bluuebunny/crossref_metadata_2025 huggingface dataset:
New-onset syncope in diabetic patients treated with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors: A Chinese population-based cohort study
Authors: Gao Xinyi , Zhang Nan , Lu Lei , Gao Tianyu , Chou Oscar Hou In , Wong Wing Tak , Chang Carlin , Wai Abraham Ka Chung , Lip Gregory Y. H. , Zhang Qingpeng , Tse Gary , Liu Tong , Zhou Jiandong
Published: July 2023

Background and Aims

Syncope and post-syncopal adverse events lead to a heavy burden in the healthcare systems with negative impact on the economy globally. However, no effective treatments have been identified to prevent the risk of new-onset syncope. This study compared the preventive effect of incident syncope between sodium-glucose cotransporter-2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i).

Methods

This was a retrospective, territory-wide cohort study enrolling type 2 diabetes mellitus (T2DM) patients treated with SGLT2i or DPP4i between January 1st, 2016, and December 31st, 2020, in Hong Kong, China. The outcomes were new-onset syncope, cardiovascular mortality, and all-cause mortality. Multivariable Cox regression and different approaches using the propensity score were used to evaluate the association between SGLT2i vs. DPP4i with incident syncope and mortality.

Results

After matching, a total of 37502 patients with T2DM were included (18751 SGLT2i users, 18751 DPP4i users). During a median follow-up of 5.56 years, compared to DPP4i users, SGLT2i therapy was associated with a 51% lower risk of new-onset syncope (HR, 0.49; 95%CI [0.41-0.57], P<0.001), 65% lower risk of cardiovascular mortality (HR, 0.35; 95%CI [0.26-0.46], P<0.001), and a 70% lower risk of all-cause mortality (HR, 0.30; 95%CI [0.26-0.34], P<0.001) in the fully adjusted model. Similar association with syncope was observed for dapagliflozin (HR, 0.70; 95%CI [0.58-0.85], P<0.001), canagliflozin (HR, 0.48; 95%CI [0.36-0.63], P<0.001) and ertuglifolzin (HR, 0.45; 95%CI [0.30-0.68], P<0.001), but was attenuated for empagliflozin (HR, 0.79; 95%CI [0.59-1.05], P=0.100) after adjusting for potential confounders. Subgroup analyses suggested that, compared to DPP4i, SGLT2i showed a significantly protective effect in incident syncope among T2DM patients, regardless of gender, age, comorbidities burden and other medication history, as well as among patients with different levels of fasting glucose, HbA1c, and glycemic variability.

Conclusions

Compared to DPP4i, SGLT2i could significantly reduce the risk of new-onset syncope in patients with T2DM, regardless of gender, age, comorbidities, other medication history, and degree of glycemic control. Our findings suggest a promising future of SGLT2i in preventing incident syncope.

Abstract Figure

Structured graphical abstract

CI: confidence interval; DPP4i: dipeptidyl peptidase-4 inhibitor; HR: hazard ratio; SGLT2i: sodium-glucose cotransporter-2 inhibitor.
Trialling an Optimised social Groups intervention in services to Enhance social connecTedness and mental Health in vulnERable young people (TOGETHER): Study protocol for a feasibility randomised controlled trial
Authors: Vella Claire , Berry Clio , Easterbrook Matthew J. , Bibby-Jones Anna-Marie , Michelson Daniel , Bogen-Johnston Leanne , Fowler David
Published: July 2023

Background

Calls have been made to rethink the mental health support currently available for young people. This study aims to help re-focus and reduce the inaccessibility of mental health services by offering an adapted version of a theoretically-driven, evidence-based, guided psychosocial intervention known as ‘Groups 4 Health’ (G4H). To date, the G4H intervention has mainly been trialled in Australia, with promising positive effects on social connection, mental health and well-being. The present study examines the feasibility of running a randomised controlled trial when delivering the G4H intervention for young people in the UK.

Methods

The TOGETHER study is a feasibility randomised controlled trial of an adapted version of the G4H intervention. Participants are aged 16-25, currently experiencing mental health difficulties and recruited from mental health services. The target sample size is 30, with 15 in each trial arm. Participants are randomly allocated to either G4H plus treatment as usual, or treatment as usual alone. The primary outcomes of interest are the feasibility of recruitment, randomisation, data collection and retention to the study at 10 and 14 week follow up, as well as the acceptability, and accessibility of the study protocol and G4H intervention.

Discussion

The results of this study will indicate if further optimisation is required to improve the feasibility, acceptability and accessibility of the intervention and study protocol procedures as perceived by end users and practitioners. This offers a significant opportunity to support the local and national demand for accessible, innovative, and effective psychosocial youth mental health support.

