bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure-Kinetic Relationship for Drug Design Revealed by PLS Model with Retrosynthesis-Based Pre-trained Molecular Representation and Molecular Dynamics Simulation
Authors: Zhou Feng , Yin Shiqiu , Xiao Yi , Lin Zaiyun , Fu Weiqiang , Zhang Yingsheng J.
Published: November 2022

Drug design based on their molecular kinetic properties is growing in application. Pre-trained molecular representation based on retrosynthesis prediction model (PMRRP) was trained from 501 inhibitors of 55 proteins and successfully predicted the koffvalues of 38 inhibitors for HSP90 protein from an independent dataset. Our PMRRP molecular representation outperforms others such as GEM, MPG, and common molecular descriptors from RDKit. Furthermore, we optimized the accelerated molecular dynamics to calculate relative retention times for 128 inhibitors of HSP90. We observed high correlation between the simulated, predicted, and experimental -log(koff) scores. Combining machine learning (ML) and molecular dynamics (MD) simulation help design a drug with specific selectivity to the target of interest. Protein-ligand interaction fingerprints (IFPs) derived from accelerated MD further expedite the design of new drugs with the desired kinetic properties. To further validate our koffML model, from the set of potential HSP90 inhibitors obtained by similarity search of commercial databases, we identified two novel molecules with better predicted koffvalues and longer simulated retention time than the reference molecules. The IFPs of the novel molecules with the newly discovered interacting residues along the dissociation pathways of HSP90 shed light on the nature of the selectivity of HSP90 protein. We believe the ML model described here is transferable to predict koffof other proteins and enhance the kinetics-based drug design endeavor.
The importance of vaccinated individuals to population-level evolution of pathogens
Authors: Gutierrez Maria A. , Gog Julia R.
Published: November 2022

Virus evolution shapes the epidemiological patterns of infectious disease, particularly via evasion of population immunity. At the individual level, host immunity itself may drive viral evolution towards antigenic escape. Using compartmental SIR-style models with imperfect vaccination, we allow the probability of immune escape to differ in vaccinated and unvaccinated hosts. As the relative contribution to selection in these different hosts varies, the overall effect of vaccination on the antigenic escape pressure at the population level changes.

We find that this relative contribution to escape is important for understanding the effects of vaccination on the escape pressure and we draw out some fairly general patterns. If vaccinated hosts do not contribute much more than unvaccinated hosts to the escape pressure, then increasing vaccination always reduces the overall escape pressure. In contrast, if vaccinated hosts contribute significantly more than unvaccinated hosts to the population level escape pressure, then the escape pressure is maximised for intermediate vaccination levels. Past studies find only that the escape pressure is maximal for intermediate levels with fixed extreme assumptions about this relative contribution. Here we show that this result does not hold across the range of plausible assumptions for the relative contribution to escape from vaccinated and unvaccinated hosts.

We also find that these results depend on the vaccine efficacy against transmission, particularly through the partial protection against infection. This work highlights the potential value of understanding better how the contribution to antigenic escape pressure depends on individual host immunity.
A systematic review exploring the association between the human gut microbiota and brain connectivity in health and disease
Authors: Mulder Danique , Aarts Esther , Vasquez Alejandro Arias , Bloemendaal Mirjam
Published: November 2022

1

A body of pre-clinical evidence shows how the gut microbiota influence brain functioning, including brain connectivity. A growing number of studies have investigated the association between the gut microbiota and brain connectivity in humans. Linking brain connectivity measures to the gut microbiota can provide important mechanistic insights into the bi-directional gut-brain communication. In this systematic review, we therefore synthesized the available literature assessing this association, evaluating the degree of consistency in microbiota-connectivity associations. Following the PRISMA guidelines, a PubMed search was conducted, including studies published up to September 1, 2022. We identified 16 studies that met the inclusion criteria. Several bacterial genera, includingPrevotella,Bacteroides,RuminococcusandBlautiawere most consistently reported in association with brain connectivity. Additionally, the salience (specifically the insula and anterior cingulate cortex), default mode and frontoparietal networks were most frequently associated with the gut microbiota, both in terms of microbial diversity and composition. Altogether, based on our synthesis, there is evidence for an association between the gut microbiota and brain connectivity. However, the specificity of the signal is yet unclear as most findings were poorly replicated across studies. The current studies show substantial inter-study heterogeneity in methodology and reporting, limiting the robustness and reproducibility of the findings and emphasizing the need to harmonize methodological approaches. To enhance comparability and replicability, future research should focus on further standardizing processing pipelines and employ data-driven multivariate analysis strategy.
Visuo-proprioceptive recalibration and the sensorimotor map
Authors: Block Hannah J. , Liu Yang
Published: November 2022

