bluuebunny/crossref_metadata_2025 huggingface dataset:
24. Citizenship of the European Union
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. This chapter reviews EU citizenship law. It considers the rights of free movement and residence of EU citizens, political rights of citizenship, and Directive 2004/38 on the rights of free movement and residence for EU citizens and their families. The status of EU citizenship created by EU law has been criticized on various grounds, including the thinness of the rights created and their economic focus, the conditions to which they are subject, the reinforcement of the distinction between third-country nationals and EU nationals, the limited impact of the new electoral rights, and the reluctant pace of implementation. On the other hand, the legal rights of citizenship have been expanded by the European Court of Justice, even in the face of vocal Member State opposition. The case law in this area continues to develop and the chapter provides a considered evaluation of this difficult body of law. The UK version contains a further section analysing issues concerning EU conceptions of citizenship and the UK post-Brexit.
20. Free Movement of Goods: Quantitative Restrictions
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. This chapter considers Articles 34–37 of the Treaty on the Functioning of the European Union (TFEU). Article 34 is the central provision and states that: ‘quantitative restrictions on imports and all measures having equivalent effect shall be prohibited between Member States’. Article 35 contains similar provisions relating to exports, while Article 36 provides an exception for certain cases in which a state is allowed to place restrictions on the movement of goods. The European Court of Justice’s interpretation of Articles 34–37 has been important in achieving single market integration. It has given a broad interpretation to the phrase ‘measures having equivalent effect’ to a quantitative restriction (MEQR), and has construed the idea of discrimination broadly to capture both direct and indirect discrimination. The UK version contains a further section analysing issues concerning free movement of goods between the EU and the UK post-Brexit.
23. Freedom of Establishment and to Provide Services
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. The Treaty on the Functioning of the European Union (TFEU) has two separate chapters on self-employed persons who move on a permanent or temporary basis between Member States: the chapters on freedom of establishment and freedom to provide services. The central principles governing freedom of establishment and the free movement of services are laid down in the TFEU and have been developed through case law. Important developments have also been brought about through secondary legislation in sectors such as insurance, broadcasting, financial services, electronic commerce, telecommunications, and other ‘services of general economic interest’. This chapter focuses on the broad constitutional principles applicable to every sector. The UK version contains a further section analysing issues concerning freedom of establishment and the provision of services between the EU and the UK post-Brexit.
3. Resolution of commercial disputes
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter covers the resolution of commercial disputes. Due to the nature and complexity of commercial activity, disputes inevitably arise especially within transactions involving large amounts of money. Generally, businesses often prefer to avoid litigation if possible as it is costly and time consuming while also generating bad publicity and damaging a trading relationship. The chapter then introduces the practice of arbitration, which is a popular method of settling business disputes that come out of contractual relationships. It considers the systems for alternative dispute resolutions (ADR), some of which are variants of arbitration or litigation that may offer advantages for the resolution of commercial disputes.
10. Duties of the parties
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter details the duties of the parties as part of a contract sale according to the Sale of Goods Act 1979 (SGA). Section 27 of the SGA does not contain a complete statement of the parties' duties, but Section 28 does define the relationship between the duties of seller and buyer. Each party's duty to perform is conditional on the readiness and willingness of the other to perform and commercial agreements normally provide for the goods to be delivered on credit terms so that payment is due after delivery. SGA's Section 27 indicates that the duties of parties revolve around delivery, acceptance, and payment in accordance with the terms of the contract. The chapter then analyses the notion of exclusion clauses.
12. The condition of the goods and statutory implied terms
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter tackles the condition of the goods and statutory implied terms. If the terms of the broken contract between the seller and buyer involve a condition, the buyer may be entitled to reject the goods and terminate the contract. Sections 12 to 15 of the Sale of Goods Act 1979 (SGA) indicate the conditions of implied terms. The chapter explains that implied terms require the goods supplied to conform to the buyer's legitimate expectations, which then may allow the buyer to complain about a breach if their expectations are not met. It also considers how the seller's power to exclude the implied terms, or liability for their breach, is limited by the Unfair Contract Terms Act 1977.
17. Title conflicts in sale transactions
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter focuses on title conflicts in sale transactions. Despite the technological changes in improving data capture, storage, and analysis that can help provide a greater capacity to record tidal and goods information, it is not the panacea to title conflicts arising from information asymmetry since it also occurs due to conflicting interests. Section 21 of the Sale of Goods Act 1979 (SGA) preserves the basic common law principle (nemo dat quod non habet) that is subjected to exceptions. The provision also contains the principle of estoppel. The chapter acknowledges that the nemo dat principle itself is simple but some of its laws and exceptions are outdated.
20. Financing The Transaction
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter looks into the process of financing transactions. It starts with how to satisfy a buyer's obligation of payment, which includes alternatives like giving a promissory note or having a third party finance the payment. The circumstances of whether or not the seller provides the buyer with credit ultimately depend on the relative bargaining power of the parties. The chapter then discusses how digitalization affected commercial technologies, referencing the development of blockchains and cryptocurrencies. It explains that aspects of digitalization relate to the control of assets and security over intangible assets, while the growth in importance and value of digital assets raised questions about the reformation of the current law.
Vidal v Elster: US Supreme Court confirms constitutionality of Lanham Act prohibition on registration of trade marks comprising names of living people without their consent
Authors: Macedo Charles R , Goldberg David P , Jacobson Joshua
Published: September 2024

