bluuebunny/crossref_metadata_2025 huggingface dataset:
Crosstalk between the aryl hydrocarbon receptor and hypoxia inducible factor 1α pathways impairs downstream dioxin response in human islet models
Authors: Gang Noa , van Allen Kyle A. , Willmore William G. , Lynn Francis C. , Bruin Jennifer E.
Published: September 2024

The incidence of type 2 diabetes (T2D) is increasing globally at a rate that cannot be explained solely by genetic predisposition, diet, or lifestyle. Epidemiology studies report positive associations between exposure to persistent organic pollutants, such as dioxins, and T2D. We previously showed that 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) activates the xenobiotic-sensitive aryl hydrocarbon receptor (AHR) in pancreatic islets. The AHR is known to crosstalk with the hypoxia inducible factor 1α (HIF1α) in hepatocytes but whether this crosstalk occurs in islet cells remains unknown. We assessed AHR-HIF1α pathway crosstalk by treating human donor islets and stem cell-derived islets (SC-islets) with TCDD +/- hypoxia and examined the changes in downstream targets of both AHR (e.g.,CYP1A1) and HIF1α (e.g.,HMOX1).

SC-islets showed consistent crosstalk between AHR and HIF1α pathways; co-treatment of SC-islets with TCDD + hypoxia robustly suppressed the magnitude ofCYP1A1induction compared with TCDD treatment alone. In human islets, only 2 of 6 donors showing suppressedCYP1A1induction following TCDD + hypoxia co-treatment. In both SC-islets and human donor islets we observed an unexpected hypoxia-mediated suppression of glucose-6-phosphate catalytic subunit 2 (G6PC2) expression.

Our study shows AHR-HIF1α crosstalk occurs in both SC-islets and primary human donor islets, but the response of human islets varied between donors. In both models, the HIF1α pathway dominated over the AHR pathway during TCDD + hypoxia co-treatment. Our study is the first to examine whether AHR-HIF1α crosstalk occurs in islet cells and presents novel data on the impact of hypoxia onG6PC2gene expression.
Interpreting Sleep Activity Through Neural Contrastive Learning
Authors: Chen Zhongtao , Zheng Hui , Zhou Jianyang , Zheng Lin , Lin Peiyang , Wang Haiteng , Dolan Ray , Behrens Tim , Liu Yunzhe
Published: September 2024

Memories are spontaneously replayed during sleep, but capturing this process in the human brain has been challenging due to the dominance of slow, rhythmic background activity in sleep, which differs significantly from wakefulness. Each sleep stage, such as NREM and REM, has distinct rhythms, making it even harder for models trained on awake tasks to generalise and decode memory replay during sleep. To overcome this, we developed the Sleep Interpreter (SI), an artificial neural network. We first collected a large EEG dataset from 135 participants, recording brain activity during both awake tasks and overnight sleep. Using a Targeted Memory Reactivation (TMR) technique with 15 pairs of auditory cues and visual images, we tracked when specific memories were reactivated during sleep. The SI model was then trained separately for NREM and REM stages, using contrastive learning to align neural patterns between wakefulness and sleep while filtering out the background rhythms that previously hindered decoding. We also examined how specific sleep rhythms, such as slow oscillations and their coupling with spindles, influenced decoding performance. In a 15-way classification task during sleep, our model achieved a Top-1 accuracy of up to 40.05% on unseen subjects, surpassing all other available decoding models. Finally, we developed a real-time sleep decoding system by integrating an online automatic sleep staging process with the SI model for each sleep stage. This ability to decode brain activity during sleep opens new avenues for exploring the functional roles of sleep. By making our dataset and decoding system publicly available, we provide a valuable resource for advancing research into sleep, memory, and related disorders.
The Neural Correlates of Alcohol Approach Bias – New Insights from a Whole-Brain Network Analysis Perspective
Authors: Muller Angela M. , Manning Victoria , Wong Christy Y.F. , Pennington David L.
Published: September 2024

Alcohol approach bias, a tendency to approach rather than to avoid alcohol and alcohol-related cues regardless of associated negative consequences, is an emerging key characteristic of alcohol use disorder (AUD). Reaction times from the Approach-Avoidance Task (AAT) can be used to quantify alcohol approach bias. However, only a handful of studies have investigated the neural correlates of implicit alcohol approach behavior. Graph Theory Analysis (GTA) metrics, specifically, weighted global efficiency (wGE), community detection, and inter-community information integration were used to analyze functional magnetic resonance imaging (fMRI) data of an in-scanner version of the AAT from 31 heavy drinking Veterans with AUD (HDV) engaged in out-patient treatment and 19 healthy Veterans as controls (HC). We found a functional imprint of alcohol approach bias in HDVs. HDVs showed significantly higher wGE values for approaching than for avoiding alcohol, indicating that their brain was more efficiently organized or functionally set to approach alcohol in the presence to alcohol-related external cues. In contrast, Brains of HCs did not show such a processing advantage for either the approach or avoid condition. Further post-hoc analyses revealed that HDVs and HCs differed in how they implemented top-down control when approaching/avoiding alcohol and in how the fronto-parietal control network interacted with subsystems of the default mode network. These findings contribute to understanding the complex neural underpinnings of alcohol approach bias and lay the foundation for developing more potent and targeted interventions to modify these neural patterns in AUD patients.
Cost-effectiveness analysis of COVID-19 mRNA XBB.1.5 Fall 2023 vaccination in the Netherlands
Authors: Zeevat Florian , van der Pol Simon , Westra Tjalke , Beck Ekkehard , Postma Maarten J. , Boersma Cornelis
Published: September 2024

Objective

This study aims to assess the cost-effectiveness of the Fall 2023 COVID-19 mRNA XBB.1.5 vaccination campaign in the Netherlands, comparing the XBB1.5 updated mRNA-1273.222 with the XBB1.5 updated BNT162b2 vaccine.