Spatial perception of our hand is closely linked to our ability to move the hand accurately. We might therefore expect that reach planning would take into account any changes in perceived hand position; in other words, that perception and action relating to the hand should depend on a common sensorimotor map. However, there is evidence to suggest that changes in perceived hand position affect a body representation that functions separately from the body representation used to control movement. Here we examined target-directed reaching before and after participants either did (Mismatch group) or did not (Veridical group) experience a cue conflict known to elicit recalibration in perceived hand position. For the reaching task, participants grasped a robotic manipulandum that positioned their unseen hand for each trial. Participants then briskly moved the handle straight ahead to a visual target, receiving no performance feedback. For the perceptual calibration task, participants estimated the locations of visual, proprioceptive, or combined cues about their unseen hand. The Mismatch group experienced a gradual 70 mm forward mismatch between visual and proprioceptive cues, resulting in forward proprioceptive recalibration. Participants made significantly shorter reaches after this manipulation, consistent with feeling their hand to be further forward than it was, but reaching performance returned to baseline levels after only 10 reaches. The Veridical group, after exposure to veridically-aligned visual and proprioceptive cues about the hand, showed no change in reach distance. These results are not fully consistent with a single common sensorimotor map, but could suggest multiple, interacting body representations.

NEW & NOTEWORTHY

If perceived hand position changes, we might assume this affects the sensorimotor map and, in turn, reaches made with that hand. However, there is evidence for separate body representations involved in perception vs. action. After a cross-sensory conflict that results in proprioceptive recalibration in the forward direction, participants made shorter reaches as predicted, but only briefly. This is not fully consistent with a single common sensorimotor map, but could suggest multiple, interacting body representations.
A Brain-Wide Genome-Wide Association Study of Candidate Quantitative Trait Loci Associated with Structural and Functional Phenotypes of Pain Sensitivity
Authors: Zhang Li , Pan Yiwen , Huang Gan , Liang Zhen , Li Linling , Zhang Zhiguo
Published: November 2022

Individual pain sensitivity is influenced by many factors, such as the differentiation of brain regional features and genetic variations. However, its heritability remains largely unclear. The present study conducted a brain-wide genome-wide association study (GWAS) to explore the genetic bases of structural and functional neuroimage phenotypes of pain sensitivity. In total 432 normal participants were firstly divided into high and low pain sensitivity groups according to laser quantitative test threshold and related brain regions’ gray matter density (GMD) features were identified. Consequently, GWAS was performed on each GMD phenotype using quality-controlled genotypes. Based on the heatmap and hierarchical clustering results from GWAS, the right insula was selected for further refined analysis in terms of sub-regions GMD and resting-state functional connectivity (rs-FC) phenotypes. The results indicate that the right insula GMD in the high sensitivity group is significantly lower than the low sensitivity group. Also, the TT/TC group at locus rs187974 may lead to a lower GMD in the right insula than the CC group. Meanwhile, loci at gene CYP2D6 may lead to a variation of rs-FC between the right insula and left putamen. In conclusion, our study suggests multiple candidate loci associated with pain sensitivity that may influence brain phenotypes.
A general model-based causal inference method overcomes the curse of synchrony and indirect effect
Authors: Park Se Ho , Ha Seokmin , Kim Jae Kyoung
Published: November 2022

To identify causation, model-free inference methods, such as Granger Causality, have been widely used due to their flexibility. However, they have difficulty distinguishing synchrony and indirect effects from direct causation, leading to false predictions. To overcome this, model-based inference methods that test the reproducibility of data with a specific mechanistic model to infer causality were developed. However, they can only be applied to systems described by a specific model, greatly limiting their applicability. Here, we address this limitation by deriving an easily testable condition for a general monotonic ODE model to reproduce time-series data. We built a user-friendly computational package, GOBI (General ODE-Based Inference), which is applicable to nearly any monotonic system with positive and negative regulations described by ODE. GOBI successfully inferred positive and negative regulations in various networks at both the molecular and population levels, unlike existing model-free methods. Thus, this accurate and broadly applicable inference method is a powerful tool for understanding complex dynamical systems.
SARS-CoV-2 Vaccine Booster Elicits Robust Prolonged Maternal Antibody Responses and Passive Transfer Via The Placenta And Breastmilk
Authors: Marshall Nicole E. , Blanton Madison B. , Doratt Brianna M. , Malherbe Delphine C. , Rincon Monica , True Heather , Mcdonald Taylor , Beauregard Caroline , Adatorwovor Reuben , Messaoudi Ilhem
Published: November 2022

Background

Infection during pregnancy can result in adverse outcomes for both pregnant persons and offspring. Maternal vaccination is an effective mechanism to protect both mother and neonate into post-partum. However, our understanding of passive transfer of antibodies elicited by maternal SARS-CoV-2 mRNA vaccination during pregnancy remains incomplete.

Objective

We aimed to evaluate the antibody responses engendered by maternal SARS-CoV-2 vaccination following initial and booster doses in maternal circulation and breastmilk to better understand passive immunization of the newborn.

Study Design

We collected longitudinal blood samples from 121 pregnant women who received SARS-CoV-2 mRNA vaccines spanning from early gestation to delivery followed by collection of blood samples and breastmilk between delivery and 12 months post-partum. During the study, 70% of the participants also received a booster post-partum. Paired maternal plasma, breastmilk, umbilical cord plasma, and newborn plasma samples were tested via enzyme-linked immunosorbent assays (ELISA) to evaluate SARS-CoV-2 specific IgG antibody levels.

