bluuebunny/crossref_metadata_2025 huggingface dataset:
Small Molecule Modulators of β-arrestins
Authors: Kahsai Alem W. , Pakharukova Natalia , Kwon Henry Y. , Shah Kunal S. , Liang-Lin Jason G. , del Real Caroline T. , Shim Paul J. , Lee Mason A. , Ngo Van A. , Shreiber Bowie N. , Liu Samuel , Schwalb Allison M. , Espinoza Emmanuel F. , Thomas Brittany N. , Kunzle Cal A. , Smith Jeffrey S. , Wang Jialu , Kim Jihee , Zhang Xingdong , Rockman Howard A. , Thomsen Alex R. B. , Rein Lindsay A.M. , Shi Lei , Ahn Seungkirl , Masoudi Ali , Lefkowitz Robert J.
Published: December 2024

β-arrestins (βarrs) are key regulators of G protein-coupled receptors (GPCRs), essential for modulating signaling pathways and physiological processes. While current pharmacological strategies target GPCR orthosteric and allosteric sites, as well as G protein transducers, comparable tools for studying βarrs are lacking. Here, we present the discovery and characterization of novel small-molecule allosteric inhibitors of βarrs through comprehensive biophysical, biochemical, pharmacological, and structural analyses. These inhibitors disrupt βarr interactions with agonist-activated GPCRs, impairing receptor internalization, desensitization, and βarr-mediated physiological functions. A cryo-EM structure of βarr1 in complex with the allosteric inhibitor Cmpd-5, complemented by molecular dynamics simulations and mutagenesis studies, reveals that Cmpd-5 binds within a cryptic cleft formed by the middle, C-, and lariat loops–a critical site for βarr activation and recruitment to GPCRs. Thus, Cmpd-5 acts as a molecular lock, hindering βarr1 activation via an allosteric mechanism. These findings introduce novel strategies and tools for probing βarr functions.

Highlights

Small molecule strategies for modulating βarr functions in both GPCR-dependent and independent contexts.

Modulators disrupt βarr interaction with GPCRs, impairing their critical functions.

Cryo-EM structures reveal the allosteric inhibitor Cmpd-5 binding to a cryptic pocket between the N and C domains in the central crest of βarr1, inhibiting its activation.

Structural analyses, including cryo-EM, MD simulations, and mutagenesis, reveal a unique βarr1 conformation induced by Cmpd-5, shedding light on its mechanism of allosteric inhibition.
Combinations of genomic alterations and immune microenvironmental features associate with patient survival in multiple cancer types
Authors: Bayati Masroor , Klein Zoe P. , Bahcheli Alexander T. , Slobodyanyuk Mykhaylo , To Jeffrey , Cheng Kevin C. L. , Mishra Jigyansa , Pellegrina Diogo , Guevara-Hoyer Kissy , McIntosh Chris , Bhat Mamatha , Reimand Jüri
Published: December 2024

Oncogenesis and tumor progression are shaped by somatic alterations in the cancer genome and features of the tumor immune microenvironment (TME). How interactions of these two systems influence tumor development and clinical outcomes remains incompletely understood. To address this challenge, we developed the multi-omics analysis framework PACIFIC to systematically integrate genetic cancer drivers and infiltration profiles of immune cells with clinical information. In an analysis of 8500 cancer samples, we report 34 immunogenomic interactions (IGXs) in 13 cancer types in which context-specific combinations of genomic alterations and immune cell activities associate with disease outcomes. Risk associations of IGXs are potentially explained by tumor-intrinsic and microenvironmental metrics of immunogenicity and differential expression of therapeutic targets. In luminal-A breast cancer,MEN1deletion combined with reduced neutrophils is associated with poor prognosis and deregulation of immune signalling pathways. These findings help elucidate how cancer drivers interact with TME to contribute to tumorigenesis.
Determination of Gaussian curvature modulus and spontaneous curvature via membrane buckling
Authors: Wang Mei-Ting , Jiang Gao-Xiao , Ma Rui , Wu Chen-Xu
Published: December 2024

