bluuebunny/crossref_metadata_2025 huggingface dataset:
Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy
Authors: Yeong Joe , Lum Huey Yew Jeffrey , Teo Chong Boon , Tan Benjamin Kye Jyn , Chan Yiong Huak , Tay Ryan Yong Kiat , Choo Joan Rou-En , Jeyasekharan Anand D. , Miow Qing Hao , Loo Lit-Hsin , Yong Wei Peng , Sundar Raghav
Published: June 2022

Background

Immune checkpoint inhibitors (ICI) are now standard-of-care treatment for patients with metastatic gastric cancer (GC). To guide patient selection for ICI therapy, programmed death ligand-1 (PD-L1) biomarker expression is routinely assessed via immunohistochemistry (IHC). However, with an increasing number of approved ICIs, each paired with a different PD-L1 antibody IHC assay used in their respective landmark trials, there is an unmet clinical and logistical need for harmonization. We investigated the interchangeability between the Dako 22C3, Dako 28–8 and Ventana SP-142 assays in GC PD-L1 IHC.

Methods

In this cross-sectional study, we scored 362 GC samples for PD-L1 combined positive score (CPS), tumor proportion score (TPS) and immune cells (IC) using a multiplex immunohistochemistry/immunofluorescence technique. Samples were obtained via biopsy or resection of gastric cancer.

Results

The percentage of PD-L1-positive samples at clinically relevant CPS ≥ 1, ≥ 5 and ≥ 10 cut-offs for the 28–8 assay were approximately two-fold higher than that of the 22C3 (CPS ≥ 1: 70.3 vs 49.4%, p < 0.001; CPS ≥ 5: 29.1 vs 13.4%, p < 0.001; CPS ≥ 10: 13.7 vs 7.0%, p = 0.004). The mean CPS score on 28–8 assay was nearly double that of the 22C3 (6.39 ± 14.5 vs 3.46 ± 8.98, p < 0.001). At the clinically important CPS ≥ 5 cut-off, there was only moderate concordance between the 22C3 and 28–8 assays.

Conclusion

Our findings suggest that scoring PD-L1 CPS with the 28–8 assay may result in higher PD-L1 scores and higher proportion of PD-L1 positivity compared to 22C3 and other assays. Until stronger evidence of inter-assay concordance is found, we urge caution in treating the assays as equivalent.
The cost of living in larger primate groups includes higher fly densities
Authors: Gogarten Jan F. , Jahan Mueena , Calvignac-Spencer Sébastien , Chapman Colin A. , Goldberg Tony L. , Leendertz Fabian H. , Rothman Jessica M.
Published: June 2022

Flies are implicated in carrying and mechanically transmitting many primate pathogens. We investigated how fly associations vary across six monkey species (Cercopithecus ascanius, Cercopithecus mitis, Colobus guereza, Lophocebus albigena, Papio anubis, and Piliocolobus tephrosceles) and whether monkey group size impacts fly densities. Fly densities were generally higher inside groups than outside them, and considering data from these primate species together revealed that larger groups harbored more flies. Within species, this pattern was strongest for colobine monkeys, and we speculate this might be due to their smaller home ranges, suggesting that movement patterns may influence fly–primate associations. Fly associations increase with group sizes and may thus represent a cost to sociality.
Applying GMRES to the Helmholtz equation with strong trapping: how does the number of iterations depend on the frequency?
Authors: Marchand P. , Galkowski J. , Spence E. A. , Spence A.
Published: June 2022

We consider GMRES applied to discretisations of the high-frequency Helmholtz equation with strong trapping; recall that in this situation the problem is exponentially ill-conditioned through an increasing sequence of frequencies. Our main focus is on boundary-integral-equation formulations of the exterior Dirichlet and Neumann obstacle problems in 2- and 3-d. Under certain assumptions about the distribution of the eigenvalues of the integral operators, we prove upper bounds on how the number of GMRES iterations grows with the frequency; we then investigate numerically the sharpness (in terms of dependence on frequency) ofbothour boundsandvarious quantities entering our bounds. This paper is therefore the first comprehensive study of the frequency-dependence of the number of GMRES iterations for Helmholtz boundary-integral equations under trapping.
Characterisation of recombinant GH 3 β-glucosidase from β-glucan producing Levilactobacillus brevis TMW 1.2112
Authors: Bockwoldt Julia A. , Ehrmann Matthias A.
Published: June 2022

Levilactobacillus (L.) brevis TMW 1.2112 is an isolate from wheat beer that produces O2-substituted (1,3)-β-D-glucan, a capsular exopolysaccharide (EPS) from activated sugar nucleotide precursors by use of a glycosyltransferase. Within the genome sequence of L. brevis TMW 1.2112 enzymes of the glycoside hydrolases families were identified. Glycoside hydrolases (GH) are carbohydrate-active enzymes, able to hydrolyse glycosidic bonds. The enzyme β-glucosidase BglB (AZI09_02170) was heterologous expressed in Escherichia coli BL21. BglB has a monomeric structure of 83.5 kDa and is a member of the glycoside hydrolase family 3 (GH 3) which strongly favoured substrates with β-glycosidic bonds. Km was 0.22 mM for pNP β-D-glucopyranoside demonstrating a high affinity of the recombinant enzyme for the substrate. Enzymes able to degrade the (1,3)-β-D-glucan of L. brevis TMW 1.2112 have not yet been described. However, BglB showed only a low hydrolytic activity towards the EPS, which was measured by means of the D-glucose releases. Besides, characterised GH 3 β-glucosidases from various lactic acid bacteria (LAB) were phylogenetically analysed to identify connections in terms of enzymatic activity and β-glucan formation. This revealed that the family of GH 3 β-glucosidases of LABs comprises most likely exo-active enzymes which are not directly associated with the ability of these LAB to produce EPS.
A Priori Analysis on Deep Learning of Filtered Reaction Rate
Authors: Shin Junsu , Hansinger Maximilian , Pfitzner Michael , Klein Markus
Published: June 2022

