bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of montelukast therapy on clinical course, pulmonary function, and mortality in patients with COVID‐19
Authors: Kerget Buğra , Kerget Ferhan , Aydın Murat , Karaşahin Ömer
Published: December 2021

The inflammatory/anti‐inflammatory balance has an important role in the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) (coronavirus disease [COVID‐19]) infection, which has affected over 200 million people since it first appeared in China in December 2019. This study aimed to determine the effectiveness of montelukast, which has known anti‐inflammatory and bronchodilatory effects, in these patients. The prospective randomized controlled study included 180 patients who were hospitalized in the infectious diseases department of our hospital between May and July 2021 and were diagnosed with the delta variant of SARS‐CoV‐2 by real‐time polymerase chain reaction of nasopharyngeal swabs. The patients were divided into three groups and received only standard treatment according to national guidelines (Group 1) or standard treatment plus 10 mg/day montelukast (Group 2) or 20 mg/day montelukast (Group 3). Laboratory parameters and pulmonary function tests (PFTs) at admission and on Day 5 of treatment were compared. Comparison of laboratory parameters on Day 5 showed that Groups 2 and 3 had significantly lower levels of lactate dehydrogenase, fibrinogen, D‐dimer, C‐reactive protein, and procalcitonin compared with Group 1 (p = 0.04, 0.002, 0.05, 0.03, and 0.04, respectively). In the comparison between Groups 2 and 3, only fibrinogen was significantly lower in Group 3 (p = 0.02). PFT results did not differ between the groups at admission, while on Day 5, only Group 3 showed significant improvements in forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow 25–75 compared with admission (p = 0.001 for all). Montelukast may be beneficial in COVID‐19 patients to maintain the inflammatory/anti‐inflammatory balance, prevent respiratory failure through its bronchodilator activity, and reduce mortality.
L‐arginine protects cementoblasts against hypoxia‐induced apoptosis through Sirt1‐enhanced autophagy
Authors: Xu Lei , Tan Xi , Bai Siyu , Wu Hongyan , Luo Hong , Ye Yusi , Fang Lingli , Dai Hongwei , Huang Lan
Published: December 2021

Background

L‐arginine (L‐arg) can reduce apoptosis in a variety of cells. Cementoblast apoptosis is related to root resorption during orthodontic treatment. In the present study, we aimed to study the regulatory effect and potential mechanism of L‐arg on cementoblast apoptosis and root resorption.

Methods

The apoptosis‐related mRNA and protein expression of murine cementoblast (OCCM‐30) was assessed after L‐arg treatment. To investigate the role of Sirtuin 1 (Sirt1) and autophagy in L‐arg resistance to cementoblast apoptosis and root absorption, resveratrol, and EX527 were used to activate or inhibit Sirt1, and chloroquine (CQ) was used to inhibit autophagy.

Results

In vitro, L‐arg inhibited hypoxia‐induced apoptosis in OCCM‐30. Further, L‐arg increased Sirt1 expression whereas Sirt1 suppression by EX527 reversed the inhibitory effect of L‐arg on cell apoptosis. Sirt1 activator resveratrol increased the ratio of microtubule‑associated protein light chain 3 (LC3) II/I and decreased the expression of SQSTM1/p62 (p62), suggesting autophagy activation. Autophagy enhancement could reduce apoptosis. Caspase‐3 and Bax expression was decreased, and Bcl‐2 expression was increased. When autophagy was inhibited by CQ, the positive effects of Sirt1 were attenuated. In vivo, L‐arg application reduced root resorption in rats, as demonstrated by decreased root absorption volume. Similarly, L‐arg upregulated Sirt1, which activated autophagy in the root resorption model, and less root resorption was observed in the Sirt1 activation group.

Conclusion

L‐arg reduced cementoblast apoptosis in hypoxia and reduced root resorption induced by loading force in rats, which may be partly mediated by Sirt1‐enhanced autophagy.
Enantioselective HPLC analysis of escitalopram oxalate and its impurities using a cellulose‐based chiral stationary phase under normal‐ and green reversed‐phase conditions
Authors: Cantatore Chiara , Bertocchi Paola , De Orsi Daniela , Panusa Alessia , Cirilli Roberto
Published: December 2021

Normal‐phase and reversed‐phase high‐performance liquid chromatography methods for the separation of the active pharmaceutical ingredient escitalopram from its (R)‐enantiomer impurity have been developed on the cellulose‐based Chiralcel OJ‐H chiral stationary phase. Both methods share two features: they use ethanol as a cosolvent and are able to give a complete enantioseparation without interference from other associated chiral impurities. With the green eluent mixture ethanol–water–diethylammine 70:30:0.1 (v/v/v), the resolution between escitalopram and (R)‐enantiomer was 2.09 at 30°C. The limits of quantification for the (S) and (R) enantiomers were 4.5 and 3.8 μg mL−1, respectively.
Fabrication of Hydrophobic Multilayered Fabric for Passive Daytime Radiative Cooling
Authors: Ji Yating , Sun Yilan , Muhammad Javed , Li Xiaoyan , Liu Ziqiang , Tu Pengpeng , Wang Youquan , Cai Zaisheng , Xu Bi
Published: December 2021

