bluuebunny/crossref_metadata_2025 huggingface dataset:
A Forceful “Dendrite‐Killer” of Polyoxomolybdate with Reusability Effectively Dominating Dendrite‑Free Lithium Metal Anode
Authors: Song Jian , Jiang Yuanyuan , Lu Yizhong , Cao Yundong , Zhang Yuxi , Fan Linlin , Liu Hong , Gao Guanggang
Published: June 2023

In this work, a series of Mo‐containing polyoxometalates (POMs) modified separators to inhibit the growth of lithium dendrites, and thus improving the lifespan and safety of the cells is proposed. When the deposited lithium forms dendrites and touches the separator, the optimized Dawson‐type POM of (NH4)6[P2Mo18O62]·11H2O (P2Mo18) with the stronger oxidizability, acts like a “killer”, is more inclined to oxidize Li0 into Li+, thus weakening the lethality of lithium dendrites. The above process is accompanied by the formation of Lix[P2Mo18O62] (x = 6–10) in its reduced state. Converting to the stripping process, the reduced state Lix[P2Mo18O62] (x = 6–10) can be reoxidized to P2Mo18, which achieves the reusability of P2Mo18 functional material. Meanwhile, lithium ions are released into the cell system to participate in the subsequent electrochemical cycles, thus the undesired lithium dendrites are converted into usable lithium ions to prevent the generation of “dead lithium”. As a result, the Li//Li symmetrical cell with P2Mo18 modified separator delivers exceptional cyclic stability for over 1000 h at 3 mA cm−2 and 5 mAh cm−2, and the assembled Li–S full cell maintains superior reversible capacity of 600 mAh g−1 after 200 cycles at 2 C.
Boosting the Hydrogen Evolution Reaction Performance of P‐Doped PtTe2 Nanocages via Spontaneous Defects Formation
Authors: Ma Hancheng , Huang Xiang , Li Luyu , Peng Wei , Lin Sheng , Ding Yao , Mai Liqiang
Published: June 2023

PtTe2, a member of the noble metal dichalcogenides (NMDs), has aroused great interest in exploring its behavior in the hydrogen evolution reaction (HER) due to the unique type‐II topological semimetallic nature. In this work, a simple template‐free hydrothermal method to obtain the phosphorus‐doped (P‐doped) PtTe2 nanocages with abundant amorphous and crystalline interface (A/C‐P‐PtTe2) is developed. Revealed by density functional theory calculations, the atomic Te vacancies can spontaneously form on the basal planes of PtTe2 by the P doping, which results in the unsaturated Pt atoms exposed as the active sites in the amorphous layer for HER. Owing to the defective structure, the A/C‐P‐PtTe2 catalysts have the fast Tafel step determined kinetics in HER, which contributes to an ultralow overpotential (η = 28 mV at 10 mA cm−2) and a small Tafel slope of 37 mV dec−1. More importantly, benefiting from the inner stable crystalline P‐PtTe2 nanosheets, limited decay of the performance is observed after chronopotentiometry test. This work reveals the important role of the inherent relationship between structure and activity in PtTe2 for HER, which may bring another enlightenment for the design of efficient catalysts based on NMDs in the near future.
Ionizable Lipid with Supramolecular Chemistry Features for RNA Delivery In Vivo
Authors: Manning Alanna M. , Tilstra Grayson , Khan Aniqa B. , Couture‐Senécal Julien , Lau Yan Ming Anson , Pang Janice , Abow Amina A. , Robbins Clinton S. , Khan Omar F.
Published: June 2023

Lipid nanoparticles (LNPs) and ribonucleic acid (RNA) technology are highly versatile tools that can be deployed for diagnostic, prophylactic, and therapeutic applications. In this report, supramolecular chemistry concepts are incorporated into the rational design of a new ionizable lipid, C3‐K2‐E14, for systemic administration. This lipid incorporates a cone‐shaped structure intended to facilitate cell bilayer disruption, and three tertiary amines to improve RNA binding. Additionally, hydroxyl and amide motifs are incorporated to further enhance RNA binding and improve LNP stability. Optimization of messenger RNA (mRNA) and small interfering RNA (siRNA) formulation conditions and lipid ratios produce LNPs with favorable diameter (<150 nm), polydispersity index (<0.15), and RNA encapsulation efficiency (>90%), all of which are preserved after 2 months at 4 or 37 °C storage in ready‐to‐use liquid form. The lipid and formulated LNPs are well‐tolerated in animals and show no deleterious material‐induced effects. Furthermore, 1 week after intravenous LNP administration, fluorescent signal from tagged RNA payloads are not detected. To demonstrate the long‐term treatment potential for chronic diseases, repeated dosing of C3‐K2‐E14 LNPs containing siRNA that silences the colony stimulating factor‐1 (CSF‐1) gene can modulate leukocyte populations in vivo, further highlighting utility.
InBi Bimetallic Sites for Efficient Electrochemical Reduction of CO2 to HCOOH
Authors: Wang Qinru , Yang Xiaofeng , Zang Hu , Liu Changjiang , Wang Jiahao , Yu Nan , Kuai Long , Qin Qing , Geng Baoyou
Published: June 2023

