bluuebunny/crossref_metadata_2025 huggingface dataset:
A multi-scenario risk assessment strategy applied to mixtures of chemicals of emerging concern in the River Aconcagua basin in Central Chile
Authors: Inostroza Pedro A. , Elgueta Sebastian , Krauss Martin , Brack Werner , Backhaus Thomas
Published: August 2023

Streams and rivers are characterised by the presence of various chemicals of emerging concern (CECs), including pesticides, pharmaceuticals, personal care products, and industrial chemicals. While these chemicals are found usually only in low (ng/L) concentrations, they might still harm aquatic life and disrupt the ecological balance of aquatic ecosystems due to their high ecotoxicological potency. Environmental risk assessments that account for the complexity of exposures are needed in order to evaluate the toxic pressure of these chemicals, which also provide suggestions for risk mitigation and management, if necessary. Currently, most studies on the co-occurrence and environmental impacts of CECs are conducted in countries of the Global North, leaving massive knowledge gaps in countries of the Global South.

In this study, we implement a multi-scenario risk assessment strategy to improve the assessment of both the exposure and hazard components in the chemical risk assessment process. Our strategy incorporates a systematic consideration and weighting of CECs that were not detected, as well as an evaluation of the uncertainties associated with Quantitative Structure-Activity Relationships (QSARs) predictions for chronic ecotoxicity. Furthermore, we present a novel approach to identifying mixture risk drivers. To expand our knowledge beyond well-studied aquatic ecosystems, we applied this multi-scenario strategy to the River Aconcagua basin of Central Chile. The analysis revealed that the concentrations of CECs exceeded acceptable risk thresholds for selected organism groups and the most vulnerable taxonomic groups. Streams flowing through agricultural areas and sites near the river mouth exhibited the highest risks. Notably, the eight risk drivers among the 153 co-occurring chemicals accounted for 66-92% of the observed risks in the river basin. Six of them are pesticides and pharmaceuticals, chemical classes known for their high biological activity in specific target organisms.

Graphical abstract

Highlights

153 chemicals of emerging concern detected in complex multi-component mixtures.

108 possible mixture risk assessment scenarios were investigated.

Non-detects, QSARs, and experimental ecotoxicological data were integrated for risk assessment.

8 chemicals of emerging concern were responsible for driving chronic environmental risks.
Machine learning identifies phenotypic profile alterations of human dopaminergic neurons exposed to bisphenols and perfluoroalkyls
Authors: Di Credico Andrea , Weiss Amélie , Corsini Massimo , Gaggi Giulia , Ghinassi Barbara , Wilbertz Johannes H. , Di Baldassarre Angela
Published: August 2023

Parkinson’s disease (PD) is the second most common neurodegenerative disease and is characterized by the loss of midbrain dopaminergic neurons. Endocrine disruptors (EDs) are active substances that interfere with hormonal signaling. Among EDs, bisphenols (BPs) and perfluoroalkyls (PFs) are chemicals leached from plastics and other household products, and humans are unavoidably exposed to these xenobiotics. Data from animal studies suggest that ED exposure may play a role in PD, but data about the effect of BPs and PFs on human models of the nervous system are lacking. Previous studies demonstrated that machine learning (ML) applied to microscopy data can classify different cell phenotypes based on image features. In this study, the effect of BPs and PFs at different concentrations within the real-life exposure range (0.01, 0.1, 1, and 2 μM) on the phenotypic profile of human stem cell-derived midbrain dopaminergic neurons (mDANs) was analyzed. Cells exposed for 72 hours to the xenobiotics were stained with neuronal markers and evaluated using high content microscopy yielding 126 different phenotypic features. Two different ML models (XGBoost and LightGBM) were trained to classify ED-treated versus control mDANs. ED-treated mDANs were identified with high accuracy (0.92). Assessment of the phenotypic feature contribution to the classification showed that EDs induced a significant increase of alpha-synuclein (αSyn) and tyrosine hydroxylase (TH) staining intensity within the neurons. Moreover, microtubule-associated protein 2 (MAP2) neurite length and branching were significantly diminished in treated neurons. Our study shows that human mDANs are adversely impacted by exposure to EDs, causing their phenotype to shift and exhibit more characteristics of PD. Importantly, ML-supported high-content imaging can identify concrete but subtle subcellular phenotypic changes that can be easily overlooked by visual inspection alone and that define EDs effects in mDANs, thus enabling further pathological characterization in the future.
Information propagation through enzyme-free catalytic templating of DNA dimerization with weak product inhibition
Authors: Cabello Garcia Javier , Mukherjee Rakesh , Bae Wooli , Stan Guy-Bart V. , Ouldridge Thomas E.
Published: August 2023