A filtered reaction rate model driven by deep learning is proposed and analyzed a priori in the context of large eddy simulation (LES). A deep artificial neural network (ANN) is trained on the explicitly filtered reaction rate source term extracted from a database comprised of turbulent premixed planar flame direct numerical simulations (DNSes) employing single-step chemistry. The filtered DNS database to be used for the training of the ANN covers a wide range of turbulence intensities and LES filter widths. An interpretation technique of deep learning is employed to search the principal input parameters in the high dimensional database to alleviate the model complexity. The deep learning filtered reaction rate model is then tested on the unseen filtered planar flames featuring untrained turbulence intensities and LES filter widths, in conjunction with another canonical type of flame configuration that it has not been trained on. The deep learning filtered reaction rate model achieves good agreement with the filtered DNS results and also provides a quantitatively accurate surrogate model when compared to existing algebraic models and other combustion models from the literature.
Monitoring and modeling non-native invasive green iguana population response to harvesting on Grand Cayman, Cayman Islands
Authors: Rivera-Milán Frank F. , Haakonsson Jane , Bodden Vaughn , Oyog TayVanis , O’Hehir Sophie
Published: June 2022

Registered hunters harvested over 1.3 million non-native invasive green iguanas (Iguana iguana) on Grand Cayman between October 2018 and August 2021. We used islandwide post-reproduction survey-based abundance estimates in August 2014–2021 and model-based abundance predictions for August 2022–2030 to assist natural resource managers with reassessment and modification of the harvest strategy due to diminishing returns to hunters paid per green iguana harvested. We need harvest rates > 0.600 for desired abundance ≤ 50,000 and > 0.700 for desired abundance ≤ 10,000 green iguanas. With harvest rates < 0.600, the population would likely remain above desired abundance. Without harvesting, the green iguana population would likely reach carrying capacity by August 2026.
An accelerated minimax algorithm for convex-concave saddle point problems with nonsmooth coupling function
Authors: Boţ Radu Ioan , Csetnek Ernö Robert , Sedlmayer Michael
Published: June 2022

In this work we aim to solve a convex-concave saddle point problem, where the convex-concave coupling function is smooth in one variable and nonsmooth in the other and not assumed to be linear in either. The problem is augmented by a nonsmooth regulariser in the smooth component. We propose and investigate a novel algorithm under the name of OGAProx, consisting of an optimistic gradient ascent step in the smooth variable coupled with a proximal step of the regulariser, and which is alternated with a proximal step in the nonsmooth component of the coupling function. We consider the situations convex-concave, convex-strongly concave and strongly convex-strongly concave related to the saddle point problem under investigation. Regarding iterates we obtain (weak) convergence, a convergence rate of order $$\mathcal {O}(\frac{1}{K})$$

O
(

1
K

)

and linear convergence like $$\mathcal {O}(\theta ^{K})$$

O
(

θ
K

)

with $$\theta < 1$$

θ
<
1

, respectively. In terms of function values we obtain ergodic convergence rates of order $$\mathcal {O}(\frac{1}{K})$$

O
(

1
K

)

, $$\mathcal {O}(\frac{1}{K^{2}})$$

O
(

1

K
2

)

and $$\mathcal {O}(\theta ^{K})$$

O
(

θ
K

)

with $$\theta < 1$$

θ
<
1

, respectively. We validate our theoretical considerations on a nonsmooth-linear saddle point problem, the training of multi kernel support vector machines and a classification problem incorporating minimax group fairness.
A framework for a green accounting system-exploratory study in a developing country context, Colombia
Authors: Gonzalez Candy Chamorro , Peña-Vinces Jesús
Published: June 2022

Current accounting systems assume a purely financial approach, without including environmental information, such as environmental costs and companies’ expenses. On the one hand, this study proposes a framework that considers the environmental impact of firms within their accounting system, the Green Accounting System (GAS). On the other hand, and in the context of developing countries, Colombia carried out an exploratory study. With a sample of 150 Colombian industrial and commercial companies, this research revealed that 100% of them had not yet implemented environmental practices within the accounting system. Therefore, this research would be useful not only for academia, but also for practitioners and governments. As GAS would contribute to traceability in the quantification of environmental accounting, it would simultaneously generate a movement toward cleaner production that would increase environmental quality.
BRCA1/2 pathogenetic variant carriers and reproductive decisions: Gender differences and factors associated with the choice of preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND)
Authors: Lombardi Lucia , Trumello Carmen , Stuppia Liborio , Antonucci Ivana , Brandão Tânia , Babore Alessandra
Published: June 2022

Purpose

To investigate the way carriers of a BRCA1/2 pathogenetic variant make their reproductive decisions and to examine the factors associated with the choice of preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND).

Methods

We conducted a comprehensive literature search in PubMed, Scopus, and Web of Science in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method.