Trial registration

ISRCTN registry (ISRCTN12505807). Registration date: 11/04/2022.
Design, Synthesis, and Biological Evaluation of Novel Mitochondria-targeting Exosomes
Authors: Yan Xin , Chen Xinqian , Shan Zhiying , Bi Lanrong
Published: July 2023

Mitochondrial dysfunction is implicated in both brain tumors and neurodegenerative diseases, leading to various cellular abnormalities that can promote tumor growth and resistance to thera-pies, as well as impaired energy production and compromised neuronal function. Developing targeted therapies aimed at restoring mitochondrial function and improving overall cellular health could potentially be a promising approach to treating these conditions. Brain-derived exosomes (BR-EVs) have emerged as potential drug delivery vessels for neurological conditions. Herein, we report a new method for creating mitochondria-targeting exosomes and test its application in vitro and in vivo.
Identification of critical cell-types using genetic modules: A case study of neurodevelopmental disorders
Authors: Chow Julie , Tomkova Marketa , Thomas Ashleigh , Rahmani Elior , Shifman Sagiv , Hormozdiari Fereydoun
Published: July 2023

Identifying the critical cell-types impacted by various diseases is crucial for understanding disease mechanisms and developing targeted therapeutics. Recent advances in disease genetic module discovery and single-cell technologies provide a unique opportunity to study critical cell-types based on functional pathways and modules. Disease genetic modules are defined as sets of genes with correlated expression that are part of the same biological pathways and are disrupted in the disease. Critical cell-types for a biological function are defined as clusters of similar cells most “active” or “involved” in that biological function. In this paper, we provide a formal problem definition for the critical cell discovery problem using the recently introduced local correlation concept, and show that the proposed problem is intractable in theory. We propose a novel method, MoToCC (Module To Critical Cell-types), to find sets of similar cells with local correlated gene expression activity for input modules. We evaluated MoToCC on four neurodevelopmental disorder modules using single-cell expression data from the developing human cortex. Finally, we demonstrate that the objective value returned by MoToCC for the tested modules is an acceptable approximation to the optimal solution. Overall, our work provides a valuable tool for studying critical cell-types and their role in disease mechanisms, which could lead to the development of more effective targeted therapeutics. The MoToCC package is available athttps://github.com/jchow32/MoToCC
Mosquito Adult Bioassays
Authors: Li Ting , Wang Yifan , Liu Nannan
Published: July 2023

Topical application and bottle bioassays measure the responses of adult mosquitoes to specific doses of an insecticide (dose–response). Topical application bioassays are generally used to measure the dose–response of adult mosquitoes to insecticides in which the amount (dose) of insecticides the mosquitoes receive is known in the laboratory. Here, a 0.5-µL drop of the insecticide dissolved in a relatively nontoxic solvent, such as acetone, is applied to the thorax of insects, and the insects’ susceptibility to the insecticide is determined in terms of either the median lethal dose (LD50) or 90% of the mortality lethal dose (LD90). Bottle bioassays measure the dose–responses in which the exact amount of insecticide in a bottle is known while the exact amount of insecticide that mosquitoes (field-collected or laboratory-susceptible) receive is not known. Bottle bioassays can be either single dose tests or multiple dose applications. The bottle bioassay described in this protocol is a modified form of the World Health Organization (WHO) and U.S. Centers for Disease Control (CDC) bottle bioassays. For the single bottle assay, a detailed protocol with the amount (dose/bottle) of each insecticide and threshold times is provided by the CDC; here we provide protocols for topical and bottle bioassay applications with multiple doses.
Single-Pair Courtship and Competition Assays inDrosophila
Authors: von Philipsborn Anne C. , Shohat-Ophir Galit , Rezaval Carolina
Published: July 2023

Courtship inDrosophila melanogasterinvolves a series of innate, complex behaviors that allow male and female flies to exchange sensory information and assess the quality of a potential mate. Although highly robust and stereotypical, courtship behaviors can be modulated by internal state and experience. This protocol describes methods for designing and carrying out experiments that measure courtship performance in single-pair assays, in which a male is paired with a female, or in competitive assays, in which a male is presented with a female and with a male competitor. It also includes approaches for measuring female sexual receptivity during courtship.
The prevalence of horizontal violence with different cultural dimensions
Authors: Verma Pratima
Published: July 2023

Purpose

The study aims to look at the link between horizontal violence (HV) and organizational culture aspects. Bullying and hostility including intergroup conflict are referred to as HV. HV is a significant issue that is encountered in various professions. The different cultural typologies of group, developmental, hierarchical and rational culture have been addressed in this study. Additionally, it is identified that the prevalence of HV in organizations with different cultural dimensions.

Design/methodology/approach

Using a non-probability multistage sampling strategy, a quantitative method was used and questionnaires were circulated to collect data from the information technology sector. The data were analyzed using multiple regression analysis.

Findings

The findings demonstrated that HV has a positive and substantial association with the group and developmental culture, whereas HV has a negative link with hierarchical and rational culture.

Research limitations/implications

These results provide a valuable tool for human resource managers and policymakers in promoting a healthy work environment and employee interpersonal collaboration, which will improve the organization’s overall performance.

Originality/value

This study is a novel work exploring the HV among employees in technological firms, and also combining the concepts of HV and organizational culture and also assists future researchers in many folds.
Design and analysis of high-gain DC–DC chopper topologies for PV-fed BLDC motor drive system
Authors: Elbarbary Zakaria Mohamed Salem , Alaifi Ahmed A. , Alqahtani Saad Fahed , Shaik Irshad Mohammad , Gupta Sunil Kumar , Gali Vijayakumar
Published: July 2023

Purpose

Switching power converters for photovoltaic (PV) applications with high gain are rapidly expanding. To obtain better voltage gain, low switch stress, low ripple and cost-effective converters, researchers are developing several topologies.