Methods

A one-year decision tree-based cost-effectiveness model was developed, considering three scenarios: no Fall 2023 vaccination, BNT162b2 vaccination and mRNA-1273 vaccination in the COVID-19 high-risk population in the Netherlands. The high-risk population includes everyone of 60 and older, and younger adults at high risk as identified by the Dutch Health Council. Costs were included from a societal perspective and the modelled period started in October 2023 and ended in September 2024, including life years lost with a lifetime horizon. Sensitivity and scenario analyses were conducted to evaluate model robustness.

Results

In the base case, mRNA-1273 demonstrated substantial benefits over BNT162b2, potentially averting 20,629 symptomatic cases, 924 hospitalizations (including 32 ICU admissions), 207 deaths, and 2,124 post-COVID cases. Societal cost savings were €12.9million (excluding vaccination costs), with 1,506 QALYs gained. The break-even incremental price of mRNA-1273 compared to BNT162b2 was €16.72 or €34.32 considering a willingness to pay threshold (WTP) of 20,000 or 50,000 euro per QALY gained.

Conclusion

This study provides a comprehensive cost-effectiveness analysis supporting the adoption of the mRNA-1273 vaccine in the national immunization programme in the Netherlands, provided that the Dutch government negotiates a vaccine price that is at most €34.32 per dose higher than BNT162b2. Despite limitations, the findings emphasize the substantial health and economic benefits of mRNA-1273 over BNT162b2 in the high-risk population.
Reducing Functional Dysconnectivity in Schizophrenia Spectrum Disorders
Authors: Wunderlich Stephan , Keeser Daniel , Spaeth Johanna , Maurus Isabel , Alici Cagatay , Schmitt Andrea , Falkai Peter , Stoecklein Sophia , Roell Lukas
Published: September 2024

Background

As a condition of dysconnectivity, schizophrenia spectrum disorders (SSD) are characterized by positive, negative, and cognitive symptoms. To improve these symptoms in SSD, physical exercise interventions show promise. We examined if reductions of functional dysconnectivity following exercise therapy are associated with clinical improvements in SSD and explored potential genetic underpinnings.

Methods

The study utilized data from the ESPRIT C3 trial, investigating the effects of aerobic exercise versus flexibility, strengthening, and balance training on different health outcomes in individuals with SSD. Functional dysconnectivity in 23 patients relative to a healthy reference sample, was assessed both pre- and post-intervention. Changes of functional dysconnectivity after exercise and their clinical relevance were evaluated. An imaging transcriptomics approach was used to study the link between changes in functional dysconnectivity and gene expression profiles.

Results

We observed substantial reductions of functional dysconnectivity on the whole-brain level linked to enhanced gene expression mainly in oligodendrocytes. With regard to the clinical implications, decreases of dysconnectivity in the default-mode network were associated with improvements in global functioning. Reductions of dysconnectivity within the salience network were linked to improvements in symptom severity. Lastly, reductions of functional dysconnectivity in language regions such as Broca’s area were related to cognitive benefits.

Conclusions

Our study supports a recent theory of oligodendrocyte pathology in SSD and suggests that reducing functional dysconnectivity in the default-mode, salience, and language network reflect a potential therapeutic target to improve global functioning, total symptom severity, and cognitive impairments in post-acute SSD.

Trial name: ESPRIT C3

Registry: International Clinical Trials Database,ClinicalTrials.govRegistration number:NCT03466112

URL:https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1
Detecting Wolff-Parkinson-White from Lead-I ECG Using Transfer Learning and Wavelets
Authors: Bharadwaj Shreyas , Altman Sarah , Wang Jessica , Alam Ridwan
Published: September 2024