In Vidal v Elster, the US Supreme Court upheld the constitutionality of a Lanham Act prohibition against the registration of trade marks comprising the name of living people withut their consent. Although all Justices agreed on the result, their reasoning differed, with the majority opinion highlighting the increasing importance of historical analysis in trademark cases.
From bench to clinic: the development of VLA1553/IXCHIQ, a live-attenuated chikungunya vaccine
Authors: Chen Lin H , Fritzer Andrea , Hochreiter Romana , Dubischar Katrin , Meyer Stéphanie
Published: September 2024

Background

Over the past 20 years, over 5 million cases of chikungunya, a mosquito-transmitted viral disease, have been reported in over 110 countries. Until recently, preventative strategies for chikungunya were largely ineffective, relying on vector control and individual avoidance of mosquito bites.

Methods

This review outlines the preclinical and clinical efficacy and safety data that led to the approval of VLA1553 (IXCHIQ®), a live-attenuated vaccine against chikungunya disease. It also describes the innovative development pathway of VLA1553, based on an immunological surrogate of protection, and discusses ongoing and future post-licensure studies.

Results

In mice and non-human primate models, VLA1553 elicited high titres of neutralizing antibodies, conferred protection against wild-type chikungunya virus challenge and raised no safety concerns. A Phase 1 clinical trial of VLA1553 demonstrated 100% seroconversion among 120 healthy participants, with sustained neutralizing antibody titres after 12 months. These results and determination of a surrogate marker of protection led to advancement of VLA1553 directly into Phase 3 clinical development, as agreed with the US Food and Drug Administration (FDA) and the European Medicines Agency. The pivotal Phase 3 trial met its primary immunogenicity endpoint, achieving seroprotective levels based on immuno-bridging in baseline seronegative participants 28 days post-vaccination. These findings enabled submission of a Biologics Licence Application to the FDA for accelerated approval of VLA1553 in the US for adults aged ≥18 years. Ongoing and planned studies will confirm the clinical efficacy/effectiveness and safety of VLA1553 in adults and younger individuals, and will generate data in chikungunya endemic countries that have the highest unmet need.

Conclusion

VLA1553 is the first vaccine approved for the prevention of chikungunya disease in adults, following accelerated development based on a serological surrogate marker of protection. VLA1553 adds to strategies to reduce the spread and burden of chikungunya in endemic populations and travellers.
Mean-motion resonances with interfering density waves
Authors: Yang Huan , Li Ya-Ping
Published: September 2024

In this work, we study the dynamics of two less massive objects moving around a central massive object, which are all embedded within a thin accretion disc. In addition to the gravitational interaction between these objects, the disc–object interaction is also crucial for describing the long-term dynamics of the multibody system, especially in the regime of mean-motion resonances. We point out that near the resonance the density waves generated by the two moving objects generally coherently interfere with each other, giving rise to extra angular momentum fluxes. The resulting backreaction on the objects is derived within the thin-disc scenario, which explicitly depends on the resonant angle and sensitively depends on the smoothing scheme used in the two-dimensional theory. We have performed hydrodynamical simulations with planets embedded within a thin accretion disc and have found qualitatively agreement on the signatures of interfering density waves by measuring the torques on the embedded objects, for the cases of $2:1$ and $3:2$ resonance. By including in interference torque and the migration torques in the evolution of a pair of planets, we show that the chance of resonance trapping depends on the sign of the interference torque. For negative interference torques the pairs are more likely located at off-resonance regimes. The negative interference torques may also explain the $1~{{\ \rm per\ cent}}-2~{{\ \rm per\ cent}}$ offset (for the period ratios) from the exact resonance values as observed in Kepler multiplanet systems.
Outcomes of Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome in Pediatric Trauma Patients
Authors: Ahmed Nasim , Kuo Yen-Hong
Published: September 2024

IMPORTANCE:

Acute respiratory distress syndrome (ARDS) is associated with high mortality and morbidity. Extracorporeal membrane oxygenation (ECMO) is one of the interventions that have been in practice for ARDS for decades.

OBJECTIVES:

The purpose of the study was to investigate the outcomes of ECMO in pediatric trauma patients who suffered from ARDS.

DESIGN:

Observational cohort study.

SETTING AND PARTICIPANTS:

The Trauma Quality Improvement Program database for years 2017 to 2019 and 2021 through 2022 was accessed for the study. All children younger than 18 years old who were admitted to the hospital after trauma and suffered from ARDS were included in the study. Other variables included in the study were patients’ demographics, clinical characteristics, Injury Severity Score (ISS), Glasgow Coma Scale (GCS) score, comorbidities, and outcomes.

MAIN OUTCOMES AND MEASURES:

ECMO is the exposure, and the outcomes are in-hospital mortality and hospital complications (acute kidney injury [AKI], pneumonia and deep vein thrombosis [DVT]).

