bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-micelle-like Amyloid Aggregate Stabilizes Amyloid β (1-42) Growth Nuclei Formation
Authors: Kurisaki Ikuo , Tanaka Shigenori
Published: December 2022

Protein aggregate formations are essential processes to regulate biochemical networks in the cell, while anomalously formed aggregates such as amyloid fibrils cause serious neuronal diseases. It has been discussed for a quarter century that protein crowding milieus, such as micelle-like aggregates, promote the formation of growth nuclei, fibril-growth competent aggregates which trigger rapid growth of pathogenic amyloid fibrils, but the mechanisms are still elusive, in particular at microscopic level. In this study, we examined the long-standing problem by employing atomistic molecular dynamics simulations for amyloid β(1-42) (Aβ42), the paradigmatic amyloid-forming peptide. First, we constructed an atomistic model of Aβ42growth nuclei in Aβ42aggregate milieu, the pentameric Aβ42protomer dimer surrounded by 40 Aβ42monomers. Next, we simulated Aβ42monomer dissociation from the Aβ42growth nuclei and examined the effect of Aβ42aggregate milieu on the process. Aβ42aggregates spatially restrict Aβ42monomer dissociation pathways, while such spatial restriction itself does not significantly suppress Aβ42monomer dissociation from the growth nuclei. Rather, Aβ42aggregate milieus thermodynamically stabilize an Aβ42monomer binding to the growth edge by making atomic contacts with the monomer and contributes to stable formation of growth nuclei.

A part of the aggregate milieu anchors dissociating monomer to the remaining part of growth nuclei, suggesting cooperative suppression of Aβ42monomer dissociation from Aβ42growth nuclei. Since the Aβ42aggregate milieu does not take a micelle-like configuration, we here discuss a new mechanism for stable formation of Aβ42growth nuclei in the presence of aggregate milieu.
Electrochemical study on using aminated MIL–101(Cr) as corrosion inhibitor for mild steel in acidic environment
Authors: Hassan Hassan M. , Alsohaimi Ibrahim H. , El-Aassar Mohamed R. , El-Hashemy Mohammed A. , Alraddadid Thamer S.
Published: December 2022

Purpose

The purpose of this paper is to confirm the importance of using metal–organic frameworks (MOFs) in the field of corrosion control due to their potential use as corrosion inhibitors.

Design/methodology/approach

NH2–MIL–101(Cr), an amine-functionalized chromium-based MOF [Cr(III)-MOF], was prepared by solvothermal technique. Thereafter, Cr-MOF was used as an anticorrosion additive for mild steel (MS) in 1 m HCl solution. This inhibition behavior was tested by electrochemical tests including electrochemical impedance spectroscopy and potentiodynamic polarization (PDP).

Findings

Increasing the added amount of Cr-MOF enhances its inhibition performance, which attained 96.40% at 30 ppm. The obtained data from PDP measurements describe Cr-MOF as a mixed-type inhibitor. Based on SEM/EDS and FTIR analysis, the adsorption of Cr-MOF on the surface of MS that prevents MS corrosion has been demonstrated. Furthermore, Langmuir model is the most adequate adsorption isotherm for the obtained experimental data.

Originality/value

This study revealed that NH2–MIL–101(Cr), an amine-functionalized chromium-based MOF (Cr(III)-MOF), is a potential corrosion inhibitor for MS in 1 m HCl solution.
Live projects: a mixed-methods exploration of existing scholarship
Authors: Smith Sebastian G. , Dupre Karine , Crough Julie
Published: December 2022

Purpose

This paper aims to investigate trends and themes within the literature pertaining to live projects, and in so doing, highlight possible areas of future exploration and research.

Design/methodology/approach

This paper utilises a Systematic Quantitative Literature Review (SQLR) method, wherein keywords and phrases are entered into selected citation databases generating a reproducible list of literature. This is then refined using a specified list of criteria and read for relevance. The resulting literature forms the basis of qualitative and quantitative analyses and review.

Findings

The reviewed scholarship demonstrates a surge in publications since the early 2000s, with 75% of publications originating from the USA, Canada, or the UK Furthermore, themes related to live project definitions, outputs and rationales were examined, demonstrating that common factors such as “community”, “construction” and “pedagogy” are not mutually exclusive but tend to overlap, making the topic hard to define. These results also demonstrate a proclivity for projects with a built output. Barriers to live projects were also assessed, and it was found that administrative hurdles, such as time and budget constraints, were the biggest concern to live project practitioners. Finally, critical voices were examined and showed that live projects need to reflect on the nature of their engagement with the community.

Research limitations/implications

This method, while capturing a substantial portion of the published scholarship, does not capture all live project literature due to limitations such as language and a strong focus on peer-reviewed publications. Furthermore, this research only captures literature that has been published. It does not reflect the variety and extent of live project activity occurring globally. For reasons such as unfamiliarity and inconsistencies with the use of live project terminologies, doubtless many unpublished live projects are conducted–yet not represented in these findings. This study may help live project execution by providing valuable examples of existing trends.

Originality/value

This paper captures the metadata from 110 live project publications, allowing for wide-ranging analysis, categorisation and discussion on the topic.
Ferrofluid squeeze film lubrication: surface roughness effect
Authors: Atlassi Khalil , Nabhani Mohamed , El Khlifi Mohamed
Published: December 2022

Purpose

This study aims to investigate the combined effects of roughness and ferrofluid lubricant on finite journal bearing load capacity and squeeze time.