Results

Vaccine-elicited maternal antibodies were detected in both cord blood and newborn blood, albeit at lower levels than maternal circulation, demonstrating transplacental passive immunization. Booster vaccination significantly increased spike specific IgG antibody titers in maternal plasma and breastmilk. Finally, SARS-CoV-2 specific IgG antibodies in newborn blood correlated negatively with days post initial maternal vaccine dose.

Conclusion

Vaccine-induced maternal SARS-CoV-2 antibodies were passively transferred to the offspringin uterovia the placenta and after birth via breastfeeding. Maternal booster vaccination, regardless of gestational age at maternal vaccination, significantly increased antibody levels in breastmilk and maternal plasma, indicating the importance of this additional dose to maximize passive protection against SARS-CoV-2 infection for neonates and infants until vaccination eligibility.
Cell dichotomous role of STING in pulmonary hypertension
Authors: Pham Ann T. , Oliveira Aline C. , Fu Chunhua , Alves Matthew D. , Dupee Zadia , Mukhsinova Laylo , Ebrahimi Elnaz , Patel Harsh , Patel Reeha , Nguyen Amy , Jin Lei , Bryant Andrew J.
Published: November 2022

Rationale

Patients with constitutive activation of DNA sensing pathway through stimulator of interferon genes (STING), such as those with STING-Associated Vasculopathy with onset in Infancy (SAVI), frequently have complications related to pulmonary hypertension (PH). However, the role of STING-signaling in adult PH patients is heretofore undescribed.

Objective

To investigate the role of STING in PH development.

Methods and Results

PH was induced in global STING deficient or cell-specific STING deficient mice using either bleomycin or chronic hypoxia exposure. PH development was evaluated with right ventricular systolic pressure, Fulton index, histological and flow cytometric measurements. STING expression in patient lungs were examined using both immunohistochemistry and flow cytometry. Herein, we describe how STING overactivation in a SAVI mouse model results in a baseline elevation in pulmonary pressures, while global STING deficiency protects mice from PH development. Furthermore, STING-associated PH appears to be independent of type I Interferon (IFN) signaling. We further demonstrate a cellular dichotomous role of STING in PH development with STING expression by smooth muscle cells contributing to PH, and its activation on myeloid cells being pivotal in severe disease prevention. Finally, we demonstrate a STING-PD-L1 axis as necessary for disease progression, suggesting future potential therapeutic applications.

Conclusions

Overall, these data provide concrete evidence of STING involvement in PH, establishing biologic plausibility for STING-related therapies in PH treatment.

Graphical abstract
PAMP-Induced secreted Peptide-Like 6 (PIPL6) functions as an amplifier of plant immune response through RLK7 and WRKY33 module
Authors: Najafi Javad , Gjennestad Ragnhild Sødal , Kissen Ralph , Brembu Tore , Bartosova Zdenka , Winge Per , Bones Atle M
Published: November 2022

Plant peptide hormones are engaged in the regulation of plant developmental programs and immunity. PAMP-Induced Peptide (PIP) hormones are new class of signaling peptide with diverse functional roles in the regulation of plant development and stress responses. In this study, we have investigated the function of PAMP-Induced secreted Peptide-Like 6 (PIPL6) as an amplifier of plant immunity against necrotrophic fungal pathogens inArabidopsis thaliana. We have applied an integrated omics approach to unveil the function and downstream signaling pathways initiated by PIPL6.PIPL6is highly and transiently induced by treatment with different elicitors. Exogenous application of synthetic peptide designed from the C-terminal conserved domain of PIPL6 resulted in strong transcriptional induction of many genes involved in the regulation of plant immunity. Further gene expression analysis revealed that induction of marker genes by PIPL6 peptide requires the receptor-like kinase 7 (RLK7). Immunoblotting and gene expression analysis demonstrated that exogenous applications of PIPL6 peptide activates MAPK6, MAPK3, and WRKY33 module in an RLK7-dependent manner. The levels of salicylic acid, jasmonic acid, camalexin, and glucosinolates were differentially regulated inPIPL6knock-down and overexpression lines challenged by necrotrophic pathogenBotrytis cinerea. Bioassays using the necrotrophic fungal pathogensBotrytis cinereaandAlternaria brassicaeshowed thatpipl6knock-down lines were more susceptible to these pathogens whilePIPL6overexpression lines exhibited enhanced resistance. Altogether, these results indicate that the PIPL6 peptide functions as a new damage-associated molecular pattern (DAMP) and acts as an amplifier of Arabidopsis immunity.
Novel multi-component crystals of berberine with improved pharmaceutical properties
Authors: Zhang Guoshun , Yang Xirui , Shang Xiaoqing , Han Wei , Wang Fengfeng , Ban Shurong , Zhang Shuqiu
Published: November 2022