Passive daytime radiative cooling (PDRC) has attracted great attention recently due to its high potential for reducing global energy consumption. However, PDRC materials are easily contaminated in practical applications, which will seriously attenuate their long‐term cooling performance. In this work, a multilayered PDRC fabric that is composed of polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), and cotton is shown. This multilayered fabric displays a high solar reflectivity (0.94) and an appropriate atmospheric window emissivity (0.79). A practical application test demonstrates the glass covered by this PDRC fabric can lower the temperature up to 7.8 °C under a solar intensity of ≈495 W m−2. Meanwhile, the multilayered PDRC fabric exhibits self‐cleaning property due to its high water contact angle of 118°. Rolling water can effectively remove the contaminants on the fabric surface. It is believed that this multilayered fabric is a promising material to alleviate the energy crisis and reduce greenhouse gas emissions.
Linear and Nonlinear Viscoelasticity of Polypropylene Containing Cross‐Linked Gels
Authors: Tsai Chia‐Ying , Laux Kevin , Chang Chao‐Shun , Sue Hung‐Jue
Published: December 2021

The dynamic viscoelastic and elongational flow behaviors of polypropylene (PP) with increased loading of micron‐sized gelled particles have been investigated. The results reveal that incorporating gel particles can significantly enhance the PP melt storage and loss modulus, complex viscosity, and degree of strain hardening. The gel particle, acting as a soft, deformable filler, exhibits a core–corona structure. The core is made of cross‐linked PP, with the corona region consisting of chain loops, dangling chains, and strongly constrained PP matrix chains. The matrix chains bridge globally between the adjacent gel particles once the interparticle distance is shorter than the PP random coil size. This, in turn, results in a gel‐like behavior of the entire PP matrix. The present findings serve to advance fundamental understanding on the rheological behavior of polymeric systems containing self‐similar soft particles for improving melt strength.
Sobolev embeddings in grand Morrey spaces
Authors: Mizuta Yoshihiro , Ohno Takao , Shimomura Tetsu
Published: December 2021

The aim in this paper is to show that the Riesz potential operator embeds from grand Morrey spaces to grand Campanato–Morrey spaces. We are also concerned with Sobolev type inequalities for Riesz potentials in grand Morrey spaces.
The top management team and enterprise innovation: An empirical study from growth enterprise market listed companies in China
Authors: Zhao Minshu , Yuan Fangying
Published: December 2021

The characteristics of top management teams are one of the main factors affecting the innovation performance of a company. In this study, a fixed effect model is constructed by introducing salary and equity incentives as moderating variables, using growth enterprise market (GEM) listed companies as research samples for empirical analysis to explore the impact of different executive characteristics on enterprise innovation performance and the related influencing mechanism. The results show that the different characteristics of top management teams have different influences on the intensity of research and development (R&D) investment efficiency and innovation output. Importantly, equity incentives play a more significant moderating role than salary incentives. After distinguishing the nature of regions, we found that location factors result in different preferences for executives, which will affect the correlation between executive characteristics and innovation performance. We found that, combined with China's unique political system, the impact of team tenure and education level on innovation performance is opposite based on the nature of property rights. Finally, corresponding management suggestions are made covering three aspects: governance structure, incentive scheme, and measures relating to local conditions.
Multiplicity of solutions to class of nonlocal elliptic problems with critical exponents
Authors: Hurtado Elard Juárez , Miyagaki Olimpio H. , Rodrigues Rodrigo S.
Published: December 2021

In this paper, we establish existence of infinitely many weak solutions for a class of quasilinear stationary Kirchhoff‐type equations, which involves a general variable exponent elliptic operator with critical growth. Precisely, we study the following nonlocal problem:

where Ω is a bounded smooth domain of
, with homogeneous Dirichlet boundary conditions on ∂Ω, the nonlinearity
is a continuous function,
is a function of the class
is a continuous function, whose properties will be introduced later, λ is a positive parameter and
. We assume that
, where
is the critical Sobolev exponent. We will prove that the problem has infinitely many solutions and also we obtain the asymptotic behavior of the solution as λ → 0+. Furthermore, we emphasize that a difference with previous researches is that the conditions on a(·) are general overall enough to incorporate some interesting differential operators. Our work covers a feature of the Kirchhoff's problems, that is, the fact that the Kirchhoff's function M in zero is different from zero, it also covers a wide class of nonlocal problems for p(x) > 1, for all
. The main tool to find critical points of the Euler–Lagrange functional associated with this problem is through a suitable truncation argument, concentration‐compactness principle for variable exponent found in Bonder and Silva (2010), and the genus theory introduced by Krasnoselskii. The result of this paper extends or complements, or else completes recent papers and is new in several directions for the stationary Kirchhoff equations involving the p(x)‐Laplacian type operators.
“Some things are even worse than telling a child he is going to die”: Pediatric oncology healthcare professionals perspectives on communicating with children about cancer and end of life
Authors: Laronne Anat , Granek Leeat , Wiener Lori , Feder‐Bubis Paula , Golan Hana
Published: December 2021

Introduction

This study explored pediatric oncology healthcare professionals’ (HCPs) perspectives on direct communication with children with advanced disease about their disease, palliative care, and end‐of‐life (EOL) communication.