RESULTS:

Of 453 patients who qualified for the study, propensity score matching found 50 pairs of patients. There were no significant differences identified between the groups, ECMO+ vs. ECMO– on patients’ age in years (16 yr; interquartile range [IQR], 13.25–17 yr vs. 16 yr [14.25–17 yr]), race (White; 62.0% vs. 66.0%), sex (male; 78% vs. 76%), ISS (23 [IQR, 9.25–34] vs. 22 [9.25–32]), and GCS (15 [IQR, 3–15] vs. 13.5 [3–15]), mechanism of injury; and comorbidities. There was no difference between the groups, ECMO+ vs. ECMO–, in-hospital mortality (10.0% vs. 20.0%; p = 0.302), hospital complications (AKI 12.0% vs. 2.0%; p = 0.131), pneumonia (10.0% vs. 20.0%; p = 0.182 > ), and DVT (16% vs. 6%; p = 0.228).

CONCLUSIONS AND RELEVANCE:

No difference in mortality was observed in injured children who suffered from the ARDS and were placed on ECMO when compared with patients who were not placed on ECMO. Patients with trauma and ARDS who require ECMO have comparable outcomes to those who do not receive ECMO. A larger sample size study is needed to find the exact benefit of ECMO in this patients’ cohort.
High- Versus Low-Dose Paclitaxel-Coated Balloons for Femoropopliteal Disease: A systematic review and meta-analysis
Authors: Jin Gan , Sun Zhaokun , Liu Chunjiang , Xu Miaojun
Published: September 2024

To evaluate the comparative effectiveness of high- and low doses of paclitaxel in endovascular revascularization procedures for patients with femoropopliteal disease. The databases (Embase, PubMed, Scopus, and Web of Science) were searched for studies that had compared outcomes of high-dose and low-dose paclitaxel-coated balloons (PCBs) in the treatment of patients with femoropopliteal disease. Randomized controlled trials and nonrandomized comparative studies (eg, cohort studies and case-control studies) were eligible for inclusion. The primary outcomes of interest were patency rates, risk of restenosis, and clinically-driven target lesion revascularization (CD-TLR). Pooled effect sizes were reported as relative risk (RR) with 95% confidence intervals (CI). The analysis included 7 studies. High-dose PCB use was associated with higher patency (RR, 1.10; 95% CI, 1.00–1.21), reduced risk of restenosis (RR, 0.60; 95% CI, 0.46–0.79), and reduced need for CT-TLR (RR, 0.57; 95% CI, 0.41–0.79) compared to low-dose PCB. Rates of limb salvage (RR, 1.01; 95% CI, 0.99–1.04), freedom from major adverse limb events (RR, 1.39; 95% CI, 0.79–2.42), and overall survival (RR, 1.02; 95% CI, 0.99–1.05) were comparable in the 2 groups. There was no evidence of publication bias. High-dose PCB correlates with superior outcomes in patients with femoropopliteal disease, particularly in terms of better vascular patency, reduced restenosis risk, and lower need for target lesion revascularization, compared to low-dose PCB.
The Multi-Country Multi-City Collaborative Research Network: An international research consortium investigating environment, climate, and health
Authors: Gasparrini Antonio , Vicedo-Cabrera Ana Maria , Tobias Aurelio ,   on behalf of the MCC Collaborative Research Network
Published: September 2024

Research on the health risks of environmental factors and climate change requires epidemiological evidence on associated health risks at a global scale. Multi-center studies offer an excellent framework for this purpose, but they present various methodological and logistical problems. This contribution illustrates the experience of the Multi-Country Multi-City Collaborative Research Network, an international collaboration working on a global research program on the associations between environmental stressors, climate, and health in a multi-center setting. The article illustrates the collaborative scheme based on mutual contribution and data and method sharing, describes the collection of a huge multi-location database, summarizes published research findings and future plans, and discusses advantages and limitations. The Multi-Country Multi-City represents an example of a collaborative research framework that has greatly contributed to advance knowledge on the health impacts of climate change and other environmental factors and can be replicated to address other research questions across various research fields.
Sabbath Observance and Delayed Primary Repair of Lacerations: Experience from a Plastic Surgery Practice
Authors: Scheinman Marcel
Published: September 2024

Background:

Despite public and medical professionals’ misconceptions about the timing of laceration repair and its consequences, it has been shown that the concept of the “golden period” has not been established, and in many uncomplicated wounds, may extend beyond 24 hours. This author presents his experience with delaying primary repairs, which may represent one of the largest published casuistries.

Methods:

A retrospective review of cases over a 14-year practice and review of the literature on the topic of the golden period and delayed primary repair of lacerations were performed.

Results:

Of a total of 6408 lacerations repaired, 313 were identified as planned delayed repairs (4.9%). The time of delay was estimated to be between 3 and 28 hours from the injury until treatment. There were no reported complications on the delayed repairs.