Design/methodology/approach

It was decided to use the particle swarm optimization approach for this system in order to compute the precise PI controller gain parameters under steady state and dynamic changing circumstances. A high-gain q- ZS boost converter is used as an intermittent converter between a PV and brushless direct current (BLDC) motor to attain maximum power point tracking, which also reduces the torque ripples. A MATLAB/Simulink environment has been used to build and test the positive output quadratic boost high gain converters (PQBHGC)-1, PQBHGC-8, PQBHGC-4 and PQBHGC-3 topologies to analyse their effectiveness in PV-driven BLDC motor applications. The simulation results show that the PQBHGC-3 topology is effective in comparison with other HG cell DC–DC converters in terms of efficiency, reduced ripples, etc. which is most suitable for PV-driven BLDC applications.

Findings

The simulation results have showed that the PQBHGC-3 gives better performance with minimum voltage ripple of 2V and current ripple of 0.4A which eventually reduces the ripples in the torque in a BLDC motor. Also, the efficiency for the suggested PQBHGC-3 for PV-based BLDC applications is the best with 99%.

Originality/value

This study is the first of its kind comparing the different topologies of PQBHGC-1, PQBHGC-8, PQBHGC-4 and PQBHGC-3 topologies to analyse their effectiveness in PV-driven BLDC motor applications. This study suggests that the PQBHGC-3 topology is most suitable in PV-driven BLDC applications.
How e-commerce platforms build channel power: the role of AI resources and market-based assets
Authors: Deng Guangkuan , Zhang Jianyu , Xu Ying
Published: July 2023

Purpose

Considering the emergence of e-commerce platforms and their integration into marketing channels, this paper aims to investigate how artificial intelligence (AI) resources – both technological and human – possessed by e-commerce platforms can enhance their channel power by acquiring market-based assets (relational and intellectual).

Design/methodology/approach

Based on resource-based theory and resource orchestration theory, the authors developed a framework tested using survey data gathered from the sellers, which incorporated six key variables: the e-commerce platform’s AI technology resources and human resources, rational and intellectual market-based assets, intraplatform competition and channel power. The analyses are performed using the regression analysis technique.

Findings

The empirical findings indicate that both technological and human AI resources are crucial in building channel power. In addition, market-based assets serve as a mediator in this relationship, while intraplatform competition moderates the effect of intellectual market-based assets on channel power negatively.

Originality/value

This study contributes to the existing literature by exploring how e-commerce platforms’ AI resources affect their channel power. The results offer valuable guidance to managers and researchers on optimizing AI resources to improve channel power.
Essential 4: a shared commitment to reflection, innovation and generative knowledge
Authors: Stoicovy Donnan , Badiali Bernard , Burns Rebecca West , Coler Cynthia , Cosenza Michael , Goree Krystal , Polly Drew , Zenkov Kristien
Published: July 2023

Purpose

The purpose of this paper is to describe the key aspects and give examples of Essential 4 of the Second Edition of the National Association for Professional Development Schools (NAPDS) Nine Essentials.
The Travels of Treason
Authors: Lobban Michael
Published: July 2023

The law of treason has been criticised for being based on ‘outdated’ statutes which are inflexible and unsuitable for modern needs. However, a historical examination of the evolution of treason in Britain and its empire suggests that the law was often adaptable. In nineteenth century England, jurists wished to rein in older constructive treasons, to leave the 1351 Act as the appropriate law for wartime treasons, while the more lenient 1848 Act was to be used against ‘political’ conspiracies to subvert the state by force. However, the ‘constructive’ treasons remained part of the law, and were given new life in imperial contexts. In Ireland and Canada, the idea that plotting the king's ‘political’ death was treason remained central to understandings of the 1351 Act. In India, the interpretation of the provision of the penal code against ‘waging war’ against the government was influenced by old English ideas of ‘constructive’ treason and used against those who challenged British rule. Imperial understandings of treason were also shaped by cases arising out of the Boer war, where the underlying law was Roman‐Dutch law. Rather than being restrictive and unable to adapt to modern needs, the law of treason was flexible and malleable.
The beer component hordenine inhibits alcohol addiction‐associated behaviours in mice
Authors: Li Yan , Vogel Christina , Kalinichenko Liubov S. , Hübner Harald , Weikert Dorothee , Schaefer Natascha , Gmeiner Peter , Villmann Carmen , Pischetsrieder Monika , Müller Christian P.
Published: July 2023

Alcohol consumption is a widespread behaviour that may eventually result in the development of alcohol use disorder (AUD). Alcohol, however, is rarely consumed in pure form but in fruit‐ or corn‐derived preparations, like beer. These preparations add other compounds to the consumption, which may critically modify alcohol intake and AUD risk. We investigated the effects of hordenine, a barley‐derived beer compound on alcohol use‐related behaviours. We found that the dopamine D2 receptor agonist hordenine (50 mg/kg) limited ongoing alcohol consumption and prophylactically diminished relapse drinking after withdrawal in mice. Although not having reinforcing effects on its own, hordenine blocked the establishment of alcohol‐induced conditioned place preference (CPP). However, it independently enhanced alcohol CPP retrieval. Hordenine had a dose‐dependent inhibitory effect on locomotor activity. Chronic hordenine exposure enhanced monoamine tissue levels in many brain regions. Further characterization revealed monoaminergic binding sites of hordenine and found a strong binding on the serotonin and dopamine transporters, and dopamine D3, and adrenergic α1A and α2A receptor activation but no effects on GABAA receptor or glycinergic signalling. These findings suggest that natural ingredients of beer, like hordenine, may work as an inhibitory and use‐regulating factor by their modulation of monoaminergic signalling in the brain.
The effect of a preparation containing glycocholic acid on the biocidal efficacy of sodium hypochlorite in a biofilm laboratory model
Authors: Haddad Yoseif , Chan Wing Chuan , Ha William Nguyen , Conde Antonio , Estevez Roberto , Lopez Alejandro Peña , Gates Georgia Charlotte , Rossi‐Fedele Giampiero
Published: July 2023