Information propagation by sequence-specific, template-catalyzed molecular assembly is the source of the biochemical complexity of living systems. Templating allows the production of thousands of sequence-defined proteins from only 20 distinct building blocks. By contrast, exploitation of this powerful chemical motif is rare in non-biological contexts, particularly in enzyme-free environments, where even the template-catalyzed formation of dimers is a significant challenge. The main obstacle is product inhibition: the tendency of products to bind to their templates more strongly than individual monomers, preventing the effective catalytic templating of longer polymers. Here we present a rationally designed enzyme-free system in which a DNA template catalyzes, with weak competitive product inhibition, the production of sequence-specific DNA dimers. We demonstrate the selective templating of 9 different dimers with high specificity and catalytic turnover. Most importantly, our mechanism demonstrates a rational design principle for engineering information propagation by molecular templating of longer polymers.
Effects of biological and environmental factors on filovirus serology in bats in Guinea
Authors: Champagne Maëliss , Cappelle Julien , Caron Alexandre , Pouliquen Thibault , Samoura Aboubacar , Doumbouya Mohamed Idriss , Thaurignac Guillaume , Ayouba Ahidjo , Keita Alpha Kabinet , Peeters Martine , Bourgarel Mathieu , De Nys Hélène M.
Published: August 2023

We investigated factors which might influence the circulation of ebolaviruses in fruit bats in Guinea in order to better understand their role in the ecology of ebolaviruses and evaluate risks of spill-over to other animals or humans. We performed serological tests on populations of 4 bat species (Eidolon helvum,Hypsignathus monstrosus,Lissonycteris angolensisandRousettus aegyptiacus) sampled longitudinally for 18 months (2018-2020). The analysis of 1,427 bat samples for antibodies directed against different ebolavirus species allowed to test the influence of biological and environmental variables on seropositivity. Results showed that species (Eidolon helvum and Rousettus aegyptiacus), sex (males), age (sexually immature adults, and thus reproductive life-cycle), as well as season (dry) have a significant positive effect on the presence of antibodies against ebolaviruses in bats. These factors may play an important role in the circulation of filoviruses. Search for viral evidence and surveillance strategies should take these into consideration.
Voxel-wise regression without intensity normalization provides better sensitivity when identifying injury regions after stroke in FDG-PET images
Authors: He Wuxian , Tang Hongtu , Li Jia , Shen Xiaoyan , Zhang Xuechen , Li Chenrui , Liu Huafeng , Yu Weichuan
Published: August 2023

Background

In the analysis of brain fluorodeoxyglucose positron emission tomography (FDG-PET), intensity normalization is a necessary step to reduce inter-subject variability. However, the choice of an appropriate normalization method in stroke studies remains unclear, leading to inconsistent findings in the literature.

Materials and methods

Here, we propose a regression-based and single-subject-based model for analyzing FDG-PET images without intensity normalization. Two independent data sets were collected before and after middle cerebral artery occlusion (MCAO), with one comprising 120 rats and the other comprising 96 rats. After data preprocessing, voxel intensities in the same region and hemisphere were paired before and after the MCAO scan. A linear regression model was applied to the paired data, and the coefficient of determination was calculated to measure the linearity. The results between the ipsilateral and contralateral hemispheres were compared, and significant regions were defined as those having reduced linearity. Our method was compared with existing intensity normalization methods and validated using the triphenyl tetrazolium chloride (TTC) staining data.

Results

The proposed method detected more injury areas compared to existing approaches, as confirmed by the ground truth provided by TTC. The area under the curve (AUC) of the average receiver operating characteristic (ROC) curves using our method reached 0.84, whereas the AUCs using existing methods ranged from 0.77 ∼ 0.79. The average false positive rate (FPR) and true positive rate (TPR) of the individual analysis results using our method (FPR = 0.06, TPR = 0.56) were better than the group-wise analysis results usingt-tests (FPR = 0.10, TPR = 0.51). The identified injury regions were consistent in the two independent data sets. Some of them were confirmed by other publications.

Conclusions

The proposed method offers a new quantitative approach to analyzing FDG-PET images. The calculation does not involve intensity normalization and can be applied to a single subject. The method yields more sensitive results than existing intensity normalization methods.
The pharynx of the iconic stem-group chondrichthyanAcanthodes(Agassiz, 1833) revisited with micro computed tomography
Authors: Dearden Richard P. , Herrel Anthony , Pradel Alan
Published: August 2023

Acanthodeshas long been the primary source of information on the pharyngeal skeleton of ‘acanthodians’, a stem-group chondrichthyan grade. Because of this its anatomy has played an outsized role in attempts to understand the evolution of the jawed vertebrate pharynx and the clade as a whole. However, the anatomy of the pharynx ofAcanthodesremains poorly understood and subject to several competing interpretations. We use computed tomography (CT) to image the articulated pharyngeal skeletons of three specimens ofAcanthodes confususfrom Lebach, Germany.Acanthodeshad amélangeof osteichthyan-like and chondrichthyan-like morphologies in its pharyngeal skeleton. Like other stem-chondrichthyans,Acanthodeshad a basihyal with no hypohyals, and four pairs of posteriorly oriented pharyngobranchials. Like osteichthyans,Acanthodespossessed an interhyal, but lacked the separate infra- and supra-pharyngobranchial elements present in osteichthyans and the crown-chondrichthyanOzarcus. Using this new data we build and animated a digital 3D model of the pharyngeal endoskeleton inAcanthodes, showing that the jaws would have swung outwards during the opening cycle, increasing the anteriorly facing area of the gape for suspension feeding. These new data provide a more definitive picture of the anatomy of a taxon that has long been of great significance in early vertebrate palaeontology.
Age-dependent extinction and the neutral theory of biodiversity
Authors: Saulsbury James G. , Parins-Fukuchi C. Tomomi , Wilson Connor J. , Reitan Trond , Liow Lee Hsiang
Published: August 2023