Design/methodology/approach

The stochastic theory of Christensen is applied to study the surface roughness effect. The Shliomis model is used to take into account the effects of the rotational viscosity of ferromagnetic particles and their magnetic moment. A finite wire located in the center of the shaft produces the applied magnetic field. A developed computing code allows predicting the effect of the surface roughness on the performance of the considered journal bearing. The good agreement with the results of the literature validates the used approach.

Findings

This study shows that unlike longitudinal roughness, the presence of transverse roughness makes the use of ferrofluid more beneficial in terms of increasing the performance of finite journal bearings. This increase is more significant for large relative eccentricities, which present an ideal confinement.

Originality/value

This study shows the effect of two surface roughness patterns on the squeezing performance of a finite journal bearing lubricated by a ferrofluid.
Electronic trust-building for hotel websites: a social exchange theory perspective
Authors: Nasrolahi Vosta Leila , Jalilvand Mohammad Reza
Published: December 2022

Purpose

This study aims to contribute to the context of electronic trust (e-trust) research with an emphasis on the determination of tourists’ e-trust in hotel websites. This research used social exchange theory to elaborate how perceived attributes of a hotel website influence purchase behaviour of tourists. This area is often neglected because most studies focus on website users’ adoption or acceptance of other service industries. It is expected that trust-generating mechanisms have different impacts on the e-trust level in the hospitality services.

Design/methodology/approach

A comprehensive literature review identified the major antecedents and outcomes of e-trust. Data was collected from an online survey and 586 usable questionnaires were achieved. Structural equation modelling was used to examine the hypothesized model.

Findings

The results of this study demonstrated that the more tourists perceive influences positively, the more they are possibly to trust in hotel website. Findings revealed that perceptions about the attributes of hotel website, including security, privacy, usefulness, ease of use and compatibility are the main antecedents of trust in hotel website, which, in turn, lead to actual usage of the website for booking online.

Originality/value

This study is based on a large sample of tourists and broadens the understanding of e-trust in hotel websites by considering factors rarely discussed in prior tourism and hospitality literature.
A meta-analytical study on the role of religiosity on purchase intention in the theory of planned behavior
Authors: Kaur Jaspreet , Bhardwaj Neha , Fernandes Reynal , Vidya Vidya , Farooqui Nafees Akhter
Published: December 2022

Purpose

Religion plays a crucial role as a sociocultural factor to assess consumer behavior. Stemming from the above, this study aims to analyze the impact of religion and ethnic concern on the purchase intention (PI) of consumers based on the theory of planned behavior.

Design/methodology/approach

The research method adopted for this study includes a meta-analysis of the extant literature for the past 20 years focusing on the relationship between religiosity and PI. Data of 24 values from 23 studies were used to assess the impact of religiosity on the PI of consumers.

Findings

The findings of this study indicate that religiosity has a strong impact on the PI of consumers. Further, this study identifies that location, sample size and product category play a vital role as moderators toward the relationship between religiosity and PI. This study identifies critical and pertinent implications for brands as they reach out to religious and cultural groups across various geographies, in the context of identifying target markets and adapting marketing strategies.

Originality/value

This study acts in response to the consistent call for research to focus on religion-related variables and fills the gap calling for empirical research into religiosity and its impact on PIs. This study makes notable theoretical, managerial and methodological contributions to the field.
A study on the coloration effectiveness of Chromolaena odorata on the worsted wool fabric
Authors: Pham Chau Thi Ngoc , Phan Hung Ngoc , Hoang Thao Thanh , Dao Tien Thi Thuy , Bui Huong Mai
Published: December 2022

Purpose

The health and environmental hazards associated with synthetic dyes have led to a revival of natural dyes that are non-toxic, environmentally benign and coupled with various functions. The study aims to investigate and develop the potentiality of a popular herb called Chromolaena odorata (C. odorata) as a sustainable and stable dyestuff in textiles.

Design/methodology/approach

Natural colorant extracted from C. odorata leaves is used to dye the worsted fabric, which is one of the premier end-use of wool in fashion, via the padding method associated with pre-, simultaneous and post-mordanting with chitosan, tannic acid and copper sulfate pentahydrate. The effects of extraction, dyeing and mordanting processes on fabric’s color strength K/S and color difference ΔECMC are investigated via International Commission on Illumination’s L*a*b* color space, Fourier transform infrared spectroscopy, scanning electron microscope, color fastness to washing, rubbing, perspiration and light.

Findings

The results obtained indicate extraction with ethanol 90% with a solid/liquid ratio of 1:5 within 1 h, and coloration with a liquor ratio of 1:5 (pH 5) within 2 h under padding pressure of 0.3 MPa are the most effective for coloring worsted fabric.

Practical implications

The C. odorata’s application as a highly effective dyestuff possessing good colorimetric effectiveness has expanded this herb's economic potential, contributing partly to economic growth and adding value to wool in global supply chain.