The elastic properties of membranes are typically characterized by a few phenomenological parameters, including bending and Gaussian curvature moduli measuring the membrane rigidity against its deformation and topological change, as well as spontaneous curvature arising from the asymmetry between the two leaflets in the lipid bilayers. Though tether-based and fluctuation-based experiments are commonly utilized to measure the bending modulus, measuring the Gaussian curvature modulus and the spontaneous curvature of the membrane is considered to be much more difficult. In this paper, we study the buckling process of a circular membrane with nonzero spontaneous curvature under compressive stresses. It is found that when the stress exceeds a critical value, the circular membrane will transform from a spherical cap to a buckled shape, with its buckling degree enhanced with the increase of stress until its base is constricted to almost zero. As the stress-strain relationship of the buckled membrane strongly depends on the Gaussian curvature modulus and the spontaneous curvature,we therefore propose a method to determine the Gaussian curvature modulus and the spontaneous curvature simultaneously by measuring its stress-strain relationship during a buckling process.
Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency
Authors: Tiwari Vinod , Jin Byungchang , Sun Olivia , Lopez Gonzalez Edwin D.J. , Chen Min-Hsuan , Wu Xiwei , Shah Hardik , Zhang Andrew , Herman Mark A. , Spracklen Cassandra N. , Goodman Russell P. , Brenner Charles
Published: December 2024

Citrin Deficiency (CD) is caused by inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. We discovered that SLC25A13 loss causes accumulation of glycerol-3-phosphate (G3P), which activates carbohydrate response element binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol, and to transcribe key genes ofde novolipogenesis. Mouse and human data establish G3P-ChREBP as a new mechanistic component of the Randle Cycle that contributes to metabolic dysfunction-associated steatotic liver disease (MASLD) and forms part of a system that communicates metabolic states from liver to brain in a manner that alters food and alcohol choices. The data provide a framework for understanding FGF21 induction in varied conditions, suggest ways to develop FGF21-inducing drugs, and drug candidates for both lean MASLD and support of urea cycle function in CD.
Effects of meglumine antimoniate and allopurinol treatment on the fecal microbiome profile in dogs with leishmaniosis
Authors: Martí-Carreras Joan , Carrasco Marina , Noguera-Julian Marc , Francino Olga , Oliveira Leal Rodolfo , Ferrer Lluís , Oliva Gaetano , Molina Jenifer , Roura Xavier
Published: December 2024

The combination of meglumine antimoniate and allopurinol is considered one of the most effective treatments for canine leishmaniosis caused byLeishmania infantum. This study investigated the effects of this treatment on the gut microbiome of 10 dogs from Spain, Portugal, and Italy via fecal shotgun metagenomic sequencing over six months. Dogs were sampled at baseline (BL) and at one (M1) and six (M6) months post-treatment. The gut microbiome ofLeishmania-infected dogs (BL) is dominated byPrevotella,Collinsella,Bacteroides, andBlautia, with individual variability being the primary determinant of microbiome composition. No significant changes in alpha diversity (Shannon index, gene number) or beta diversity (Bray-Curtis dissimilarity, UniFrac distance) were detected between pre- and post-treatment time points, suggesting that treatment with meglumine antimoniate and allopurinol does not disrupt the gut microbiota. Minor trends in taxonomic shifts were noted, with slight increases inBifidobacterium pseudocantenulatum,Collinsella tanakaei, andSlackia piriformisafter treatment, but these changes were not statistically significant after correction for multiple testing. Linear discriminant analysis and multivariable modeling confirmed that the microbial community structure was resilient to treatment effects. Individual-specific microbiome differences in diversity accounted for 52% of the observed variability, underscoring the personalized nature of the gut microbiota in dogs. Importantly, no adverse microbiome disruptions were detected, even with prolonged allopurinol use. This study highlights the robustness of the canine gut microbiome during antileishmanial therapy and highlights the use of meglumine antimoniate and allopurinol without compromising gut microbial diversity or health. Further studies with larger cohorts are recommended to confirm these findings and explore the functional roles of the gut microbiota in modulating immune responses inLeishmania-infected dogs.
Huntingtin interactome reveals huntingtin role in regulation of double strand break DNA damage response (DSB/DDR), chromatin remodeling and RNA processing pathways
Authors: Ratovitski Tamara , Holland Chloe D. , O’Meally Robert N. , Shevelkin Alexey V. , Shi Tianze , Cole Robert N. , Jiang Mali , Ross Christopher A.
Published: December 2024