Results

A total of 16 articles published from 2000 to 2021 were included in this review. Data were overall collected from 3564 participants (86% females). Three important themes were identified across studies: changes in family planning, factors associated with family plans, and with acceptance or regret of PGD and PND.

Conclusion

This review may contribute to the knowledge of the experience of those who have a BRCA1/2 mutation and want a child. These results may help genetic counselors and healthcare professionals that support people with a BRCA pathogenetic variant with reproductive issues.
Carbodiimide Bridged Network Structure of [RE6O(NCN)6] Clusters in the Structure of RE8O(CN2)10Br2, RE = La, Ce, Pr, Nd
Authors: Siai Amira , Brand Catharina-Darine , Ströbele Markus , Enseling David , Jüstel Thomas , Meyer H.-Jürgen
Published: June 2022

New rare earth (RE) carbodiimides having the formula RE8O(CN2)10Br2 were synthesized by solid-state metathesis reactions. Structure determinations and refinements, based on single-crystal X-ray diffraction data, are performed with the space group P͞3c1. Homologous compounds with RE = La, Ce, Pr, and Nd are assigned isotypically. The refined crystal structure appears most unusual for rare earth carbodiimide compounds. The structure is characterized by the formally neutral [RE6O(NCN)8] fragment that is tightly interconnected by carbodiimide ions into a network structure, and contains additional RE3+ ions in the structure. Crystals of the compounds show characteristic colors of their corresponding RE3+ ions and behave stable in air. The presence of (CN2)2− ions was confirmed by infrared spectroscopy. Ce8O(CN2)10Br2 is a photoluminescent material that is showing a broad and efficient emission band in the yellow region of the visible spectrum.
Synthesis of magnetite nanoparticles coated with polyvinyl alcohol for hyperthermia application
Authors: Darwish Mohamed S. A. , Al-Harbi L. M. , Bakry Ahmed
Published: June 2022

One of the main challenges in hyperthermia treatment is how to improve the heating performance of nanoparticles with high specific loss power (SLP). To tackle this challenge, magnetite nanoparticles (MNPs) and coated magnetite nanoparticles with polyvinyl alcohol (PVA@MNPs) were fabricated via ultrasonic-assisted coprecipitation technique. The obtained nanoparticles were characterized by using FT-IR, TEM, TGA, XRD, ICP-OES, DLS, zeta potential, VSM and UV–Vis spectroscopy. The self-heating properties of the MNPs and PVA@MNPs were studied under alternating magnetic strength, frequency and induction time. MNPs and PVA@MNPs showed that the nanoparticles have a nearly spherical shape ranging between 12.3 ± 3.2 and 10 ± 2.5 nm, respectively. The higher value of zeta potentials of PVA@MNPs (− 11.49 mV) implies that the nanoparticle may show good stability in aqueous solutions. The magnetization saturation values were 41.98 and 45.08 emu g−1 for MNPs and PVA@MNPs, respectively. The prepared nanoparticles showed small coercivity and a remanence magnetization due to the soft magnetic nature of the prepared nanoparticles. The highest SLP value was 163.81 W g−1 for PVA@MNPs, while the lowest SLP value was 4.84 W g−1 for MNPs under the same magnetic field condition. The presence of PVA shell improved the particle stability and the magnetization for PVA@ MNPs. This successfully caused an improvement in the heating performance and magnetic hyperthermia as well. These features make the prepared PVA@MNPs in this study applicable as hyperthermic agents for biomedical applications.
Improved energy estimates for a class of time-dependent perturbed Hamiltonians
Authors: Marcelli Giovanna
Published: June 2022

We consider time-dependent perturbations which are relatively bounded with respect to the square root of an unperturbed Hamiltonian operator, and whose commutator with the latter is controlled by the full perturbed Hamiltonian. The perturbation is modulated by two auxiliary parameters, one regulates its intensity as a prefactor and the other one controls its time-scale via a regular function, whose derivative is compactly supported in a finite interval. We introduce a natural generalization of energy conservation in the case of time-dependent Hamiltonians: the boundedness of the two-parameter unitary propagator for the physical evolution with respect to then/2-thpower energy normfor all$$n\in \mathbb {Z}$$n∈Z. We provide bounds of then/2-th power energy norms, uniformly in time and in the time-scale parameter, for the unitary propagators, generated by the time-dependent perturbed Hamiltonian and by the unperturbed Hamiltonian in the interaction picture. The physically interesting model of Landau-type Hamiltonians with an additional weak and time-slowly-varying electric potential of unit drop is included in this framework.
Simulation and experimental studies of a vibro-impact capsule system driven by an external magnetic field
Authors: Zhang Jiajia , Liu Yang , Zhu Dibin , Prasad Shyam , Liu Caishan
Published: June 2022

This paper studies the electromagnetic field used for driving a vibro-impact capsule prototype for small bowel endoscopy. Mathematical models of the electromagnetic field and the capsule system are introduced, and analytical solution of the magnetic force applied on the capsule is derived and verified by experiment. The impact force between the inner mass of the capsule and the capsule body is also compared via numerical simulation and experimental testing. By comparing the capsule’s progressions under different control parameters (e.g. the excitation frequency and duty cycle), the merits of using the vibro-impact propulsion are revealed. Based on the experimental results, the optimised speed of the prototype can achieve up to 3.85 mm/s. It is therefore that the potential feasibility of using the external electromagnetic field for propelling the vibro-impact capsule system is validated.
Analysis on functionalities and security features of Internet of Things related protocols
Authors: Rizzardi Alessandra , Sicari Sabrina , Coen-Porisini Alberto
Published: June 2022