Methods

Forty‐six pediatric oncologists, nurses, psychosocial team members, and other HCPs from six hospital centers in Israel participated in semi‐structured interviews. The Grounded Theory method was used. Data were analyzed line‐by‐line with codes and categories developed inductively from participants’ narratives.

Results

HCPs viewed communication about disease progression and EOL as vital because children were often aware of their prognosis, because lack of communication could lead to emotional distress, and because communication is a prerequisite for shared decision‐making. HCPs identified several barriers for communication including HCP barriers (such as emotional strains, lack of training), parental barriers, guardianship law, and language and culture. HCPs also described strategies to promote EOL communication. Direct strategies include tailoring communication, allowing for silence, echoing children's questions, giving information gradually, and answering direct questions honestly. Indirect strategies included encouraging parents to talk to their children and teamwork with colleagues.

Conclusions

Open communication with children who have cancer is essential. Nevertheless, multiple barriers persist. The rising accessibility of online information calls for urgent training of HCPs in communication so that children will not turn to unmediated and potentially misleading information online in the absence of HCP communication. Evidence‐based effective communication training modules and emotional support should be offered to HCPs. Knowledge about children's development, age‐appropriate communication, and cultural sensitivity should be included in this training.
Data sources for drug utilization research in Latin American countries—A cross‐national study: DASDUR‐LATAM study
Authors: Lopes Luciane C. , Salas Maribel , Osorio‐de‐Castro Claudia Garcia Serpa , Leal Lisiane Freitas , Doubova Svetlana V. , Cañás Martín , Dreser Anahi , Acosta Angela , Baldoni Andre Oliveira , de Cássia Bergamaschi Cristiane , Mota Daniel Marques , Gómez‐Galicia Diana L. , Sepúlveda‐Viveros Dino , Delgado Edgard Narvaez , da Costa Lima Elisangela , Chandia Felipe Vera , Ferre Felipe , Marin Gustavo H. , Olmos Ismael , Zimmermann Ivan R. , Fulone Izabela , Roldán‐Saelzer Juan , Sánchez‐Salgado Juan Carlos , Castro‐Pastrana Lucila I. , de Souza Luiz Jupiter Carneiro , Beltrán Manuel Machado , Silva Marcus Tolentino , Mena María Belén , de França Fonteles Marta Maria , Urtasun Martín A. , Tarapués Mónica , Hernández Patricia Granja , Medero Natalia , Herrera‐Comoglio Raquel , Barberato‐Filho Silvio , Galvão Taís Freire , Luiza Vera Lucia , Santa‐Ana‐Tellez Yared , Rodríguez ‐ Tanta Yesenia , Elseviers Monique
Published: December 2021

Purpose

Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region.

Methods

A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed.

Results

We identified 125 data sources for DUR in nine LatAm countries. Thirty‐eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient‐level data.

Conclusions

Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol‐driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication‐related problems that need further exploration.
Empirical likelihood confidence interval for sensitivity to the early disease stage
Authors: Rahman Husneara , Zhao Yichuan ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: December 2021

Disease status can naturally be classified into three or more ordinal stages rather than just being binary stages. Many works have been done for the estimation and inference procedure regarding three ordinal disease stages, which are non‐disease, early disease, and full disease stages. The early disease stage can be very important for therapeutic intervention and prevention potentiality. As a diagnostic measure, sensitivity to the early disease stage is often used. In this article, we propose confidence intervals for the sensitivity to early disease stage based on given target specificity for non‐disease stage and target sensitivity to full disease stage using both empirical likelihood (EL) and adjusted EL procedures. We compare the performance of the proposed EL confidence intervals with other procedures in our simulation study. The proposed procedures are further applied to Alzheimer's Disease Neuroimaging Initiative data set.
Potential COVID‐19 therapeutic approaches targeting angiotensin‐converting enzyme 2; An updated review
Authors: Zanganeh Saba , Goodarzi Nima , Doroudian Mohammad , Movahed Elaheh
Published: December 2021

COVID‐19 has spread swiftly throughout the world posing a global health emergency. The significant numbers of deaths attributed to this pandemic have researchers battling to understand this new, dangerous virus. Researchers are looking to find possible treatment regimens and develop effective therapies. This study aims to provide an overview of published scientific information on potential treatments, emphasizing angiotensin‐converting enzyme II (ACE2) inhibitors as one of the most important drug targets. SARS‐CoV‐2 receptor‐binding domain (RBD); as a viral attachment or entry inhibitor against SARS‐CoV‐2, human recombinant soluble ACE2; as a genetically modified soluble form of ACE2 to compete with membrane‐bound ACE2, and microRNAs (miRNAs); as a negative regulator of the expression of ACE2/TMPRSS2 to inhibit SARS‐CoV2 entry into cells, are the potential therapeutic approaches discussed thoroughly in this article. This review provides the groundwork for the ongoing development of therapeutic agents and effective treatments against SARS‐COV‐2.
The athletic heart syndrome in web service evolution
Authors: Zarras Apostolos V. , Dinos Ioannis , Vassiliadis Panos
Published: December 2021