Red Queen (RQ) theory states that adaptation does not protect species from extinction because their competitors are continually adapting alongside them. RQ was founded on the apparent independence of extinction risk and fossil taxon age, but analytical developments have since demonstrated that age-dependent extinction is widespread, usually most intense among young species. Here we develop ecological neutral theory as a general framework for modeling fossil species survivorship under incomplete sampling. We show that it provides excellent fit to a high-resolution dataset of species durations for Paleozoic zooplankton, and more broadly can account for age-dependent extinction seen throughout the fossil record. Unlike widely used alternative models, the neutral model has parameters with biological meaning, thereby generating testable hypotheses on changes in ancient ecosystems. The success of this approach suggests novel interpretations of mass extinctions and of scaling in eco-evolutionary systems. Intense extinction among young species does not necessarily refute RQ or require a special explanation, but can instead be parsimoniously explained by neutral dynamics operating across species regardless of age.

Significance Statement

Red Queen theory predicts that competition among species should cause extinction risk to be independent of species age, but recent analyses have refuted this central prediction. To fill the resulting theoretical vacuum, we used ecological neutral theory to build a model of the lifespans of incompletely sampled species evolving under zero-sum competition. This model predicts survivorship among fossil zooplankton with surprising accuracy and accounts for empirical deviations from the predictions of Red Queen more generally. A neutral model of background extinction allows for interpreting survivorship curves in terms of biological process, suggests a novel understanding of mass extinctions, and supports a role for competition in extinction.
Defining unique structural features in the MAFA and MAFB transcription factors that controlInsulingene activity
Authors: Cha Jeeyeon , Tong Xin , Coate Katie C. , Guo Min , Liu Jin-hua , Reynolds Garrett , Walker Emily M. , Stein Richard A. , Mchaourab Hassane , Stein Roland
Published: August 2023

MAFA and MAFB are related basic-leucine-zipper domain containing transcription factors which have important overlapping and distinct regulatory roles in a variety of cellular contexts, including hormone production in pancreatic islet α and β cells. Here we first examined how mutating conserved MAF protein-DNA contacts obtained from X-ray crystal structure analysis impacted their DNA-binding andInsulinenhancer-driven activity. While most of these interactions were essential and their disruption severely compromised activity, we identified that regions outside of the contact areas also contributed to activity. AlphaFold 2, an artificial intelligence-based structural prediction program, was next used to determine if there were also differences in the three-dimensional organization of the non-DNA binding/dimerization sequences of MAFA and MAFB. This analysis was conducted on the wildtype (WT) proteins as well as the pathogenic MAFASer64Pheand MAFBSer70Alatrans-activation domain mutants, with differences revealed between MAFAWTand MAFBWTas well as between MAFASer64Pheand MAFAWT, but not between MAFBSer70Alaand MAFBWT. Moreover, dissimilarities between these proteins were also observed in their ability to cooperatively stimulateInsulinenhancer-driven activity in the presence of other islet-enriched transcription factors. Analysis of MAFA and MAFB chimeras disclosed that these properties were greatly influenced by unique C-terminal region structural differences predicted by AlphaFold 2. Importantly, these results have revealed features of these closely related proteins that are functionally significant in islet biology.
PKCδ splicing variant (PKCδIII) induces neurite outgrowth in PC12 cells in the absence of NGF
Authors: Yamasaki Hiroyuki , Nakai Tomoko , Kitatani Kanae , Kato Chikara , Takekoshi Susumu
Published: August 2023

Protein kinase C (PKC)δ is a serine/threonine kinase involved in many cellular processes in response to diverse stimuli, including cell proliferation, differentiation, apoptosis, tumor inhibition, and cell migration. PKCδ consists of the N terminal regulatory domain and the C terminal catalytic domain, which are linked with a hinge region. An alternative splicing variant of rat PKCδ (also known as PKCδIII) has been reported, and this PKCδ splicing variant (SV) has only the regulatory domain without the catalytic domain. However, its function remains unclear. In this study, we found that PKCδ SV induced neurite outgrowth in the absence of nerve growth factor (NGF) in PC12 cells. Immunoblot analysis revealed that ERK was phosphorylated by NGF treatment, but not by PKCδ SV induction, indicating that PKCδ SV-mediated neurite outgrowth was different from NGF-mediated one. In addition, we showed that PKCδ full length and SV increased their mRNA expression after NGF treatment and that PKCδ SV was more susceptible to its proteasomal degradation. Our findings provided insights into the role of PKCδSV in neurite outgrowth.
Transient overdominance, coadaptation, and the fixability of heterosis
Authors: Schneemann Hilde , Welch John J.
Published: August 2023