This study assessed the antimicrobial effect of sodium hypochlorite (NaOCl) mixtures combined with Keratobacter (KB) using an engineered biofilm root canal model. Clinical and reagent grade NaOCl were mixed with KB (9:1‐vol/vol) to assess pH values over 1 min to select the ideal solution with a pH just below the pKa of hypochlorous acid. The samples were randomly divided into five groups: 1% and 4% NaOCl reagents, a mixture of NaOCl:KB using 1% and 4% NaOCl reagents and distilled water. Outcome measures were colony‐forming units (CFUs/mL) and positive/negative cultures. No significant differences were observed in the pairwise comparisons between 1%, 4% NaOCl and 4% NaOCl+KB for the outcome CFUs/mL. Only 4% NaOCl presented with negative cultures in all samples, whereas 1% NaOCl and 4% NaOCl+KB had similar results (54% vs. 40%). The addition of KB has a limited effect on the antimicrobial efficacy of 4% NaOCl in this laboratory model.
Shape analysis of fossa masseterica and processus coronoideus in domestic cats (Felis catus) and domestic dogs (Canis familiaris)
Authors: Gündemir Ozan
Published: July 2023

Fossa masseterica, to which the musculus masseter is attached, is the pit on the lateral surface of the ramus mandibulae. Processus coronoideus is a protrusion on the upper part of fossa masseterica. Carnivores have a more developed fossa masseterica and a wider processus coronoideus than other species, due to their well‐developed jaw muscles. However, there is limited information about the differences of these two structures among carnivorous species. In this study, it was investigated whether fossa masseterica and processus coronoideus differ in shape in domestic cats and domestic dogs. For this purpose, 22 dogs and 20 cats were examined by 3D geometric morphometry. Eighty‐one landmarks were used on the fossa masseterica and processus coronoideus. The difference in centroid sizes and shape for cats and dogs was statistically significant (p < 0.0001). PC1 explained 26.47% of the total variance. It was seen that cats and dogs were completely separated according to PC1 results. In cats with a high PC1 value, the processus coronoideus was narrower than in dogs. Also, feline processus coronoideus was more curved than domestic canine processus coronoideus. In addition, the caudal inclination of processus coronoideus was deeper in dogs than in cats. Dogs had a negative PC1 value except for one sample (German Shepherd). The sample with the lowest PC1 value was the French Bulldog (female, 7 years, and 13 kg). Discriminant analysis results showed that the domestic cats and domestic dogs used in the study were completely separated from each other, and this difference was statistically significant. The results of this study showed that dogs with stronger jaw muscles had a deeper fossa masseterica and a wider processus coronoideus than cats.
Iron supplements in pregnant women with normal iron status: A systematic review and meta‐analysis
Authors: Hansen Rebecka , Sejer Emilie P. F. , Holm Charlotte , Schroll Jeppe B.
Published: July 2023

Introduction

Effects of daily iron supplementation in iron replete pregnancy are unclear. This systematic review aimed to assess benefits and harms of oral iron supplements in pregnant women without anemia and iron deficiency.

Material and methods

We predefined and registered a protocol in PROSPERO (CRD42020186210) and performed the review following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) methodology. We searched for randomized clinical trials (RCTs) and observational studies comparing daily oral iron supplementation with no iron supplements in non‐anemic iron replete pregnant women. Searches were conducted in MEDLINE (by PubMed), EMBASE (by OVID), Cochrane Library, and ClinicalTrials.gov from inception to September 2022 without language restrictions. Two authors independently screened records, extracted data, and assessed risk of bias using the revised Cochrane risk of bias tool (RoB2). One author read full‐texts, assessed certainty of evidence by GRADE and conducted meta‐analyses using a random‐effects model. Primary outcomes included iron deficiency anemia, iron deficiency, hemoglobin >130 g/L, elevated iron status, small for gestational age newborns, low birthweight newborns, preterm birth, and congenital anomalies.

Results

Eight RCTs (2822 women) but no observational studies were eligible for inclusion. Daily oral iron supplementation in pregnancy probably reduces iron deficiency anemia at term (risk ratio [RR]: 0.51, 95% confidence interval [CI]: 0.38–0.70; 4 RCTs, 1670 women; I2 = 13%; moderate‐certainty evidence) and the incidence of low birthweight babies (RR: 0.30, 95% CI: 0.13–0.68; 2 RCTs, 361 infants; I2 = 0%; moderate‐certainty evidence). In addition, it may reduce iron deficiency at term (RR: 0.74, 95% CI: 0.60–0.92; 4 RCTs, 1663 women; I2 = 58%; low‐certainty evidence) and the incidence of small for gestational age babies (RR: 0.39, 95% CI: 0.17–0.86; 1 RCT, 213 infants; I2 not estimable; low‐certainty evidence).