Despite the particular standards, technologies, and trends (W3C, RESTful, microservices, etc.) that a team decides to follow for the development of a service‐oriented system, most likely the team members will have to use one or more services that solve general‐purpose problems like cloud computing, networking and content delivery, storage and database, management and governance, and application integration. Typically, general‐purpose services are long‐lived, they have several responsibilities, their interfaces are complex, and they grow over time. The way that these services evolve also affects the evolution of any system that will depend on them. Consequently, the selection of the particular services that will be used is a main concern for the team. In this paper, we report a pattern, calledthe athletic heart syndrome, which facilitates the selection of services that evolve properly. Patterns specify best practices that emerge from multiple real‐world cases. In our context,the athletic heart syndromecomes out from a study that concerns the evolution of a set of popular, long‐lived Amazon services that cover different domains. According tothe athletic heart syndrome, the developers should select services whose heartbeat of changes looks like the heartbeat of an athlete when he is at rest. Specifically, the heartbeat of changes should consist mostly of calm periods, interrupted by few spikes of change. Similarly, the incremental growth of the services should involve mainly calm periods of maintenance, separated by spikes of growth. Selecting services that adhere to the pattern signifies high chances that the services evolve to deal with changing requirements. The pattern further guarantees that the service evolution involves both the expansion of the services with new functionalities and the maintenance of existing ones. The pattern also assures that the complexity increase in the service interfaces will be smooth and tolerable. Finally, conformance with the pattern implies that the growth of the services will be predictable.
Modeling of the Dynamic Recrystallization of Ti Microalloyed High‐Strength Steel
Authors: Zhou Xiaoguang , Wang Xixiang , Li Xin , Liu Zhenyu
Published: December 2021

The dynamic recrystallization (DRX) and austenite microstructure evolution of Ti microalloyed high‐strength steel are investigated and modeled by thermal simulation experiments. The corresponding mathematical models are established based on DRX‐type flow stress curves and the austenite microstructure. A highly accurate austenite grain growth model under different heating conditions is established, which can predict the initial austenite grain sizes before deformation. Considering the effect of initial austenite grain sizes and deformation conditions, the key parameters (peak stress, steady stress, peak strain, and constants C and C1) of the DRX‐type flow stress model are determined, and the predicted DRX‐type flow stresses are in good agreement with the experimental values. The relationships between critical strain and peak strain(εc = 0.77εp), critical stress, and peak stress(σc = 0.82σp) are determined for experimental steel. The relationships between the initial austenite grain size and the key parameters (k, M, a, h) in the DRX kinetic model and the DRX grain size model are determined. The calculated and experimental DRX volume fractions and grain sizes are in good agreement. The results show that these mathematical models can accurately describe the DRX behavior of experimental steel.
Experiment for validation of numerical models of coupled heat and mass transfer around energy cables
Authors: Verschaffel‐Drefke Christoph , Balzer Constantin , Schedel Markus , Hinrichsen Volker , Sass Ingo
Published: December 2021

The increasing decentralization of electrical energy production as well as an increasing number of fluctuating regenerative energy sources require significant investments in grid expansion. Among other assessments, an exact prediction of the thermal behavior of the cable environment is necessary to be able to design cable routes both technically and economically sufficient. To investigate the coupled thermal and hydraulic processes around a cable‐like heat source with high temporal and spatial resolution under controlled boundary conditions, a cylindrical laboratory test was designed and experiments with two soils conducted. The data collected can be used to validate models of coupled heat and mass transfer around power cables. Within this study, the experimental data was compared with a modified model approach that is based on experimentally determined input data for the thermal and hydraulic properties of the examined soils. Although overall good agreement in the temperature field around the central heat source was observed, differences in the spatial distribution of the dry‐out zone near the heat source led to some shift between the measured and simulated temperatures.
Prioritizing climate‐smart agriculture: An organizational and temporal review
Authors: Gardezi Maaz , Michael Semhar , Stock Ryan , Vij Sumit , Ogunyiola Ayorinde , Ishtiaque Asif
Published: December 2021

Extant systematic literature reviews on the topic of climate smart agriculture (CSA) have mainly focused on two issues: reviewing framing of the CSA discourse in the academic and policy literature; and policy initiatives in the Global South that enhance the adoption of climate‐smart agricultural practices. Yet, there is little systematic investigation into how international organizations can help smallholder farmers manage agricultural systems to respond to climate change. Analyzing these organization's priorities and highlighting their knowledge gaps are crucial for designing future pathways of CSA. We intend to use this article to identify overarching CSA themes that can guide large international organizations to focus their CSA agenda in the hope of achieving goals associated with food security and sustainable intensification. We specifically ask the following question:How have the key CSA topics and themes emerged in the gray literature of international organizations between 2010 and 2020?We adopted a topic modeling approach to identify how six international organizations engaged with several topics related to CSA. Following the Latent Dirichlet Allocation (LDA) approach, we identified eight topics in the documents, representing four overarching themes: gender research, weather and climate, CSA management and food security. We found that there is insufficient discussion on the issues relating to governance measures and gender mainstreaming, with a larger focus on techno‐managerial measures of CSA. We conclude that research and training related to CSA must offer opportunities for marginalized and disproportionately vulnerable populations to participate and raise their voices and share innovative ideas at different levels of governance.