As an extremely popular natural product, berberine (BER) is mainly used for gastroenteritis and diarrhoea caused by bacteria. Research has also revealed the potent and extensive pharmacological properties of BER including its anti-arrhythmic, anti-tumour, anti-inflammatory and hypoglycemic activities and so on; therefore, BER is a promising drug for further development. However, its commercial form with hydrochloride exhibits poor stability and solubility, which are detrimental to its clinical therapeutic effects. For these purposes, the salt form was regulated via the reactive crystallization of 8-hydroxy-7,8-dihydroberberine (8H-HBER) with five pharmaceutically suitable organic acids including malonic acid (MA), L-tartaric acid (LTA), D-tartaric acid (DTA), DL-tartaric acid (DLTA) and citric acid (CA), resulting in the six novel solid forms 1BER-1LTA-1W, 1BER-1DTA-1W, 1BER-1DLTA and 2BER-2CA as well as two rare multi-stoichiometric solid forms 1BER-1MA and 1BER-2MA-2W. The preparation of the multi-stoichiometric products was greatly influenced by both the crystallization solvent type and the molar ratio of reactants. The structures of these multi-component solid forms were determined using single-crystal X-ray diffraction and further characterized by powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy. Stability experiments showed that all samples prepared had superior physical stability under high temperature and high humidity. Furthermore, dissolution experiments demonstrated that the maximum apparent solubilities (MAS) of all the products were significantly improved compared with the commercial form of BER in dilute hydrochloric solution (pH = 1.2). In particular, the MAS of 1BER-1MA in dilute hydrochloric solution is as high as 34 times that of the commercial form. In addition, it is preliminarily confirmed that the MAS of the samples prepared in pure water and dilute hydrochloric solution is primarily influenced by a combination of factors including the packing index, intermolecular interactions, affinity of the counter-ion to the solvent, the molar ratio of the drug to counter-ion in the product and the common ion effect. These novel solids are potential candidates for BER solid forms with improved oral dosage design and may prompt further development.
Effects of personal environmental awareness and environmental concern on employees' voluntary pro-environmental behavior: a mediation analysis in emerging countries
Authors: Saifulina Nailya , Carballo-Penela Adolfo , Ruzo-Sanmartín Emilio
Published: November 2022

Purpose

Successful stimulation of employee engagement in pro-environmental behavior (PEB) at work can reduce organizational environmental footprint and boost its green performance. The aim of this paper is to investigate the individual factors that may promote such behavior at work, offering a complex model with mediating relationships not studied before.

Design/methodology/approach

In this paper data was collected through a survey of 331 bank employees from different banks in Kazakhstan and Ecuador. Structural equation modeling was used to test the relationships between the different constructs.

Findings

The results identified that environmental values and attitudes mediate the relationship between (1) personal environmental awareness and (2) environmental concern and employees' voluntary PEB at work. Harmonious environmental passion (HEP) mediates the relationship between environmental values and attitudes and employees' voluntary PEB at work.

Practical implications

This study presents important organizational policymaking implications with regard to organizational greening. The importance of environmental awareness is underlined, guiding managers to offer environmental education and training to the employees with the aim of improving environmental knowledge that may lead to employees' voluntary PEB at work. Also, managers should work on enhancing HEP.

Originality/value

Prior literature on this topic is still scarce. This research presents important contributions by discussing how individual antecedents may act as stimuli of employees' voluntary PEB at work in the context of the banking sector in two emerging countries that are often neglected by prior literature.
Typographic design of outdoor signage, restaurant authenticity, and consumers’ willingness to dine: extending semiotic theory
Authors: Song Hanqun , Ding Qing Shan , Xu Jing Bill , Kim Jonghyeong , Chang Richard C.Y.
Published: November 2022

Purpose

Restaurants’ outdoor signage plays an irreplaceable role in attracting potential diners, as it conveys important functional and symbolic meanings of the businesses. The purpose of this study is to investigate the effect of typographic design elements of outdoor signage on consumers’ perceptions of authenticity. This study also tests the linkage between authenticity and willingness to dine, as well as the moderating effect of frequency of dining in ethnic restaurants on the relationship.

Design/methodology/approach

Using a 2 (simplified vs traditional Chinese characters) × 2 (calligraphy vs computer font) × 2 (vertical vs horizontal text flow) between-subject design, the authors did two experiments with 786 Chinese diners. Restaurant authenticity and willingness to dine are dependent variables, and openness to ethnic cuisine is the control variable.

Findings

Display characters and text flow significantly affect restaurant authenticity. Furthermore, the results of this study demonstrate that display characters interact with typeface to influence restaurant authenticity. Consumers’ perceived authenticity significantly increases their willingness to dine. The frequency of dining in ethnic restaurants moderates the relationship between restaurant authenticity and willingness to dine.

Practical implications

Ethnic restaurateurs should pay attention to the outdoor signage design, as it affects potential consumers’ authenticity perceptions. Specifically, in Mainland China, traditional Chinese characters and vertical text direction increase potential consumers’ authenticity perceptions.