The Internet of Things (IoT) paradigm is characterized by the adoption of different protocols and standards to enable communications among heterogeneous and, often, resource-constrained devices. The risk of violation is high due to the wireless nature of the communication protocols usually involved in the IoT environments (e.g., e-health, smart agriculture, industry 4.0, military scenarios). For such a reason, proper security countermeasures must be undertaken, in order to prevent and react to malicious attacks, which could hinder the data reliability. In particular, the following requirements should be addressed: authentication, confidentiality, integrity, and authorization. This paper aims at investigating such security features, which are often combined with native functionalities, in the most known IoT-related protocols: MQTT, CoAP, LoRaWAN, AMQP, RFID, ZigBee, and Sigfox. The advantages and weaknesses of each one will be revealed, in order to point out open issues and best practices in the design of efficient and robust IoT network infrastructure.
Bisphenol A in edible tissues of rams exposed to repeated low-level dietary dose by high-performance liquid chromatography with fluorescence detection
Authors: Cerkvenik-Flajs Vesna , Škibin Andrej , Švara Tanja , Gombač Mitja , Pogačnik Milan , Šturm Sabina
Published: June 2022

The presented work deals with levels and distribution of bisphenol A (BPA) in the edible tissues of a large food-producing animal species. An experimental animal study included 14 young Istrian pramenka rams (Ovis aries), of which seven were exposed for 64 days to a low dietary dose of BPA at 25 µg/kg b.w./day, and seven served as a control group. Residue analysis of both aglycone and total BPA was performed in the muscle tissue, liver, kidney and fat tissue of the individual animals by means of enzymatic deconjugation (for total BPA), organic solvent extraction, molecularly imprinted polymer solid-phase extraction (MISPE) clean-up and high-performance liquid chromatography with fluorescence detection (HPLC-FLU). The analysis was optimized and validated for aglycone BPA in the fat tissue and for the total BPA in all tissues investigated. Edible tissues of the control group of rams generally remained BPA-free, while there were concentration differences between the control and treated groups for liver and kidney post last administration. The human health risk resulting from this study was assessed by the estimated dietary exposure in adults, which was < 0.1% related to the valid European Union Tolerable Daily Intake (TDI) value of 4 µg/kg b.w./day. However, it would be 58-fold higher than the newly proposed TDI value of 0.04 ng/kg b.w./day.
Effect of Niobium Supersaturation in Austenite on the Static Recrystallization Behavior of Carbon Structural Steels
Authors: Rakshe B. , Patel J. , Palmiere E. J.
Published: June 2022

This work describes the effect of Nb supersaturation in austenite on the suppression of static recrystallization of austenite during an isothermal holding period following hot deformation. The investigation involved three carbon structural steels with varying Nb concentration at constant C (0.20 pct) and N (0.007 pct) levels. The isothermal double-hit deformation technique led to the determination of T
5 pct and T
95 pct (recrystallization-stop and full recrystallization temperatures, respectively) as a function of a true strain and interpass time. The results indicate that the T
5 pct increases with increasing Nb supersaturation in austenite at a rate of 40 °C per 0.006 pct Nb supersaturation for a true stain ε=0.40. At each respective T
5 pct, all tested steels exhibited an Nb supersaturation ratio ≥ 7.5 in austenite. A high, localized strain-induced precipitation of Nb(CN) was observed at the austenite subgrain boundaries in the unrecrystallized microstructure. This translated into higher values for local precipitate-pinning forces (F
PIN), which were significantly higher than that predicted from equilibrium thermodynamics. The critical FPIN for retardation of static recrystallization was found to be 1.6 MPa at the respective T
5 pct for each steel. The present study has contributed to advancing our knowledge of the interplay between Nb solute supersaturation and volume fraction of Nb(CN) precipitation in particular for carbon structural steels. It has also highlighted an opportunity to apply niobium, even an ultra-low addition (i.e., < 100 ppm) to commodity-grade structural steels to reduce overall alloying costs.
Localization of cavities in cast components via impulse excitation and a finite element analysis
Authors: Lechner Philipp , Reberger Erwin , Gruber Maximilian , Kammerloher Simon , Hartmann Christoph , Volk Wolfram
Published: June 2022

In this work, the acoustic resonance testing method has been extended by a finite element analysis of the examined component to localize cavities within die casting parts. This novel method aims at a fast and efficient quality inspection which allows hidden cavities in cast components to be detected, which is only possible with X-ray technology at the moment. The promising results show that this method enables the localization of shrinkage cavities. Furthermore, the influence of product scatter has been analyzed regarding the accuracy of the calculated position of artificial defects.
A Lagrangian Klein bottle you can’t squeeze
Authors: Evans Jonathan David
Published: June 2022

Suppose you have a nonorientable Lagrangian surface $$L$$
L
in a symplectic 4-manifold. How far can you deform the symplectic form before the smooth isotopy class of $$L$$
L
contains no Lagrangians? I solve this question for a particular Lagrangian Klein bottle. I also discuss some related conjectures.
What Will You Do When They Think It Was You? Counter-interrogation Strategies of Innocent Interviewees Under Suspicion vs. No Suspicion
Authors: Clemens Franziska , Grolig Tuule
Published: June 2022