Conclusions

Daily iron supplementation in iron replete non‐anemic pregnant women probably reduces the risk of maternal iron deficiency anemia at term and low birthweight.
Postoperative reflux esophagitis in laparoscopic distal gastrectomy with Billroth‐I reconstruction for gastric cancer: Nutritional effect and preoperative risk factors
Authors: Tsuchiya Hiroshi , Yasufuku Itaru , Fukada Masahiro , Higashi Toshiya , Asai Ryuichi , Sato Yuta , Tajima Jessi Yu , Kiyama Shigeru , Tanaka Yoshihiro , Okumura Naoki , Murase Katsutoshi , Takahashi Takao , Matsuhashi Nobuhisa
Published: July 2023

Introduction

Postoperative reflux esophagitis represents a major complication of laparoscopic distal gastrectomy (LDG) with Billroth‐I reconstruction (LDGBI). This study aimed to evaluate the nutritional effect and preoperative risk factors of postoperative reflux esophagitis in patients undergoing LDGBI for gastric cancer.

Methods

We retrospectively analyzed data of patients with (reflux [+]) and without (reflux [−]) postoperative reflux esophagitis who underwent LDGBI in our institution. Patient backgrounds, surgical outcomes, and perioperative nutritional status were compared. Preoperative risk factors for postoperative reflux esophagitis were also evaluated.

Results

Between January 2009 and December 2016, 242 patients underwent LDG for gastric cancer. Of these, 218 underwent Billroth‐I reconstruction. Seventy‐three patients were excluded because of nutritional or oncological reasons. Finally, 23 patients were enrolled as the reflux (+) group and 122 as the reflux (−) group. Although the preoperative/postoperative bodyweight ratio and albumin and hemoglobin values plateaued beyond 6 months postoperatively in the reflux (−) group, these parameters continued to decrease beyond this time in the reflux (+) group. The mean ± SD bodyweight ratios at 3 years postoperatively were 82.83% ± 9.73% and 89.45% ± 8.04% for the reflux (+) and reflux (−) group, respectively (P = .0006). Multivariate analysis revealed that postoperative reflux esophagitis was associated with postoperative body weight loss. Another multivariate analysis revealed preoperative hiatal hernia as an independent predictive factor for postoperative reflux esophagitis.

Conclusion

The risk of reflux esophagitis after LDGBI in patients with hiatal hernia should be considered when deciding therapeutic approaches for such patients.
Institutional pressures and the adoption of responsible management education at universities and business schools in Central and Eastern Europe
Authors: Preuss Lutz , Elms Heather , Kurdyukov Roman , Golob Urša , Zaharia Rodica Milena , Jalsenjak Borna , Burg Ryan , Hardi Peter , Jacquemod Julija , Kooskora Mari , Manzhynski Siarhei , Mostenska Tetiana , Novelskaite Aurelija , Pučėtaitė Raminta , Pušinaitė‐Gelgotė Rasa , Ralko Oleksandra , Rok Boleslaw , Stanny Dominik , Stefanova Marina , Tomancová Lucie
Published: July 2023

Business schools, and universities providing business education, from across the globe have increasingly engaged in responsible management education (RME), that is in embedding social, environmental and ethical topics in their teaching and research. However, we still do not fully understand the institutional pressures that have led to the adoption of RME, in particular concerning under‐researched regions like Central and Eastern Europe (CEE). Hence, we undertook what is to our knowledge the most comprehensive study into the adoption of RME in CEE to date (including 13 countries: Belarus, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Russia, Slovenia and Ukraine). We find that, with regard to RME, isomorphic pressures seem to shape teaching and research in different ways, which suggests that the idea of a holistic approach to RME, promoted by, for example, the Principles of Responsible Management Education (PRME), needs to be revisited; rather, different trajectories of organizational engagement may emerge for each principle. As a contribution to institutional theory, we discuss how a highly fragmented organizational field—like RME with its multiple dimensions—impacts on notions of actor centrality, where actors achieve centrality with regard to some dimensions of the field but fail to do so for others. In particular, we found that the European Union holds centrality in the area of RME teaching, but not in RME research. Our findings thus suggest that the concept of field centrality needs further clarification.
A Semiparametric Cox–Aalen Transformation Model with Censored Data
Authors: Ning Xi , Pan Yinghao , Sun Yanqing , Gilbert Peter B.
Published: July 2023

We propose a broad class of so-called Cox–Aalen transformation models that incorporate both multiplicative and additive covariate effects on the baseline hazard function within a transformation. The proposed models provide a highly flexible and versatile class of semiparametric models that include the transformation models and the Cox–Aalen model as special cases. Specifically, it extends the transformation models by allowing potentially time-dependent covariates to work additively on the baseline hazard and extends the Cox–Aalen model through a predetermined transformation function. We propose an estimating equation approach and devise an expectation-solving (ES) algorithm that involves fast and robust calculations. The resulting estimator is shown to be consistent and asymptotically normal via modern empirical process techniques. The ES algorithm yields a computationally simple method for estimating the variance of both parametric and nonparametric estimators. Finally, we demonstrate the performance of our procedures through extensive simulation studies and applications in two randomized, placebo-controlled human immunodeficiency virus (HIV) prevention efficacy trials. The data example shows the utility of the proposed Cox–Aalen transformation models in enhancing statistical power for discovering covariate effects.
Outcomes of transecting versus non‐transecting urethroplasty for bulbar urethral stricture: a meta‐analysis
Authors: Oszczudlowski Maciej , Yepes Christian , Dobruch Jakub , Martins Francisco E.
Published: July 2023

Objectives

To assess outcomes of transecting vs non‐transecting urethroplasty for bulbar urethral stricture in terms of stricture recurrence rate, sexual dysfunction, and patient‐reported outcome measures (PROMs) related to lower urinary tract (LUT) function.