Huntington’s Disease (HD), a progressive neurodegenerative disorder with no disease-modifying therapies, is caused by a CAG repeat expansion in the HD gene encoding polyglutamine-expanded huntingtin (HTT) protein. Mechanisms of HD cellular pathogenesis and cellular functions of the normal and mutant HTT proteins are still not completely understood. HTT protein has numerous interaction partners, and it likely provides a scaffold for assembly of multiprotein complexes many of which may be altered in HD. Previous studies have implicated DNA damage response in HD pathogenesis. Gene transcription and RNA processing has also emerged as molecular mechanisms associated with HD. Here we used multiple approaches to identify HTT interactors in the context of DNA damage stress. Our results indicate that HTT interacts with many proteins involved in the regulation of interconnected DNA repair/remodeling and RNA processing pathways. We present evidence for a role for HTT in double strand break repair mechanism. We demonstrate HTT functional interaction with a major DNA damage response kinase DNA-PKcs and association of both proteins with nuclear speckles. We show that S1181 phosphorylation of HTT is regulated by DSB, and can be carried out (at leastin vitro) by DNA-PK. Furthermore, we show HTT interactions with RNA binding proteins associated with nuclear speckles, including two proteins encoded by genes at HD modifier loci, TCERG1 and MED15, and with chromatin remodeling complex BAF. These interactions of HTT may position it as an important scaffolding intermediary providing integrated regulation of gene expression and RNA processing in the context of DNA repair mechanisms.
Cell Morphology accurately predicts the nuclear shape of adherent cells
Authors: Lawton Sebastian , Danzman Rosaline A. , Spagnuolo Renzo , Stephan Skylar , Graul Sydney , Wiggan O’Neil , Ghosh Soham , Prasad Ashok
Published: December 2024

Cells are internally tensed, or prestressed, largely by actomyosin contractility. We hypothesized that nuclear shape is quantitatively predictable from cell shape since prestress couples them both. We trained machine learning models on a publicly available image database of the WTC-11 cell line and predicted shape modes of the nucleus with high accuracy. We develop a U-Net architecture-based model, Cell2Nuc, that predicted nuclear voxels from the cell membrane with accuracies between 74%-87%. To investigate prestress, we cultured and imaged HeLa cells after inhibiting actomyosin contractility. The Cell2Nuc model retrained on the HeLa cells predicted nuclear voxels with slightly lower accuracy. Statistical analysis revealed changes in nuclear size and chromatin organization upon prestress inhibition. Similar trends were seen in images taken from NIH3T3 cells. Thus, cell shape encodes features of nuclear shape, their coupling is partly due to actomyosin contractility, whose abrogation leads to changes in chromatin organization of mechanosensitive origin.
The spiraling effect of incivility enacted through information and communication technology (ICT) in the workplace
Authors: Zivnuska Suzanne , Harris Ken , Valle Matthew , Harris Ranida , Carlson John , Carlson Dawn S.
Published: December 2024

Purpose

This research provides an empirical test of Andersson and Pearson’s (1999) theoretical incivility spiral. Rather than investigate the incidence of incivility perpetration following incivility victimization in face-to-face interactions, this study tests for evidence of an incivility spiral due to communications enacted through information and communication technology (ICT) based on affective events theory (AET) (Weiss and Cropanzano, 1996). Further, the moderating impacts of both gender and incivility climate on this relationship are considered.

Design/methodology/approach

The sample for this Time 1–Time 2 survey-based research was comprised of 354 full-time working adults from a wide range of organizations. We employed hierarchical moderated regression analyses as our primary data analytic technique.

Findings

Results demonstrate that victims of ICT incivility at Time 1 are likely to be perpetrators of ICT incivility at Time 2. Furthermore, this relationship is stronger for men than it is for women and is exacerbated in cultures that have a low tolerance for ICT incivility.

Originality/value

This is the first known test of the incidence of an incivility spiral due to communications enacted through ICT. There is special cause for concern given the often-impersonal nature of ICT use (and abuse) in organizations. Individuals may feel emboldened by the distance and perceived safety ICT mediation affords and may be less likely to moderate their online interactions with colleagues. Absent the physical intimacy and non-verbal signals that face-to-face interactions provide, individuals may be more likely to perpetuate incivility in ICT interactions even if there is no implicit intent to harm others.
Analyzing the influence of coopetition on resilience in the open innovation network from the perspective of knowledge diffusion
Authors: Lv Jiaxin , Zou Xingqi , Yang Qing , Zhang Ke
Published: December 2024

Purpose

In the realm of open innovation (OI) networks, coopetition—where competition and cooperation coexist—plays a pivotal role in shaping the dynamics between diverse projects. This dual relationship is crucial for the propagation of knowledge and the bolstering of the network's overall resilience. While competition drives the quality of products and services, thereby reinforcing network resilience, cooperation facilitates knowledge diffusion, which is essential for the network's robustness.