The current imaginary mock-crime study examined innocent interviewees’ (N = 128) planned counter-interrogation strategies and their willingness to disclose critical information as a function of (a) the type of secondary act (irrelevant to the crime under investigation) they imagined having executed at the crime scene (lawful act vs. unlawful act) and (b) the presence of suspicion directed towards the interviewees (suspicion vs. no suspicion). Results show that, to be honest, was the most frequently reported strategy among lawful as well as unlawful act participants. In contrast, none of the lawful act participants reported the strategy to be deceptive, whereas 35.9% of the unlawful act participants did. When no suspicion (vs. suspicion) was directed towards unlawful act participants, they were less willing to voluntarily share critical information on their true intentions at the crime scene. Consequently, seemingly easy “no suspicion” situations appear to promote the application of more deceptive and evasive behavior in unlawful act interviewees and might therefore put them at risk of being wrongfully assessed as guilty of the crime under investigation.
Fortification of Durum Wheat Fresh Pasta with Maqui (Aristotelia chilensis) and Its Effects on Technological, Nutritional, Sensory Properties, and Predicted Glycemic Index
Authors: Bianchi Federico , Giuberti Gianluca , Cervini Mariasole , Simonato Barbara
Published: June 2022

Pasta, a staple food worldwide consumed, was fortified with maqui (Aristotelia chilensis) berry powder (MBP) and the effect of MBP inclusion was evaluated concerning technological, nutritional, and sensory properties. Fresh pasta samples were formulated by replacing 0, 7.5, and 15 g 100 g−1 of durum wheat semolina with MBP. The inclusion of MBP did not affect the moisture content, but the water activity decreased in the fortified samples, while pH values decreased with increasing MBP levels in the recipe. The pasta fully cooking time and the swelling index were reduced, while the cooking loss and the firmness increased with increasing MBP levels. In addition, MBP increased the total dietary fiber, ash, and phenol contents, along with the in vitro antioxidant activities. The starch hydrolysis index and the predicted glycemic index of cooked fresh pasta decreased along with the increase of MBP addition. The MPB addition to fresh pasta could represent a valuable strategy for increasing its nutritional value, maintaining pasta’s technological properties without affecting the sensory acceptability.
Variation in Anti-inflammatory, Anti-arthritic, and Antimicrobial Activities of Different Extracts of Common Egyptian Seaweeds with an Emphasis on Their Phytochemical and Heavy Metal Contents
Authors: Shobier Aida H. , Ismail Mona M. , Hassan Sahar W. M.
Published: June 2022

The anti-inflammatory, anti-arthritic, and antimicrobial activities of some common Egyptian seaweeds in addition to their phytochemical and heavy metal contents were investigated. Phytochemical screening of the seaweed extracts showed the presence of different primary and secondary metabolites with different concentrations according to their species and the used solvent. The ethanolic extract ofColpmenia sinuosa(CSBE2) exhibited the maximum anti-inflammatory and anti-arthritic activity at 1000 μg/ml concentration compared to other seaweed extracts. The dichloromethane extract ofCorallina officinalis(CORM) exerted the highest antimicrobial activity with an average inhibition zone diameter (AV) = 15.29 mm and activity index (AI) = 1.53 and with the highest antagonistic activity againstEscherichia coli(28 mm). It is followed byUlva linzaethanolic extract (ULGE2) which recorded (AV) of 14.71 mm and (AI) of 1.30 with the highest antifungal activity againstCandida albicans(30 mm). The collected seaweeds would therefore be a very promising source for treating inflammatory, arthritic, and microbial diseases. Moreover, the investigated seaweeds showed variable concentrations of heavy metals among various species. The mean concentrations of the heavy metals took the following order: Fe > Zn > Mn > Ba > Cu > As > Cr > Ni > Pb > V > Cd > Se > Co > Mo. Based on the permissible limits set by the WHO and CEVA, Pb and Ni in the studied seaweeds were found to be within the permissible limits, whereas Cd and Zn contents were at the borderline. Significant correlations were observed between studied parameters. The estimated daily intakes for most heavy metals were lower than the recommended daily intakes.
Nebulization Therapy with Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes for COVID-19 Pneumonia
Authors: Chu Meiping , Wang Hao , Bian Linjie , Huang Jiehui , Wu Danping , Zhang Ruiting , Fei Fangli , Chen Yigang , Xia Jiazeng
Published: June 2022

Background

Scientists have been facing numerous challenges in the development of an effective therapeutic strategy for the treatment of COVID-19 pneumonia. Several studies have suggested that improving patient immunity and reducing lung injury induced by SARS-CoV-2 may be effective for treating patients with COVID-19.

Methods

A pilot trial of nebulization therapy with exosomes of mesenchymal stem cells (MSCs) was performed on seven patients with COVID-19 pneumonia. Exosomes secreted from MSCs were collected and purified using multiple ultrafiltration steps. All patients were treated with nebulization of MSC-derived exosomes, and primary safety and efficacy outcomes were evaluated.

Results

Our clinical study demonstrated that nebulization of MSC-derived exosomes is a novel method that might be utilized in the treatment of COVID-19 pneumonia. Nebulization of MSC-derived exosomes did not induce acute allergic or secondary allergic reactions but did promote the absorption of pulmonary lesions and reduce the duration of hospitalization for mild cases of COVID-19 pneumonia.

Conclusions

Nebulization of MSC-derived exosomes is a safe, effective, and simple method, and their application at the beginning of treatment may be more beneficial.

Trial Registration

Chinese Clinical Trial Registry, ChiCTR2000030261. Registered on 26 February 2020.