Conclusion:

Delayed repair of uncomplicated wounds does not increase the rate of infection or impact the final cosmetic outcome and may be applied safely by qualified professionals in carefully selected cases.
A Case Report About Cardiac Arrest After Left Ventricular Assist Device Explantation
Authors: Nemer Edisson , Rassam Rami , Hallberg Kristensen Ann , Thorvaldsen Tonje , Dalén Magnus , Najjar Emil
Published: September 2024

Hemodynamic unloading by left ventricular assist devices (LVADs) in patients with advanced heart failure can result in reverse remodeling and cardiac recovery allowing pump removal. Ventriculoplasty during explantation may cause fibrosis and ventricular scars which can provide a substrate for reentry, a common cause of ventricular arrythmias. In this case report, we describe the clinical course of a patient who suffered a cardiac arrest in the following few months after undergoing LVAD explantation because of cardiac recovery. This case highlights a potential risk related to complete LVAD explantation with ventriculoplasty and patch repair of the apex.
Association and risk of metabolic syndrome and kidney stone disease: outcomes from a systematic review and meta-analysis
Authors: Dassanayake Sohani N. , Lafont Tanguy , Somani Bhaskar K.
Published: September 2024

Purpose of review

Metabolic syndrome (MetS) has emerged as a potential contributor to the development of kidney stone disease (KSD). This study aims to conduct a systematic review of the literature, and meta-analysis of the association between MetS and KSD.

Recent findings

Systematic review revealed Fifteen articles (433 201 patients) were eligible for analysis. Meta-analysis of 11 studies identified a statistically significant association between MetS and KSD with unadjusted odds ratio of 2.02 [95% confidence interval (CI) 1.96–2.08, P < 0.001], and pooled adjusted odds ratio of 1.22 [95% CI 1.09–1.37, P < 0.001]. Of the different MetS traits, hypertension and impaired glucose tolerance were the most significantly associated with KSD.

This study confirms a significant association between MetS and KSD. Despite variations in MetS definitions across different studies analysed, consistent associations were observed across studies. This may have clinical implications in that guidelines do not currently recommend routine MetS screening in KSD patients.
Nocardiopsis codii sp. nov., and Rhodococcus chondri sp. nov., two novel actinomycetal species isolated from macroalgae collected in the northern Portuguese coast
Authors: Girão Mariana , Lequint Zoé , Rego Adriana , Costa Isabel , Proença Diogo Neves , Morais Paula V. , Carvalho Maria F.
Published: September 2024

Two novel actinomycetal strains, designated CC-R113T and CC-R104T, were isolated from the tissues of two macroalgae collected on the northern Portuguese coast. Phylogenetic analyses based on the 16S rRNA gene showed that strain CT-R113T belongs to the genus Nocardiopsis, being closely related to Nocardiopsis umidischolae 66/93T and Nocardiopsis tropica VKM Ac-1457T, with 98.65 and 98.39 % sequence similarity, respectively. The clade formed between the three type strains was confirmed by phylogenomic analysis. The genome of strain CT-R113T was 7.27 Mb in size with a G+C content of 71.3 mol %, with average nucleotide identity (ANI) values of 89.59 and 90.14 % with strains 66/93T and VKM Ac-1457T, respectively. The major cellular fatty acids were identified as C18 : 1
 ω9c, iso-C16 : 0 and anteiso-C17 : 0. Menaquinone 10 (MK-10) was the major respiratory quinone. Comparative analysis of 16S rRNA gene sequences showed that strain CC-R104T belongs to the genus Rhodococcus and is most closely related to Rhodococcus pyridinivorans DSM 44555T, with 98.24 % sequence similarity. However, phylogenomic analysis revealed that strain CC-R104T establishes a clade with Rhodococcus artemisae DSM 45380T, being more distant from Rhodococcus pyridinivorans DSM 44555T. The genome of strain CC-R104T was 5.34 Mb in size with a G+C content of 67.01 mol%. The ANI value between strains CC-R104T and DSM 45380T was 81.2 % and between strains CC-R104T and DSM 44555T was 81.5 %. The major cellular fatty acids were identified as C18 : 1
 ω9c, C16 : 0 and summed feature 3. Menaquinone 8 (MK-8) was the only respiratory quinone. For both CC-R113T and CC-R104T, optimum growth was observed at pH 7.0, 28 °C and 0–5 % NaCl and whole-cell hydrolysates contained meso-diaminopimelic acid as the cell-wall diamino acid. On the basis of phenotypic, molecular and chemotaxonomic characteristics, strains CT-R113T and CC-R104T are considered to represent novel species, for which the names Nocardiopsis codii sp. nov. (type strain CT-R113T=LMG33234T=UCCCB172T) and Rhodococcus chondri sp. nov. (type strain CC-R104T=LMG33233T=UCCCB171T) are proposed.
Luteipulveratus flavus sp. nov. isolated from two lichen species
Authors: Xiong Lian-Shuang , Fan Ming-Qun , Yang Zu-Zhen , Zuo Shu-Ya , Yuan Qing , Wang Li-Song , Jiang Cheng-Lin , Wang Xin-Yu , Jiang Yi
Published: September 2024