Design/methodology/approach

We delve into the interplay between coopetition intensity and network resilience through the lens of knowledge diffusion. Our methodology begins with a sensitivity analysis to gauge the direct effects of coopetition on resilience. This is followed by a principal component analysis to identify the key determinants of coopetition intensity among projects. Finally, we utilize linear regression and moderation analysis to explore the mediating role of knowledge diffusion in the resilience of OI networks.

Findings

Our work is grounded in network theory, which provides a robust theoretical framework for understanding project coopetition and knowledge diffusion within the OI paradigm. This research not only offers a nuanced understanding of coopetition's impact on OI network resilience but also highlights the significance of knowledge diffusion as a critical mediating variable.

Originality/value

1) Identifies the significant influences in project coopetition (competition and cooperation). (2) Puts the conceptual framework and calculation method of the open innovation network resilience based on the project coopetition and knowledge diffusion. (3) Explores the moderating role of knowledge diffusion in project coopetition influencing open innovation networks resilience. (4) Measures the influence of project coopetition relationship on open innovation network resilience from the perspective of knowledge diffusion. (5) Encourages project management to consider the portfolios of coopetition.
Guidelines to enhance stakeholder management in higher education institutions
Authors: Anholon Rosley , Rampasso Izabela Simon , Ávila Lucas Veiga , Sigahi Tiago F.A.C. , Moraes Gustavo Hermínio Salati Marcondes de , Pavan Serafim Milena , Leal Filho Walter
Published: December 2024

Purpose

The relationship with internal and external actors on the part of higher education institutions (HEIs) is a fundamental factor for them to fully exercise their role in sustainable development and the evolution of individuals, organizations and society as a whole. In this sense, this study aims to analyze the literature about stakeholder management in HEIs and to provide guidelines to support managers of HEIs to enhance stakeholder management practices.

Design/methodology/approach

This research was conducted through a bibliometric analysis followed by a content analysis to propose the guidelines to support HEIs’ managers in improving stakeholder management practices.

Findings

The guidelines were proposed for each of the following seven areas: engagement and governance; innovation and knowledge management; education for sustainable development; responsible research, innovation and collaborative partnerships; organisational change management; social responsibility; and performance management and sustainability report.

Originality/value

Although the topic addressed has gained traction in the academic community, the literature fails to provide guidelines to support managers of HEIs enhance stakeholder management practices. From a theoretical standpoint, the increasing recognition of the importance of stakeholder engagement reflects a paradigm shift in understanding sustainability and social responsibility in HEIs. On a practical level, managers can use the guidelines to promote effective dialogue, increase stakeholder engagement and collaborative partnerships.
SDG4 academic research productivity in the EU27: economic factors and COVID-19 impacts
Authors: Alfirević Nikša , Malešević Perović Lena , Mihaljević Kosor Maja
Published: December 2024

Purpose

This paper aims to examine the factors influencing 2018–2022 research productivity related to Sustainable Development Goal 4 (SDG4) in the EU-27 considering the COVID-19 epidemic.

Design/methodology/approach

This paper applies the two-panel estimators to bibliometric data from Scopus and relevant indicators, focusing on the previously achieved scientific productivity levels, national GDP, government education expenditures and the COVID-19 contingency variables. This study addresses the information gap regarding pertinent elements influencing SDG4 research productivity.

Findings

Research productivity in SDG4 is negatively impacted by government spending on education and the SDG4 goal score and positively impacted by the lagged number of prior SDG4 publications and GDP per capita.

Research limitations/implications

The robustness of the results across several panel estimators, the necessity of evaluating interactions with other SDGs and the possibly restricted generalizability of the findings outside the EU-27 sample are limitations acknowledged in this work.