Originality/value

C. odorata dyestuff has prevailed over other natural colorants because of its impressive color fastness against washing, rubbing, perspiration and especially color stability for pH change.
How companies can prepare for the coming “AI-first” world
Authors: Davenport Thomas H. , Mittal Nitin
Published: December 2022

Purpose

The authors’ research identified seven best practices of leading companies with a particularly aggressive “All-in-on-AI” approach to Artificial Intelligence technology. 10;

Design/Methodology/Approach

The article examines how successful companies are reskilling and upskilling their employees to help develop, interpret and improve AI systems.

Findings

To date, AI technologies are most commonly applied in making business processes more efficient, improving decisions and enhancing existing products and services, but “All-in-on-AI” companies eventually develop use cases across a wide variety of functions and processes, decisions and products or services.

Practical/Implications

While many have predicted that AI would replace humans, AI-powered companies see the primary goal as discovering how to get the best out of both by redesigning jobs, reskilling workers and becoming more efficient and effective in the process.

Originality Value

Companies seeking to get significant returns on their investment in AI should take note of the practices of leading firms.
Thermophilic archaeon orchestrates temporal expression of GDGT ring synthases in response to temperature and acidity stress
Authors: Yang Wei , Chen Huahui , Chen Yufei , Chen Aiping , Feng Xi , Zhao Bo , Zheng Fengfeng , Fang Hongwei , Zhang Changyi , Zeng Zhirui
Published: December 2022

Glycerol dibiphytanyl glycerol tetraethers (GDGTs) are unique archaeal membrane‐spanning lipids with 0–8 cyclopentane rings on the biphytanyl chains. The cyclization pattern of GDGTs is affected by many environmental factors, such as temperature and pH, but the underlying molecular mechanism remains elusive. Here, we find that the expression regulation of GDGT ring synthase genes grsA and grsB in thermophilic archaeon Sulfolobus acidocaldarius is temperature‐ and pH‐dependent. Moreover, the presence of functional GrsA protein, or more likely its products cyclic GDGTs rather than the accumulation of GrsA protein itself, is required to induce grsB expression, resulting in temporal regulation of grsA and grsB expression. Our findings establish a molecular model of GDGT cyclization regulated by environment factors in a thermophilic ecosystem, which could be also relevant to that in mesophilic marine archaea. Our study will help better understand the biological basis for GDGT‐based paleoclimate proxies. Archaea inhabit a wide range of terrestrial and marine environments. In response to environment fluctuations, archaea modulate their unique membrane GDGTs lipid composition with different strategies, in particular GDGTs cyclization significantly alters membrane permeability. However, the regulation details of archaeal GDGTs cyclization in response to different environmental factor changes remain unknown. We demonstrated, for the first time, thermophilic archaea orchestrate the temporal expression of GDGT ring synthases, leading to delicate control of GDGTs cyclization to respond environmental temperature and acidity stress. Our study provides insight into the regulation of archaea membrane plasticity, and the survival strategy of archaea in fluctuating environments.
Using machine‐learning algorithms to improve imputation in the medical expenditure panel survey
Authors: McClellan Chandler , Mitchell Emily , Anderson Jerrod , Zuvekas Samuel
Published: December 2022

Objective

To assess the feasibility of applying machine learning (ML) methods to imputation in the Medical Expenditure Panel Survey (MEPS).

Data Sources

All data come from the 2016–2017 MEPS.

Study Design

Currently, expenditures for medical encounters in the MEPS are imputed with a predictive mean matching (PMM) algorithm in which a linear regression model is used to predict expenditures for events with (donors) and without (recipients) data. Recipient events and donor events are then matched based on the smallest distance between predicted expenditures, and the donor event's expenditures are used as the recipient event's imputation. We replace linear regression algorithm in the PMM framework with ML methods to predict expenditures. We examine five alternatives to linear regression: Gradient Boosting, Random Forests, Extreme Random Forests, Deep Neural Networks, and a Stacked Ensemble approach. Additionally, we introduce an alternative matching scheme, which matches on a vector of predicted expenditures by sources of payment instead of a single total expenditure prediction to generate potentially superior matches.

Data Collection

Study data is derived from a large federal survey.

Principal Findings

ML algorithms perform better at both prediction and matching imputation than Ordinary Least Squares (OLS), the most common prediction algorithm used in PMM. On average, the Stacked Ensemble approach that combines all the ML algorithms performs best, improving expenditure prediction R2by 108% (0.156 points) and final imputation R2by 227% (0.397 points). Matching on a prediction vector also improves alignment of sources of payments between donor and recipient events.

Conclusions

ML algorithms and an alternative matching scheme improve the overall quality of expenditure PMM imputation in the MEPS. These methods may have additional value in other national surveys that currently rely on PMM or similar methods for imputation.
Exosomal miR‐532‐5p induced by long‐term exercise rescues blood–brain barrier function in 5XFAD mice via downregulation of EPHA4
Authors: Liang Xiaoyan , Fa Wenxin , Wang Nan , Peng Yuanming , Liu Cuicui , Zhu Min , Tian Na , Wang Yongxiang , Han Xiaolei , Qiu Chengxuan , Hou Tingting , Du Yifeng
Published: December 2022