Originality/value

This study extends the semiotic theory and applies the cue–judgment–behavior model in the hospitality literature. This study also provides new understanding of authenticity by identifying the influence of typographic design on authenticity, which confirms the semiotic theory that certain semiotic cues affect consumers’ judgments.
Parametric mathematical modeling and 3D response surface analysis for rod to plate friction welding of AISI 1020 steel/AISI 1018 steel
Authors: Thirumalaikkannan Dhamothara kannan , Paramasivam Sivaraj , Visvalingam Balasubramanian , Sonar Tushar , Sivaraj Sathiya
Published: November 2022

Purpose

Rotary friction welding (RFW) was used to solve the issues in fusion welding of rod to plate joints of low carbon steel (AISI 1020 steel/AISI 1018 steel) such solidification cracking, wider heat affected zone (HAZ), lower HAZ hardness, high residual stresses and distortion. The main objective of this investigation is to develop parametric mathematic models (PMMs), 3D response surface analysis to predict tensile strength (TS) and weld interface hardness (WIH) of rod to plate joints and correlate microstructure with TS and WIH of rod to plate joints.

Design/methodology/approach

The three-factor x five-level central composite design (CCD) consisting fewer experiments was employed for designing experimental matrix. The tensile and microhardness tests were performed to evaluate mechanical performance of joints. The PMMs of TS and WIH of rod to plate joints were developed using polynomial regression equations incorporating the RFW parameters. The 3D response surfaces were developed using response surface methodology (RSM) to optimize RFW parameters for joining AISI 1020/AISI 1018 rod to plate.

Findings

The joints made using friction pressure/friction time (FRNP/FRNT) of 3.71 MPa/s, forging pressure/forging time (FRGP/FRGT) of 3.71 MPa/s and rotational speed (RTSP) of 19.99 rps exhibited higher TS and WIH of 452 MPa and 252 HV0.5. The PMMs accurately predicted TS and WIH of rod to plate joints at less than 1.5% error and 95% confidence. The RTSP revealed greater effect on TS and WIH of rod to plate joints followed by FRGP/FRGT and FRNP/FRNT. The superior TS and WIH of joints developed using optimized process parameters is correlated to the evolution of finer bainitic microstructure in weld interface due to the dynamic recrystallization of grains ensued by optimum frictional heating and plastic deformation.

Originality/value

The PMMs were developed for predicting TS and WIH of joints. The RFW parameters were optimized to enhance TS and WIH of joints. Low carbon steel rod to plates joints were developed using RFW for automotive applications without fusion welding defects. The microstructural features of low strength and high strength rod to plate joints were correlated to the TS and WIH of rod to plate joints.
Evaluation of organizational variables of quality 4.0 in digital transformation: the study of an Indian manufacturing company
Authors: Mittal Ankesh , Kumar Vimal , Verma Pratima , Singh Arpit
Published: November 2022

Purpose

The study aims to identify organizational variables of quality 4.0 for an Indian manufacturing company in the case of digital transformation. Furthermore, the organization enhances its quality 4.0 performances to its success based on the degree of relevance of these variables, insight into these variables and sub-factors to prioritize them.

Design/methodology/approach

Initially, two rounds of the survey were conducted with 11 decision-makers from the company made to receive organizational variables scores and prioritize the factors and sub-factors. Analytic Hierarchy Process (AHP) based research methodology has been proposed to assign the criterion weights and prioritize the identified variables.

Findings

The results of this AHP model demonstrate that “Committed Leadership” is recognized as the top positioned variable and most significant organizational variable, followed by Collaboration and Quality culture, which are developed at the next level. These essential organizational variables with their sub-categories' priorities are identified as contributing attributes.

Research limitations/implications

The findings facilitate quality 4.0 in the digitalization era, which take into contemplating the current state of the business. Furthermore, the understanding of variables provides insightful guidance to analyze, solve complex problems and assess the efficacy of quality 4.0 in digital transformation.

Originality/value

The novelty of this study is to pinpoint, and evaluate the responsible organizational variables and prioritize them that lead to high productivity and competitive advantage considering the AHP method.
Local tourists' perceptions of tourist destinations' competitiveness: a comparative study of the United Arab Emirates, Egypt, and Oman
Authors: Abou-Shouk Mohamed , Zoair Nagoua , Elbaz Ahmed Mohamed , Abdel-Jalil Marwa
Published: November 2022

Purpose

Destination competitiveness is a significant contributor to tourism growth, performance and development. The current research intends to test the effect of the dimensions of the Travel and Tourism Competitiveness Index (TTCI) on destination competitiveness in the United Arab Emirates (UAE), Egypt and Oman and how competitiveness influences tourism performance and development.

Design/methodology/approach

The perspectives of 460 responses were collected from the UAE, 457 from Egypt and 301 responses from Oman. Partial least squares structural equation modelling (PLS-SEM) was utilised to measure the research model relationships.

Findings

The results showed that the competitiveness index components are significantly contributing to destination competitiveness and that this competitiveness is predicting both tourism performance and development.