Originality/value

Nations with high levels of SDG4 implementation are becoming less interested in conducting related studies or hinting at a possible systemic mismatch between research and policy at the EU level. The COVID-19 epidemic has had a positive effect on SDG4 research output, indicating that external obstacles to the research process should be contextualized by examining a range of contingency elements in addition to being perceived as general obstacles.
Effect of global oil shocks on the sectoral returns
Authors: Jarral Raazia , Rehman Mobeen Ur
Published: December 2024

Purpose

This study examines the effects of global oil shocks on sectoral returns during the Pakistani market’s bearish, normal and bullish behavior by controlling VIX and SP500.

Design/methodology/approach

We analyze daily sectoral return data from the Pakistan Stock Exchange, covering the period from January 2, 2012, to February 17, 2022. Oil shocks are classified into demand, risk and supply shocks using Ready (2018) methodology, distinguishing their unique characteristics and importance. We utilize quantile regression to evaluate how these oil shocks affect sectoral returns, considering market dynamics. Additionally, we employ the Granger causality test to validate our findings.

Findings

The quantile regression results indicate that the effects of oil shocks on each sector are heterogeneous and significant during both bullish and bearish market phases. Specifically, supply shocks demonstrate a more substantial influence than other shocks, consistent with Kilian’s (2009) findings. Furthermore, the Granger causality test outcomes, conducted after removing control variables, reinforce our findings.

Practical implications

This study offers evidence that aids investors in understanding how shocks affect sectoral returns. Additionally, it provides insights for policymakers to develop policies that respond effectively to market fluctuations caused by these shocks.

Originality/value

This study holds value for researchers investigating the causes of shocks and their implications for the stock market. Moreover, the insights from this study, focusing on the Pakistani market, could provide a fundamental reference for other oil-dependent nations aiming to mitigate the impacts of global oil price volatility.
The impact of social support on individual health knowledge creation in online patient communities: the mediating role of attitude
Authors: Zhao Haibao
Published: December 2024

Purpose

This study aims to explore the impact mechanism of social support on individual health knowledge creation among users in online patient communities, guide and promote the creation of health knowledge and provide insights into managing online patient communities.

Design/methodology/approach

A theoretical model was constructed by integrating social impact and social support theories. Data were collected through questionnaires, and 750 valid responses were analysed using a structural equation model.

Findings

This study found the following. (1) Social support influences individual health knowledge creation through the mediating effects of creative self-efficacy and positive emotions. (2) The general rule of the strength of the influencing factors on individual health knowledge creation is that creative self-efficacy > positive emotions. (3) The general pattern of the mediating effect of attitude factors between social support and health knowledge creation is that creative self-efficacy > positive emotions. (4) The key path for social support to influence individual health knowledge creation is “social support → creative self-efficacy → health knowledge creation”. (5) The dimensions of social support in online patient communities can be divided into information, emotional, respect and network support. Individual health knowledge creation can be divided into health knowledge externalisation, combination, socialisation and internalisation.

Originality/value

This study expands the application scope of social influence theory and opens up the “black box” of the impact of social support on individual health knowledge creation behaviour. Simultaneously, the dimensions of social support, individual health knowledge creation and the mediating role between social support and health knowledge creation are discussed.
Fostering open innovation in SMEs: the crucial role of high-performance working systems and the mediating influence of innovative work behaviour
Authors: Çera Elona , Çera Gentjan , Matošková Jana , Ndou Valentina , Gregar Aleš
Published: December 2024

Purpose

Owing to the growing importance of human resource practices (HRM) and open innovation (OI) in small and medium enterprises (SMEs) context, the purpose of this paper is to investigate the effect of high-performance working systems (HPWS) on inbound and outbound open innovation in SMEs through the mediating role of innovative work behaviour (IWB). Using ability-enhancing, motivation-enhancing and opportunity-enhancing (AMO) framework, this study investigates the direct and i.ndirect effects of HPWS AMO practices and SMEs open innovation through the mediation effects of IWB.

Design/methodology/approach

This study employed a random sampling method to collect data by surveying 208 participants from SMEs in high-tech manufacturing and knowledge-intensive service sectors. Partial least squares-structural equation modelling is employed to analyse the interrelationships between constructs.

Findings

The results show that ability-enhancing practices are critical HRM practices that directly influence SMEs inbound and outbound; IWB is positively and significantly related to OI approaches; IWB partially mediates the relations between AMO HPWS and inbound and outbound open innovation.