Formic acid is receiving intensive attention as being one of the most progressive chemical fuels for the electrochemical reduction of carbon dioxide. However, the majority of catalysts suffer from low current density and Faraday efficiency. To this end, an efficient catalyst of In/Bi‐750 with InOx nanodots load is prepared on a two‐dimensional nanoflake Bi2O2CO3 substrate, which increases the adsorption of *CO2 due to the synergistic interaction between the bimetals and the exposure of sufficient active sites. In the H‐type electrolytic cell, the formate Faraday efficiency (FE) reaches 97.17% at –1.0 V (vs reversible hydrogen electrode (RHE)) with no significant decay over 48 h. A formate Faraday efficiency of 90.83% is also obtained in the flow cell at a higher current density of 200 mA cm−2. Both in‐situ Fourier transform infrared spectroscopy (FT‐IR) and theoretical calculations show that the BiIn bimetallic site can deliver superior binding energy to the *OCHO intermediate, thereby fundamentally accelerating the conversion of CO2 to HCOOH. Furthermore, assembled Zn‐CO2 cell exhibits a maximum power of 6.97 mW cm−1 and a stability of 60 h.
Exotic Magnetic Anisotropy Near Digitized Dimensional Mott Boundary
Authors: Jeong Seung Gyo , Kim Jihyun , Min Taewon , Song Sehwan , Oh Jin Young , Noh Woo‐suk , Park Sungkyun , Park Tuson , Ok Jong Mok , Lee Jaekwang , Choi Woo Seok
Published: June 2023

The magnetic anisotropy of low‐dimensional Mott systems exhibits unexpected magnetotransport behavior useful for spin‐based quantum electronics. Yet, the anisotropy of natural materials is inherently determined by the crystal structure, highly limiting its engineering. The magnetic anisotropy modulation near a digitized dimensional Mott boundary in artificial superlattices composed of a correlated magnetic monolayer SrRuO3 and nonmagnetic SrTiO3, is demonstrated. The magnetic anisotropy is initially engineered by modulating the interlayer coupling strength between the magnetic monolayers. Interestingly, when the interlayer coupling strength is maximized, a nearly degenerate state is realized, in which the anisotropic magnetotransport is strongly influenced by both the thermal and magnetic energy scales. The results offer a new digitized control for magnetic anisotropy in low‐dimensional Mott systems, inspiring promising integration of Mottronics and spintronics.
Making service continuity smarter with artificial intelligence: An approach and its evaluation
Authors: Quattrocchi Giovanni , Tamburri Damian Andrew , Van Den Heuvel Willem‐Jan
Published: June 2023

Service continuity entails establishing an observable and explainable continuum between customer experience and service operations. Such continuum is currently established manually, via service customer management operations (such as service incident management (IM)) often resulting in time‐consuming, human‐detrimental, and error‐prone activities. Conversely, artificial intelligence (AI) is rapidly emerging as an automated enabler towards handling the discontinuities in the aforementioned critical business tasks. Consequently, the emerging topic of AI‐driven incident management (AIIM) addresses practices and tools to resolve incidents by means of AI‐enabled organizational processes and methodologies. Our conjecture is that AIIM could reduce unplanned interruptions of service and let customers resume their work as quick as possible. While several techniques were presented in the literature to automatically identify the problems described in incident tickets by customers, this article focuses on the qualitative analysis and feature extraction off of the provided descriptions. When an incident ticket does not describe properly the problem, the analyst must ask the customer for additional details which could require several long‐lasting interactions. This article proposes ACQUA , an AIIM approach to automatically assess the quality of ticket descriptions with the goals of removing the need of additional communications and guiding the customers to properly describe the incident. A preliminary evaluation of ACQUA was performed on a dataset provided by a large bank in Europe, showing promising results and a boost of 13% in ticket resolution times and connected service continuity.
Effects of oral propranolol on the resistive and pulsatility indices of major abdominal vasculatures in domestic short‐haired cats
Authors: Amini Masouleh Shima , Nasrollahzadeh Masouleh Mohammad , Vazir Bita , Bokaie Saied
Published: June 2023

Background

No study has been performed regarding the effects of oral administration of propranolol on pulse‐wave spectral Doppler indices of major abdominal vessels in healthy adult cats.

Objective

The objective of this study was to assess the pulse‐wave spectral Doppler indices of abdominal aorta, caudal vena cava, and portal vein in clinically normal adult domestic short‐haired (DSH) cats, before and after propranolol ingestion.

Methods

Twenty intact adult client‐owned DSH cats were evaluated (10 males and 10 females). A duplex Doppler ultrasonography machine with a 10‐MHz frequency linear transducer was used. Peak systolic velocity, end‐diastolic velocity (EDV), resistive index (RI), pulsatility index (PI), and pressure gradient were measured. All the cats received 1 mg/kg of propranolol tablet, and after 2 h, ultrasonography measurements were repeated.

Results

The mean RI of the aorta and caudal vena cava significantly decreased in male cats following oral administration of propranolol after 2 h (p = 0.03, p = 0.02). In the caudal vena cava, the PI decreased from 2.98 ± 0.62 to 1.15 ± 0.19 post‐propranolol ingestion (p = 0.01). The mean EDV in the caudal vena cava of males and portal veins of females significantly decreased after propranolol ingestion (p = 0.04, p = 0.02).