Methods

Electronic literature searches were conducted using PubMed, Cochrane Library, Web of Science and Embase databases. The studied population was limited to men with bulbar urethral stricture included in studies that compared outcomes after transecting and non‐transecting urethroplasty. The main outcome appraised was the stricture recurrence rate. Additionally, the incidence of sexual dysfunction appraised in three domains (erectile function, penile complications, and ejaculatory function) and PROMs related to LUT function after transecting vs non‐transecting urethroplasty were assessed. The pooled risk ratio (RR) respectively for stricture recurrence, erectile dysfunction and penile complications was calculated using a fixed‐effect model with inverse variance method.

Results

In all, 694 studies were screened with 72 identified as relevant. Finally, 19 studies were suitable for analysis. The pooled difference between the transecting and non‐transecting groups relating to stricture recurrence was not significant. Overall, the RR was 1.06 (95% confidence interval [CI] 0.82–1.36) and the 95% CI crossed the line of no effect (line RR = 1). Overall, the RR for erectile dysfunction was 0.73 (95% CI 0.49–1.08) and the 95% CI crossed the line of no effect (line RR = 1). Overall, the RR for penile complications was 0.47 (95% CI 0.28–0.76) and the 95% CI did not cross the line of no effect (line RR = 1). Hence, the risk of penile complications was significantly lower in the non‐transecting group.

Conclusions

Our analysis of available evidence indicates that both transecting and non‐transecting urethroplasties, are equal in terms of the recurrence rate. On the other hand, non‐transecting techniques are better in terms of sexual function, causing less penile complications.
Role of circadian clock in the chronoefficacy and chronotoxicity of clopidogrel
Authors: Ma Luyao , Yu Fangjun , He Di , Guo Lianxia , Yang Yu , Li Wangchun , Zhang Tianpeng
Published: July 2023

Background and Purpose

The role of circadian locomotor output cycles kaput (CLOCK) in regulating drug chronoefficacy and chronotoxicity remains elusive. Here, we aimed to uncover the impact of CLOCK and dosing time on clopidogrel efficacy and toxicity.

Experimental Approach

The antiplatelet effect, toxicity and pharmacokinetics experiments were conducted with Clock−/− mice and wild‐type mice, after gavage administration of clopidogrel at different circadian time points. The expression levels of drug‐metabolizing enzymes were determined by quantitative polymerase chain reaction (qPCR) and western blotting. Transcriptional gene regulation was investigated using luciferase reporter and chromatin immunoprecipitation assays.

Key Results

The antiplatelet effect and toxicity of clopidogrel in wild‐type mice showed a dosing time‐dependent variation. Clock ablation reduced the antiplatelet effect of clopidogrel, but increased clopidogrel‐induced hepatotoxicity, with attenuated rhythms of clopidogrel active metabolite (Clop‐AM) and clopidogrel, respectively. We found that Clock regulated the diurnal variation of Clop‐AM formation by modulating the rhythmic expression of CYP1A2 and CYP3A1, and altered clopidogrel chronopharmacokinetics by regulation of CES1D expression. Mechanistic studies revealed that CLOCK activated Cyp1a2 and Ces1d transcription by directly binding to the enhancer box (E‐box) elements in their promoters, and promoted Cyp3a11 transcription through enhancing the transactivation activity of albumin D‐site‐binding protein (DBP) and thyrotroph embryonic factor (TEF).

Conclusions and Implications

CLOCK regulates the diurnal rhythmicity in clopidogrel efficacy and toxicity through regulation of CYP1A2, CYP3A11 and CES1D expression. These findings may contribute to optimizing dosing schedules for clopidogrel and may deepen understanding of the circadian clock and chronopharmacology.
Targeting phosphomevalonate kinase enhances radiosensitivity via ubiquitination of the replication protein A1 in lung cancer cells
Authors: Park Seok Soon , Kwon Mi Ri , Ju Eun Jin , Shin Seol Hwa , Park Jin , Ko Eun Jung , Son Ga Won , Lee Hye Won , Kim Yeon Joo , Moon Gyeong Joon , Park Yun‐Yong , Song Si Yeol , Jeong Seong‐Yun , Choi Eun Kyung
Published: July 2023

Radiotherapy (RT) plays an important role in localized lung cancer treatments. Although RT locally targets and controls malignant lesions, RT resistance prevents RT from being an effective treatment for lung cancer. In this study, we identified phosphomevalonate kinase (PMVK) as a novel radiosensitizing target and explored its underlying mechanism. We found that cell viability and survival fraction after RT were significantly decreased by PMVK knockdown in lung cancer cell lines. RT increased apoptosis, DNA damage, and G2/M phase arrest after PMVK knockdown. Also, after PMVK knockdown, radiosensitivity was increased by inhibiting the DNA repair pathway, homologous recombination, via downregulation of replication protein A1 (RPA1). RPA1 downregulation was induced through the ubiquitin–proteasome system. Moreover, a stable shRNA PMVK mouse xenograft model verified the radiosensitizing effects of PMVK in vivo. Furthermore, PMVK expression was increased in lung cancer tissues and significantly correlated with patient survival and recurrence. Our results demonstrate that PMVK knockdown enhances radiosensitivity through an impaired HR repair pathway by RPA1 ubiquitination in lung cancer, suggesting that PMVK knockdown may offer an effective therapeutic strategy to improve the therapeutic efficacy of RT.
Updates in metabolic bariatric endoscopy
Authors: Simons Malorie , Sharaiha Reem Z.
Published: July 2023

