act synergistically, leading to an improved tanning ability in Tibetans for UV protection.
Generation of mega brown adipose tissue in adults by controlling brown adipocyte differentiation in vivo
Authors: Du Qiqiao , Wu Jieyu , Fischer Carina , Seki Takahiro , Jing Xu , Gao Juan , He Xingkang , Hosaka Kayoko , Tong Le , Yasue Akihiro , Miyake Masato , Sobajima Mitsuaki , Oyadomari Seiichi , Sun Xiaoting , Yang Yunlong , Zhou Qinjun , Ge Minghua , Tao Wei , Yao Shuzhong , Cao Yihai
Published: September 2022

Brown adipose tissue (BAT) is a highly specialized adipose tissue in its immobile location and size during the entire adulthood. In response to cold exposure and other β3-adrenoreceptor stimuli, BAT commits energy consumption by nonshivering thermogenesis (NST). However, the molecular machinery in controlling the BAT mass in adults is unknown. Here, we show our surprising findings that the BAT mass and functions can be manipulated in adult animals by controlling BAT adipocyte differentiation in vivo. Platelet-derived growth factor receptor α (PDGFα) expressed in BAT progenitor cells served a signaling function to avert adipose progenitor differentiation. Genetic and pharmacological loss-of-function of PDGFRα eliminated the differentiation barrier and permitted progenitor cell differentiation to mature and functional BAT adipocytes. Consequently, an enlarged BAT mass (megaBAT) was created by PDGFRα inhibition owing to increases of brown adipocyte numbers. Under cold exposure, a microRNA-485 (miR-485) was identified as a master suppressor of the PDGFRα signaling, and delivery of miR-485 also produced megaBAT in adult animals. Noticeably, megaBAT markedly improved global metabolism, insulin sensitivity, high-fat-diet (HFD)-induced obesity, and diabetes by enhancing NST. Together, our findings demonstrate that the adult BAT mass can be increased by blocking the previously unprecedented inhibitory signaling for BAT progenitor cell differentiation. Thus, blocking the PDGFRα for the generation of megaBAT provides an attractive strategy for treating obesity and type 2 diabetes mellitus (T2DM).
G protein–biased GPR3 signaling ameliorates amyloid pathology in a preclinical Alzheimer’s disease mouse model
Authors: Huang Yunhong , Rafael Guimarães Thais , Todd Nicholas , Ferguson Carolyn , Weiss Kathryn M. , Stauffer Fiona R. , McDermott Breanne , Hurtle Bryan T. , Saito Takashi , Saido Takaomi C. , MacDonald Matthew L. , Homanics Gregg E. , Thathiah Amantha
Published: September 2022

Biased G protein–coupled receptor (GPCR) ligands, which preferentially activate G protein or β-arrestin signaling pathways, are leading to the development of drugs with superior efficacy and reduced side effects in heart disease, pain management, and neuropsychiatric disorders. Although GPCRs are implicated in the pathophysiology of Alzheimer’s disease (AD), biased GPCR signaling is a largely unexplored area of investigation in AD. Our previous work demonstrated that GPR3-mediated β-arrestin signaling modulates amyloid-β (Aβ) generation
in vitro
and that
Gpr3
deficiency ameliorates Aβ pathology
in vivo
. However,
Gpr3
-deficient mice display several adverse phenotypes, including elevated anxiety-like behavior, reduced fertility, and memory impairment, which are potentially associated with impaired G protein signaling. Here, we generated a G protein–biased GPR3 mouse model to investigate the physiological and pathophysiological consequences of selective elimination of GPR3-mediated β-arrestin signaling
in vivo
. In contrast to
Gpr3
-deficient mice, G protein–biased GPR3 mice do not display elevated anxiety levels, reduced fertility, or cognitive impairment. We further determined that G protein–biased signaling reduces soluble Aβ levels and leads to a decrease in the area and compaction of amyloid plaques in the preclinical

App
NL-G-F

AD mouse model. The changes in amyloid pathology are accompanied by robust microglial and astrocytic hypertrophy, which suggest a protective glial response that may limit amyloid plaque development in G protein–biased GPR3 AD mice. Collectively, these studies indicate that GPR3-mediated G protein and β-arrestin signaling produce discrete and separable effects and provide proof of concept for the development of safer GPCR-targeting therapeutics with more directed pharmacological action for AD.