This article is categorized under:

Climate and Development > Social Justice and the Politics of Development

Vulnerability and Adaptation to Climate Change > Institutions for Adaptation
Direct nose to the brain nanomedicine delivery presents a formidable challenge
Authors: Yokel Robert A.
Published: December 2021

This advanced review describes the anatomical and physiological barriers and mechanisms impacting nanomedicine translocation from the nasal cavity directly to the brain. There are significant physiological and anatomical differences in the nasal cavity, olfactory area, and airflow reaching the olfactory epithelium between humans and experimentally studied species that should be considered when extrapolating experimental results to humans. Mucus, transporters, and tight junction proteins present barriers to material translocation across the olfactory epithelium. Uptake of nanoparticles through the olfactory mucosa and translocation to the brain can be intracellular via cranial nerves (intraneuronal) or other cells of the olfactory epithelium, or extracellular along cranial nerve pathways (perineural) and surrounding blood vessels (perivascular, the glymphatic system). Transport rates vary greatly among the nose to brain pathways. Nanomedicine physicochemical properties (size, surface charge, surface coating, and particle stability) can affect uptake efficiency, which is usually less than 5%. Incorporation of therapeutic agents in nanoparticles has been shown to produce pharmacokinetic and pharmacodynamic benefits. Assessment of adverse effects has included olfactory mucosa toxicity, ciliotoxicity, and olfactory bulb and brain neurotoxicity. The results have generally suggested the investigated nanomedicines do not present significant toxicity. Research needs to advance the understanding of nanomedicine translocation and its drug cargo after intranasal administration is presented.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Consistent higher order $$ \sigma \left(\mathcal{GG}\to h\right) $$, $$ \Gamma \left(h\to \mathcal{GG}\right) $$ and Γ(h → γγ) in geoSMEFT
Authors: Corbett Tyler , Martin Adam , Trott Michael
Published: December 2021

Abstract

We report consistent results for Γ(h → γγ), $$ \sigma \left(\mathcal{GG}\to h\right) $$
σ

GG
→
h

and $$ \Gamma \left(h\to \mathcal{GG}\right) $$
Γ

h
→
GG

in the Standard Model Effective Field Theory (SMEFT) perturbing the SM by corrections $$ \mathcal{O}\left({\overline{\upsilon}}_T^2/16{\pi}^2{\Lambda}^2\right) $$
O

υ
¯

T
2

/
16

π
2

Λ
2

in the Background Field Method (BFM) approach to gauge fixing, and to $$ \mathcal{O}\left({\overline{\upsilon}}_T^4/{\Lambda}^4\right) $$
O

υ
¯

T
4

/

Λ
4

using the geometric formulation of the SMEFT. We combine and modify recent results in the literature into a complete set of consistent results, uniforming conventions, and simultaneously complete the one loop results for these processes in the BFM. We emphasize calculational scheme dependence present across these processes, and how the operator and loop expansions are not independent beyond leading order. We illustrate several cross checks of consistency in the results.
Asymptotic symmetries in Carrollian theories of gravity
Authors: Pérez Alfredo
Published: December 2021

Abstract

Asymptotic symmetries in Carrollian gravitational theories in 3+1 space and time dimensions obtained from “magnetic” and “electric” ultrarelativistic contractions of General Relativity are analyzed. In both cases, parity conditions are needed to guarantee a finite symplectic term, in analogy with Einstein gravity. For the magnetic contraction, when Regge-Teitelboim parity conditions are imposed, the asymptotic symmetries are described by the Carroll group. With Henneaux-Troessaert parity conditions, the asymptotic symmetry algebra corresponds to a BMS-like extension of the Carroll algebra. For the electric contraction, because the lapse function does not appear in the boundary term needed to ensure a well-defined action principle, the asymptotic symmetry algebra is truncated, for Regge-Teitelboim parity conditions, to the semidirect sum of spatial rotations and spatial translations. Similarly, with Henneaux-Troessaert parity conditions, the asymptotic symmetries are given by the semidirect sum of spatial rotations and an infinite number of parity odd supertranslations. Thus, from the point of view of the asymptotic symmetries, the magnetic contraction can be seen as a smooth limit of General Relativity, in contrast to its electric counterpart.
Hepatitis-B-Virus-Infektionen und impfinduzierte Immunität: die Rolle von soziodemografischen Determinanten
Authors: Brodzinski Annika , Neumeyer-Gromen Angela , Dudareva Sandra , Zimmermann Ruth , Latza Ute , Bremer Viviane , Poethko-Müller Christina
Published: December 2021

Hintergrund und Ziel

Trotz niedriger Prävalenz der Hepatitis-B-Virus-(HBV-)Infektion in Deutschland ist es wichtig, vulnerable Gruppen und Ansatzpunkte für die Prävention zu identifizieren. In ersten Analysen der „Studie zur Gesundheit Erwachsener in Deutschland“ (DEGS1, 2008–2011) waren HBV-Infektion und -Impfung mit sozidemografischen Determinanten assoziiert. In dieser Arbeit werden die Ergebnisse im Detail untersucht.