The breakdown of the blood–brain barrier, which develops early in Alzheimer's disease (AD), contributes to cognitive impairment. Exercise not only reduces the risk factors for AD but also confers direct protection against cognitive decline. However, the exact molecular mechanisms remain elusive, particularly whether exercise can liberate the function of the blood–brain barrier. Here, we demonstrate that long‐term exercise promotes the clearance of brain amyloid‐β by improving the function of the blood–brain barrier in 5XFAD mice. Significantly, treating primary brain pericytes or endothelial cells with exosomes isolated from the brain of exercised 5XFAD mice improves cell proliferation and upregulates PDGFRβ, ZO‐1, and claudin‐5. Moreover, exosomes isolated from exercised mice exhibit significant changes in miR‐532‐5p. Administration or transfection of miR‐532‐5p to sedentary mice or primary brain pericytes and endothelial cells reproduces the improvement of blood–brain barrier function. Exosomal miR‐532‐5p targets EPHA4, and accordingly, expression of EphA4 is decreased in exercised mice and miR‐532‐5p overexpressed mice. A specific siRNA targeting EPHA4 recapitulates the effects on blood–brain barrier‐associated cells observed in exercised 5XFAD mice. Overall, our findings suggest that exosomes released by the brain contain a specific miRNA that is altered by exercise and has an impact on blood–brain barrier function in AD.
The N6‐methyladenosine RNA landscape in the aged mouse hippocampus
Authors: Huang He , Song Renhua , Wong Justin J.‐L. , Anggono Victor , Widagdo Jocelyn
Published: December 2022

The aged brain is associated with an inevitable decline in cognitive function and increased vulnerability to neurodegenerative disorders. Multiple molecular hallmarks have been associated with the aging nervous system through transcriptomics and proteomic studies. Recently, epitranscriptomic analysis has highlighted the role of RNA chemical modification in various biological processes. In particular, N6‐methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNAs, has been functionally linked to multiple aspects of RNA metabolism with the roles of m6A in processes such as learning and memory, leading to our current investigation of how the m6A‐transcriptomic landscape is shaped during aging. Using the inbred C57BL/6 line, we compared the m6A‐transcriptomic profiles from the hippocampi of young (3‐month‐old) and aged (20‐month‐old) mice. Methylated RNA immunoprecipitation (MeRIP)‐sequencing analysis revealed hyper‐ and hypomethylation in 426 and 102 genes, respectively, in the aged hippocampus (fold change >1.5, false discovery rate <0.05). By correlating the methylation changes to their steady‐state transcript levels in the RNA‐Seq data, we found a significant concordance between m6A and transcript levels in both directions. Notably, the myelin regulator gene Gpr17 was downregulated in the aged hippocampus concomitant with reduced m6A levels in its 3'UTR. Using reporter constructs and mutagenesis analysis, we demonstrated that the putative m6A sites in the 3'UTR of Gpr17 are important for mRNA translation but not for regulating transcript stability. Overall, the positive correlation between m6A and the transcript expression levels indicates a co‐transcriptional regulation of m6A with gene expression changes that occur in the aged mouse hippocampus.
Timing the factor zoo via deep learning: Evidence from China
Authors: Ma Tian , Liao Cunfei , Jiang Fuwei
Published: December 2022

This paper proposes a factor timing strategy with information from 146 characteristic‐based factors and a deep learning approach to capture the nonlinear predictability. The deep learning‐based factor timing strategy generates the highest economic value compared with the unconditional and alternative linear machine learning‐based portfolios and remains robust after controlling for traditional factor models and transaction costs. With the unique market structure of the Chinese stock market, we find that mispricing‐based theory helps explain the factor timing via deep learning.
Landscape features affect caiman body condition in the middle Araguaia River floodplain
Authors: Pereira A. C. , Colli G. R.
Published: December 2022

Landscape modifications often undermine habitat suitability for species’ persistence, with initial effects observed through the physiological responses of individuals and populations. However, some landscape features can allow tolerant wildlife species to persist in human‐modified landscapes, but they are still overlooked. Across distinct agricultural landscapes, we assessed landscape features affecting the body condition (estimate through scaled mass index ‐ SMI) of Caiman crocodilus (Crocodylia, Alligatoridae) in human‐modified landscapes of the Araguaia floodplain, central Brazil. We used a spatial Bayesian model averaging approach to determine the effects of landscape attributes, ectoparasites, tail damage and severe body injuries on caiman body condition. We found that caimans had higher SMI in anthropogenic (ditches and artificial ponds) than natural habitats (lakes or rivers). Overall, caiman SMI was negatively associated with wetland cohesion (an aggregation and connectivity metric). Otherwise, landscape composition did not influence caiman SMI. Further, ectoparasites and body injuries did not affect SMI, whereas tail damage negatively affected SMI. Our findings underscore that caiman populations can adapt to artificial wetlands and irrigated rice fields, provided they incorporate natural and semi‐natural habitat patches that enhance environmental heterogeneity, prey availability, and waterbody availability and connectivity.
Social genetic effects for drug use disorder among spouses
Authors: Salvatore Jessica E. , Larsson Lönn Sara , Sundquist Jan , Kendler Kenneth S. , Sundquist Kristina
Published: December 2022

Aims

Preclinical and human studies suggest that a social partner's genotype may be associated with addiction‐related outcomes. This study measured whether spousal genetic makeup is associated with risk of developing drug use disorder (DUD) during marriage and whether the risk associated with a spouse's genotype could be disentangled from potentially confounding rearing environmental effects.

Design

Univariable and multivariable logistic regression analyses.

Setting

Sweden.

Participants

Men and women born between 1960 and 1990 and in opposite‐sex first marriages before age 35 (n = 294 748 couples).