Wolff-Parkinson-White (WPW) syndrome is a congenital heart defect that can trigger ventricular fibrillation and sudden cardiac death. Expert inspection of a 12- lead clinical electrocardiogram (ECG) or a Holter record is the standard approach for detecting WPW syndrome. Smartwatches that acquire lead-I ECGs can enable automated detection of WPW episodes in out-of-hospital settings and prevent adverse outcomes. In this work, we explore deep-learning solutions to identify WPW syndromes on lead-I ECG. Scarcity of labeled ECG data for WPW and other cardiac conduction disorders poses a major challenge for training data-driven methods. Moreover, generalizability of such methods to external patient population remains unexplored. To address these challenges, first we implement and compare multiple existing strategies from time-domain augmentations on the lead-I ECG to transfer learning of Imagenet-models for ECG wavelet transformations. Training and holdout validation of these methods are conducted using about 14,000 ECGs from PTB-XL, a publicly available ECG dataset. Moreover, we explore generalization of these methods by external validation on the data from 140 patients from the Tongji Hospital ECG Database. While these methods achieve 88% sensitivity and 99% specificity in identifying a lead-I ECG with evident WPW, and an area under the receiver-operating curve (AUC) of 0.99 on the holdout set from PTB-XL, the sensitivity drops to 58% with an AUC of 0.88 on the external validation. Finally, we propose a novel data augmentation strategy by incorporating labeled data from an umbrella super-class of cardiac conduction disorders, instead of WPW alone, thus naturally reducing the data imbalance for model training. We apply these models as zero-shot transfer learning for discriminating WPW from normal ECG. While this approach achieves similar performance during holdout validation, it also demonstrates strong performance on the external Tongji dataset with sensitivity 0.78 and AUC 0.91. This result shows significant generalizability of the proposed method and highlights the potential of deep-learning solutions in monitoring WPW syndrome with lead-I ECG in outof-hospital general populace settings.
Engineered Nanobodies Bind Theranostic Main Group Metals
Authors: Ghosh Pritha , Davies Lani J. , Nitsche Christoph
Published: September 2024

Targeted theranostics heavily rely on metal isotopes conjugated to antibodies. Single-domain antibodies, known as nanobodies, are much smaller in size without compromising specificity and affinity. The conventional way of conjugating metals to nanobodies involves non-specific modification of amino acid residues with bifunctional chelating agents. We demonstrate that mutagenesis of a single residue in a nanobody creates a triple cysteine motif that selectively binds bismuth which is, for example, used in targeted alpha therapy. Two mutations create a quadruple cysteine mutant specific for gallium and indium used in positron emission tomography and single-photon emission computed tomography, respectively. Labelling is quantitative within a few minutes. The metal nanobodies maintain structural integrity and stability over weeks, resist competition from endogenous metal binders like glutathione, and retain functionality.
Combined Stochastic Models for the Evaluation of Cancer Progression and Patient Trajectories
Authors: Wieland Vincent , Hasenauer Jan
Published: September 2024

Cancer is a major burden of disease around the globe and one of the leading causes of premature death. The key to improve patient outcomes in modern clinical cancer research is to gain insights into dynamics underlying cancer evolution in order to facilitate the search for effective therapies. However, most cancer data analysis tools are designed for controlled trials and cannot leverage routine clinical data, which are available in far greater quantities. In addition, many cancer models focus on single disease processes in isolation, disregarding interaction This work proposes a unified stochastic modelling framework for cancer progression that combines (stochastic) processes for tumour growth, metastatic seeding, and patient survival to provide a comprehensive understanding of cancer progression. In addition, our models aim to use non-equidistantly sampled data collected in clinical routine to analyse the whole patient trajectory over the course of the disease. The model formulation features closed-form expressions of the likelihood functions for parameter inference from clinical data. The efficacy of our model approach is demonstrated through a simulation study involving four exemplary models, which utilise both analytic and numerical likelihoods. The results of the simulation studies demonstrate the accuracy and computational efficiency of the analytic likelihood formulations. We found that estimation can retrieve the correct model parameters and reveal the underlying data dynamics, and that this modelling framework is flexible in choosing the precise parameterisation. This work can serve as a foundation for the development of combined stochastic models for guiding personalized therapies in oncology.
The glia club: Validation of polarization biomarkers for human microglia (HMC3) using quantitative real time RT-qPCR
Authors: Franck Esmé S. M. , Storm Jasmyne A. , Lu Jueqin , Obtial Mon Francis M. , Wijenayake Sanoji
Published: September 2024

Microglia are the primary immune cells of the brain and play critical roles in neurodevelopment, neuroprotection, the maintenance of homeostasis, and neurotoxicity. Classification of microglia polarization, however, remains contentious. Identifying suitable biomarkers for gene expression analysis of microglia polarization is crucial for characterizing the biological significance of microglia in health and disease. In this study, we use human microglia clone 3 (HMC3) cells to validate and test suitable internal controls (GAPDH,PKM,18S, ACTB, PGK1, TKT1, TPI1), homeostatic (CD68, TGF-β, IBA1, BIN1, RGS10), proinflammatory (IL-6, CXCL10, CCL5, SAA, IL-1β) and anti-inflammatory (CCL2, SOCS3, IL-10, CD200R1, ARG1) markers along with their transcriptional profiles upon interferon-gamma (IFN-γ) stimulation to characterize the microglia polarization spectrum. Our study is the first to present a comprehensive list of biomarkers with detailed methodology on gene selection, primer design, RT-qPCR parameters, and transcript abundance in baseline and polarized HMC3 cells. Our study will increase the rigor of gene expression analysis and target selection in a widely used brain macrophage.
Multiturn simulation of radiative Bhabha scattering in the equivalent photon approximation
Authors: Kicsiny Peter , Buffat Xavier , Schulte Daniel , Burkhardt Helmut , Pieloni Tatiana , Seidel Mike
Published: September 2024

In this paper, we present a Monte Carlo event generator for radiative Bhabha scattering, based on the method of equivalent photons, and optimized for multiturn tracking simulations in the framework. We demonstrate the accuracy of the event generator with successful benchmarks of the luminosity and event cross section against currently existing alternative tools. Consequently, we use it to investigate existing estimates of the radiative Bhabha scattering beam lifetime at the FCC-ee, as well as the impact of radiative Bhabha scattering on the beam dynamics, using full nonlinear tracking models.