Conclusions

This study showed that propranolol decreased the PI of the aorta and PI and RI of the caudal vena cava in healthy normal cats 2 h post‐propranolol ingestion at the dosage of 1 mg/kg.
Effect of strontium ranelate and cerium oxide addition in the diet on bone quality and expression level of osteocalcin and alkaline phosphatase genes in broiler chicken
Authors: Sabir Payam Sadq , Abbas Kamaran A.
Published: June 2023

Background

In the modern broiler industry, leg and gait disorders are considerable problems. Fast‐growing broilers are especially susceptible to bone abnormalities, causing major problems for broiler producers. Strontium ranelate (SrR) has been used successfully for the treatment of osteoporosis in humans. In addition, cerium oxide (CeO) is an anti‐stress agent applied in the biological system.

Methods

This study was conducted to investigate the effect of SrR, CeO, and their combinations on tibia quality in broilers. A total of 384 one‐day‐old Ross chicks were divided into six treatments, with four replicates per treatment (16 birds per replicate). The control group was fed a standard diet, and other groups were fed SrR at levels 450, 900 mg/kg feed, CeO at levels 300 and 600 mg/kg feed and a combination of 450 SrR + 300 CeO mg/kg feed. Bone mineral density (BMD), bone mineral content (BMC), bone strength (BS), tibia area, tibia weight, bone Length, bone diameter, minerals in tibia bone of male broilers, alkaline phosphatase gene (ALP) and osteocalcin gene (OC) in male broilers were analysed.

Results

The results showed that the addition of SrR and CeO had no significant influence (p > 0.01) on BMD, BMC, BS, bone weight, bone length and bone diameter. While there was a significant interaction between sex and treatments, especially in the combination group, BS in females significantly (p < 0.01) increased compared to the control group. Generally, females were found to be more responsive to treatments than males. Significant increases in gene expression were noticed in OC with the addition of low levels of SrR and CeO and mixed group compared to the control. The gene expression of ALP was increased significantly only in a combination group compared to the control group.

Conclusion

It is concluded that SrR and CeO can be used as beneficial additives in the feed to improve the tibia quality of broilers.
Placing Property in the Landscape
Authors: Byer Amanda
Published: June 2023

To explain property’s origins in place or landscape, this chapter draws on legal, historical, geographical, etymological and archaeological research to reconstruct how people understood land before property. The chapter relies on two main sources: Kenneth Olwig’s cultural geographical research on early landscapes in pre-feudal Scandinavia and Sub-Roman/pre-enclosure Britain illustrates the relationship between land, law and people; and Nicole Graham’s etymological analysis linking property not to ownership but to proximity affirms that a specific location to which someone belonged generated relations relevant to identity, community and a sustainable way of life. Land was communal, dynamic and characterised by attachment, the polar opposite of property’s defining characteristics today (individual, exclusive and alienable).
Locke and the Homogenisation of the Landscape
Authors: Byer Amanda
Published: June 2023

This chapter examines John Locke’s contributions to the property discourse in the context of the first hallmark of property, individuality. A legal geographical analysis of his Two Treatises is employed to show how Locke’s focus on the individual and the labour theory of value required a reductionist understanding of the commons and communal land use. Locke’s influences from improvement philosophy and his role in the colonial administration of North America are also discussed in relation to his understanding of land. The chapter addresses the consequences of perceiving locally developed concepts of common land as empty space or wasteland. Property’s association with individual liberty in Anglo-American law is reinterpreted in light of its reliance on and extraction from complex Indigenous landscapes.
Blackstone and the Externalisation of Landscape
Authors: Byer Amanda
Published: June 2023

The idea of absolutist ownership in land, introduced in William Blackstone’s influential work, Commentaries on the Laws of England, is the subject of this chapter. Blackstone’s reframing of intrinsic aspects of the landscape as external encumbrances burdening the individual landowner is discussed as the watershed moment that terminated property’s social function. Blackstone applied the generic feudal pyramid of tenures to England, without considering the lived-in experiences of local communities and their ancient way of life that varied and complicated feudal practices. The chapter examines the role of the new landowning class in Parliament, which passed the Enclosure Acts to enclose common land as private property, thereby using the law to dismantle common rights and functioning local communities, and legitimise exclusion as a feature of property.
Marx and the Dephysicalisation of the Landscape
Authors: Byer Amanda
Published: June 2023

This chapter relies on Marx’s later critiques of capitalism (which focused on the relationship between property rights and nature) to explain the final hallmark of property: alienability. Using Marx's metabolic rift theory, the  chapter considers how the abstraction of land was achieved through the separation of culture and nature, which created distance between people and their embedded relations with land. This is illustrated with examples from rundale communities in Ireland and the slave colonies of the Caribbean. Converting landscapes to plantation monoculture to maximise exploitation  destabilised the landscape dynamic, facilitating displacement, oppression, and enslavement, and  socio-ecological crises such as the Famine. The chapter thus draws attention to the spatial consequences of land's dephysicalisation in property law.
Conclusion: Property’s Placelessness
Authors: Byer Amanda
Published: June 2023

The closing chapter recaps the book’s objectives, which were to determine property’s origins, now identified in pre-feudal landscape, recover the spatial parameters of the theories of Locke, Blackstone and Marx, which are foundational to classical property theory, and highlight the process of converting landscapes to property as an exercise in spatial injustice that is facilitated by the law. This process was not linear or progressive, in response to land’s environmental limits, but executed through enclosure, displacement and colonisation. As a result, the chapter contends that a legal geographical perspective reveals that property is based on detachment from place, and this placelessness has implications for sustainable land use today.
The emergence proposal in quantum gravity and the species scale
Authors: Castellano A. , Herráez A. , Ibáñez L. E.
Published: June 2023