Measurements

Outcome was DUD diagnosis (inclusive of opioids, sedatives/hypnotics/anxiolytics, cocaine, cannabis, amphetamine and other psychostimulants, hallucinogens, other drugs of abuse and combinations thereof) obtained from legal, medical and pharmacy registries. The focal predictor was family genetic risk scores for DUD (FGRS‐DUD), which were inferred from diagnoses in first‐ through fifth‐degree relatives and weighted by degree of genetic sharing. FGRS‐DUD were calculated separately for each partner in a couple.

Findings

Marriage to a spouse with a high FGRS‐DUD was associated with increased risk of developing DUD during marriage, ORmales = 1.68 (95% CI = 1.50, 1.88) and ORfemales = 1.35 (1.16, 1.56), above and beyond the risk associated with one's own FGRS‐DUD. The risk associated with a spouse's FGRS‐DUD remained statistically significant after covarying for parental education. As indicated by a series of null interaction effects, there was no evidence that the risk associated with a spouse's FGRS‐DUD differed depending on whether the spouse was DUD‐affected, probands' probable contact with in‐laws and whether the spouse was raised by his/her biological parents or in another home.

Conclusions

There is relatively robust evidence that a person's risk for developing drug use disorder is associated with the genetic makeup of the person's spouse.
Satisfied versus dissatisfied: Experiences of retirement village living
Authors: Ferguson Graham , 't Hart Brian , Shabnam Saadia
Published: December 2022

Objective

This study aims to understand and distinguish between satisfied and dissatisfied older people, through a comparison of their lived experience within a retirement village.

Methods

An exploratory qualitative research design was utilized to identify and describe consumer experiences of lifestyle living and how that experience translates to positive or negative satisfaction. The net promoter score (NPS) was employed to identify highly satisfied (Promoters) and highly dissatisfied (Detractors) people.

Results

Sixty‐two interviews in retirement lifestyle villages were analysed, including satisfied (n = 33) and dissatisfied (n = 29) consumers of the service. Results reveal that satisfied people: (1) feel grateful for a service that exceeds their purchase expectations; (2) feel connected to others inside or (3) outside the lifestyle village; (4) feel ‘heard’ by the service provider; and (5) feel that they have retained their independence. Dissatisfied people describe: (1) broken promises, specifically those made at the time of purchase; (2) not feeling ‘connected’ to others inside the village; (3) feeling unheard or ignored by the service provider; and (4) the service not meeting their needs.

Conclusions

Revealing these detailed insights clarified the nuanced, hazy and often ambiguous differences between dissatisfied and satisfied people. It also provided insights into the high priority needs, expectations and choices of people as they transition into and through older age. The research should help industry, government and society in general to provide products and services that fit into this lived experience and better meet the changing needs of older people.
Is the increasing prevalence of labor induction accompanied by changes in pregnancy outcomes? An observational study of all singleton births at gestational weeks 37–42 in Norway during 1999–2019
Authors: Haavaldsen Camilla , Morken Nils‐Halvdan , Saugstad Ola Didrik , Eskild Anne
Published: December 2022

Introduction

Induction of labor is often performed to prevent adverse perinatal and maternal outcomes, and has become increasingly common. We studied whether changes in prevalence of labor induction in gestational weeks 37–42 weeks were accompanied by changes in adverse pregnancy outcomes or mode of delivery.

Material and methods

We used data from the Medical Birth Registry of Norway, and included all singleton births in gestational weeks 37–42 in Norway, 1999–2019 (n = 1 127 945). We calculated the prevalence of labor induction and outcome measures according to year of birth. We repeated these calculations for each gestational week at birth.

Results

The prevalence of labor induction increased from 9.7% to 25.9%, and the increase was particularly high in gestational week 41. A modest decline in fetal deaths was observed in all gestational weeks, except gestational week 41. The overall decline was from 0.18% in 1999–2004 to 0.13% during 2015–2019. There were no overall changes in other perinatal outcomes. The prevalence of postpartum hemorrhage ≥500 ml increased from 11.4% in 1999 to 30.1% in 2019, and operative deliveries increased slightly. The prevalence of acute cesarean section increased from 6.5% to 9.3%, whereas vacuum and/or forceps assisted deliveries increased from 7.8% to 10.4%.

Conclusions

A high increase in labor inductions was accompanied by a modest decline in fetal deaths, but no decline in other adverse perinatal outcomes. In settings where the prevalence of adverse perinatal outcomes is low, the beneficial effect of increased use of labor induction may not outweigh the side effects or the costs.
Multisystem inflammatory syndrome in children associated with COVID‐19 presenting as cervical inflammation
Authors: Brooks Rebecca , Fisher Ron , Glicksman Charlotte , Pollak Uri , Simanovsky Natalia , Berkun Yackov
Published: December 2022

Aim

The major clinical manifestations multisystem inflammatory syndrome in children (MIS‐C) are fever, gastrointestinal and cardiac. The aim of this study was to describe MIS‐C in a series of patients who presented primarily with cervical manifestations.

Methods

We retrospectively reviewed medical records of all patients who met the Centers for Disease Control and Prevention and World Health Organization MIS‐C diagnostic criteria treated at Hadassah‐Hebrew University Medical Center between April 2020 and September 2021.