Two novel strains, YIM 133132T and YIM 133296, were isolated from lichen samples collected from Yunnan Province, Southwest PR China. YIM 133132T and YIM 133296 are aerobic, Gram-staining-positive, non-motile actinomycetes. They are also catalase-positive and oxidase-negative, and YIM 133132T formed flat yellowish colonies that were relatively dry on YIM38 agar medium. Flat yellowish colonies of YIM 133296 were also observed on YIM38 agar medium. YIM 133132T grew at 25–35 °C (optimum 25–30 °C), pH 6.0–9.0 (optimum pH 7.0) and in the presence of 0–8% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains YIM 133132T and YIM 133296 represented members of the genus Luteipulveratus and exhibited high sequence similarity (96.93%) with Luteipulveratus halotolerans C296001T. The genomic DNA G+C content of both strains was 71.8%. The DNA–DNA hybridisation (dDDH) values between YIM 133132T and YIM 133296 were 85.1%, and the DNA–DNA hybridisation value between YIM 133132T and YIM 133296 and L. halotolerans C296001T was 23.4%. On the basis of the draft genome sequences, the average nucleotide identity (ANI) between strains YIM 133132T and YIM 133296 and L. halotolerans C296001T was 80.8%. The major menaquinones that were identified were MK-8(H4), MK-9 and MK-8(H2). The polar lipids were diphosphatidylglycerol and phosphatidylinositol. On the basis of the morphological, physiological, biochemical, genomic, phylogenetic and chemotaxonomic characteristics, strains YIM 133132T and YIM 133296 can be clearly distinguished from L. halotolerans C296001T, and the two strains represent a novel species for which the name L. flavus sp. nov. is proposed. The type strain is YIM 133132T (CGMCC= 1.61357T and KCTC= 49824T).
Feasibility of Measuring Magnetic Resonance Elastography-derived Stiffness in Human Thoracic Aorta and Aortic Dissection Phantoms
Authors: Hirad Adnan , Fakhouri Faisal S. , Raterman Brian , Lakony Ronald , Wang Maxwell , Gonring Dakota , Kedwai Baqir , Kolipaka Arunark , Mix Doran
Published: September 2024

Type-B aor tic dissection (TBAD) represents a serious medical emergency with up to a 50% associated 5-year mortality caused by thoracic aorta, dissection-associated aneurysmal (DAA) degeneration, and rupture. Unfortunately, conventional size related diagnostic methods cannot distinguish high-risk DAAs that benefit from surgical intervention from stable DAAs. Our goal is to use DAA stiffness measured with magnetic resonance elastography (MRE) as a biomarker to distinguish high-risk DAAs from stable DAAs. This is a feasibility study using MRE to 1) fabricate human-like geometries TBAD phantoms with different stiffnesses. 2) measure stiffness in TBAD phantoms with rheometry and 3) demonstrate the first successful application of MRE to the thoracic aorta of a human volunteer. Aortic dissection phantoms with heterogenous wall stiffness demonstrated the correlation between MRE-derived stiffness and rheometric measured stiffness. A pilot scan was performed in a healthy volunteer to test the technique’s feasibility in the thoracic aorta.
Repurposing the plant-derived compound apigenin for senomorphic effect in antiaging pipelines
Authors: Zhang Hongwei , Xu Qixia , Jiang Zhirui , Sun Rong , Liu Sanhong , kirkland James L. , Zhang Weidong , Sun Yu
Published: September 2024

Cellular senescence is a cell fate triggered by inherent or environmental stress and characterized by stable cell cycle arrest accompanied by a hypersecretory feature, termed as the senescence-associated secretory phenotype (SASP). Senescent cell burden increases with natural aging, functionally contributing to age-related organ dysfunction and multiple disorders. In this study, we performed a large scale screening of a natural product library for senotherapeutic candidates by assessing their effects on human senescent cells. Apigenin, a dietary flavonoid previously reported with antioxidant and anti-inflammatory activities, exhibited a prominent capacity in targeting senescent cells as a senomorphic agent. In senescent cells, apigenin blocks the interactions between ATM/p38 and HSPA8, thus preventing transition of the acute stress-associated phenotype (ASAP) towards the SASP. Mechanistically, apigenin targets peroxiredoxin 6 (PRDX6), an intracellular redox-active molecule, suppressing the iPLA2 activity of PRDX6 and disrupting downstream reactions underlying the SASP development. Without reversing cellular senescence, apigenin deprives cancer cells of malignancy acquired from senescent stromal cells in culture, while reducing chemoresistance upon combination with chemotherapy in anticancer regimens. In preclinical trials, apigenin administration improves physical function of animals prematurely aged after whole body irradiation, alleviating physical frailty and cognitive impairment. Overall, our study demonstrates the potential of exploiting a naturally derived compound with senomorphic capacity to achieve geroprotective effects by modulating the SASP, thus providing a research platform for future exploration of novel natural agents against age-related conditions.
Combination ofBRCAdeep targeted sequencing and shallow whole genome sequencing to detect homologous recombination deficiency in ovarian cancer
Authors: Nguyen Thien-Phuc Hoang , Tran Nam HB , Nguyen Tien Anh , Ngo My TT , Doan Anh Duong , Nguyen Du Quyen , Tang Hung Sang , Nguyen Duy Sinh , Nguyen Thi Cam Tu , Do Thi Thanh Thuy , Nguyen Hoai-Nghia , Giang Hoa , Tu Lan N
Published: September 2024

Backgrounds

Assessing homologous recombination deficiency (HRD) has been recommended by clinical guidelines for patients with ovarian cancer (OC) as it predicts sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). However, HRD testing is complex and either inaccessible or unaffordable for majority of OC patients in developing countries. Consequently, the prevalence of HRD in OC remains unknown.