Material und Methoden

In DEGS1 lag für 7046 Teilnehmende (Alter: 18–79 Jahre) eine HBV-Serologie vor. Die stattgehabte HBV-Infektion war durch Antikörper gegen das Hepatitis-B-Core-Antigen (Anti-HBc) definiert, die impfinduzierte Immunität durch alleinigen Nachweis von Antikörpern gegen das Hepatitis-B-Surface-Antigen (Anti-HBs). Seroprävalenzen von HBV-Infektions- und -Impfstatus wurden geschlechtsstratifiziert geschätzt und Assoziationen mit Alter, Gemeindegröße, Einkommen, formaler Bildung, Krankenversicherung und Migrationsgeneration in logistischen Regressionen analysiert.

Ergebnisse

Die HBV-Infektion war bei Männern und Frauen unabhängig mit den Altersgruppen 34–64 und ≥ 65 Jahre, erster Migrationsgeneration und Leben in größeren Gemeinden assoziiert, zudem bei Männern mit niedrigem Einkommen und bei Frauen mit niedriger Bildung. Die impfinduzierte Immunität war bei Männern und Frauen unabhängig mit den Altersgruppen 18–33 und 34–64 Jahre, mittlerer und hoher Bildung und hohem Einkommen assoziiert, darüber hinaus bei Männern mit mittlerem Einkommen und privater Krankenversicherung und bei Frauen mit fehlendem Migrationshintergrund.

Diskussion

Die Berücksichtigung von Migrationsstatus, Einkommen und Bildung könnte zur zielgenauen Ausrichtung der HBV-Prävention beitragen.
Development of SARS-CoV-2 packaged RNA reference material for nucleic acid testing
Authors: Lee Sang-Soo , Kim Seil , Yoo Hee Min , Lee Da-Hye , Bae Young-Kyung
Published: December 2021

Nucleic acid tests to detect the SARS-CoV-2 virus have been performed worldwide since the beginning of the COVID-19 pandemic. For the quality assessment of testing laboratories and the performance evaluation of molecular diagnosis products, reference materials (RMs) are required. In this work, we report the production of a lentiviral SARS-CoV-2 RM containing approximately 12 kilobases of its genome including common diagnostics targets such as RdRp, N, E, and S genes. The RM was measured with multiple assays using two different digital PCR platforms. To measure the homogeneity and stability of the lentiviral SARS-CoV-2 RM, reverse transcription droplet digital PCR (RT-ddPCR) was used with in-house duplex assays. The copy number concentration of each target gene in the extracted RNA solution was then converted to that of the RM solution. Their copy number values are measured to be from 1.5 × 105 to 2.0 × 105 copies/mL. The RM has a between-bottle homogeneity of 4.80–8.23% and is stable at 4 °C for 1 week and at −70 °C for 6 months. The lentiviral SARS-CoV-2 RM closely mimics real samples that undergo identical pre-analytical processes for SARS-CoV-2 molecular testing. By offering accurate reference values for the absolute copy number of viral target genes, the developed RM can be used to improve the reliability of SARS-CoV-2 molecular testing.
[18F]FDG-PET accurately identifies pathological response early upon neoadjuvant immune checkpoint blockade in head and neck squamous cell carcinoma
Authors: Vos Joris L. , Zuur Charlotte L. , Smit Laura A. , de Boer Jan Paul , Al-Mamgani Abrahim , van den Brekel Michiel W. M. , Haanen John B. A. G. , Vogel Wouter V.
Published: December 2021

Purpose

To investigate the utility of [18F]FDG-PET as an imaging biomarker for pathological response early upon neoadjuvant immune checkpoint blockade (ICB) in patients with head and neck squamous cell carcinoma (HNSCC) before surgery.

Methods

In the IMCISION trial (NCT03003637), 32 patients with stage II‒IVb HNSCC were treated with neoadjuvant nivolumab with (n = 26) or without (n = 6) ipilimumab (weeks 1 and 3) before surgery (week 5). [18F]FDG-PET/CT scans were acquired at baseline and shortly before surgery in 21 patients. Images were analysed for SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG). Major and partial pathological responses (MPR and PPR, respectively) to immunotherapy were identified based on the residual viable tumour in the resected primary tumour specimen (≤ 10% and 11–50%, respectively). Pathological response in lymph node metastases was assessed separately. Response for the 2 [18F]FDG-PET-analysable patients who did not undergo surgery was determined clinically and per MR-RECIST v.1.1. A patient with a primary tumour MPR, PPR, or primary tumour MR-RECIST-based response upon immunotherapy was called a responder.