Abstract

In the Emergence Proposal in Quantum Gravity it is conjectured that all light-particle kinetic terms are absent in the fundamental ultraviolet theory and are generated by quantum corrections in the infrared. It has been argued that this may provide for some microscopic understanding of the Weak Gravity and Distance conjectures. In the present paper we take the first steps towards a systematic study of Emergence in the context of string theory. We emphasize the crucial role of the species scale in any effective field theory coupled to gravity, and discuss its computation in string theory and general systems with light towers of states. We then introduce the notion of Emergence and show how kinetic terms for moduli, gauge bosons and fermions may be generated. One-loop computations play an important role in Emergence, so we present detailed calculations in d spacetime dimensions for the wave-function renormalization of scalars, vectors and fermions. We extend and check the Emergence Proposal in a number string vacua, including 4d $$ \mathcal{N} $$
N
= 2 theories arising from type IIA on a CY3, where the towers at strong coupling are comprised by D0 and (wrapped) D2-branes, and also elaborate on how instanton corrections would fit within the emergence picture. Higher dimensional examples are also discussed, including 6d and 7d models arising from F-/M-theory on an elliptic CY3 or a K3 surface. We also consider 10d string theories and study in some detail the emergence mechanism in type IIA. We show as well how the flux potential in 4d may be obtained from the emergence prescription, by analyzing the corresponding decompactification limits to M-theory. We find that the required kinetic terms for the dual 3-form fields can arise upon integrating out towers of massive gravitini (and bosonic superpartners). Our analysis renders support to the Emergence Proposal, and to the idea that infinite distance singularities may arise in Quantum Gravity as an intrinsic infrared phenomenon.
Ladder and zig-zag Feynman diagrams, operator formalism and conformal triangles
Authors: Derkachov S. E. , Isaev A. P. , Shumilov L. A.
Published: June 2023

Abstract

We develop an operator approach to the evaluation of multiple integrals for multiloop Feynman massless diagrams. A commutative family of graph building operators Hα for ladder diagrams is constructed and investigated. The complete set of eigenfunctions and the corresponding eigenvalues for the operators Hα are found. This enables us to explicitly express a wide class of four-point ladder diagrams and a general two-loop propagator-type master diagram (with arbitrary indices on the lines) as Mellin-Barnes-type integrals. Special cases of these integrals are explicitly evaluated. A certain class of zig-zag four-point and two-point planar Feynman diagrams (relevant to the bi-scalar D-dimensional “fishnet” field theory and to the calculation of the β-function in ϕ4-theory) is considered. The graph building operators and convenient integral representations for these Feynman diagrams are obtained. The explicit form of the eigenfunctions for the graph building operators of the zig-zag diagrams is fixed by conformal symmetry and these eigenfunctions coincide with the 3-point correlation functions in D-dimensional conformal field theories. By means of this approach, we exactly evaluate the diagrams of the zig-zag series in special cases. In particular, we find a fairly simple derivation of the values for the zig-zag multi-loop two-point diagrams for D = 4. The role of conformal symmetry in this approach, especially a connection of the considered graph building operators with conformal invariant solutions of the Yang-Baxter equation is investigated in detail.
Where is M-theory in the space of scattering amplitudes?
Authors: Guerrieri Andrea , Murali Harish , Penedones Joao , Vieira Pedro
Published: June 2023

Abstract

We use the S-matrix bootstrap to carve out the space of unitary, analytic, crossing symmetric and supersymmetric graviton scattering amplitudes in nine, ten and eleven dimensions. We extend and improve the numerical methods of our previous work in ten dimensions. A key new tool employed here is unitarity in the celestial sphere. In all dimensions, we find that the minimal allowed value of the Wilson coefficient α, controlling the leading correction to maximal supergravity, is very close but not equal to the minimal value realized in Superstring theory or M-theory. This small difference may be related to inelastic effects that are not well described by our numerical extremal amplitudes. Although α has a unique value in M-theory, we found no evidence of an upper bound on α in 11D.
Webbasierter Kontaminantenrechner in der Risikobewertung – ein hilfreiches Tool?
Authors: Mielke Hans , Abraham Klaus , Beyvers Stephanie , Blume Katrin , Böl Gaby-Fleur , Ehlers Anke , Flor Matthias , Gürtler Rainer , Kolbaum Anna Elena , Kühn Juana , Lindtner Oliver , Lohmann Mark , Merkel Stefan , Pabel Ulrike , Schäfer Bernd , Schafft Helmut , Sieke Christian , Stehfest Susann , Uhlig Katrin , Müller-Graf Christine , Greiner Matthias
Published: June 2023

Ziel dieser Arbeit ist die Beschreibung der Entwicklung einer webbasierten, interaktiven Darstellung von maximalen tolerierbaren Verzehrmengen für ausgewählte Lebensmittel, die beispielsweise in einer Ereignissituation als potenziell kontaminiert angenommen werden („Kontaminantenrechner“). Die vorliegende Arbeit beschreibt einen Katalog wissenschaftlicher Anwendungskriterien für einen solchen Kontaminantenrechner. Als Anwendungsbeispiel wird der Fipronil-Ereignisfall im Sommer 2017 verwendet.
Establishing Equal-Channel Angular Pressing (ECAP) for sheet metals by using backpressure: manufacturing of high-strength aluminum AA5083 sheets
Authors: Gruber Maximilian , Illgen Christian , Lichte Felix , Hartmann Christoph , Frint Philipp , Wagner Martin F.-X. , Volk Wolfram
Published: June 2023