Originality/value

This study developed and empirically tested the effect of an integrative model of the competitiveness index on destination competitiveness from the perspective of local visitors in three Muslim and Arab nations. This study gives scholars valuable perceptions into how socio-cultural variations between residents and locals in various nations might result in significantly diverse behaviours.
Random noise attenuation of ocean bottom seismometers based on a substep deep denoising autoencoder
Authors: Lin Haoran , Xu Jian , Xing Lei , Li Qianqian , Liu Huaishan
Published: November 2022

Ocean bottom seismometer data usually contain a large amount of random noise, which seriously reduces the signal‐to‐noise ratio of the data and affects subsequent imaging. Hence, random noise attenuation is one of the most essential steps in ocean bottom seismometer data processing. In this paper, a novel approach is proposed to attenuate the marine seismic random noise of ocean bottom seismometers based on a six‐dense‐layer denoising autoencoder. We input the domain data into the denoising autoencoder, the encoder compresses the signal and noise and extracts the main features and the decoder finally reconstructs the denoised data with the same dimension as the input. In this approach, because few raw labelled examples are available, we first constructed the pretraining, training and test data sets by patch processing. Then, we pretrained the encoder based on clean synthetic seismic data through unsupervised learning and pretrained the decoder based on noisy synthetic seismic data through supervised learning. Next, the pretrained model was fine‐tuned with the encoder–decoder on a raw seismic data set in an unsupervised manner. Finally, we used the model to attenuate the random noise in raw ocean bottom seismometer data for testing. Synthetic and raw examples are used to compare the deconvolution, multichannel singular spectrum analysis, deep denoising autoencoder and substep deep denoising autoencoder approaches. Experimental tests demonstrate that the proposed method has higher processing efficiency and precision.
Everyday Economy and Levelling Up
Authors: Raikes Luke
Published: November 2022

Levelling up and the everyday economy are two crucial concepts for understanding the direction of policy making in the UK, but the relationship between them has not yet been fully explored. Moreover, the UK's industrial and regional policies are woefully underdeveloped. This article suggests how levelling up and the everyday economy concepts could contribute to Labour's emerging industrial and regional policies. It argues that Labour is right to pursue an economic growth agenda, but must make growth work for communities and workers, and the everyday economy can help. The everyday economy can contribute to, and benefit from, local productivity growth, but regions still need companies that export or are at the technological frontier to raise demand, productivity and pay. Labour should work with the government's Levelling Up White Paper, but this was overly focussed on cities and knowledge intensive business services: there is an economic case for including towns and manufacturing too, and they should prioritise connecting places and sectors, building on the diverse strengths which different places can offer, and setting a long‐term direction of travel. Over time, Labour should try to ensure that cities, towns and smaller communities are better connected, better coordinated and more specialised within larger regions. Labour should, therefore, set out an industrial and regional strategy; work up an economic development toolkit; and devolve economic powers to Mayoral Combined Authorities and councils.
Why Strike Ballots are Undemocratic
Authors: Saunders Ben
Published: November 2022

Since 2016, new legislation governing strike ballots has made it more difficult for trade unions to achieve a mandate for industrial action. Such a mandate now requires that a majority of members vote in the ballot. This article argues that these balloting processes are undemocratic. The turnout requirement means that a mandate for industrial action does not simply depend on its level of popular support amongst union members. This has surprising consequences. Sometimes opponents of action would be better advised to abstain, rather than to vote against it. Thus, it is not always clear how they should vote. Whatever they do, their actions may be counterproductive. Further, even when they do know how best to promote their desired outcome, there may be a conflict between voting strategically and clearly expressing their true preferences. Consequently, there is no guarantee that the outcome of the ballot accurately reflects what people really want.
Pollen metabarcoding reveals the floral resources and niche overlap of honeybees in forest areas
Authors: Do Yuno , Park Woong‐Bae , Park Jun‐Kyu , Kim Chang‐Jun , Kim Il‐Kwon , Choi Moon Bo
Published: November 2022

We investigated the floral resources of the honeybee (Apis mellifera) by pollen DNA metabarcoding as the first step in honeybee conservation. We attempted to identify as many floral resources and as wide resource availability as possible in areas and compared the richness of floral resources between forests and national parks. We found that both forest and national parks can sufficiently support honeybee floral resources; however, national parks were more stable habitats with more complex vegetation structure than those of forests. Also, honeybee's preferences for floral resources were determined using niche breadth, niche overlap, and network analysis among the floral resources in forest areas. Quercus and Actinidia were the most frequently detected taxa of pollen resources in both forests and national parks by pollen metabarcoding. Even though we anticipated that more various pollen resource taxa would be found in national parks than forests, no differences in the number pollen resource taxa were detected between them. According to the niche overlap analysis result, the honeybee preferred the pollen resources in both forests and national parks, and the co‐occurrence pattern analysis of pollen resource taxa in both forests and national parks showed a simple network. Altogether, our findings suggested that DNA metabarcoding of pollen collected by the honeybee can provide useful information on the flowering plants in a given area. As the use of floral pollen resources varies spatially and temporally, periodic monitoring of pollen resources can identify which pollen is required to maintain the health of honeybee colonies.
Co‐designing research with Aboriginal and Torres Strait Islander consumers of mental health services, mental health workers, elders and cultural healers
Authors: Milroy Helen , Kashyap Shraddha , Collova Jemma , Mitchell Michael , Derry Kate Loren , Alexi Joanna , Chang Ee Pin , Dudgeon Pat
Published: November 2022

Introduction

The disparity in mental health outcomes compared with non‐Indigenous Australians means that there is an urgent need to develop an evidence base around how services can better support Aboriginal and Torres Strait Islander communities. A critical first step is to embed cultural safety into research methodologies.