Many species pairs form F1 hybrids that are fitter than their parents. Such heterosis can arise if the parents carry recessive deleterious mutations; and in this case, the heterosis should be fixable, because selecting out the deleterious mutations yields a high-fitness homozygous hybrid. However, heterosis might not be fixable if caused by overdominance (an intrinisic advantage to heterozygosity) or if the parents contain coadapted gene complexes. These alternatives have been tested with introgression lines, where small regions of genome are scored in the heterospecific background. We develop predictions for introgression line data under a simple model of phenotypic selection, where parents diverge by fixing deleterious mutations via genetic drift. We show that this simple process can generate complex patterns in the data, misleading tests for both overdominance and coadaptation. We also suggest new ways to analyse the data to overcome these difficulties. Reanalyses of published data fromSolanumandGossypiumsuggest that the model can account for the qualitative patterns observed, though not the extent of apparent overdominance.
Mild uncoupling of mitochondria synergistically enhances senolytic specificity and sensitivity of BH3 mimetics
Authors: Fielder Edward , Ishaq Abbas , Low Evon , Laws Joseph , Calista Aisha , Castle Jemma , von Zglinicki Thomas , Miwa Satomi
Published: August 2023

Anti-senescence interventions are exceptionally effective in alleviating a wide range of age-associated diseases and disabilities. However, the sensitivity and specificity of current senolytic interventions are limited. Mitochondrial dysfunction is an integral part of the senescent phenotype and we demonstrate that specific loss of complex I-linked coupled respiration and the inability to maintain mitochondrial membrane potential upon respiratory stimulation are early and persistent features in a cell’s progression towards senescence.

We thus identify senescence-associated mitochondrial dysfunction as a targetable vulnerability of senescent cells and show that further decreasing mitochondrial membrane potential of senescent cells with a low concentration of a mitochondrial uncoupler synergistically enhances thein vitrosenolytic efficacy of BH3 mimetic drugs, including Navitoclax, by up two orders of magnitude.

Moreover, in anin vivomouse model of radiation-induced premature ageing, we show that a short-term intervention combining the mitochondrial uncoupler BAM15 with Navitoclax at a dose two orders of magnitude lower than typically used reduces frailty and improves cognitive function for at least 8 months after irradiation. Therefore our study shows that compromised mitochondrial functional capacity is a specific vulnerability of senescent cells which can be targeted by mild uncouplingin vitroandin vivo.
The H3K27 acetyltransferase p300 is dispensable for thermogenic adipose tissue formation and function
Authors: Gamu Daniel , Cameron Makenna S. , Gibson William T.
Published: August 2023

Brown adipose tissue (BAT) is specialized for thermogenesis because it contains uncoupling protein (UCP)-1. BAT is also an endocrine organ, producing many signalling molecules important for regulating the metabolism of peripheral organs. Mounting evidence suggest that histone modifying enzymes are integral for the development, tissue maintenance, and postnatal functioning of brown and beige adipocytes. p300 and its functional homologue CREB-binding protein (CBP) are histone acetyltransferases that form the transcriptionally activating histone 3 acetyl-lysine 27 (H3K27ac) mark. UsingUcp1-Cre, we examined the requirement of p300 activity specifically within thermogenic adipocytes. We hypothesized that loss of p300 activity would impair gene programming integral for BAT development/function, rendering knockouts susceptible to metabolic dysfunction and unable to form beige adipocytes. Despite successful knockdown, brown fat was completely unaffected by p300 deletion. As such, knockout mice showed a comparable metabolic profile to littermate controls in response to diet-induced obesity. Furthermore,de novobeige adipogenesis within subcutaneous fat by a β3adrenergic agonist remained intact in knockout mice. Although p300 and CBP have non-overlapping roles in other tissues, our results indicate p300 HAT activity is dispensable within thermogenic fats, likely due to functional compensation by CBP.
RAD52 and ERCC6L/PICH have a compensatory relationship for genome stability in mitosis
Authors: Osia Beth , Merkell Arianna , Lopezcolorado Felicia Wednesday , Ping Xiaoli , Stark Jeremy M.
Published: August 2023

The mammalian RAD52 protein is a DNA repair factor that has both strand annealing and recombination mediator activities, yet is dispensable for cell viability. To characterize genetic contexts that reveal dependence on RAD52 to sustain cell viability (i.e., synthetic lethal relationships), we performed genome-wide CRISPR knock-out screens. Subsequent secondary screening found that depletion of ERCC6L in RAD52-deficient cells causes reduced viability and elevated genome instability, measured as accumulation of 53BP1 into nuclear foci. Furthermore, loss of RAD52 causes elevated levels of anaphase ultrafine bridges marked by ERCC6L, and conversely depletion of ERCC6L causes elevated RAD52 foci both in prometaphase and interphase cells. These effects were enhanced with combination treatments using hydroxyurea and the topoisomerase IIα inhibitor ICRF-193, and the timing of these treatments are consistent with defects in addressing such stress in mitosis. Thus, loss of RAD52 appears to cause an increased reliance on ERCC6L in mitosis, and vice versa. Consistent with this notion, combined depletion of ERCC6L and disrupting G2/M progression via CDK1 inhibition causes a marked loss of viability in RAD52-deficient cells. We suggest that RAD52 and ERCC6L play compensatory roles in protecting genome stability in mitosis.
Methylphenidate for Children and Adolescents with Attention Deficit Hyperactivity Disorder (ADHD) – unpublished or unregistered randomised clinical trials
Authors: Kristensen Magnus Tang , Gluud Christian , Storebø Ole Jakob
Published: August 2023

Introduction

This is a follow-up study on our recent systematic review by Storebø and colleagues on methylphenidate for children and adolescents with attention-deficit/hyperactivity disorder (ADHD) published in The Cochrane Library. We aim to investigate the risks of research waste and publication bias in randomised clinical trials investigating methylphenidate versus placebo or no intervention for children and adolescents with ADHD.