Obesity and its associated comorbid conditions have been increasing globally. Endoscopic bariatric and metabolic therapies (EBMTs) were initially designed to replicate bariatric surgery physiology for those who are not or choose not to be surgical candidates. Now, newer procedures target the complicated pathophysiology underlying obesity and its comorbidities. EBMT has been categorized based on its therapeutic target (stomach or small intestine), but innovations have expanded to include extraintestinal organs including the pancreas. Gastric EBMTs, namely space‐occupying balloons, gastroplasty with suturing or plication, and aspiration therapy, are primarily used for weight loss. Small bowel EBMTs are designed to cause malabsorption, epithelial endocrine remodeling, and other changes to intestinal physiology to ultimately improve the metabolic comorbidities of obesity rather than induce weight loss alone. These include duodenal mucosal resurfacing, endoluminal bypass sleeves, and incisionless anastomosis systems. Extraluminal or pancreatic EBMT is aimed to restore the production of normal pancreatic proteins that are involved in the progression of type 2 diabetes. This review discusses the current and new technologies of metabolic bariatric endoscopy, their pros and cons, and areas for future research.
The impact of obesity on cardiovascular and kidney outcomes in patients with chronic kidney disease and type 2 diabetes treated with finerenone: Post hoc analysis of the FIDELITY study
Authors: Rossing Peter , Anker Stefan D. , Filippatos Gerasimos , Pitt Bertram , Ruilope Luis M. , Billings Liana K. , Green Jennifer B. , Koya Daisuke , Mosenzon Ofri , Pantalone Kevin M. , Ahlers Christiane , Lage Andrea , Lawatscheck Robert , Scalise Andrea , Bakris George L.
Published: July 2023

Aim

To assess the effect of finerenone on the risk of cardiovascular and kidney outcomes in patients with chronic kidney disease and type 2 diabetes, with and without obesity.

Materials and methods

A post hoc analysis of the prespecified pooled FIDELITY dataset assessed the association between waist circumference (WC), composite cardiovascular and kidney outcomes, and the effects of finerenone. Participants were stratified by WC risk groups (representing visceral obesity) as low‐risk or high–very high‐risk (H‐/VH‐risk).

Results

Of 12 986 patients analysed, 90.8% occupied the H‐/VH‐risk WC group. Incidence of the composite cardiovascular outcome was similar between finerenone and placebo in the low‐risk WC group (hazard ratio [HR] 1.03; 95% confidence interval [CI], 0.72‐1.47); finerenone reduced the risk in the H‐/VH‐risk WC group (HR 0.85; 95% CI, 0.77‐0.93). For the kidney outcome, the risk was similar in the low‐risk WC group (HR 0.98; 95% CI, 0.66‐1.46) and reduced within the H‐/VH‐risk WC group (HR 0.75; 95% CI, 0.65‐0.87) with finerenone versus placebo. There was no significant heterogeneity between the low‐risk and H‐/VH‐risk WC groups for cardiovascular and kidney composite outcomes (P interaction = .26 and .34, respectively). The apparent greater benefit of finerenone on cardiorenal outcomes but lack of significant heterogeneity observed in H‐/VH‐risk WC patients may be because of the small size of the low‐risk group. Adverse events were consistent across WC groups.

Conclusion

In FIDELITY, benefits of finerenone in lowering the risk of cardiovascular and kidney outcomes were not significantly modified by patient obesity.
Foreign aid, human agency, and self‐reliance in the Pacific: Lessons from the pandemic
Authors: Teaurere Rerekura , Latu Siulua Tokilupe , de Waegh Roxane , Orams Mark , Lück Michael
Published: July 2023

Motivation

Amid the highly polarized discourse on development aid in Pacific Islands, few studies explore the perspectives of local people. Missing from the literature is how the subjective experiences of Pacific Islands people responding and adapting to a sudden global disruption influence their perceptions of foreign aid. Faced by the sudden shutdown of export markets, tourism, and labour migration, the COVID‐19 pandemic offered an opportunity to investigate how disruptions from international events affect Pacific Island peoples' perception of foreign aid.

Purpose

We investigated how the lived experiences of people in the Cook Islands and Tonga during COVID‐19 may have influenced their perceptions of foreign aid.

Methods and approach

Semi‐structured interviews guided by open‐ended questions were conducted with 25 individuals in the Cook Islands and 24 in Tonga. Interviewees were purposively selected from staff in government ministries and environmental non‐governmental organizations; from people working in tourism and private enterprise; from members of youth empowerment groups; and from among traditional leaders, faith leaders, high school teachers, fisherfolk, and farmers. The interviews explored their subjective experiences during the COVID‐19 pandemic and the meanings they attributed to them.

Findings

The pandemic closed down tourism and interrupted labour emigration in both countries. In response, people switched to farming and fishing and found ways to redeploy their skills. The pandemic saw increased local innovation, strengthened traditional practices, increased local agricultural output, and enhanced collaboration between foreign donor partners and recipient countries in the development of local human capacity.