Published by the American Physical Society
2024
Role of inhibition in overcoming interferences of misconception under similar feature saliency: An eye-tracking study of the projectile motion problem
Authors: Wen Yanrou , Lin Jiabei , Ming Yue , Zhang Junpeng , Wu Xianqiu , Bao Lei , Yu Keke , Xiao Yang
Published: September 2024

Misconceptions coexisting with scientific understanding pose significant challenges in physics education. Inhibitory control may enable individuals to overcome interference from misconceptions. However, discerning the role of inhibitory control becomes intricate when the saliency of scientific- and misconception-related features varies in a problem. This study investigates the role of inhibitory control in overcoming such misconceptions when scientific and misconception-related features are similarly salient, particularly focusing on the range-time (range determines flight time) misconception. We adopted a negative priming (NP) paradigm with the eye-tracking technique in the study. Thirty-six college physics majors participated in the experiment. In the NP paradigm, the participants first compared the flight times in a neutral (same range) or incongruent (longer range, less flight time) primes and then completed the same task in a congruent (longer range, more flight time) probe. Results revealed longer reaction times for incongruent primes compared to neutral primes and longer reaction times to respond to congruent probes following incongruent primes than when neutral primes were present beforehand, suggesting that the inhibitory control may be involved in overcoming the interference from the range-time misconception. Moreover, the eye-tracking analysis highlighted an early overt attention to the salient misconception-related feature (longer range) during primes, along with additional attentional investment necessary to inhibit the range-time misconception. During probes, an early shift of attention away from the salient misconception-related feature and a greater investment of attention on processing the congruent probes after the incongruent primes than that after the neutral primes were observed, indicating a possible effect of the previous inhibitory control in the primes on the subsequent cognitive process on the probes. These findings contribute to a deeper understanding of the cognitive process underlying physics conceptual change and provide insights into physics education.

Published by the American Physical Society
2024
Knowledge structure and theme trends on mHealth apps for COVID-19: bibliometric analysis
Authors: Ramzy Mina
Published: September 2024

Purpose

Recently, mHealth apps for COVID-19 have emerged as a new research area due to the diverse efforts to control the COVID-19 epidemic. Although there are many bibliometric studies on mHealth and its applications, no bibliometric study sheds light on mHealth apps for COVID-19 as a new research area. To address the above-mentioned research gap, the current study conducts a bibliometric analysis of research in mHealth apps for COVID-19. It aims to provide a comprehensive overview of the new area and its directions.

Design/methodology/approach

The study uses a bibliometric approach to provide an analysis of the overall status of research in mHealth apps for COVID-19. The Scopus database provided by Elsevier was used to extract the analyzed data in this study. SciVal was used to perform the analyses, while VOSviewer was used for scientific mapping.

Findings

A total of 457 publications were published between 2020 and 2021 (until Tuesday, June 1) and cited 3,559 times. Publications were written by 2,375 authors, with an average of 5.20 authors per publication. Articles play a pivotal role in the literature on mHealth apps for COVID-19 in terms of production and impact. The research area of mHealth apps for COVID-19 is multidisciplinary. The United States made the largest contribution to this area, while the UK was the most influential. This study reveals the most productive and influential sources, institutions and authors. It also reveals the research hotspots and major thematic clusters in mHealth apps for COVID-19, highly cited publications and the international collaboration network.

Originality/value

mHealth apps for COVID-19 are gaining more and more importance due to their influential role in controlling the COVID-19 epidemic. Using bibliometric analysis, the study contributes to defining the knowledge structure of global research in mHealth apps for COVID-19 as a new, interdisciplinary area of research that has not previously been studied. Therefore, the study results and the comprehensive picture obtained about research in mHealth apps for COVID-19, especially at the level of Internet of Things (IoT) and artificial intelligence applications, make it an effective supplement to the expert evaluation in the field.
Advancing the software development process through the development of technology-enabled dynamic capabilities in a project-based firm: insights from action design research
Authors: Sebrek Szabolcs Szilárd , Semenova Viktoriia , Kosztyán Zsolt Tibor
Published: September 2024

Purpose

This study aims to extend the dynamic capabilities (DCs) perspective to the project management context. The authors present supporting evidence for analyzing the creation process of DCs during the redesign of the software development process, and they examine the impact of those capabilities on organizational performance and transformation.

Design/methodology/approach

An action design research approach, combined with simulation and qualitative analysis, is adopted to examine the emergence of technology-enabled DCs supported by their microfoundations and the modernization of the software development process in the target firm.

Findings

Analyzing the successful internal transformation of a software development company that was facing a slow and inconsistent product development process reveals the effectiveness of extending the DC perspective to a project-based setting. The implementation of a new project methodology and the introduction of an innovative document-handling system facilitated the renewal of the company's software development process. This led to improvements in lead time and total costs, resulting in enhanced project performance as well as customer and employee satisfaction.

Practical implications

This study draws managerial attention to the microlevel activities of technology-enabled DC formation, such as precise calculations, external expert consultations and tool deployment.