Method

The method used includes our initial cohort of randomised clinical trials selected from searchingClinicaltrials.govand the EUCTR with the following criteria: methylphenidate versus placebo or no intervention with or without co-interventions for children or adolescents with ADHD, randomised clinical trials, any dosage, any delivery method, and at least 75% children and adolescents with ages less than 18 years as well as a time period of 1999-2022.

Our primary objective is to assess how many randomised clinical trials of methylphenidate on children and adolescents with ADHD are registered in protocol databases, but never published in academic literature or as tabular summary results. The number of participants included in these trials is a secondary objective. Our third objective is to examine the relationship between trial results and the chance of being published. Our fourth objective is to assess the time from registry to publication of randomised clinical trials of methylphenidate on children and adolescents with ADHD in either a journal or as summary results, and the number of participants in these trials. The cutoff time for a publication to be considered timely published will be 6 months, as per European Medicines Agency guidelines for clinical trials involving children.

Results

This is our protocol for the study and no results are presently available.
Electrocardiogram and Photoplethysmogram-based Heart Rate Variability Are Not Equivalent: A Bayesian Simulation Analysis
Authors: Dewig Hayden G , Cohen Jeremy N , Renaghan Eric J , Leary Miriam E , Leary Brian K , Au Jason S. , Tenan Matthew S
Published: August 2023

Background

Heart rate variability (HRV) is a common measure of autonomic and cardiovascular system function assessed via electrocardiography (ECG). Consumer wearables, commonly employed in epidemiological research, use photoplethysmography (PPG) to report HRV metrics (PRV), although these may not be equivalent. One potential cause of dissociation between HRV and PRV is the variability in pulse transit time (PTT). This study sought to determine if PPG-derived HRV (i.e., PRV) is equivalent to ECG-derived HRV and ascertain if PRV measurement error is sufficient for a biomarker separate from HRV.

Methods

The ECG data from 1,084 subjects were obtained from the PhysioNet Autonomic Aging dataset, and individual PTT variances for both the wrist (n=42) and finger (n=49) were derived from Mol et al. A Bayesian simulation was constructed whereby the individual arrival times of the PPG wave were calculated by placing a Gaussian prior on the individual QRS-wave timings of each ECG series. The standard deviation of the prior corresponds to the PTT variances. This was simulated 10,000 times for each PTT variance. The root mean square of successive differences (RMSSD) and standard deviation of N-N intervals (SDNN) were calculated for both HRV and PRV. The Region of Practical Equivalence bounds (ROPE) were set a priori at ±0.2% of true HRV. The Highest Density Interval (HDI) width, encompassing 95% of the posterior distribution, was calculated for each PTT variance.

Results

The lowest PTT variance (2.0 SD) corresponded to 88.4% within ROPE for SDNN and 21.4% for RMSSD. As the SD of PTT increases, the equivalence of PRV and HRV decreases for both SDNN and RMSSD. Thus, between PRV and HRV, RMSSD is nearly never equivalent and SDNN is only somewhat equivalent under very strict circumstances. The HDI interval width increases with increasing PTT variance, with the HDI width increasing at a higher rate for RMSSD than SDNN.

Conclusions

For individuals with greater PTT variability, PRV is not a surrogate for HRV. When considering PRV as a unique biometric measure, our findings reveal that SDNN has more favorable measurement properties than RMSSD, though both exhibit a non-uniform measurement error.
Innovative quantitative PCR assays for the assessment of HIV-associated cryptococcal meningoencephalitis in Sub-Saharan Africa
Authors: Mbangiwa Tshepiso , Sturny-Leclère Aude , Lechiile Kwana , Kajanga Cheusisime , Boyer-Chammard Timothée , Hoving Jennifer C. , Leeme Tshepo , Moyo Melanie , Youssouf Nabila , Lawrence David S. , Mwandumba Henry , Mosepele Mosepele , Harrison Thomas S , Jarvis Joseph N , Lortholary Olivier , Alanio Alexandre
Published: August 2023

Background

Cryptococcal meningitis (CM) accounts for about 10-20% of AIDS-defining illnesses with a 10-week mortality rate of 25-50%. Fungal load assessed by colony-forming unit (CFU) counts is used as a prognostic marker and to monitor response to treatment in research studies. PCR-based assessment of fungal load could be more rapid and less labor-intensive.