Policy implications

Rather than repeating history by integrating Pacific Island societies into the globalized economy, or providing bail‐outs through economic restructuring, donors should strive to support the agency and self‐determination of Pacific Islands people. They should start by recognizing the resourcefulness and capacity to adapt shown by participants during the pandemic.
Public preferences for nutritional, environmental and food safety characteristics of upcycled foods in Sweden
Authors: Moshtaghian Hanieh , Bolton Kim , Rousta Kamran
Published: July 2023

This study investigates people's preferences for nutritional, environmental and food safety characteristics of upcycled foods according to their age group and assesses the association between age and the importance of these characteristics in a Swedish population. A food choice questionnaire was used for data collection, and 681 Swedish residents aged ≥18 years participated in this study. In young, middle‐aged and older adults, environmental (environmentally friendly preparation and packaging, local production and contribution to food waste reduction) and food safety (absence of additives, chemicals, genetically modified ingredients and contamination) characteristics of upcycled foods were more important than most nutritional characteristics (low energy and fat content and high fibre and protein content). There was a positive association between age and the importance score of nutritional characteristics, such as rich in vitamins and minerals, low energy and fat content and minimal food processing (P‐value < 0.05). A negative association was observed between age and the importance score of contribution to food waste reduction (P‐value = 0.014). There was a positive association between age and the importance score of food safety characteristics, such as the absence of additives, chemicals and genetically modified ingredients (P‐value < 0.05). Therefore, the environmental benefits and food safety aspects of upcycled foods can be considered for product development and marketing to facilitate the acceptability of these foods in all age groups. Since the nutritional attributes of upcycled foods were less important than their environmental and food safety characteristics, strategies should be introduced to educate people regarding desirable nutritional features to enable them to choose healthy upcycled foods.
Risk factor analysis for diabetic foot ulcer‐related amputation including Controlling Nutritional Status score and neutrophil‐to‐lymphocyte ratio
Authors: Zhu Yandan , Xu Hongtao , Wang Yuzhen , Feng Xia , Liang Xinyu , Xu Liying , Liang Zhiqiang , Xu Zhongjia , Li Yawen , Le Yi , Zhao Manchen , Yang Jianfei , Li Ji , Cao Yemin
Published: July 2023

Diabetic foot ulcer often leads to amputation, and both nutritional status and immune function have been associated with this process. We aimed to investigate the risk factors of diabetic ulcer‐related amputation including the Controlling Nutritional Status score and neutrophil‐to‐lymphocyte ratio biomarker. We evaluated data from hospital in patients with diabetic foot ulcer, performing univariate and multivariate analyses to screen for high‐risk factors and Kaplan–Meier analysis to correlate high‐risk factors with amputation‐free survival. Overall, 389 patients underwent 247 amputations over the follow‐up period. After correction to relevant variables, we identified five independent risk factors for diabetic ulcer‐related amputation: ulcer severity, ulcer site, peripheral arterial disease, neutrophil‐to‐lymphocyte ratio and nutritional status. Amputation‐free survival was lower for the moderate‐to‐severe versus mild cases, for the plantar forefoot versus hindfoot location, for the concomitant peripheral artery disease versus without and in the high versus low neutrophil‐to‐lymphocyte ratio (all p < 0.01). The results showed that ulcer severity (p < 0.01), ulcer site (p < 0.01), peripheral artery disease (p < 0.01), neutrophil‐to‐lymphocyte ratio (p < 0.01) and Controlling Nutritional Status score (p < 0.05) were independent risk factors for amputation in diabetic foot ulcer patients and have predictive values for diabetic foot ulcer progression to amputation.
Persistent Helicobacter pylori infection leads to elevated fasting plasma glucose level: A retrospective cohort study based on a nondiabetes Chinese population
Authors: You Ningning , Chen Yi , Yan Xiaodan , Gu Binbin , Wang Jun , Zhang Jinshun
Published: July 2023

Background and Aim

The relationship between Helicobacter pylori (H. pylori) and fast plasma glucose (FPG) on nondiabetes populations is still inconclusive. Nowadays, not only the high infection rate of H. pylori but also the high FPG level is threatening the Chinese people.

Methods

A retrospective cohort study has been established to analyze the relationship between H. pylori infection and FPG level, 18 164 individuals performed healthy examination in Taizhou Hospital Health Examination Center from 2017 to 2022 were included, and hematological indicators, body parameters, and H. pylori detection by 13C‐urea breath test were collected from patients. The follow‐up intervals were greater than 12 months.

Results

H. pylori infection was regarded as an independent risk factor for elevated FPG after multivariate logistic regression. Additionally, the average interval time were 33.6 ± 13.3 months. Mean changed FPG values in the persistent infection group were higher than in the subgroup of persistent negative (P = 0.029) as well as eradication infection (P = 0.007). The aforementioned changes began to appear after 2 years of follow‐up. Similarly, when compared with the subgroup of persistent infection, mean changed triglyceride/high density lipoprotein (TG/HDL) values were much lower in the subgroup of persistent negative (P = 0.008) and eradication infection (P = 0.018), but the differences appeared after 3 years of follow‐up.

Conclusions

H. pylori infection is an independent risk factor for elevated FPG in non‐diabetes mellitus (DM) individuals. Persistent H. pylori infection causes an increase in FPG level and TG/HDL, which may be a risk factor for diabetes mellitus.