Originality/value

By applying the sensing–seizing–transforming framework with concomitant microfoundations in a longitudinal way, this article explains the role that technology plays as the basis for DCs and analyzes the cost–benefit balance of DC development in project-based organizations.
Examining the nexus between technostress and turnover intention: the moderating influence of PsyCap in Indian information management contexts
Authors: Sharma Indu , Tiwari Vivek , Gupta Shivam , Rana Nripendra P.
Published: September 2024

Purpose

The recent pandemic (COVID-19) and the continuous ICT advancements have resulted in increased levels of technostress. On this basis, the present work tried to explore how technostress influences employees’ turnover intention with the mediation of work-exhaustion. Deploying the theoretical lens of job demands-resources theory, the authors also aim to investigate the part that positive psychological capital (PsyCap) has to play as a moderator in between technostress and work-exhaustion.

Design/methodology/approach

The study utilizes a time-lagged methodological design; data was gathered from 544 Indian IT employees. Additionally, PLS-SEM was used to carry out the aforementioned moderation-mediation analysis.

Findings

All the hypotheses proposed were confirmed. It was found that technostress significantly impacts employees’ turnover intention. Additionally, work-exhaustion does mediate the relationship between technostress and employees’ turnover intention. Furthermore, PsyCap did play the role of a moderator between Technostress and work-exhaustion.

Practical implications

This paper provides an augmented understanding of technostress in IT organizations and highlights the role of personal resources in aiding employees’ to deal with technostress.

Originality/value

This study is one of the early studies to highlight the role of positive psychological capital in mitigating the impact of technology-induced exhaustion and employees’ turnover intention.
Bimekizumab efficacy and safety in Korean patients with moderate to severe plaque psoriasis: A phase 3, randomized, placebo‐controlled, double‐blinded study
Authors: Youn Sang Woong , Jo Seong Jin , Park Chul Jong , Kim Dong Hyun , Shin Bong Seok , Jeong Ki Heon , Bang Chul Hwan , Cross Nancy , Thirlwell Jackie , Hoepken Bengt
Published: September 2024

Bimekizumab treatment has demonstrated significant improvements in clinical outcomes in patients with moderate to severe plaque psoriasis; however, studies so far have focused on predominantly White patient populations from North America and Europe, with one smaller study in a Japanese population. Here, clinical responses, safety, and tolerability of bimekizumab treatment in Korean patients are reported. Korean patients with moderate to severe plaque psoriasis were randomized to bimekizumab 320 mg every 4 weeks (Q4W) or placebo Q4W to week 16. Co‐primary efficacy end points were achievement of ≥90% improvement from baseline in the Psoriasis Area and Severity Index (PASI 90) and Investigator's Global Assessment score of 0/1 (clear/almost clear) at week 16. Secondary efficacy end points included achievement of PASI 75 at week 4 and Dermatology Life Quality Index 0/1 at week 16. Safety outcomes were also assessed. Statistical analysis of the co‐primary efficacy end points was performed using a type I error rate, at a two‐sided α level of 0.05. Overall, 47 Korean patients were randomized to treatment (bimekizumab: 32, placebo: 15). At week 16, bimekizumab‐treated patients had significantly higher clinical responses versus placebo‐treated patients (PASI 90: 81.3% vs. 0%; IGA 0/1: 87.5% vs. 0%, p < 0.001 for both). Bimekizumab showed a rapid onset of clinical response, with 75.0% of patients achieving PASI 75 by week 4 (0% in placebo patients [nominal p < 0.001]). A higher proportion of bimekizumab‐treated patients achieved DLQI 0/1 at week 16 (46.9% vs. 6.7% in placebo patients, nominal p = 0.007), indicating greater improvements in health‐related quality of life (HRQoL) following bimekizumab treatment. Bimekizumab was well‐tolerated in Korean patients, with no new safety signals identified. Treatment with bimekizumab led to rapid improvements in clinical responses and HRQoL versus placebo in Korean patients, consistent with responses in global populations. These findings suggest that bimekizumab is an effective and well‐tolerated treatment option in Korean patients with psoriasis.
There and there again: Hydrothermal vent communities at Mokuyo Seamount, 30 years apart
Authors: Chen Chong , Methou Pierre , Yamamoto Daiki , Kayamori Maki , Nomaki Hidetaka
Published: September 2024

Deep‐sea hydrothermal vents are biological hotspots driven by microbial chemosynthetic primary production and characterized by a high proportion of endemic, specially adapted species. Vent communities can be unstable depending on the geological setting, as the underlying geofluid supply may change in location and chemical composition over a decadal timescale. Although the Izu‐Ogasawara Arc in Japan is home to many vent fields within an Ecologically or Biologically Significant Marine Area (EBSA), no observations of decadal changes have been conducted. On Mokuyo Seamount, venting was first confirmed by several submersible dives between 1990 and 1993, but only fragmentary information has been published on its biodiversity. Here, we revisited Mokuyo on two dives between 2021 and 2024, three decades after its discovery. We found changes in venting activities, with the fluid supply on the northern caldera wall almost completely waned, while the northeastern face of the central cone has become increasingly active. The northwestern ridge of the central cone was covered in a dense white plume, under which xenophyophores (giant protists) thrive. The first comprehensive faunal sampling at Mokuyo greatly updated the faunal list from three to 18 species. Our results suggest vent communities on the Izu‐Ogasawara Arc shift on a decadal scale, providing key baseline data for future conservation planning of the EBSA.
Mitochondrial Genetic Diversity and Demographic History of Critically Endangered Oreochromis karongae (Trewavas, 1941) Along Lake Nyasa, Tanzania
Authors: Nehemia Alex , Mwakalesi Alinanuswe J.
Published: September 2024