Methods

We developed and validated species-specific qPCR assays based on DNA amplification of a Quorum Sensing Protein 1 (QSP1);QSP1A,QSP1B/C, andQSP1D that are specific toC. neoformans,C. deneoformansandC. gattiispecies, respectively, and a pan-Cryptococcusassay based on a multicopy28S rRNAgene. We tested these assays for species identification (QSP1) and quantification (QSP1 ans 28S) on cerebrospinal fluid (CSF) of 209 CM patients at baseline (Day 0) and during anti-fungal therapy (Day 7 and Day 14), from the AMBITION-cm trial in Botswana and Malawi (2018-2021).

Findings

When compared to quantitative cryptococcal culture (QCC) as the reference, the sensitivity of the28S rRNAandQSP1assays were 98.2% [95% CI: 95.1-99.5] and 90.4% [95% CI: 85.2-94.0] respectively in cerebrospinal fluid (CSF) at Day 0. Quantification of the fungal load withQSP1and28S rRNAqPCR correlated with QCC (R2=0.73, R2=0.78, respectively). Both Botswana and Malawi had a predominantC. neoformansprevalence of 67% [95% CI: 55, 75] and 68% [95% CI: 57, 73], respectively and lowerC. gattiirates of 21% [95% CI: 14, 31] and 8% [95% CI: 4, 14], respectively. We identified 10 patients that, after 14 days of treatment, harboured viable but non-culturable yeasts based onQSP1RNA detection (without any positive CFU in CSF culture).

Interpretation

QSP1and28S rRNAassays are useful in identifyingCryptococcusspecies. qPCR results correlated well with baseline QCC and showed a similar decline in fungal load during induction therapy. These assays have a quick turnaround time and could be used in place of QCC to determine fungal load clearance. The clinical implications of the detection of possibly viable but non-culturable cells in CSF during induction therapy remain unclear.

Funding

The AMBITION-cm clinical trial which was funded by the European and Developing Countries Clinical Trials Partnership; Swedish International Development Cooperation Agency; Wellcome Trust / Medical Research Council (UK) / UKAID Joint Global Health Trials and National Institute for Health Research (UK).
AAM/goods delivery: main enablers for BVLOS routine operations within environment at low and medium risk
Authors: Menichino Aniello , Di Vito Vittorio , Ariante Gennaro , Del Core Giuseppe
Published: August 2023

Purpose

Theadvanced air mobility (AAM) is defined by National Aeronautics and Space Administration (NASA) as safe, accessible, automated and affordable air transportation system for passengers and cargo, capable of serving previously hard-to-reach urban and rural sites. The purpose of this paper is to focus on explaining potential solutions, under study by the authors, which could support beyond visual line of sight (BVLOS) operations for goods delivery in a safe way.

Design/methodology/approach

According to recent NASA-commissioned market studies, by 2030, there will be as many as 500 million flights a year for package delivery services and 750 million flights a year for passengers’ transportation (AAM). A significant number of these aircrafts will be unmanned aerial vehicles, meaning that they are self-flying or autonomous, of which the smallest ones are quadcopters: they are relatively inexpensive and are capable to perform various tasks, such as aerial observation, crop monitoring and treatment, search and rescue, power line monitoring and goods delivery. On the other hand, there are still many difficulties in introducing them into medium- and low-risk BVLOS routine operations for goods delivery: unfortunately, there are no regulations and technologies yet that enable these operations.

Findings

This conceptual paper outlines the studies about possible solutions, identified by authors, which could support BVLOS operations in a medium- and low-risk environment; in particular, the following aspects have been analysed: regulations, integrating control systems for drones, sensors (on board obstacle detection and avoidance), emergency management (emergency on ground system to identify safe landing areas), concepts of droneway (or flight corridors) and drones recovery hub.

Originality/value

The purpose of this paper is to provide a conceptual description of the possible solutions, under study by the authors, which could contribute enabling the BVLOS operations in a medium- and low-risk environment. The paper aims describing the state of the art, terms of regulations, classifications and limitations and describing possible conceptual solutions that could guarantee safety in introducing unmanned aircraft system operations inside urban areas.
An analysis of dependency of stock markets after unlimited QE announcements during COVID-19 pandemic
Authors: Puarattanaarunkorn Ornanong , Autchariyapanitkul Kittawit , Kiatmanaroch Teera
Published: August 2023

Purpose

Unlimited quantitative easing (QE) is one of the monetary policies used to stimulate the economy during the coronavirus disease 2019 (COVID-19) pandemic. This policy has affected the financial markets worldwide. This empirical research aims at studying the dependence among stock markets before and after unlimited QE announcements.

Design/methodology/approach

The copula-based GARCH (1,1) and minimum spanning tree models are used in this study to analyze 14 series of stock market data, on 6 ASEAN and 8 other countries outside the region. The data are divided into two periods to compare the differences in dependence.

Findings

The findings show changes in dependence among the volatility of daily returns in 14 stock markets during each period. After the unlimited QE announcement, the upper tail dependence became more apparent, while the role of the lower tail dependence was reduced. The minimum spanning tree can show the close relationships between stock markets, indicating changes in the connection network after the announcement.