Results

Of 37 children diagnosed with MIS‐C (median age: 10.2 years, range 1.5–18 years, 20 male) five, 13.5% (median age: 14.4 years, range 9.2–17.5 years) presented with cervical symptoms mimicking neck infections. One was hospitalised with a working diagnosis of retropharyngeal abscess, and four with acute cervical lymphadenitis that did not respond to early antibiotic treatment. All developed full MIS‐C phenotype.

Conclusion

MIS‐C may present as cervical inflammation. An ill‐appearing child with symptoms and/or signs of cervical inflammation should be evaluated for clinical and laboratory features of MIS‐C, thereby facilitating prompt treatment of this potentially fatal disorder.
Meta‐analysis: The efficacy of therapeutic drug monitoring of anti‐TNF‐therapy in inflammatory bowel disease
Authors: Sethi Sonika , Dias Shiluka , Kumar Aditi , Blackwell Jonathan , Brookes Matthew J. , Segal Jonathan P.
Published: December 2022

Background and Aims

This systematic review and meta‐analysis aimed to determine whether the use of therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients on anti‐tumour necrosis factor (anti‐TNF) therapy results in improved rates of clinical and endoscopic remission, surgery, corticosteroid‐free remission and hospitalisation.

Methods

MEDLINE, EMBASE, EMBASE classic, PubMed, Cochrane central databases register of controlled trials and Cochrane Specialised Trials Register were searched between 01 Janurary 1946 and 08 April 2022. Randomised controlled trials (RCTs) and prospective and retrospective observational studies were included, comparing TDM to standard of care (SOC) or reactive vs proactive TDM. Results were reported as pooled relative risks (RR) with 95% confidence intervals (95% CI).

Results

Twenty‐six studies, including 9 RCTs, were included. Compared to SOC, proactive TDM was associated with a significantly decreased risk of treatment failure (RR 0.64, 95% CI 0.48–0.85 p<0.01), and a non‐significant decrease in need for surgery (RR 0.51, 95% CI 0.25–1.02) and hospitalisation (RR 0.64, 95% CI 0.40–1.00). Furthermore compared to SOC, Proactive TDM was associated with higher rates of endoscopic remission (RR 1.19, 95% CI 0.93–1.53) and clinical remission (RR 1.07, 95% CI 0.97–1.18). Compared to reactive TDM, proactive TDM was associated with significant decreased risk of treatment failure (RR 0.46, 95% CI 0.21 = 0.98, p = 0.04) and significant reduction in hospitalisation (RR 0.33, 95% CI 0.21–0.54, p < 0.01).

Conclusions

Compared to SOC, proactive TDM was associated with significant benefit in reducing treatment failure. Compared to reactive TDM, proactive TDM led to a significant reduction in hospitalisation and treatment failure. More studies with larger RCTs and standardised assays are needed to substantiate these results and validate the cost‐effectiveness of TDM.
Population pharmacokinetics of nadroparin for thromboprophylaxis in COVID‐19 intensive care unit patients
Authors: Romano Lorenzo G. R. , Hunfeld Nicole G. M. , Kruip Marieke J. H. A. , Endeman Henrik , Preijers Tim
Published: December 2022

Aims

Nadroparin is administered to COVID‐19 intensive care unit (ICU) patients as thromboprophylaxis. Despite existing population pharmacokinetic (PK) models for nadroparin in literature, the population PK of nadroparin in COVID‐19 ICU patients is unknown. Moreover, optimal dosing regimens achieving anti‐Xa target levels (0.3–0.7 IU/mL) are unknown. Therefore, a population PK analysis was conducted to investigate different dosing regimens of nadroparin in COVID‐19 ICU patients.

Methods

Anti‐Xa levels (n = 280) from COVID‐19 ICU patients (n = 65) receiving twice daily (BID) 5700 IU of subcutaneous nadroparin were collected to perform a population PK analysis with NONMEM v7.4.1. Using Monte Carlo simulations (n = 1000), predefined dosing regimens were evaluated.

Results

A 1‐compartment model with an absorption compartment adequately described the measured anti‐Xa levels with interindividual variability estimated for clearance (CL). Inflammation parameters C‐reactive protein, D‐dimer and estimated glomerular filtration rate based on the Chronic Kidney Disease Epidemiology Collaboration equation allowed to explain the interindividual variability of CL. Moreover, CL was decreased in patients receiving corticosteroids (22.5%) and vasopressors (25.1%). Monte Carlo simulations demonstrated that 5700 IU BID was the most optimal dosing regimen of the simulated regimens for achieving prespecified steady‐state t = 4 h anti‐Xa levels with 56.7% on target (0.3–0.7 IU/mL).

Conclusion

In our study, clearance of nadroparin is associated with an increase in inflammation parameters, use of corticosteroids, vasopression and renal clearance in critically ill patients. Furthermore, of the simulated regimens, targeted anti‐Xa levels were most adequately achieved with a dosing regimen of 5700 IU BID. Future studies are needed to elucidate the underlying mechanisms of found covariate relationships.
Diagnostic evaluation of upper tract urothelial carcinoma: can we safely omit diagnostic ureteroscopy?
Authors: Trail Matthew , Rahman Muhammad Sajid Waheed , Broadhurst William J. , Blackmur James P. , Sharma Abhishek , Chew Etienne , O'Donnell Marie , Keanie Julian Y. , Brush John , Taylor John , Phipps Simon , Thomas Ben , Mains Edward A.A. , McNeill S. Alan , Leung Steve , Cutress Mark L. , Laird Alexander
Published: December 2022

Objective

To identify clinicopathological or radiological factors that may predict a diagnosis of upper urinary tract urothelial cell carcinoma (UTUC) to inform which patients can proceed directly to radical nephroureterectomy (RNU) without the delay for diagnostic ureteroscopy (URS).