Fish provide food and income opportunities for millions of people in Lake Nyasa, also known as Lake Malawi in Malawi and Lake Niassa in Mozambique. Oreochromis karongae (Trewavas, 1941), which is native to Lake Nyasa, Lake Malombe and the Shire River, is at the verge of extinction and has been listed as critically endangered species by the International Union for Conservation of Nature (IUCN), primarily due to overfishing. Using 632 bp of partial mitochondrial cytochrome oxidase subunit I (COI) sequences from 115 samples, this work aims to assess the population genetic status and demographic history of this species to better manage and advance its conservation. The analysis of molecular variance (AMOVA) revealed a low and non‐significant genetic differentiation index across the populations under study (ΦST = 0.003, p = 0.278), indicating a lack of population genetic structure. Phylogenetic analysis, grouped together all COI haplotypes of O. karongae from the six sampled sites. Nonetheless, the results showed signs of population expansion from a historic bottleneck, consistent with most data from the Western Indian Ocean Fauna. The findings from this study could be used to improve management and conservation strategies for critically endangered O. karongae in Lake Nyasa.
Intrathecal catheter placement after inadvertent dural puncture in the obstetric population: management for labour and operative delivery. Guidelines from the Obstetric Anaesthetists' Association
Authors: Griffiths Sarah K. , Russell Robin , Broom Malcolm A. , Devroe Sarah , Van de Velde Marc , Lucas D. N.
Published: September 2024

Background

Anaesthetists of all grades who work on a labour ward are likely to be involved in the insertion or management of an intrathecal catheter after inadvertent dural puncture at some point in their careers. Although the use of intrathecal catheters after inadvertent dural puncture in labour has increased in popularity over recent decades, robust evidence on best practice has been lacking.

Methods

The Obstetric Anaesthetists' Association set up an expert working party to review the literature. A modified Delphi approach was used to produce statements and recommendations on insertion and management of intrathecal catheters for labour and operative delivery following inadvertent dural puncture during attempted labour epidural insertion. Statements and recommendations were graded according to the US Preventive Services Task Force grading methodology.

Results

A total of 296 articles were identified in the initial literature search. Further screening identified 111 full text papers of relevance. A structured narrative review was produced which covered insertion of an intrathecal catheter; initial dosing; maintenance of labour analgesia; topping‐up for operative delivery; safety features; complications; and recommended follow‐up. The working party agreed on 17 statements and 26 recommendations. These were generally assigned a low or moderate level of certainty. The safety of mother and baby were a key priority in producing these guidelines.

Conclusions

With careful management, intrathecal catheters can provide excellent labour analgesia and may also be topped‐up to provide anaesthesia for caesarean or operative vaginal delivery. The use of intrathecal catheters, however, also carries the risk of significant drug errors which may result in high‐ or total‐spinal anaesthesia, or even cardiorespiratory arrest. It is vital that all labour wards have clear guidelines on the use of these catheters, and that staff are educated as to their potential complications.
Unveiling the intricacies of chronic kidney disease: From ocular manifestations to therapeutic frontiers
Authors: Kanbay Mehmet , Guldan Mustafa , Ozbek Lasin , Copur Sidar , Mallamaci Francesca , Zoccali Carmine
Published: September 2024

Background

Shared anatomical, histological and physiological pathways between the kidney and the eye are well documented, demonstrating that ocular manifestations serve as valuable prognostic indicators in chronic kidney disease (CKD), providing insights into disease severity and progression. Through non‐invasive imaging modalities such as retinal fundus photography, early retinal microvascular alterations indicative of CKD progression can be detected, enabling timely intervention and risk stratification. However, the conclusions drawn from the review primarily demonstrate a strong or independent association between glaucoma or retinopathy and CKD.

Results and Conclusion

Multiple shared pathophysiological events have been implicated in the pathogenesis in the alterations at eye and kidney including renin‐angiotensin‐aldosterone system. Patients with CKD are more likely to experience glaucoma, age‐related macular degeneration, cataracts, uremic optic neuropathy and retinopathy. To establish the role of ocular manifestations in predicting CKD progression, it is crucial to address the limitations of correlation and explore the underlying causality with further research on common disease pathogenesis. Additionally, specific methods for risk stratification based on retinal changes, the effectiveness of timely interventions, and the development of predictive tools combining ocular and renal data are of utmost importance research topics to enlighten the bidirectional causality.
No gold‐diggers here: Women investors in colonial Australian mining
Authors: Fleming Grant , Liu Zhangxin (Frank) , Merrett David , Ville Simon
Published: September 2024