Graphical Abstract
Hydroquinone predisposes for retinal pigment epithelial (RPE) cell degeneration in inflammatory conditions
Authors: Bhattarai Niina , Hytti Maria , Reinisalo Mika , Kaarniranta Kai , Mysore Yashavanthi , Kauppinen Anu
Published: June 2022

In addition to hypoxia, inflammation is capable of inducing vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells. Excessive levels of VEGF promote choroidal neovascularization and thereby contribute to the pathogenesis of wet age-related macular degeneration (AMD). Intravitreal anti-VEGF injections ameliorate pathological vessel neoformation in wet AMD but excessive dampening of VEGF can result in a degeneration of the RPE. In the present study, we induced VEGF production by exposing human ARPE-19 cells to the pro-inflammatory IL-1α and subsequently to hydroquinone, a component of tobacco smoke that is a major environmental risk factor for AMD. Effects were monitored by measuring the levels of VEGF and anti-angiogenic pigment epithelium-derived factor (PEDF) using an enzyme-linked immunosorbent assay (ELISA) technique. In addition, we measured the production of reactive oxygen species (ROS) using the 2′,7′-dichlorofluorescin diacetate (H2DCFDA) probe and studied the effects of two anti-oxidants, ammonium pyrrolidinedithiocarbamate (APDC) and N-acetyl-cysteine (NAC), on VEGF production. Cellular and secreted VEGF as well as secreted PEDF levels were reduced at all tested hydroquinone concentrations (10, 50, or 200 µM); these effects were evident prior to any reduction of cell viability evoked by hydroquinone. Cell viability was carefully explored in our previous study and verified by microscoping in the present study. APDC further reduced the VEGF levels, whereas NAC increased them. The 50 μM concentration of hydroquinone increased ROS production in ARPE-19 cells primed with IL-1α. Hydroquinone disturbs the regulatory balance of VEGF and PEDF in inflammatory conditions. These data support the idea that hydroquinone mediates RPE degeneration by reducing VEGF levels and may predispose to dry AMD since VEGF is as well important for retinal integrity.
The Regulation of MiTF/TFE Transcription Factors Across Model Organisms: from Brain Physiology to Implication for Neurodegeneration
Authors: Agostini Francesco , Agostinis Rossella , Medina Diego L. , Bisaglia Marco , Greggio Elisa , Plotegher Nicoletta
Published: June 2022

The microphthalmia/transcription factor E (MiTF/TFE) transcription factors are responsible for the regulation of various key processes for the maintenance of brain function, including autophagy-lysosomal pathway, lipid catabolism, and mitochondrial homeostasis. Among them, autophagy is one of the most relevant pathways in this frame; it is evolutionary conserved and crucial for cellular homeostasis. The dysregulation of MiTF/TFE proteins was shown to be involved in the development and progression of neurodegenerative diseases. Thus, the characterization of their function is key in the understanding of the etiology of these diseases, with the potential to develop novel therapeutics targeted to MiTF/TFE proteins and to the autophagic process. The fact that these proteins are evolutionary conserved suggests that their function and dysfunction can be investigated in model organisms with a simpler nervous system than the mammalian one. Building not only on studies in mammalian models but also in complementary model organisms, in this review we discuss (1) the mechanistic regulation of MiTF/TFE transcription factors; (2) their roles in different regions of the central nervous system, in different cell types, and their involvement in the development of neurodegenerative diseases, including lysosomal storage disorders; (3) the overlap and the compensation that occur among the different members of the family; (4) the importance of the evolutionary conservation of these protein and the process they regulate, which allows their study in different model organisms; and (5) their possible role as therapeutic targets in neurodegeneration.
Gender differences in mental distress and affect balance during the first wave of COVID-19 pandemic in Spain
Authors: Matud M. Pilar , Zueco Jesús , Díaz Amelia , del Pino Mª José , Fortes Demelsa
Published: June 2022

The COVID-19 pandemic is a major threat to the health and well-being of people around the world that has impacted freedom of movement, social interaction and the economy. The aim of the present work was twofold: first, to study the presence of mental distress, positive and negative experiences and affect balance in women and men in Spain in two different phases of the COVID-19 pandemic, the initial “first state of alarm” phase, characterized by maximum restrictions, and in the “new normal” phase with minimal restrictions, and second, to study the protective role of age, educational level, self-esteem, marital status and social support against mental distress, and as factors that increase the affect balance of women and men in the above mentioned phases of the first wave of the COVID- 19 pandemic in Spain. The study sample consisted of 652 women and 652 men from the general population, aged between 18 and 88 years, who were evaluated through self-reports. Results show greater mental distress in women than men but, strikingly, the magnitude of such differences were greater in the “new normal” phase than in the maximum restriction phase. In addition, in this last phase, women also experienced more negative feelings and less affect balance than men. High self-esteem and social support were also found to be protective factors for mental health, both in women and men, during the two phases of the pandemic studied. In conclusion, our study shows that the COVID-19 pandemic has especially impacted the well-being of women.
The Effect of Junction Gutters for the Upscaling of Droplet Generation in a Microfluidic T-Junction
Authors: Viswanathan H.
Published: June 2022