Practical implications

The effects of HPWS practices are important in fostering OI in SMEs operating in Czech Republic. In addition, IWB is a partial intermediation that strengthens the relation between AMO HPWS and inbound and outbound OI.

Originality/value

This study adds to our understanding of the direct and indirect interactions between HPWS practices, IWB and inbound and outbound open innovation in high-tech manufacturing and knowledge-intensive service SMEs in Czech Republic.
The impact of COVID-19 on the efficiency of exchange rate, stock and cryptocurrency markets
Authors: Kumar Satish , Pathak Rajesh
Published: December 2024

Purpose

We investigate how the COVID-19 pandemic affected the efficiency of exchange rate, stock and cryptocurrency returns by analyzing a well-known calendar anomaly, the turn-of-the-month (TOM) effect.

Design/methodology/approach

We define the TOM days as the final trading day of a month and the initial three trading days of the immediate next month. To understand the TOM effect, we estimate the typical ordinary least squares regression model using the Heteroskedasticity and Autocorrelation Consistent (HAC) standard errors and covariances.

Findings

Our findings indicate that the returns during TOM days are significantly higher relative to those of non-TOM days. Nonetheless, our findings further reveal that the COVID-19 pandemic intensifies the TOM effect for the equity markets but weakens it for the exchange rate and Ethereum markets. We then develop a trading strategy that is found to beat the typical buy-and-hold (BH) approach.

Practical implications

Based on these results, we create a trading strategy which is found to surpass the BH strategy. Our results provide useful implications for investors and policymakers, as the considered markets can be timed by taking positions, especially based on the behavior of the TOM effect.

Originality/value

First, this paper is the inaugural study to examine the TOM effect across equity, currency and cryptocurrency markets. Previous studies have not addressed the TOM effect in Ethereum markets. Second, our paper conducts a battery of validity tests to ensure that the studied anomaly is not confounded by erstwhile anomalies. Third, our paper explores the performance of studied anomalies both prior to and throughout the COVID-19 pandemic to gain a deeper understanding of market efficiency. Finally, we validate our findings using the Kruskal–Wallis test, free from the assumptions of normal distribution.
Exploring staff experiences of formulation processes in a secure children’s home
Authors: Lawrence Harriet , Matthews Tom , Turgoose David
Published: December 2024

Purpose

This study aims to explore experiences of the Framework for Integrated Care's team formulation process within a secure children’s home in northern England, from the perspective of care and education staff.

Design/methodology/approach

Four focus groups were facilitated, with a total of 25 participants. The focus groups discussed a number of key areas, including: staff experiences of team formulation; the usefulness of the process; the wider impact of the process; and ways the formulation process could be developed. The data set was analysed using Rapid Qualitative Analysis (Hamilton, 2013).

Findings

Six overarching themes and a number of accompanying subthemes were developed. The six themes were: (i) new ways of understanding; (ii) enabling communication; (iii) young person should be at the centre; (iv) practical considerations; (v) developing accessibility: a systemic lens; and (vi) developing the focus.

Practical implications

Ten implications for practice within secure children’s homes and wider establishments are outlined. These relate to various aspects of the formulation process, including the preparatory work, meeting attendance, the focus of the formulation and dissemination.

Originality/value

Research within the context of secure children’s homes is expanding and has included the direct involvement of young people. To the best of the authors’ knowledge, this is the first study utilising a qualitative, focus group method to consider the experiences of team formulation from the perspective of the wider care and education staff team in a secure children’s home.
Progression of artificial intelligence/machine learning in geotechnical engineering
Authors: Shahin Mohamed
Published: December 2024

Purpose

This short review paper aims to examine the evolution of artificial intelligence (AI)/machine learning (ML) in the realm of geotechnical engineering.

Design/methodology/approach

This paper gives a brief overview of AI/ML technology and discusses its current trend and future directions in geotechnical engineering.

Findings

Despite limitations, the use of AI/ML techniques has several significant benefits that make them powerful and practical tools in the field of geotechnical engineering.