We draw upon an extensive database of investors in colonial Australian mining, during the 1850s–80s, to provide the first historical analysis of the nature of women's share investing in Australia. Women were a minority of investors by number and value of holdings and faced a series of obstacles, yet their presence grew throughout the period. Most women invested independently neither drawing on male relatives nor other women. Many opted for only a single investment in this high‐risk industry, but a small minority built significant portfolios. We reveal that women managed these risks differently from men, taking account of their attitudes towards company characteristics, investor location, portfolio diversification, and the cyclical trends in mining.
A classification model for resectability in hepatocellular carcinoma patients
Authors: Nakamura Ikuo , Yoh Tomoaki , Nishimura Takashi , Okuno Masayuki , Okamoto Tomohiro , Sueoka Hideaki , Iida Kenjiro , Tada Masaharu , Ishii Takamichi , Seo Satoru , Fujimoto Yasuhiro , Iijima Hiroko , Hirono Seiko , Hatano Etsuro
Published: September 2024

Aim

Some patients undergoing liver resection for hepatocellular carcinoma (HCC) have poor outcomes. Therefore, we aimed to propose a new resectability classification for patients with HCC.

Methods

We classified patients into three categories: resectable (R), borderline resectable (BR), and unresectable (UR). Patients (n = 409) who underwent hepatectomy for HCC were assigned to the non‐UR (R and BR classes combined; n = 285) and UR‐HCC classes (n = 68; training cohort). Patient characteristics in the BR‐HCC and R‐HCC groups were compared. The new criteria were tested in a validation cohort (n = 295).

Results

Of the 285 patients, 229 and 56 were classified into the R‐ and BR‐HCC classes, respectively, using macrovascular invasion, tumor size, and future liver remnant/modified albumin‐bilirubin scores. Patients with BR‐HCC demonstrated significantly worse progression‐free and overall survival (p < 0.0001 and p < 0.0001, respectively) than patients with R‐HCC in the training cohort. Similar results were observed in the validation cohort. Multivariate analysis of the non‐UR‐HCC group in the training cohort revealed that the tumor number and BR‐HCC were independent predictive factors for poor overall survival.

Conclusions

This classification can help select patients with BR‐HCC for preoperative treatment before considering surgery.
Improvement of functional properties of Chlorella‐inulin conjugates via Maillard reaction
Authors: Riaz Rabaila , Tas Ozan , Oztop Mecit Halil , Niazi Muhammad Bilal Khan , Janjua Hussnain Ahmed
Published: September 2024

Functionalities of proteins for the formulation of protein‐fortified products are crucial, impacting the use of protein from sustainable sources such as algae. Glycation (the initial step of the Maillard browning reaction) is a standout modification technique explored to improve the functions of the protein in the food matrices. In this study, Chlorella powder was conjugated with inulin using a wet glycation method. It is a quick, scalable and easy method for improving the functionality of food proteins. In this study, conjugation was performed for three different Chlorella to inulin molar ratios (S1:1, S3:1 and S5:1). The solution of each molar ratio was heated at 90°C for 30 min under alkaline state (9.0 pH). Characterisation was conducted employing OPA assay, browning intensity and FTIR spectroscopy techniques. The results suggested glycation achieved the highest for the Chlorella‐inulin ratio of 1:1. Glycation extent influenced the solubility of this conjugate significantly (P < 0.05) under an acidic medium. Other functional properties including hydration, moisture uptake, oil‐binding and emulsifying activity were also significantly (P < 0.05) enhanced compared to unmodified Chlorella powder. Chlorella conjugate with molar ratio 1:1 also displayed higher antioxidant properties suggesting glycation's role in improving Chlorella powder free radical scavenging capabilities (1.25‐fold increase) and reducing power (2.24‐fold increase). The total scavenging activity and total reducing power of S1:1 were 2.526 × 10−3 and 1.872 × 10−3 mg mL−1 mg−1(Trolox Eq.), respectively. The results provide an understanding of different functionalities for glycated conjugates promising utilisation in the food and beverage industry.
Mental Health Status and the Intention to Leave the Profession of Nurses Employed Across Catalonia, Spain: A Cross‐Sectional Study
Authors: Giménez‐Díez David , Leyva‐Moral Juan M. , Watson Carolina E. , Bernabeu‐Tamayo Maria Dolors
Published: September 2024

Introduction

The relationship between nurses' mental well‐being and intention to leave the profession remains a pressing issue.

Aim

To determine the mental health status and the intention to leave the profession of nurses employed across diverse healthcare sectors in Catalonia, Spain.

Methods

This cross‐sectional study included 1051 Registered Nurses in Catalonia, Spain, using convenience sampling through social media platforms and personal contacts. Participants completed four standardised instruments online to measure anxiety, insomnia, depression and posttraumatic stress disorder, along with an ad hoc sociodemographic questionnaire. The methodology of this study was guided by the STROBE checklist.

Results

The analysis revealed that a significant proportion of participants exhibited mental health issues: 44% showed moderate to severe anxiety, 31% experienced moderate to severe insomnia, 40% suffered from moderate to severe depression and 42% had moderate to severe posttraumatic stress disorder. Participants who had worked in COVID hospital units were 1.38 times more likely to experience poor mental health status. Although not all associations were statistically significant, nurses working in primary healthcare, intensive care units and nursing homes had increased odds of poor mental health. Additionally, 53% of participants had reconsidered their working status, with 69% of them expressing an intention to leave the nursing profession.