Originality/value

This study allows the dependency to be compared between stock market volatility before and after the announcement of unlimited QE during the COVID-19 pandemic. Moreover, the study fills the literature gap by combining the copula-based GARCH and the minimum spanning tree models to analyze and reveal the systemic network of the relationships.
A brand loyalty–risk framework in the luxury watch market
Authors: Silva Pedro , Moreira António Carrizo , Almeida Sílvia , Moutinho Victor
Published: August 2023

Purpose

In a society that encourages consumption, attributes such as exclusivity and social recognition are important in what is intended to be restricted to a certain exclusive segment. Luxury is something that is more desirable than necessary. This study develops and tests a model that analyses the brand loyalty–risk relationship in the luxury watch market.

Design/methodology/approach

To test the proposed research model, a sample of 306 international consumers and enthusiasts of luxury brand watches was collected. The data were analysed using structural equation modelling.

Findings

The results show that perceived quality has a negative indirect influence on brand risk and brand trust has a strong direct negative effect on brand risk. However, the findings also show that in the luxury market, the greater the affection for the brand, the greater the risk perceived by consumers.

Research limitations/implications

The study was conducted in a single market, luxury watches and the sample includes both enthusiasts and consumers of the luxury brands.

Practical implications

Managers should be aware of the double-edged role of brand affect on brand risk. The quality of a brand and the trust in its promise decrease the risk to the consumer.

Originality/value

This pioneering study is one of the first to approach an underexplored topic as is the case of the risk associated with a brand in the context of the luxury goods market. Moreover, it relies on an international sample composed of consumers from several countries.
Critical factors influencing the internet of things technology adoption behavior of construction companies: evidence from China
Authors: Zhao Yaqi , Hao Shengyue , Chen Zhen , Zhou Xia , Zhang Lin , Guo Zhaoyang
Published: August 2023

Purpose

Limited use of Internet of Things (IoT) technology on construction sites has restricted its value in the construction industry. To propel its widespread application, this paper explores the influencing factors and action paths of construction companies' IoT technology adoption behavior.

Design/methodology/approach

First, literature research, technology adoption theories, and semi-structured expert interviews were employed to build the adoption model. Second, a questionnaire survey was conducted among Chinese construction contractors to collect empirical data. Third, the structural equation model method and regression analysis were used to test the adoption model. Finally, the findings were further validated with interviews, case studies, and field observations.

Findings

External environmental pressure (EEP), perceived benefit (PB), top management support (TMS), company resource readiness (CRR), adoption intention (AI), and perceived compatibility (PCA) have a direct positive impact on adoption behavior (AB). In contrast, perceived cost (PC) and perceived complexity (PCL) exert a direct negative impact on AB. The EEP, PB, and PC are critical factors affecting AB, whereas AI is strongly affected by CRR and TMS. Besides, AI plays a part mediating role in the relationship between seven factors and AB. Company size and nature positively moderate AI's positive effect on AB.

Originality/value

This paper contributes to the knowledge of IoT technology adoption behavior in the construction sector by applying the technology adoption theories. Exploring the implementation barriers and drivers of IoT technology in construction sites from the perspective of organizational technology adoption behavior and introducing moderating variables to explain adoption behavior are innovations of this paper. The findings can help professionals better understand the IoT technology adoption barriers and enhance construction companies' adoption awareness, demand, and ability. This work also provides a reference for understanding the impact mechanism of the adoption behavior of other innovative technologies in construction.
How to improve the smart construction technology usage behavior of construction enterprise employees? — TOE framework based on configuration study
Authors: Xue Hong , Zhang Sujie , Wu Zezhou , Zhang Lin
Published: August 2023

Purpose

Despite smart construction technology's great potential to improve the productivity of the architectural, engineering and construction (AEC) industry, the implementation of smart construction technology has failed to achieve the expected benefits due to the negative usage behaviors of construction enterprise employees. This study aims to identify the determinants and their configuration effects on the smart construction technology usage behavior (SCTUB) based on the Technology-Organization-Environment (TOE) framework. This study then verifies the practical paths to improve the employee's SCTUB from the configuration perspective.

Design/methodology/approach

A mixed-method approach involving survey and qualitative comparative analysis (QCA) is conducted in this study. Based on the detailed literature review and semi-structured interview, this study identifies the factors and proposes the TOE framework to determine the configuration conditions affecting employee's SCTUB and verify practical paths to promote this user behavior.

Findings

The TOE framework's technical, organizational and environmental elements are interdependent. The emergence of a high SCTUB is not determined by a single determinant but by configuration conditions. Four equifinal conditions (e.g. organization-technology type, technology-organization type, environment type and organization-technology balanced type) are verified to promote construction enterprise employee's SCTUB.

Practical implications

The four verified configuration conditions could guide construction enterprises to formulate complementary strategies for promoting the construction enterprises' employees to implement smart construction technology and achieve the enterprise's digital transformation.

Originality/value

The inter-dependence of the three-dimension factors, namely technical, organizational and environmental elements are explored to enrich the literature on the TOE framework. Meanwhile, the configuration effects of these factors on usage behavior are identified, expanding the literature on the information technology acceptance model.
How risk factors lead to the early termination of public–private partnership projects in China: a multi-case study based on social network analysis and interpretive-structure modeling
Authors: Liu Yunfeng , Wang Xueqing , Zhang Jingxiao , Guo Sijia
Published: August 2023

Purpose

Early termination of public–private partnerships (PPPs) in China is caused by various risk factors, resulting in significant losses. This study aimed to clarify the key factors and identify the causal relationships among these factors.