Methods

We examined HRD status of 77 Vietnamese patients with OC using a new laboratory-developed test (HRD Insight, Gene Solutions). Tumor DNA was extracted from FFPE samples, followed by next-generation sequencing to detect deleterious or suspected deleterious variants inBRCA1/2genes. Shallow whole genome sequencing was performed to determine the whole Genomic Instability (wGI) score by assessing the presence of large-scale intra-chromosomal copy number alterations.

Results

The assay was first benchmarked against commercial HRD kits including TruSight Oncology 500 HRD (Illumina), SOPHiA DDM HRD Solutions (Sophia Genetics) and HRD Focus Panel (AmoyDx), and showed an overall percent agreement of 90.0%, 96.3%, and 96.4% respectively. The successful rate of sequencing was 94.8% (73/77) and the prevalence of HRD in OC patients was 54.8% (40/73).BRCAmutations and positive wGI scores were found in 16.4% (12/73) and 47.9% (35/73) of the patients respectively. Among those with wild-typeBRCA1/2, 40.5% of them had positive wGI scores and hence positive HRD. Age at diagnosis was not affected by bothBRCAand wGI status.

Conclusions

HRD Insight assay could accurately and robustly determine the HRD status of ovarian tissue samples, including those with low quality.
Driving engagement in metaverse-mediated tourism environments: exploring the role of perceived realism
Authors: Cheung Man Lai , Leung Wilson K.S. , Chang Man Kit , Wong Randy Y.M. , Tse Sin Yan
Published: September 2024

Purpose

Despite the promising development and marketing potential of the metaverse, our understanding of how realistic metaverse environments impact user engagement and behaviours remains limited. This study investigates the role of perceived realism in influencing user engagement, thereby affecting external search behaviour and visit intentions.

Design/methodology/approach

We surveyed 270 active metaverse users to test the research model. The data were analysed using partial least squares structural equation modelling (PLS-SEM).

Findings

The results of our study show that three dimensions of realism – avatar involvement, perceptual pervasiveness and social realism – significantly enhance user engagement, which in turn influences external search behaviour and visit intention. In contrast, simulation realism and freedom of choice have minimal effects on absorption and dedication.

Research limitations/implications

This study highlights the role of perceived realism in enhancing user engagement with the metaverse and its impact on physical world behaviours. It contributes to metaverse literature by demonstrating that engagement within the metaverse significantly influences physical world behaviours, including visit intentions and external search behaviours.

Practical implications

This study offers practical guidance for developers to enhance user engagement in metaverse environments. Specifically, our findings advocate for visual and audio quality enhancements, greater persuasiveness of virtual spaces, improved avatar representativeness and a closer alignment of metaverse activities with real-life events.

Originality/value

This study advances the theoretical understanding of perceived realism by examining how its dimensions – such as visual and audio quality, avatar representativeness and alignment with real-life events – impact user engagement in the metaverse. It also explores how this engagement influences offline behaviours, thus bridging the gap between virtual and real-world interactions.
Adapting accounting education to evolving business paradigm-an Indian perspective
Authors: Nanjundaswamy Abhishek , Divyashree M.S. , Suraj Neethu , Kulal Abhinandan , Rahiman Habeeb Ur , Kodikal Rashmi
Published: September 2024

Purpose

This study examines the need for an accounting curriculum to evolve in response to the changing business landscape. Specifically, this study aims to explore the relationship between various market forces, the shifting dynamics of business, and the importance of adapting accounting education to these changes.

Design/methodology/approach

This study is a combination of both quantitative and qualitative research. A structured questionnaire was administered to 320 professionals to gather data, and the study employed descriptive analysis, one-sample t-tests, and structured equation modeling to analyze the relationship between the variables.

Findings

The findings reveal a strong correlation between business transformation and the imperative to adapt accounting education. This study emphasizes the significance of modifying accounting curricula to align with the current market trends. Furthermore, this study addresses the pressing concern of sustainability and the triple bottom line (TBL), advocating specialized education in sustainability accounting programs.

Research limitations/implications

Despite its contributions, this study acknowledges a limitation in its focus solely on the perceptions of professionals and academicians regarding the impact of business transformation on accounting education, without directly examining the prevailing accounting education system. Future research should address this limitation by undertaking a qualitative exploration of the actual accounting education landscape and market requirements.

Practical implications

The implications of the study span the theoretical, regulatory, environmental, and social domains, stressing the need for educational institutions, regulatory bodies, and industry to collaborate in shaping competent and future-ready accounting professionals. A systematic approach would validate and extend the findings of this study, providing deeper insights into the transformative processes necessary to enhance accounting education in response to evolving business landscapes and environmental dynamics.