Results

Median ΔSUVmax, ΔSUVmean, ΔMTV, and ΔTLG decreased in the 8 responders and were significantly lower compared to the 13 non-responders (P = 0.05, P = 0.002, P < 0.001, and P < 0.001). A ΔMTV or ΔTLG of at least − 12.5% detected a primary tumour response with 95% accuracy, compared to 86% for the EORTC criteria. None of the patients with a ΔTLG of − 12.5% or more at the primary tumour site developed a relapse (median FU 23.0 months since surgery). Lymph node metastases with a PPR or MPR (5 metastases in 3 patients) showed a significant decrease in SUVmax (median − 3.1, P = 0.04). However, a SUVmax increase (median + 2.1) was observed in 27 lymph nodes (in 11 patients), while only 13 lymph nodes (48%) contained metastases in the corresponding neck dissection specimen.

Conclusions

Primary tumour response assessment using [18F]FDG-PET-based ΔMTV and ΔTLG accurately identifies pathological responses early upon neoadjuvant ICB in HNSCC, outperforming the EORTC criteria, although pseudoprogression is seen in neck lymph nodes. [18F]FDG-PET could, upon validation, select HNSCC patients for response-driven treatment adaptation in future trials.

Trial registration

https://www.clinicaltrials.gov/, NCT03003637, December 28, 2016.
Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study
Authors: Hribernik Nežka , Huff Daniel T , Studen Andrej , Zevnik Katarina , Klaneček Žan , Emamekhoo Hamid , Škalic Katja , Jeraj Robert , Reberšek Martina
Published: December 2021

Purpose

To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT.

Methods

18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers — SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs — were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake.

Results

A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL].

Conclusions

Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear.
Serum n-6 polyunsaturated fatty acids and risk of atrial fibrillation: the Kuopio Ischaemic Heart Disease Risk Factor Study
Authors: Tajik Behnam , Tuomainen Tomi-Pekka , Isanejad Masoud , Salonen Jukka T. , Virtanen Jyrki K.
Published: December 2021

Purpose

N-6 polyunsaturated fatty acids (PUFA), particularly linoleic acid (LA), have been associated with lower risk of coronary heart disease (CHD), but little is known about their antiarrhythmic properties. We investigated the association of the serum n-6 PUFAs with the risk of atrial fibrillation (AF), the most common type of cardiac arrhythmia.

Methods

The study included 2450 men from the Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42–60 years at baseline. The total n-6 PUFA includes linoleic acid (LA), arachidonic acid (AA), γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA). Cox proportional hazards regression was used to estimate hazard ratio (HR) of incident events.

Results

During the mean follow-up of 22.4 years, 486 AF cases occurred. The multivariable-adjusted HR in the highest versus the lowest quartile of total serum n-6 PUFA concentration was 0.79 (95% CI 0.58–1.08, P trend = 0.04). When evaluated individually, only serum LA concentration was inversely associated with AF risk (multivariable-adjusted extreme-quartile HR 0.69, 95% CI 0.51–0.94, P trend = 0.02). These associations were stronger among the men without history of CHD or congestive heart failure at baseline, compared to men with such disease history (P for interaction = 0.05 for total n-6 PUFA and LA). Similar associations were observed with dietary LA and AA intakes. No significant associations were observed with serum AA, GLA or DGLA concentrations.

Conclusions

Higher circulating concentration and dietary intake of n-6 PUFA, mainly LA, are associated with lower risk of AF, especially among men without history of CHD or congestive heart failure.
Non-contrast myocardial perfusion in rest and exercise stress using systolic flow-sensitive alternating inversion recovery
Authors: Henningsson Markus , Carlhäll Carl-Johan , Ebbers Tino , Kihlberg Johan
Published: December 2021

Objective

To evaluate systolic flow-sensitive alternating inversion recovery (FAIR) during rest and exercise stress using 2RR (two cardiac cycles) or 1RR intervals between inversion pulse and imaging.

Materials and methods

1RR and 2RR FAIR was implemented on a 3T scanner. Ten healthy subjects were scanned during rest and stress. Stress was performed using an in-bore ergometer. Heart rate, mean myocardial blood flow (MBF) and temporal signal-to-noise ratio (TSNR) were compared using paired t tests.

Results

Mean heart rate during stress was higher than rest for 1RR FAIR (85.8 ± 13.7 bpm vs 63.3 ± 11.1 bpm; p < 0.01) and 2RR FAIR (83.8 ± 14.2 bpm vs 63.1 ± 10.6 bpm; p < 0.01). Mean stress MBF was higher than rest for 1RR FAIR (2.97 ± 0.76 ml/g/min vs 1.43 ± 0.6 ml/g/min; p < 0.01) and 2RR FAIR (2.8 ± 0.96 ml/g/min vs 1.22 ± 0.59 ml/g/min; p < 0.01). Resting mean MBF was higher for 1RR FAIR than 2RR FAIR (p < 0.05), but not during stress. TSNR was lower for stress compared to rest for 1RR FAIR (4.52 ± 2.54 vs 10.12 ± 3.69; p < 0.01) and 2RR FAIR (7.36 ± 3.78 vs 12.41 ± 5.12; p < 0.01). 2RR FAIR TSNR was higher than 1RR FAIR for rest (p < 0.05) and stress (p < 0.001).