Severe plastic deformation (SPD) processes offer the possibility of improving the mechanical properties of metallic materials by grain refinement. However, this great potential has so far mostly been applied on a laboratory scale or on small series. Equal-Channel Angular Pressing (ECAP) also enables to integrate the advantages in industrial processes with large output—so far, mainly for bars or thick plates. In this paper, we investigate the ECAP process for sheet metal. Preliminary investigations have shown that cracks form on the surface when aluminum AA5083 sheets are processed. To solve this problem, we determined the Johnson–Cook fracture criterion for the material and modeled the process numerically. The simulation was carried out with the superposition of a backpressure and subsequently implemented and validated experimentally. The semi-finished sheet metal products from the ECAP investigation were then mechanically characterized with microhardness measurements and tensile tests. In addition, the microstructure was investigated with Electron Back Scatter Diffraction (EBSD). Even comparatively small amounts of backpressure (10 MPa) already result in a significant suppression of the crack formation in the numerical and experimental investigations. The microhardness measurements indicate a more homogeneous strain distribution for a sufficient level of applied backpressure which enables the processing of crack-free sheets in multiple ECAP passes. As with ECAP of bulk materials, tensile tests on the processed sheets show a reduced elongation to failure (− 73%) but a significantly increased yield strength (+ 157%) compared to the initial condition of the material. Distinct substructures are found in the EBSD measurements and explain this behavior. The findings provide the basis for using ECAP on an application-oriented scale and demonstrate an advanced manufacturing method for the production of high-strength aluminum sheets.
A Nomothetic Span Approach to the Construct Validation of Sustained Attention Consistency: Re-Analyzing Two Latent-Variable Studies of Performance Variability and Mind-Wandering Self-Reports
Authors: Welhaf Matthew S. , Kane Michael J.
Published: June 2023

The ability to sustain attention consistency is frequently assessed using either objective behavioral measures, such as reaction time (RT) variability, or subjective self-report measures, such as rates of task-unrelated thought (TUT). The current studies examined whether the individual-difference covariation in these measures provides a more construct valid assessment of attention consistency than does either alone. We argue that performance and self-report measures mutually validate each other; each measurement approach has its own sources of error, so their shared variance should best reflect the attention consistency construct. We reanalyzed two latent-variable studies where RT variability and TUTs were measured in multiple tasks (Kane et al. in J Exp Psychol Gen 145:1017–1048, 2016; Unsworth et al. in J Exp Psychol Gen 150:1303–1331, 2021), along with several nomological network constructs to test the convergent and discriminant validity of a general attention consistency factor. Confirmatory factor analyses assessing bifactor (preregistered) and hierarchical (non-preregistered) models suggested that attention consistency can be modeled as the shared variance among objective and subjective measures. This attention consistency factor was related to working memory capacity, attention (interference) control, processing speed, state motivation and alertness, and self-reported cognitive failures and positive schizotypy. Although bifactor models of general attention consistency provide the most compelling construct validity evidence for a specific ability to sustain attention, multiverse analyses of outlier decisions suggested they are less robust than hierarchical models. The results provide evidence for the general ability to sustain attention consistency and suggestions for improving its measurement.
Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study
Authors: Zhou Qing , Zhang He-Long , Jiang Li-Yan , Shi Yuan-Kai , Chen Yuan , Yu Jin-Ming , Zhou Cai-Cun , He Yong , Hu Yan-Ping , Liang Zong-An , Pan Yue-Yin , Zhuo Wen-Lei , Song Yong , Wu Gang , Chen Gong-Yan , Lu You , Zhang Cui-Ying , Zhang Yi-Ping , Cheng Ying , Lu Shun , Wang Chang-Li , Zhou Jian-Ying , Liu Yun-Peng , He Jian-Xing , Wang Jie , Wu Yi-Long
Published: June 2023

Purpose

ASTRIS study aimed the largest to evaluate the effectiveness and safety of second- or higher-line osimertinib in patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non–small cell lung cancer (NSCLC) in the real-world setting. Here we report the results of Chinese patients in ASTRIS study.

Methods

Adults with EGFR T790M-positive advanced NSCLC pretreated with EGFR-tyrosine kinase inhibitor (EGFR-TKI), having a WHO performance status score of 0–2 and asymptomatic, stable central nervous system (CNS) metastases were included. All patients received once-daily osimertinib 80 mg orally. The outcomes included investigator-assessed clinical response, progression-free survival (PFS), time-to-treatment discontinuation (TTD), and safety.

Results

A total of 1350 patients were included. Response rate was 55.7% (95% confidence interval [CI] 0.53–0.58). The median PFS and the median TTD were 11.7 months (95% CI 11.1–12.5) and 13.9 months (95% CI 13.1–15.2), respectively. Overall, 389 patients (28.8%) had at least one protocol-specified adverse event (AE); AEs of interstitial lung diseases/pneumonitis-like events and QT prolongation were reported in 3 (0.2%) and 59 (4.4%) patients, respectively.

Conclusion

Osimertinib was effective in Chinese patients with T790M-positive NSCLC who had progressed after first- or second-generation EGFR-TKI in real-word setting and the results were consistent with ASTRIS study overall population and AURA studies. No new safety signals or events were identified.