Objective

Here, we aim to establish the foundation of a research project through co‐designing a qualitative interview with Aboriginal and Torres Strait Islander consumers and community members about experiences of cultural safety with mainstream mental health services.

Design

Voices of Aboriginal and Torres Strait Islander peoples must be empowered across all stages of research. An Aboriginal‐led research team conducted focus groups to understand clear, sensitive, and culturally appropriate ways of asking about experiences in mental health care, to co‐design an interview on this topic. Participants were Aboriginal and Torres Strait Islander consumers of mental health services, carers, mental health workers, Elders and Cultural Healers, living in Metropolitan and Regional Western Australia.

Findings

Results suggest that Indigenous governance, together with investing in ongoing, and meaningful cultural awareness and cultural safety training (cultural awareness being a first step towards safety) for non‐Indigenous researchers, together with taking the time to build respectful partnerships with communities through ongoing consultation, were appropriate and comprehensive methods of co‐designing an interview.

Discussion

The process of working with Aboriginal and Torres Strait Islander peoples in research is as important as the outcome. Aboriginal and Torres Strait Islander leadership, self‐determination, and relationship building with communities are essential.

Conclusion

Empowering co‐design methodologies are flexible, iterative, and ensure that the experiences and views of participants are valued, leading to more meaningful results.
Early‐life fecal metabolomics of food allergy
Authors: Lee‐Sarwar Kathleen A. , Chen Yih‐Chieh , Lasky‐Su Jessica , Kelly Rachel S. , Zeiger Robert S. , O'Connor George T. , Bacharier Leonard B. , Jia Xiaojiong , Beigelman Avraham , Gold Diane R. , Laranjo Nancy , Bunyavanich Supinda , Weiss Scott T. , Litonjua Augusto A. , Brennan Patrick J.
Published: November 2022

Background

Intestinal microenvironmental perturbations may increase food allergy risk. We hypothesize that children with clinical food allergy, those with food sensitization, and healthy children can be differentiated by intestinal metabolites in the first years of life.

Methods

In this ancillary analysis of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we performed untargeted metabolomic profiling in 824 stool samples collected at ages 3–6 months, 1 year and 3 years. Subjects included 23 with clinical food allergy at age 3 and/or 6 years, 151 with food sensitization but no clinical food allergy, and 220 controls. We identified modules of correlated, functionally related metabolites and sought associations of metabolite modules and individual metabolites with food allergy/sensitization using regression models.

Results

Several modules of functionally related intestinal metabolites were reduced among subjects with food allergy, including bile acids at ages 3–6 months and 1 year, amino acids at age 3–6 months, steroid hormones at 1 year, and sphingolipids at age 3 years. One module primarily containing diacylglycerols was increased in those with food allergy at age 3–6 months. Fecal caffeine metabolites at age 3–6 months, likely derived from breast milk, were increased in those with food allergy and/or sensitization (beta = 5.9, 95% CI 1.0–10.8, p = .02) and were inversely correlated with fecal bile acids and bilirubin metabolites, though maternal plasma caffeine levels were not associated with food allergy and/or sensitization.

Conclusions

Several classes of bioactive fecal metabolites are associated with food allergy and/or sensitization including bile acids, steroid hormones, sphingolipids, and caffeine metabolites.
Chronic spontaneous urticaria: Focus on pathophysiology to unlock treatment advances
Authors: Kaplan Allen , Lebwohl Mark , Giménez‐Arnau Ana M. , Hide Michihiro , Armstrong April W. , Maurer Marcus
Published: November 2022

Chronic spontaneous urticaria (CSU) is a debilitating skin disease characterized by intensely itchy wheals, angioedema, or both. Symptoms recur spontaneously, on a near‐daily basis, over >6 weeks; many patients experience flare‐ups over several years and, consequently, reduced quality of life. Differences between the inflammatory profiles of the skin of CSU patients (wheals and nonlesional sites) and healthy controls indicate that key drivers such as mast cells, eosinophils, and basophils interact, release vasoactive mediators, and prime the skin, leaving patients predisposed to symptoms. Many cytokines and chemokines involved in these inflammatory networks and their corresponding intracellular signaling cascades have been identified. These insights informed the development of therapies such as omalizumab, dupilumab, and Bruton's tyrosine kinase (BTK) inhibitors, marking a renewed focus on pathogenesis in CSU clinical research. Despite progress, current therapies provide symptomatic control but do not appear to redress the inflammatory balance in the skin permanently. A deeper understanding of CSU pathogenesis will permit a more targeted approach to developing novel treatments with curative intent. Here, we review what is known about the pathogenesis of CSU and consider how this can be used to identify rational targets to improve patient care further.
Does choroidal thickness predict persistent subretinal fluid after rhegmatogenous retinal detachment repair? A retrospective study with fellow eye comparison
Authors: Albanese Giuseppe Maria , Visioli Giacomo , Iannetti Ludovico , Giovannetti Francesca , Armentano Marta , Romano Enrico , Macario Federico , Fino Pasquale , Gharbiya Magda
Published: November 2022

Purpose

To evaluate whether choroidal thickness (CT) is associated with persistent subretinal fluid (pSRF) after simple primary rhegmatogenous retinal detachment (RRD) repair.