The influence of drop formation due to micro rib-like structures, viz., the Junction Gutters (JGs) within a standard microfluidic T-junction, is numerically investigated. Hydrodynamic conditions that lead to various flow regimes are identified characterized by the Capillary number (Ca) and velocity ratios of the dispersed and continuous phases (q) within a standard T-junction. Subsequently, under such conditions, a range of gutter configurations is introduced in the standard channel. The results predict that the introduction of JGs can favourably alter the formation frequency and morphology of drops and, consequently, promote upscaling significantly for the hydrodynamic conditions associated with low Ca. Detailed flow maps are presented that reveal a plethora of transitions during the formation of droplets with higher Ca and q that would otherwise signify a dripping or a jetting regime in a standard junction. However, specific gutter configurations are identified where JGs are unfavourable for generating monodisperse droplets.
A Family of Free Boundary Minimal Surfaces in the Unit Ball
Authors: Siffert Anna , Wuzyk Jan
Published: June 2022

Using equivariant differential geometry, we provide a family of free boundary minimal surfaces in the unit ball $${\mathbb {B}}^n\subset {\mathbb {R}}^n$$

B

n

⊂

R

n

.
Robustness and disturbances in public transport
Authors: Ge Liping , Voß Stefan , Xie Lin
Published: June 2022

Network-based systems are at the core of our everyday life. Whether it is electronic networking, electricity grids or transportation, users expect the networks to function properly and provide a feeling of safety and security. However, there may be disturbances. In this paper, we consider disturbances in the context of public transportation. The focus in this respect is on public transport planning and operations. To classify and cope with disturbances, one can find many ideas, including robustness, resilience, vulnerability, disruption mitigation or delay management. We survey related streams of literature and put them into perspective. As a major insight we show that different strands of literature exist that may benefit from becoming better connected and intertwined. Together with recent advances in information technology and solution methods, more integrated problem settings incorporating robustness and disturbances can play a major role in future planning and operations.
Super-forecasting the ‘technological singularity’ risks from artificial intelligence
Authors: Radanliev Petar , De Roure David , Maple Carsten , Ani Uchenna
Published: June 2022

This article investigates cybersecurity (and risk) in the context of ‘technological singularity’ from artificial intelligence. The investigation constructs multiple risk forecasts that are synthesised in a new framework for counteracting risks from artificial intelligence (AI) itself. In other words, the research in this article is not just concerned with securing a system, but also analysing how the system responds when (internal and external) failure(s) and compromise(s) occur. This is an important methodological principle because not all systems can be secured, and totally securing a system is not feasible. Thus, we need to construct algorithms that will enable systems to continue operating even when parts of the system have been compromised. Furthermore, the article forecasts emerging cyber-risks from the integration of AI in cybersecurity. Based on the forecasts, the article is concentrated on creating synergies between the existing literature, the data sources identified in the survey, and forecasts. The forecasts are used to increase the feasibility of the overall research and enable the development of novel methodologies that uses AI to defend from cyber risks. The methodology is focused on addressing the risk of AI attacks, as well as to forecast the value of AI in defence and in the prevention of AI rogue devices acting independently.
Reappraisal of the braincase anatomy of the ornithopod dinosaurs Telmatosaurus and Zalmoxes from the Upper Cretaceous of the Haţeg Basin (Romania) and the taxonomic reassessment of some previously referred specimens
Authors: Augustin Felix J. , Dumbravă Mihai D. , Bastiaans Dylan , Csiki-Sava Zoltán
Published: June 2022

The hadrosauroid Telmatosaurus and the rhabdodontid Zalmoxes were the first and second dinosaur taxa that were described in detail from the famous Upper Cretaceous continental deposits of the Haţeg Basin by Franz Baron Nopcsa at the beginning of the twentieth century. Although they are among the most common and best-known dinosaurs discovered from these deposits, there are still many open questions as to their taxonomy and anatomy. Here, we re-describe two partial braincases from the uppermost Cretaceous of the Haţeg Basin that have been recently referred to the rhabdodontid Zalmoxes and re-assign them to hadrosauroids, possibly to Telmatosaurus. These specimens both exhibit basicranial features that are characteristic of derived hadrosauroids but are absent in more basal iguanodontians. These include an antero-posteriorly short basioccipital lacking a distinct neck, the presence of two well-developed sphenoccipital tubercles on the ventral aspect of the braincase and that are directly positioned anterior to the basioccipital, as well as a deep depression on the ventral aspect of the braincase between the sphenoccipital tubercles. The comparison provided herein demonstrates several important differences between the basicranium of hadrosauroids and that of rhabdodontids, which allows for the confident identification of even isolated and incomplete specimens. Moreover, the removal of the only basicranium that has been referred to Zalmoxes shqiperorum prompts a revised diagnosis of that species.
Modelling Sub-daily Precipitation Extremes with the Blended Generalised Extreme Value Distribution
Authors: Vandeskog Silius M. , Martino Sara , Castro-Camilo Daniela , Rue Håvard
Published: June 2022

A new method is proposed for modelling the yearly maxima of sub-daily precipitation, with the aim of producing spatial maps of return level estimates. Yearly precipitation maxima are modelled using a Bayesian hierarchical model with a latent Gaussian field, with the blended generalised extreme value (bGEV) distribution used as a substitute for the more standard generalised extreme value (GEV) distribution. Inference is made less wasteful with a novel two-step procedure that performs separate modelling of the scale parameter of the bGEV distribution using peaks over threshold data. Fast inference is performed using integrated nested Laplace approximations (INLA) together with the stochastic partial differential equation approach, both implemented in . Heuristics for improving the numerical stability of with the GEV and bGEV distributions are also presented. The model is fitted to yearly maxima of sub-daily precipitation from the south of Norway and is able to quickly produce high-resolution return level maps with uncertainty. The proposed two-step procedure provides an improved model fit over standard inference techniques when modelling the yearly maxima of sub-daily precipitation with the bGEV distribution. Supplementary materials accompanying this paper appear on-line.
Quotients, $$\ell _\infty $$ and abstract Cesàro spaces
Authors: Kiwerski Tomasz , Kolwicz Paweł , Tomaszewski Jakub
Published: June 2022