Clinical trial number

NCT02474355.
Association of CDKN2A/B mutations, PD-1, and PD-L1 with the risk of acute lymphoblastic leukemia in children
Authors: Ruan Yang , Xie Longlong , Zou Aijun
Published: June 2023

Purpose

Currently, the significance of CDKN2A/B mutations in the pathogenesis and prognosis of acute lymphoblastic leukemia (ALL) is inconclusive. In this study, we analyzed the genetic and clinical features of children with CDKN2A/B mutations in ALL. In addition, we evaluated the expression and significance of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in serum and explored their role in the susceptibility of childhood ALL.

Methods

We sequenced CDKN2A/B in the peripheral blood of 120 children with ALL and 100 healthy children with physical examination. The levels of CD4+ T, CD8+ T, and NK cells were measured by flow cytometry (FCM). Furthermore, the expression of PD-1 and PD-L1 was detected by ELISA.

Results

We found 32 cases of CDKN2A rs3088440 and 11 of CDKN2B rs2069426 in 120 ALL children. Children with ALL in the CDKN2A rs3088440 were more likely to have hepatosplenomegaly (P = 0.019) and high risk (P = 0.014) than the wild group. In contrast, CDKN2B rs2069426 was more likely to develop lymph node metastasis (P = 0.017). The level of PD-L1 in the serum of ALL children was significantly higher than that of the control group, and there was no significant difference in PD-1 (P < 0.001). Additionally, children with CDKN2A rs3088440 had reduced CD8+ T cell counts than the wild group (P = 0.039).

Conclusion

CDKN2A rs3088440 and CDKN2B rs2069426 may be related to the occurrence and development of ALL in Chinese children. Additionally, PD-1/PD-L1 may be involved in the immune escape process of ALL, which is expected to become a new target for the treatment of the disease.
Psychotherapeutische Medizin in der psychiatrischen Fachärzt:innenausbildung in Österreich
Authors: Löffler-Stastka Henriette , Lugsch Martin , Aigner Martin
Published: June 2023

Die vorliegende Arbeit beschreibt die Entwicklung der psychotherapeutischen Medizin innerhalb der ärztlich-psychiatrischen Fachärzt:innen-Ausbildung. Die Grundlage für die Kompetenzdarstellung bilden die einzelnen Rasterzeugnisse der Ausbildungsordnungen 1994, 2006, 2011 sowie 2015. Die Entwicklung der psychotherapeutischen Kompetenzen innerhalb der ärztlich-psychiatrischen Identität wird anhand des Qualifikations- und Kompetenzprofils sowie der Lernziele dargestellt.
Early neurological deterioration in Wilson’s disease: a systematic literature review and meta-analysis
Authors: Antos Agnieszka , Członkowska Anna , Smolinski Lukasz , Bembenek Jan , Przybyłkowski Adam , Skowrońska Marta , Kurkowska-Jastrzębska Iwona , Litwin Tomasz
Published: June 2023

Introduction

Neurological deterioration, soon after anti-copper treatment initiation, is problematic in the management of Wilson’s disease (WD) and yet reports in the literature are limited. The aim of our study was to systematically assess the data according to early neurological deteriorations in WD, its outcome and risk factors.

Methods

Using PRISMA guidelines, a systematic review of available data on early neurological deteriorations was performed by searching the PubMed database and reference lists. Random effects meta-analytic models summarized cases of neurological deterioration by disease phenotype.

Results

Across the 32 included articles, 217 cases of early neurological deterioration occurred in 1512 WD patients (frequency 14.3%), most commonly in patients with neurological WD (21.8%; 167/763), rarely in hepatic disease (1.3%; 5/377), and with no cases among asymptomatic individuals. Most neurological deterioration occurred in patients treated with d-penicillamine (70.5%; 153/217), trientine (14.2%; 31/217) or zinc salts (6.9%; 15/217); the data did not allow to determine if that reflects how often treatments were chosen as first line therapy or if the risk of deterioration differed with therapy. Symptoms completely resolved in 24.2% of patients (31/128), resolved partially in 27.3% (35/128), did not improve in 39.8% (51/128), with 11 patients lost to follow-up.

Conclusions

Given its occurrence in up to 21.8% of patients with neurological WD in this meta-analysis of small studies, there is a need for further investigations to distinguish the natural time course of WD from treatment-related early deterioration and to develop a standard definition for treatment-induced effects.
New degrees of freedom for differential forms on cubical meshes
Authors: Lohi Jonni
Published: June 2023

We consider new degrees of freedom for higher order differential forms on cubical meshes. The approach is inspired by the idea of Rapetti and Bossavit to define higher order Whitney forms and their degrees of freedom using small simplices. We show that higher order differential forms on cubical meshes can be defined analogously using small cubes and prove that these small cubes yield unisolvent degrees of freedom. Importantly, this approach is compatible with discrete exterior calculus and expands the framework to cover higher order methods on cubical meshes, complementing the earlier strategy based on simplices.
The α-(1,3)-glucan synthase gene agsE impacts the secretome of Aspergillus niger
Authors: Lyu Jun , Torchia Costanza , Post Harm , Moran Torres Juan P. , Altelaar A. F. Maarten , de Cock Hans , Wösten Han A. B.
Published: June 2023