Methods

This single‐centre, retrospective, observational study included patients who underwent RRD repair with at least 12‐month follow‐up. Preoperative and postoperative parameters were evaluated for association with pSRF. CT measurements were obtained at the central 1 mm area on enhanced depth imaging (EDI) OCT scans, using a semiautomatic method. Multiple logistic regression analyses were assessed to determine predictive factors for pSRF.

Results

Overall, 100 eyes of 100 patients, mean age of 59.9 ± 12.6 years were included. pSRF was found in 21.0% of eyes and resolved over time in 85.7% of eyes at 12 months. In the pSRF group both RRD and fellow eyes showed lower mean choroidal and RPE thickness values as compared to those without pSRF (p < 0.05). A significant correlation was found between pSRF occurrence and choroidal thinning (p = 0.02). After multiple regression analyses, macula‐off RRD (p = 0.005) and scleral buckling (SB) technique (p = 0.001) were retained as final predictors for pSRF. In macula‐off SB eyes, detachment duration was the only factor associated with pSRF (p = 0.046). There were no significant differences in best‐corrected visual acuity outcomes between the pSRF and the no‐pSRF eyes.

Conclusions

Patients with pSRF showed lower choroidal and RPE thickness as compared to those without pSRF. CT did not turn out to be a final predictor for pSRF, as this was mainly associated with macular involvement, surgical technique and detachment duration.
Clinical impact of biofire gastrointestinal panel testing for hospitalised children with acute gastroenteritis
Authors: Sever Aviv , Ben Zvi Haim , Melamed Shirel Barnea , Sachs Nimrod , Krause Irit , Bilavsky Efraim
Published: November 2022

Aim

To investigate the clinical impact of BioFire FilmArray Gastrointestinal Panel (FGP) testing in real‐life diarrhoeal episodes of hospitalised paediatric patients.

Methods

Children hospitalised between October 2018 and September 2020 for whom stool specimens for FGP were submitted at the clinician's discretion were retrospectively observed. For each episode, demographics, clinical information and stool tests were collected.

Results

The clinical impact for each case was evaluated by changing the antibiotic prescription, following the result of the FGP testing. Out of 140 diarrhoeal episodes, 25 pathogens were found in 24 cases using conventional methods, whereas, FGP testing identified 75 pathogens in 56 cases (p < 0.05). The pathogens more frequently identified by FGP testing were Campylobacter, Shigella, Rotavirus, Giardia lamblia and Cryptosporidium. The clinical impact of FGP testing was observed in 17/140 (12%) diarrhoeal episodes, and higher rates in previously healthy (19%) and solid organ–transplanted children (15%).

Conclusion

We found that using FGP testing for hospitalised children with diarrhoeal episodes could increase pathogen identification and impact clinical decisions, especially in healthy and transplant patients.
Do more, with less: The realities of local government in rural Ontario
Authors: Gibson Ryan , Dale John
Published: November 2022

Over the past 30 years, the responsibilities, mandates, and activities of local governments in Ontario have undergone substantial transformations. Influenced by New Public Management, policy changes are characterized by marketization and managerialism resulting in downloading of responsibilities to local governments. This research examines the ebbs and flows of policy changes among different provincial governments since 1990 and the impacts of these policies on rural local governments in Ontario. Interviews were conducted with elected officials and senior staff in eight local governments to understand their realities. The findings demonstrate the continual policy changes led to the “do more, with less” approach currently faced by rural local governments—increased regulatory requirements, limited human and financial capacities, and small tax bases to support their activities. This experience, combined with limited fiscal levers, hinders the ability of rural local governments to address both new demands for infrastructure and existing infrastructure deficits, housing stock and affordability, and economic and workforce development strategies. The reality has necessitated local governments to seek alternative strategies to deliver programs and services through partnerships and collaboration.
Behavioral inhibition, negative parenting, and social withdrawal: Longitudinal associations with loneliness during early, middle, and late adolescence
Authors: Verhagen Maaike , Derks Mare , Roelofs Karin , Maciejewski Dominique
Published: November 2022

Adolescent loneliness can have detrimental effects on physical and mental health, but there is limited understanding of its antecedents in infancy and childhood. A 20‐year longitudinal, multi‐informant, and multi‐methods study (first data collection in 1998) was conducted to examine mechanisms underlying adolescent loneliness (N = 128, 52% boys, Mage_baseline = 1.23, SD = 0.02, 99% White, recruitment in Dutch urban, healthcare centers). Structural equation modeling showed that high infant behavioral inhibition (BI) was indirectly associated with high loneliness during adolescence via high childhood social withdrawal. This indirect effect was equally strong during early, middle, and late adolescence. Contrary to expectations, infant parenting did not moderate the relation between BI and social withdrawal. The results suggest a developmental cascade with infant BI showing long‐lasting indirect effects on adolescent loneliness up to 20 years later via childhood social withdrawal.