Originality/value

The outcome of the study assists educational institutions and regulatory bodies in framing policies to adapt accounting education to the evolving business landscape by updating the accounting curriculum as per the changes in the market forces to make graduates relevant and competent.
The effect of politically homogenous neighbourhoods on affective polarization: Evidence from Britain
Authors: TILLEY JAMES , HOBOLT SARA B.
Published: September 2024

Affective polarization is increasingly evident around the world. This has been attributed in part to residential segregation by partisanship. The ‘Big Sort’ has meant that neighbourhoods in the United States, and elsewhere, have become more homogenous in terms of vote. Yet there is little systematic evidence on the relationship between homogenous partisan neighbourhoods and affective polarization. Does living among fellow partisans make people more negative towards the other side? In this Research Note, we use unique data from Britain to show that while people accurately recognize that their local area is more or less politically homogenous, neighbourhood political homogeneity is not correlated with any measure of affective polarization. These findings are robust to the type of political divide (partisanship or Brexit identity), the level of geography, length of residence and controls for ideology and social characteristics. We therefore suggest that while geographical sorting is an important phenomenon, it is unlikely to be a major cause of affective polarization.
Short‐term germinated legume flours as functional ingredients in food products
Authors: Onwuka Queeneth Ijeoma , Chinma Chiemela Enyinnaya , Ezeocha Vanessa Chinelo , Otegbayo Bolanle , Oyeyinka Samson Adeoye , Adebo Janet Adeyinka , Wilkin Jon , Bamidele Oluwaseun Peter , Adebo Oluwafemi Ayodeji
Published: September 2024

Unlocking the potential of legumes through short‐term germination offers an innovative approach to improving the functionality of the resultant flour. This review examines the multifaceted benefits of short‐term germinated legume flour, emphasizing the enzymatic activities that breakdown complex legume compounds into simpler forms and reduce anti‐nutritional factors. This process improves digestibility, nutrient bioavailability, and health‐promoting properties. Furthermore, short‐term germination enhances the techno‐functional properties of legume flours without compromising their quality, avoiding excessive starch and protein degradation associated with prolonged germination. This review also explores the applications of short‐term germinated legume flours in developing nutritious and healthy food products tailored to diverse dietary needs. Subsequent integration of these short‐term germinated flours into food products provides a route for the development of cost‐effective, nutritious, and sustainable options that can address malnutrition and enhance overall well‐being.
Insight into the therapeutic effects of artesunate in relieving metabolic‐associated steatohepatitis from transcriptomic and lipidomics analyses
Authors: Yang Jing , Huang Lei Jie , Ren Tian Yi , Zeng Jing , Shi Yi Wen , Fan Jian Gao
Published: September 2024

Objectives

Artesunate (ART) is a water‐soluble derivative of artemisinin, which has shown anti‐inflammatory, anti‐tumor, and immunomodulating effects. We aimed to investigate the potential therapeutic effects and mechanisms of ART in metabolic dysfunction‐associated steatohepatitis (MASH).

Methods

The mice were randomly divided into the control group, high‐fat, high‐cholesterol diet‐induced MASH group, and the MASH treated with ART (30 mg/kg once daily) group. Liver enzymes, lipids, and histological features were compared among groups. The molecular mechanisms were studied by transcriptomic and lipidomics analyses of liver tissues.

Results

The mice of the MASH group had significantly increased hepatic fat deposition and inflammation in terms of biochemical indicators and pathological manifestations than the control group. The ART‐treated group had improved plasma liver enzymes and hepatic cholesterol, especially at week 4 of intervention (p < 0.05). A total of 513 differentially expressed genes and 59 differentially expressed lipids were identified in the MASH group and the MASH+ART group. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment test showed that ART regulated glycerolipid metabolism pathway and enhanced fatty acid degradation. Peroxisome proliferator‐activated receptor (PPAR)‐α acted as a key transcription factor in the treatment of MASH with ART, which was confirmed by cell experiment.

Conclusions

ART significantly improved fat deposition and inflammatory manifestations in MASH mice, with potential therapeutic effects. The mechanism of artemisinin treatment for MASH may involve extensive regulation of downstream genes by upstream transcription factors, such as PPAR‐α, to restore hepatic lipid homeostasis.
Flucloxacillin instantly decreases serum levels of valproic acid: A case report
Authors: van der Meer Douwe H. , Elting Lisa J. , van Egmond Pleun S.
Published: September 2024