Aspergillus niger is widely used as a cell factory for the industrial production of enzymes. Previously, it was shown that deletion of α-1–3 glucan synthase genes results in smaller micro-colonies in liquid cultures of Aspergillus nidulans. Also, it has been shown that small wild-type Aspergillus niger micro-colonies secrete more protein than large mirco-colonies. We here assessed whether deletion of the agsC or agsE α-1–3 glucan synthase genes results in smaller A. niger micro-colonies and whether this is accompanied by a change in protein secretion. Biomass formation was not affected in the deletion strains but pH of the culture medium had changed from 5.2 in the case of the wild-type to 4.6 and 6.4 for ΔagsC and ΔagsE, respectively. The diameter of the ΔagsC micro-colonies was not affected in liquid cultures. In contrast, diameter of the ΔagsE micro-colonies was reduced from 3304 ± 338 µm to 1229 ± 113 µm. Moreover, the ΔagsE secretome was affected with 54 and 36 unique proteins with a predicted signal peptide in the culture medium of MA234.1 and the ΔagsE, respectively. Results show that these strains have complementary cellulase activity and thus may have complementary activity on plant biomass degradation. Together, α-1–3 glucan synthesis (in)directly impacts protein secretion in A. niger.
An eco-sustainable innovative geotechnical technology for the structures seismic isolation, investigated by FEM parametric analyses
Authors: Abate Glenda , Fiamingo Angela , Massimino Maria Rossella
Published: June 2023

Geotechnical Seismic Isolation (GSI) is an innovative technique for protecting structures in earthquake-prone areas. The main idea is to improve the foundation soil so that seismic energy is partially dissipated within GSI before being transmitted to the structure. Among other materials proposed for foundation soil improvement, gravel-rubber mixtures (GRMs), with rubber grains manufactured from end-of-life tires, have attracted significant research interest thanks to their good mechanical properties. GRMs also represent a modern recycling system to reduce the stockpile of scrap tires worldwide. The present study investigated numerically the effect of a GRM layer located underneath the shallow foundations of a real structure. The structure is a typical reinforced concrete building in southern Italy. A Finite Element Modelling (FEM) was carried out to evaluate the overall static and dynamic behaviour of the soil-GRMs-structure system. Three FEM models were performed with and without the GRM layer, varying the GRM layer thickness and the seismic inputs. The comparisons among the models allow us to assess the performance of the GRM underneath the foundations as a new eco-sustainable solution for the seismic isolation of structures.
Resolving the Ethical Tension Between Creating a Civil Environment and Facilitating Free Expression Online: Comment Reordering as an Alternative to Comment Moderation
Authors: Yadin Dena , Yahav Inbal , Zalmanson Lior , Munichor Nira
Published: June 2023

Incivility in online commenting sections can create a hostile environment and result in the silencing of vulnerable voices. Accordingly, content websites and social media platforms have an ethical responsibility—one that aligns with their strategic interests—to minimize users' exposure to uncivil content. To this end, platforms invest great effort and budget in automatic and manual filtering mechanisms. Yet, these efforts create a competing ethical quandary, as they often come at the expense of free expression, particularly in cases where comments do not explicitly infringe on stated guidelines but might nevertheless be interpreted as offensive. In this paper, we examine an alternative moderation approach, based on comment reordering as opposed to deletion of uncivil comments. Specifically, we show that exposure to uncivil (vs. civil) comments located in the head or at the bottom of a list of comments increases subsequent commenters' likelihood of posting uncivil comments themselves. Exposure to uncivil comments in the middle of a list, however, does not significantly enhance commenters' likelihood of commenting uncivilly. These results offer new theoretical insight into how incivility is transferred between users in online environments. Our results also suggest a straightforward technological solution for mitigating online incivility, which is more ethical and practical than current industry standards. This involves placing civil comments at the beginning and end of the comment thread, with uncivil comments located in the middle.
Quality of virtual-non-contrast phases derived from arterial and delayed phases of fast-kVp switching dual-energy CT in patients after endovascular aortic repair
Authors: Kazimierczak Wojciech , Kazimierczak Natalia , Serafin Zbigniew
Published: June 2023

Objective of this study is: to analyze CT numbers in arteries and endoleaks in true non-contrast (TNC) and virtual non-contrast phases derived from arterial (VNCa) and delayed (VNCd) phases of dual-energy CT (DECT) in patients after endovascular aneurysm repair (EVAR); to assess the impact of image noise on subjective image quality parameters and the degree of subtraction of calcifications; to calculate effective dose (ED) reduction following replacement of TNC with VNC. The study included 97 patients after EVAR procedure. An initial single-energy TNC acquisition was followed by two DECT acquisitions. CT numbers of TNC, VNCa, VNCd were analyzed statistically. VNCd images were assessed qualitatively. The mean densities in endoleaks were 46.19 HU in TNC, 51.24 HU in VNCa, 42.24 HU in VNCd. The differences between them were statistically significant (p < 0.05). The mean signal-to-noise ratio (SNR) measured in the aorta and endoleaks was highest in VNCa, lowest in TNC images. No correlation between image noise, the results of qualitative analysis of VNCd, and the degree of subtraction of calcifications was found. Omitting TNC led to mean 6.54 ± 1.63 (SD) mSv (23.28% of total examination) ED reduction. VNC images have a higher SNR compared to TNC images with significant differences in the CT numbers between the TNC and VNC reconstructions. Image noise has no impact on the subjective image quality and the degree of subtraction of calcifications in VNCd images. The findings show a high diagnostic value of VNC images and suggest that VNCd images are optimal in the assessment of endoleaks with possible substantial ED reduction.
Inhibiting PI3K/Akt-Signaling Pathway Improves Neurobehavior Changes in Anti-NMDAR Encephalitis Mice by Ameliorating Blood–Brain Barrier Disruption and Neuronal Damage
Authors: Gong Zhuowei , Lao Dayuan , Wu Yu , Li Taiyan , Lv Sirao , Mo Xuean , Huang Wen
Published: June 2023