Discussion

We have demonstrated feasibility of systolic FAIR in rest and exercise stress. 2RR delay systolic FAIR enables non-contrast perfusion assessment during stress with relatively high TSNR.
Modelling discontinuity control on the development of Hell’s Mouth landslide
Authors: He Lingfeng , Coggan John , Stead Doug , Francioni Mirko , Eyre Matthew
Published: December 2021

This paper focuses on numerical modelling and back analysis of the Hell’s Mouth landslide to provide improved understanding of the evolution of a section of the north coast of Cornwall, UK. Discontinuity control is highlighted through the formation of a ‘zawn’ or inlet, the occurrence of two successive landslides and evidence of ongoing instability through opening of tension cracks behind the cliff top. Several integrated remote sensing (RS) techniques have been utilised for data acquisition to characterise the slope geometry, landslide features and tension crack extent and development. In view of the structural control on the rock slope failures, a 3D distinct element method (DEM) code incorporating a discrete fracture network and rigid blocks has been adopted for the stability analysis. The onset and opening of tension cracks behind the modelled slope failure zones has also been studied by analysing the displacements of two adjoining landslide blocks, between which, a joint-related tension crack developed. In addition, a sensitivity analysis has been undertaken to provide further insight into the influence of key discontinuity parameters (i.e. dip, dip direction, persistence and friction angle) on the stability of this section of the coastline. Numerical modelling and field observations indicate that block removal and preferential erosion along a fault resulted in the formation of the inlet. The development of the inlet provides daylighting conditions for discontinuities exposed on the inlet slope wall, triggering the initial landslide which occurred on 23rd September 2011. Numerical modelling, and evidence from a video of the initial landslide, suggests that the cliff instability is characterised by a combination of planar sliding, wedge sliding and toppling modes of failure controlled by the discrete fracture network geometry.
Provision of social-norms feedback to general practices whose antibiotic prescribing is increasing: a national randomized controlled trial
Authors: Gold Natalie , Ratajczak Michael , Sallis Anna , Saei Ayoub , Watson Robin , van Schaik Paul , Bowen Sarah , Chadborn Tim
Published: December 2021

Aim

The Chief Medical Officer of England writes an annual social-norms-feedback letter to the highest antibiotic-prescribing GP practices. We investigated whether sending a social-norms-feedback letter to practices whose prescribing was increasing would reduce prescribing.

Subject and methods

We conducted a two-armed randomised controlled trial amongst practices whose STAR-PU-adjusted prescribing was in the 20th–95th percentiles and had increased by > 4% year-on-year in the 2 previous financial years. Intervention practices received a letter on 1st March 2018 stating ‘The great majority (80%) of practices in England reduced or stabilised their antibiotic prescribing rates in 2016/17. However, your practice is in the minority that have increased their prescribing by more than 4%.’. Control practices received no letter. The primary outcome was the STAR-PU-adjusted rate of antibiotic prescribing in the months from March to September 2018.

Results

We randomly assigned 930 practices; ten closed or merged pre-trial, leaving 920 practices — 448 in the intervention and 472 in the control. An autoregressive and moving average model of first order ARMA(1,1) correlation structure showed no effect of the intervention (β < −0.01, z = −0.50, p = 0.565). Prescribing reduced over time in both arms (β < −0.01, z = −36.36, p < 0.001).

Conclusions

A social-norms-feedback letter to practices whose prescribing was increasing did not decrease prescribing compared to no letter.

Trial registration

NCT03582072.
Archives, linked data and the digital humanities: increasing access to digitised and born-digital archives via the semantic web
Authors: Hawkins Ashleigh
Published: December 2021

Mass digitisation and the exponential growth of born-digital archives over the past two decades have resulted in an enormous volume of archives and archival data being available digitally. This has produced a valuable but under-utilised source of large-scale digital data ripe for interrogation by scholars and practitioners in the Digital Humanities. However, current digitisation approaches fall short of the requirements of digital humanists for structured, integrated, interoperable, and interrogable data. Linked Data provides a viable means of producing such data, creating machine-readable archival data suited to analysis using digital humanities research methods. While a growing body of archival scholarship and praxis has explored Linked Data, its potential to open up digitised and born-digital archives to the Digital Humanities is under-examined. This article approaches Archival Linked Data from the perspective of the Digital Humanities, extrapolating from both archival and digital humanities Linked Data scholarship to identify the benefits to digital humanists of the production and provision of access to Archival Linked Data. It will consider some of the current barriers preventing digital humanists from being able to experience the benefits of Archival Linked Data evidenced, and to fully utilise archives which have been made available digitally. The article argues for increased collaboration between the two disciplines, challenges individuals and institutions to engage with Linked Data, and suggests the incorporation of AI and low-barrier tools such as Wikidata into the Linked Data production workflow in order to scale up the production of Archival Linked Data as a means of increasing access to and utilisation of digitised and born-digital archives.