Patients and Methods

All consecutive patients investigated for suspected UTUC in a high‐volume UK centre between 2011 and 2017 were identified through retrospective analysis of surgical logbooks and a prospectively maintained pathology database. Details on clinical presentation, radiological findings, and URS/RNU histopathology results were evaluated. Multivariate regression analysis was performed to evaluate predictors of a final diagnosis of UTUC.

Results

In all, 260 patients were investigated, of whom 230 (89.2%) underwent URS. RNU was performed in 131 patients (50.4%), of whom 25 (9.6%) proceeded directly without URS – all of whom had a final histopathological diagnosis of UTUC – and 15 (11.5%) underwent RNU after URS despite no conclusive histopathological confirmation of UTUC. Major surgery was avoided in 77 patients (33.5%) where a benign or alternative diagnosis was made on URS, and 14 patients (6.1%) underwent nephron‐sparing surgery. Overall, 178 patients (68.5%) had a final diagnosis of UTUC confirmed on URS/RNU histopathology. On multivariate logistic regression analysis, a presenting complaint of visible haematuria (hazard ratio [HR] 5.17, confidence interval [CI] 1.91–14.0; P = 0.001), a solid lesion reported on imaging (HR 37.8, CI = 11.7–122.1; P < 0.001) and a history of smoking (HR 3.07, CI 1.35–6.97; P = 0.007), were predictive of a final diagnosis of UTUC. From this cohort, 51 (96.2%) of 53 smokers who presented with visible haematuria and who had a solid lesion on computed tomography urogram had UTUC on final histopathology.

Conclusion

We identified specific factors which may assist clinicians in selecting which patients may reliably proceed to RNU without the delay of diagnostic URS. These findings may inform a prospective multicentre analysis including additional variables such as urinary cytology.
Salvage irreversible electroporation for radio‐recurrent prostate cancer – the prospective FIRE trial
Authors: Blazevski Alexandar , Geboers Bart , Scheltema Matthijs J. , Gondoputro William , Doan Paul , Katelaris Athos , Agrawal Shikha , Baretto Daniela , Matthews Jayne , Haynes Anne‐Maree , Delprado Warick , Shnier Ron , van den Bos Willemien , Thompson James E. , Lawrentschuk Nathan , Stricker Phillip D.
Published: December 2022

Objectives

To prospectively assess the safety, functional‐ and oncological‐outcomes of irreversible electroporation (IRE) as salvage therapy for radio‐recurrent focal prostate cancer in a multicenter setting.

Patients and methods

Men with focal recurrent PCa after external beam radiation or brachytherapy without metastatic disease on staging imaging and co‐registration between mpMRI and biopsies were prospectively included in this multicenter trial. Adverse events were reported following the Clavien‐Dindo classification. Validated questionnaires were used for patient‐reported functional outcomes. Follow‐up consisted of 3 monthly prostate specific antigen (PSA) levels, a 6‐month mpMRI and standardised transperineal template mapping biopsies at 12‐months. Thereafter follow‐up was guided by MRI and/or PSMA‐PET/CT and PSA. Local recurrence was defined as any ISUP score ≥2 on biopsies.

Results

37 patients were analysed with a median (interquartile range (IQR)) follow up of 29 (22–43) months. Median age was 71 (53–83), median PSA was 3.5 ng/mL (2.7–6.1). 28 (75.5%) patients harboured intermediate risk and 9 patients (24.5%) high risk PCa. Seven patients (19%) reported self‐limiting urgency, frequency, or hematuria (grade 1–2). Seven patients (19%) developed a grade 3 AE; urethral sludge requiring transurethral resection. At 12 months post treatment 93% of patients remained continent and erectile function sufficient for intercourse deteriorated from 35% to 15% (4/27). Local control was achieved in 29 patients (78%) and 27 patients (73%) were clear of local and systemic disease. Four (11%) patients had local recurrence only. Six (16%) patients developed metastatic disease with a median time to metastasis of 8 months.

Conclusion

The FIRE trial shows that salvage IRE after failed radiation therapy for localised PCa is safe with minimal toxicity, and promising functional and oncological outcomes. Salvage IRE can offer a possible solution for notoriously difficult to manage radio recurrent prostate tumours.
Non‐neuronal TRPA1 encodes mechanical allodynia associated with neurogenic inflammation and partial nerve injury in rats
Authors: De Logu Francesco , De Siena Gaetano , Landini Lorenzo , Marini Matilde , Souza Monteiro de Araujo Daniel , Albanese Valentina , Preti Delia , Romitelli Antonia , Chieca Martina , Titiz Mustafa , Iannone Luigi F. , Geppetti Pierangelo , Nassini Romina
Published: December 2022

Background and Purpose

The pro‐algesic transient receptor potential ankyrin 1 (TRPA1) channel, expressed by a subpopulation of primary sensory neurons, has been implicated in various pain models in mice. However, evidence in rats indicates that TRPA1 conveys nociceptive signals elicited by channel activators, but not those associated with tissue inflammation or nerve injury. Here, in rats, we explored the TRPA1 role in mechanical allodynia associated with stimulation of peptidergic primary sensory neurons (neurogenic inflammation) and moderate (partial sciatic nerve ligation, pSNL) or severe (chronic constriction injury, CCI) sciatic nerve injury.