Limitations

The evolving nature of the pandemic and the adaptation of healthcare workers to the new scenario may have influenced their experiences during data collection.

Implications

Highlights the increase in mental health‐related needs and high rates of psychiatric symptoms among nurses nowadays.

Recommendations

Addressing mental health needs is crucial to mitigate the intention of nurses to abandon the profession.
Unraveling the Urban Ecosystem: An Ethnographic Study of Logistics Service Providers
Authors: de Tarragon Hugo , Theodoraki Christina , Hlady‐Rispal Martine , Casteran Gauthier
Published: September 2024

Although there is a growing interest in developing sustainable cities, a significant knowledge gap persists regarding the concrete logistics choices necessary to achieve such cities. Grounded in ethnographic research on city logistics, this study examines how logistics service providers (LSPs) navigate sustainability challenges within the urban ecosystem while also meeting the efficiency demands of their business ecosystem. By repositioning LSPs as a sub‐ecosystem nested within the broader urban ecosystem, the article demonstrates how LSPs adeptly address the intricacies of the urban environment and respond to pressures from their business ecosystem. This investigation greatly enhances the understanding of the underlying issues affecting city logistics' sustainability. It deepens insight into the concept of city logistics as a sub‐ecosystem within the urban ecosystem, highlighting how its sustainability is intertwined with the structure of the urban ecosystem. From a societal perspective, this research conceptualizes city logistics as a business activity and a vital social service that bolsters urban well‐being. The findings suggest a need for further research into the role of city logistics actors as key contributors to urban sustainability.
Post‐conference review of oral session 6 and short talk in the 17th international IgA nephropathy conference, Tokyo 2023
Authors: Alexander Suceena
Published: September 2024

Oral session 6 titled ‘Clinical Trial 1’ and the short talk on ‘Landscape of Clinical Trials in IgAN‐What's beyond the Horizon?’ took place on 30 September 2023 in the symposium venue. The short talk highlighted the increase in IgAN trials in the last decade and the challenges of global clinical trials from the site investigator perspective. The talk also underlined the importance of relooking and repurposing already available and approved therapeutics. There were six oral sessions that focussed mainly on the interim results of ongoing clinical trials as well as early phase results with new investigational agents.
Utilizing complement inhibition in IgA nephropathy
Authors: Lafayette Richard
Published: September 2024

The role of complement in the pathogenesis of IgA nephropathy has been heavily explored over the past 50 years. This has led to the general acceptance that complement plays an important role in the clinical presentation and risk for progression of disease in patients with IgA nephropathy. Herein, we review the evidence for complement activation in IgA nephropathy, focusing on evidence that the lectin and alternate pathways are the main actors. We are entering an era of intense investigation of various inhibitors of complement, which should ultimately be the best indicator of contributions of the lectin, alternate and common complement pathways to disease burden. More importantly, we will see if these efforts result in the discovery of clinically relevant options in managing this important disease.
Proteolytic processing of both RXLR and EER motifs in oomycete effectors
Authors: Xu Lin , Wang Shumei , Wang Wei , Wang Haixia , Welsh Lydia , Boevink Petra C. , Whisson Stephen C. , Birch Paul R. J.
Published: September 2024

Arg‐any amino acid‐Leu‐Arg (RXLR) effectors are central oomycete virulence factors that suppress plant immunity. Relatively little is known about how they are processed post‐translationally before delivery into host cells.

A range of molecular, cell and biochemical processes were used to investigate proteolytic processing of RXLR and Glu‐Glu‐Arg (EER) motifs in Phytophthora infestans effectors.

Proteolytic cleavage at the RXLR motif occurred before secretion in all effectors tested, suggesting it is a general rule. Cleavage occurred between the leucine and the second arginine. There was no cleavage of a naturally occurring second RXLR motif in a structured region of Pi21388/AvrBlb1, or one introduced at a similar position in effector Pi04314, in keeping with the motif being positionally constrained, potentially to disordered regions closely following the signal peptide. Remarkably, independent proteolytic cleavage of the EER motif, often found immediately after the RXLR, was also observed, occurring immediately after the arginine. Full‐length effectors expressed in host plant Nicotiana benthamiana revealed that, although secreted, they were poorly processed, suggesting that RXLR and EER cleavage does not occur in all eukaryotic cells.

We conclude that, whether possessing both RXLR and EER, or either motif alone, these effectors are likely generally proteolytically processed before secretion.
Viroid and viroid‐like elements in plants and plant‐associated microbiota: a new layer of biodiversity for plant holobionts
Authors: Navarro Beatriz , Turina Massimo
Published: September 2024

The functional relevance of plant‐associated microorganisms is theoretically framed within the holobiont concept. The role of viruses in plant holobionts is being recognized both for their direct effects when hosted in plants (cryptic plant viruses) and for their indirect effects when infecting microorganisms associated with plants in tripartite interactions (e.g. mycoviruses and bacteriophages). We argue that viroids, the smallest infectious agents typically infecting only plant hosts, must also be included in plant holobiont studies. The same applies to the recently discovered large number of viroid‐like elements infecting hosts of other life kingdoms that are closely associated with plants. Here we also describe in depth the diversity of such viroid‐like elements and their initial functional characterization in plant‐associated fungi.