Design/methodology/approach

Social network analysis (SNA) was used to analyze 37 risk factors that were summarized from 97 early terminated PPP cases and to identify the relationships among these key risk factors. Interpretive structural modeling (ISM) was conducted to explore the causal relationships. Data were collected from case documents, questionnaires and interviews.

Findings

A total of 17 key risk factors were identified and distributed in a hierarchical structure with six tiers. Among these key risk factors, the root causes affecting the early termination of PPP projects were government oversight in decision-making, local government transition, policy and law changes and force majeure. The direct cause was insufficient returns. Furthermore, local government and private sector defaults were essential mediating factors. Local government transition and the low willingness of the private sector were highlighted as potential key risks.

Research limitations/implications

The cases and experts were all from China, and outcomes in other countries or cultures may differ from those of this study. Therefore, further studies are required.

Practical implications

This research provides knowledge regarding the key risk factors leading to the early termination of PPP projects and guidance on avoiding these factors and blocking the factors' transmission in the project lifecycle.

Originality/value

This study contributes to the knowledge of risk management by emphasizing the importance of local government transition, the low willingness of the private sector and project cooperation and operation, whose significance is ignored in the existing literature. The proposed ISM clarifies the role of risk factors in causing early termination and explains their transmission patterns.
Assessing the development and multidimensional constraints of the high-quality construction industry in the Chengdu-Chongqing twin-city economic circle
Authors: Wan Jiangjun , Zhao Yuxin , Chen Miaojie , Zhu Xi , Lu Qingyu , Huang Yuwei , Zhao Yutong , Zhang Chengyan , Zhu Wei , Yang Jinxiu
Published: August 2023

Purpose

The construction industry accounts for a large proportion of the economy of developing countries, but the connotation and influencing factors of high-quality development (HQD) are still unclear. This study aims to gain a more comprehensive insight into the current development status of the regional construction industry under China's HQD orientation and the obstructive factors affecting its development and to provide informative suggestions for its HQD prospects.

Design/methodology/approach

In this study, the construction industry of 16 cities in the Chengdu-Chongqing economic circle (CCEC), a new region in southwest China, was used as the research object to collect data from the 2006–2019 yearbooks, construct an evaluation index system for HQD of the construction industry, derive the development level of the construction industry using the entropy value method and spatial autocorrelation method and then apply the barrier Diagnostic model was used to compare and analyze the impact level of each index.

Findings

In terms of the time dimension, the development of the construction industry in CCEC is characterized by “high in the twin core and low in the surrounding area”, with unbalanced and insufficient development; in terms of spatial correlation, some factors have positive aggregation in spatial distribution, but the peripheral linkage decreases; through barrier analysis, the impact of different barrier factors is different.

Originality/value

This paper will help governments and enterprises in developing countries to make urban planning and management policies to fundamentally improve the development of the construction industry in underdeveloped regions.
Individual resilience and academic achievements: a soft traits approach to craft universities' placement and facilitate firms' onboarding
Authors: Cantoni Franca , Platoni Silvia , Virtuani Roberta
Published: August 2023

Purpose

Frequently the universities' Placement Service is based on the student's hard profile at the expense of soft traits. On the other side, the “person–organization fit” axiom suggests firms are looking for profiles with specific soft skills to face the increasing level of environmental turbulence. This research aims to understand if high-resilience students also have high academic achievements and how the three components of resilience (emotional intelligence, positive thinking, planfulness) can have different impact on individual performances.

Design/methodology/approach

The research was conducted on students enrolled on different courses of studies and years in an Economics and Law faculty. A questionnaire was administered during the first exam session (ante-Covid) and the second and third exam sessions (post-Covid). This questionnaire consists of 84 questions related to planfulness, emotional intelligence and positive thinking, whose combination can be considered a measure of resilience. In fact, the Principal Component Analysis (PCA) was carried to identify these three new variables (the components) based on the 84 initial ones. Finally, an ordered logit model was implemented to verify whether, and in what direction, planfulness, emotional intelligence, positive thinking and Covid 19 (the independent variables) affected the students' performance (the dependent one).

Findings

While planfulness positively affected academic performance, emotional intelligence affected it negatively. The impact of positive thinking and Covid was not significant, and thus what emerged from the preliminary analysis of the grades is not confirmed.

Research limitations/implications

This is a case study of a university experience that is paying great care in preparing students to satisfy the firms' work demands. To confirm and refine results the sample will be expanded to other faculties and other life/soft skills will be investigated.

Practical implications

This soft trait approach—that studies how various measures of soft skills are related to course grades—has a two-fold significance by crafting universities' placement activities and facilitating firms' onboarding.

Social implications

This is a case study of a university experience; a university that is paying great attention to preparing students ready to satisfy the firms' work demands but also citizens capable of supporting the growth of their nation and society in general.

Originality/value

The research can be considered a first step towards the inclusion of the formal evaluation of the students' life skills in their academic path, creating a link with their achievements.