Experimental Approach

Acute nociception and mechanical hypersensitivity associated with neurogenic inflammation and sciatic nerve injury (pSNL and CCI) were investigated in rats with TRPA1 pharmacological antagonism or genetic silencing. TRPA1 presence and function were analysed in cultured rat Schwann cells.

Key Results

Hind paw mechanical allodynia (HPMA), but not acute nociception, evoked by local injection of capsaicin or allyl isothiocyanate, the TRP vanilloid 1 (TRPV1) or the TRPA1 activators was mediated by CGRP released from peripheral sensory nerve terminals. CGRP‐evoked HPMA was sustained by a ROS‐dependent TRPA1 activation, probably in Schwann cells. HPMA evoked by pSNL, but not that evoked by CCI, was mediated by ROS and TRPA1 without the involvement of CGRP.

Conclusions and Implications

As found in mice, TRPA1 mediates mechanical allodynia associated with neurogenic inflammation and moderate nerve injury in rats. The channel contribution to mechanical hypersensitivity is a common feature in rodents and might be explored in humans.
Curaxin CBL0137 inhibits endothelial inflammation and atherogenesis via suppression of the Src‐YAP signalling axis
Authors: Ding Huanyu , Jiang Minchun , Lau Chi Wai , Luo Jianfang , Chan Andrew M. , Wang Li , Huang Yu
Published: December 2022

Background and Purpose

Atherosclerotic vascular disease is the leading cause of mortality and morbidity worldwide. Our previous study uncovered that endothelium‐specific knockdown of YAP suppresses atherogenesis, suggesting that YAP is a promising therapeutic target against atherosclerotic vascular disease. We established a drug screening platform, which aimed to identify new YAP inhibitors for anti‐atherosclerotic treatment.

Experimental Approach

Drug screening was performed by a luciferase reporter gene assay. RNA sequencing was performed to acquire the transcriptomic profile of CBL0137‐treated endothelial cells. We assessed and validated the inhibitory effect of CBL0137 on YAP activity and inflammatory response in HUVECs and HAECs. We evaluated the vasoprotective effect of CBL0137 in vivo against plaque formation in ApoE−/− mice, using both disturbed flow‐induced and chronic western diet‐induced atherosclerotic models.

Key Results

We identified CBL0137 as a novel YAP inhibitor from an FDA drug library. CBL0137 inhibited YAP activity by restraining its phosphorylation at Y357. CBL0137 inhibited YAP activity to repress endothelial inflammation. Mechanistically, CBL0137 suppressed YAP phosphorylation at Y357 via the tyrosine‐protein kinase Src. Furthermore, administration of CBL0137 ameliorated endothelial inflammation and the atherogenesis induced by disturbed flow and consumption of an atherogenic diet in ApoE−/− mice.

Conclusion and Implications

To our knowledge, this is the first study to identify CBL0137 as a novel YAP inhibitor. We have demonstrated that pharmacologically targeting YAP by CBL0137 inhibits atherogenesis. The present results suggest that CBL0137 holds promise as a new drug for the treatment of atherosclerotic vascular disease.
Review: Patient engagement in child, adolescent, and youth mental health care research – a scoping review
Authors: Ali Amber Z. , Wright Bruce , Curran Janet A. , Newton Amanda S.
Published: December 2022

Background

Youth and children's lived experiences are rarely considered in studies seeking to improve or evaluate their mental health care. We conducted a scoping review to identify approaches to child, adolescent, and youth engagement in mental health studies as well as study‐reported barriers, constraints, and facilitators to engagement.

Method

We systematically searched six electronic databases for literature. We included studies of mental health care service design, development, or evaluation that involved engagement of children, adolescents, and/or youth with mental disorders or who intentionally self‐harm. Studies could be of any design as long as patient engagement was used at any point during its design and/or conduct. Engagement could include co‐designing health services/interventions and/or participating as a co‐researcher. We assessed the reporting of patient engagement using the Guidance for Reporting Involvement of Patients and the Public 2 Long‐Form (GRIPP2‐LF) checklist and used the Experience Based Co‐design (EBCD) framework to guide data extraction and analysis.

Results

Sixteen articles were included in the review. Most studies used engagement to develop or adapt a mental health service (75%) and utilized a participatory or co‐design approach (69%). Participants were namely adolescents and youth (aged 10–24 years) with some studies including young adults (up to 29 years old). Most studies followed less than 50% of the EBCD framework, and the commonly reported study barriers were related to aspects addressed in EBCD: time restrictions, recruitment, and generalizability. Frequently reported study facilitators included study methodology, youth engagement, and having a diverse participant sample.

Conclusions

Findings from this review suggest that the EBCD framework is not commonly used to guide patient engagement in studies of mental health care services. Future initiatives should consider following the framework to ensure meaningful evaluation and improvements to youth and children's mental health care services.