Valproic acid (VPA) is used for epilepsy and bipolar disorder. It has near‐complete bioavailability and is primarily metabolized by glucuronosyltransferases and mitochondrial oxidation. This case highlights a 79‐year‐old male with bipolar disorder on VPA therapy that started with flucloxacillin for Staphylococcus aureus bacteraemia and exhibited significantly reduced VPA serum levels. During hospitalization, flucloxacillin treatment correlated with a sharp decline of 75% in VPA total serum levels, a novel drug–drug interaction not previously reported. Nonadherence and absorption issues of VPA were ruled out, confirming flucloxacillin's role in reducing VPA levels. Because free‐fraction serum levels of VPA remained within therapeutic range (5–25 mg/L) and our patient's bipolar disorder remained stable at 1000 mg twice daily, a dose increase was not necessary. Previous reports described cytochrome P450 enzyme induction as the mechanism of flucloxacillin lowering serum levels of immunosuppressants and antimycotics. Because only 10% of VPA is metabolized by cytochrome P450 enzymes, this is not plausible for this case. The proposed mechanism for the VPA–flucloxacillin drug–drug interaction is flucloxacillin as inducer of glucuronosyltransferase enzymes via the pregnane X receptor pathway, accelerating VPA metabolism. Because this case showed that free‐fraction serum levels remained within therapeutic range, it underscores the need for free‐fraction VPA monitoring in bipolar disorder and flucloxacillin therapy. When VPA is used for epilepsy, it is advised to consider alternative antibiotics to avoid this interaction.
Impacts of ecosystem service message framing and dynamic social norms on public support for tropical forest restoration
Authors: Simons D.‐L. , Bradbury R. B. , Evans K. L.
Published: September 2024

The effectiveness of strategic psychology‐based marketing techniques for increasing public support for conservation is poorly understood. We assessed how such techniques affect support for tropical rainforest restoration with a controlled online experiment with 1166 nationally representative residents of the United Kingdom. We tested whether support increased when adding ecosystem service (ES) framings to typical nongovernmental organizations’ (NGOs) biodiversity‐focused messages that emphasize benefits to UK residents or people living near the tropical restoration site and a dynamic social norm nudge that emphasized increasing popularity of environmental restoration. We considered how respondents’ psychological traits (nature connection, self‐efficacy, psychological benefits of supporting charities, awareness of environmental degradation in the Global South, and climate change skepticism) influenced responses. Outcomes included respondents’ reported advertisement sufficiency, sympathetic attitudes, behavioral support, and financial support. The study population typically found advertisements sufficient and exhibited sympathetic attitudes and financial, but not behavioral, support. Younger people exhibited greater conservation support than older respondents. Messages framed solely on biodiversity conservation were as effective as those highlighting additional ES benefits received by UK residents and people near the tropical restoration site. This suggests that framing around ESs, rather than nature's intrinsic value, may not strengthen public support for conservation. The dynamic social norm nudge had perverse effects. It reduced perceived social norms and most outcome variables. Alternative dynamic norm nudges warrant testing, but our results support research suggesting dynamic norm nudges can be ineffective when associated with activism, challenging their use by conservation NGOs. Psychological benefits of supporting charities and perceived self‐efficacy increased support for advertisements, highlighting the benefits of including impact statements relating respondents’ support to specific outcomes. Climate change skepticism decreased support, whereas nature connection and perceived static social norms increased it, highlighting the need to increase nature connection and pro‐environmental social norms to elevate public support for conservation.
Feasibility and safety of endoscopic full‐thickness resection for submucosal tumors in the upper gastrointestinal tract, including predominantly extraluminal submucosal tumors (with video)
Authors: Guo Yingjie , Yin Fan , Qi Xingsi , Zhang Peng , Sun Xueguo , Ding Xueli , Li Xiaoyu , Jing Xue , Jiang Yueping , Tian Zibin , Mao Tao
Published: September 2024

Objectives

Endoscopic full‐thickness resection (EFTR) for submucosal tumors (SMTs) has been technically challenging. This retrospective study aimed to evaluate the feasibility, safety, and efficacy of EFTR for upper gastrointestinal (GI) SMTs, including extraluminal lesions.

Methods

We retrospectively investigated 232 patients with SMTs who underwent EFTR from January 2014 to August 2023. Clinicopathologic characteristics, procedure‐related parameters, adverse events (AEs), and follow‐up outcomes were assessed in all patients.

Results

The en‐bloc resection and en‐bloc with R0 resection rates were 98.7% and 96.1%, respectively. The average endoscopic tumor size measured 17.2 ± 8.7 mm, ranging from 6 to 50 mm. The resection time and suture time were 49.0 ± 19.4 min and 22.5 ± 11.6 min, respectively. In all, 39 lesions (16.8%) exhibited predominantly extraluminal growth. Gastrointestinal stromal tumors (GISTs) were the predominant pathology, accounting for 78.4% of the cases. Twenty‐one patients (9.1%) encountered complications, including pneumothorax (1/232, 0.43%), hydrothorax (1/232, 0.43%), localized peritonitis (3/232, 1.29%), and fever (16/232, 6.9%). Although the incidence of postoperative fever was notably higher in the predominantly extraluminal group (7/39, 17.9%) compared to the predominantly intraluminal group (9/193, 4.7%, P = 0.008), there were no significant differences in outcomes of the EFTR procedure. No instances of recurrence were observed during the mean follow‐up period of 3.7 ± 2.3 years.

Conclusion

EFTR was found to be feasible, safe, and effective for resecting upper GI SMTs, including lesions with predominantly extraluminal growth. Further validation in a prospective study is warranted.