Investigating some re-arrangement properties of the norm in the quotient spaces $$X/X_a$$

X
/

X
a

we determine the properties of the codomain space X guaranteeing the existence of a lattice isometric copy of $$\ell _\infty $$

ℓ
∞

in the abstract Cesàro space CX.
The D-BEST Reference Model: A Flexible and Sustainable Support for the Digital Transformation of Small and Medium Enterprises
Authors: Sassanelli Claudio , Terzi Sergio
Published: June 2022

Nowadays, to remain competitive, manufacturing companies must address the Industry 4.0 paradigm, particularly the cyber-physical system (CPS) revolution, following sustainable challenges. Digital innovation hubs (DIHs), as ecosystems that provide technical knowhow, experimental skills, and specialist knowledge, are progressively gaining a strategic role in supporting such a transition, especially in European small and medium enterprises (SMEs). Several projects have been funded by the European Commission to support the growth and action of DIHs. However, which among the four main functionalities (networking, skills and training, test before investing, and access to funding) each DIH is capable of addressing in its daily support action to companies is still unclear. Thus, it is important to configure the service portfolios of DIHs (i.e. the set of services that each DIH can provide based on its characterising assets, knowledge, and capabilities). In this paper, the data-driven business–ecosystem–skills–technology (D-BEST) reference model is proposed and then tested through a survey. The model triggers the identification and materialisation of service-based collaboration processes among DIHs based on their service portfolio analysis and supports the modelling of Collaborative Networks 4.0, in which DIHs are a strategic player because of their ‘by-design’ innovation characteristics. Finally, through the extended adoption of the models developed by different emerging DIH networks, flexibility and interoperability can be reached, fostering the adoption of a unique digital platform to showcase and offer assets, triggering the creation of multiple inter- and intra-communications and collaborations among stakeholders belonging to the DIH ecosystems, and favouring the exchange and development of joint services.
Magnetron sputtering NbSe2 film as lubricant for space current-carrying sliding contact
Authors: Yang Yang , Pei Lulu , Zhang Hongzhang , Feng Kai , Ju Pengfei , Duan Wenshan , Ji Li , Li Hongxuan , Liu Xiaohong , Zhou Huidi , Chen Jianmin
Published: June 2022

This study demonstrates that magnetron-sputtered NbSe2 film can be used as a lubricant for space current-carrying sliding contact, which accommodates both metal-like conductivity and MoS2-like lubricity. Deposition at low pressure and low energy is performed to avoid the generation of the interference phase of NbSe3. The composition, microstructure, and properties of the NbSe2 films are further tailored by controlling the sputtering current. At an appropriate current, the film changed from amorphous to crystalline, maintained a dense structure, and exhibited excellent comprehensive properties. Compared to the currently available electrical contact lubricating materials, the NbSe2 film exhibits a significant advantage under the combined vacuum and current-carrying conditions. The friction coefficient decreases from 0.25 to 0.02, the wear life increases more than seven times, and the electric noise reduces approximately 50%.
Carbon fiber cannot always reduce the wear of PEEK for orthopedic implants under DPPC lubrication
Authors: Yan Shuai , Men Shichao , Zou Hongbo , Wang Haoji , Zhang Zhongjiang , Wang Chunshen , Sui Tianyi , Lin Bin
Published: June 2022

Excellent wear resistance is an important feature of orthopedic implants. However, although pure polyetheretherketone (PEEK) is outperformed by carbon fiber-reinforced PEEK (CF-PEEK) for stability and durability under laboratory conditions, it is not clear whether CF-PEEK should be preferred in all real-world applications. Results indicate that, under dipalmitoylphosphatidylcholine (DPPC) lubrication, the wear rates of PEEK are 35%—80% lower than the wear rates of CF-PEEK for different implant materials, speeds, loadings, and DPPC concentrations. Molecular dynamics calculations confirm that DPPC self-assembles on the PEEK surface to form an easily adsorbed continuous phospholipid lubricating film. In contrast, the carbon fibers on the CF-PEEK surface hinder the formation of the protective DPPC film and the CF-PEEK surface is thus subject to faster wear.
Deep solution operators for variational inequalities via proximal neural networks
Authors: Schwab Christoph , Stein Andreas
Published: June 2022

Following Bauschke and Combettes (Convex analysis and monotone operator theory in Hilbert spaces, Springer, Cham, 2017), we introduce ProxNet, a collection of deep neural networks with ReLU activation which emulate numerical solution operators of variational inequalities (VIs). We analyze the expression rates of ProxNets in emulating solution operators for variational inequality problems posed on closed, convex cones in real, separable Hilbert spaces, covering the classical contact problems in mechanics, and early exercise problems as arise, e.g., in valuation of American-style contracts in Black–Scholes financial market models. In the finite-dimensional setting, the VIs reduce to matrix VIs in Euclidean space, and ProxNets emulate classical projected matrix iterations, such as projected Jacobi and projected SOR methods.