The disruption of the blood–brain barrier (BBB) is hypothesized to be involved in the progression of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, but its mechanism is still unclear. Recently, the phosphatidylinositol 3-kinase (PI3K)/threonine kinase (Akt) pathway is involved in the regulation of the BBB in various diseases. This study is aimed to investigate the mechanism of BBB damage and neurobehavior changes in anti-NMDAR encephalitis mice. Female C57BL/6J mice were actively immunized to establish an anti-NMDAR encephalitis mouse model and evaluate the neurobehavior changes of mice. To study its potential mechanism, LY294002 (PI3K inhibitor, 8 mg/kg) and Recilisib (PI3K agonist, 10 mg/kg) were treated by intraperitoneal injection, respectively. Anti-NMDAR encephalitis mice showed neurological deficits, increased BBB permeability, open endothelial tight junctions (TJs), and decreased expression of TJ-related proteins zonula occludens (ZO)-1 and Claudin-5. However, administration of PI3K inhibitor significantly reduced the expression of p-PI3K and p-Akt, improved neurobehavior function, decreased BBB permeability, and upregulated the expressions of ZO-1 and Claudin-5. Furthermore, PI3K inhibition reversed the decline of NMDAR NR1 in the membranes of hippocampal neurons, which reduced the loss of neuron-specific nucleoprotein (NeuN) and microtubule-associated protein 2 (MAP2). In contrast, administration of the PI3K agonist Recilisib showed a tendency to exacerbate BBB breakdown and neurological deficits. Our results showed that the activation of PI3K/Akt, along with the changes in TJ-related proteins ZO-1 and Claudin-5, may be closely related to BBB damage and neurobehavior changes in anti-NMDAR encephalitis mice. PI3K inhibition attenuates BBB disruption and neuronal damage in mice, thereby improving neurobehavior.
Assessment of formal proceedings and out-of-court reorganisation: results from a survey among turnaround professionals in Austria
Authors: Mayr Stefan , Duller Christine , Baschinger Matthias
Published: June 2023

This study analyses the decision criteria for a specific form of reorganisation in a creditor-friendly bankruptcy system such as that of Austria. From a neoinstitutional perspective, we present different forms of bankruptcy law and the specifics of reorganisation in Austria. Next, we show several distinctive criteria and influencing factors for formal reorganisation and workouts. We group these factors into constitutions and institutional settings, process and handling, and implementation of the reorganisation. Using a sample of 411 survey responses from turnaround professionals, our empirical study analyses the decision criteria for a specific form of reorganisation. We apply a multivariate approach comprising two-sided paired samples Wilcoxon tests to assess the derived hypotheses and a hierarchical cluster analysis. Our results indicate significant differences in the valuation of the two forms: the turnaround professionals rate public perception much higher for out-of-court reorganisation, whereas legal certainty is rated significantly better for formal proceedings. Regarding process and handling, transparency and the handling of blocking positions are arguments for formal reorganisation, whereas flexibility is valuated better for workouts. In terms of implementation, respondents see advantages for out-of-court reorganisation, as it facilitates the implementation of both financial and operational measures. Taxation, the handling of blocking positions, and the improvement of public perception were identified as key development aspects for the legal framework conditions of the various reorganisation forms.
Novel Green Synthesis of UV-Sunscreen ZnO Nanoparticles Using Solanum Lycopersicum Fruit Extract and Evaluation of Their Antibacterial and Anticancer Activity
Authors: Elbrolesy Aya , Abdou Y. , Elhussiny F. A. , Morsy Reda
Published: June 2023

This work aimed at the green synthesis of multifunctional zinc oxide nanoparticles (ZnO NPs) using Solanum Lycopersicum (SL) fruit juice to act as antibacterial/cancer/UV sunscreens. The obtained ZnO NPs were examined for optical properties, cytotoxicity of human lung fibroblast (WI-38) and hepatocellular carcinoma (HePG2) cell lines, and antibacterial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. The antioxidant activity and in vitro sun protection factor (SPF) of the synthesized nanoparticles were carried out by spectrophotometric methods. The formation of pure phase structure and characteristic functional group of the synthesized ZnO NPs were confirmed by XRD, FTIR, and UV–Vis diffuse reflectance analysis. SEM image showed that the ZnO NPs have a quasi-spherical shape with a size of about 39 ± 12 nm. ZnO NPs showed high potency as sunscreens (in vitro SPF = 16.8) and as mild antioxidant agents. Notably, ZnO NPs enhanced the cytotoxic activity against hepatocellular carcinoma cells and confirmed their antibacterial activity against pathogenic bacteria. SL fruit juice can play a triple role by acting as a solvent, reducing agent and stabilizer which facilitates the synthesis of ZnO NPs sunscreen that has antibacterial and anti-carcinogenic properties.