Originality/value

This paper explored the integration of AI/ML promising technology into geotechnical design and practice and highlighted its transformative impacts in terms of benefits, limitations and potential future directions.
Salt-free-multifunctional dyeing approaches for cotton and CVC fabrics with direct and reactive dyes using chitosan and keratin
Authors: Beg Tahreem , Farrukh Maha , Naeem Farhana
Published: December 2024

Purpose

Reactive and direct dyes are the most frequently used dyes for cotton fabrics. Cellulosic fibers pose a great affinity toward them. However, both dyes consume large quantities of salts for exhaustion; these electrolytes (salt) are discharged as effluents posing environmental problems and disorders in aquatic life. Therefore, this study aims to explore alternative approaches to minimize salt consumption.

Design/methodology/approach

For this study, the combination of chitosan and keratin, being sustainable biopolymers, are used as mordants instead of salts for the cationization of 100% cotton and chief value cotton (CVC) during dyeing with direct and reactive dyes. Color strength, exhaustion rates and color fastness to washing, rubbing and perspiration have been evaluated in this paper. In this research, keratin solution is applied on cotton and CVC (with the cotton to polyester ratio of 80%:20%) fabrics by pad-dry-cure, while chitosan solution has been applied with the exhaust method. The pretreated fabrics are dyed with both direct and reactive dyes with 2% and 4% depth of shade (DOS). The performance of the cationized fabrics with salt-free dyeing method was compared with the conventional dyeing.

Findings

The results of this study showed positive impact on exhaustion rates ranged from 19% to 69% of the values obtained without salt in 2% DOS and a range of 22%–47% in 4% DOS of reactive and direct dyes with treated samples. Color fastness to crocking results indicated the improvement of results by a factor of 0.5–1 after treatment and good wash fastnesses rating (4.5/5) were achieved for the chitosan-keratin treated fabrics equivalent to untreated samples. In addition, antimicrobial testing was performed on both treated and untreated fabrics of cotton and CVC. The results indicated that chitosan treated samples showed greater inhibition toward microbial activity as compared to keratin treated samples. Fourier transform infrared (FTIR) spectroscopy was used to identify the functional groups of chitosan and keratin treated fabric samples to confirm their presence. In the FTIR spectra, the chitosan was characterized by its hydroxyl, carbonyl and amide III peaks indicating the presence of chitosan and keratin was detected by the presence of primary amines. Scanning electron microscopy analysis was conducted in which it was visibly seen that the fibers have been coated with chitosan and keratin laid after being dyed.

Originality/value

For the first time, direct and reactive dyes are applied on chitosan and keratin-treated cotton and CVC to obtain multifunctional and eco-friendly fabrics.
An interdisciplinary approach to improve oral motor fluency and speech production
Authors: Schepp Jamie , Tsamoutales Lorilee , Yeich Richele , Amey Jonathan , Bradbury Sophie Louise , Solomon Risca
Published: December 2024

Purpose

Precision teaching (PT) has been used to teach functional daily living skills by identifying motor movement deficits, teaching them to fluency in isolation and then practising the daily living skill. However, little research has focused on using PT strategies to teach speech. Therefore, the purpose of this study is to evaluate the effects of directly teaching component oral motor skills using tactile prompting techniques on the fluency of the oral motor component skills and the composite skill of speech production.

Design/methodology/approach

A pre/post design was used to measure the effects of oral motor exercises and tactile prompting procedures on the fluency of oral motor movements and speech production with an individual with Fragile X syndrome. Fluency timings of oral motor movements and a standardised speech assessment were conducted pre- and post-intervention. An intervention derived from speech and language therapy was adopted using behaviour analytic principles and implemented with the participant.

Findings

The pre/post fluency timing scores revealed an increase in the fluency of oral motor movements targeted during the intervention. An increase was also observed in the standardised speech assessment scores post-intervention.

Originality/value

There is very limited literature applying principles of PT to speech production. As such, the present study suggests the intervention was successful at increasing speech production by first targeting oral motor skills.
A comprehensive review on arsenic exposure and risk assessment in infants and young children diets: Health implications and mitigation interventions in a global perspective
Authors: Shu Lin , Yang Guiling , Liu Shufang , Huang Nan , Wang Ruike , Yang Mengxue , Chen Chen
Published: December 2024

The early stages of human development are critical for growth, and exposure to arsenic, particularly through the placenta and dietary sources, poses significant health risks. Despite extensive research, significant gaps remain in our comprehension of regional disparities in arsenic exposure and its cumulative impacts during these developmental stages. We hypothesize that infants in certain regions are at greater risk of arsenic exposure and its associated health complications. This review aims to fill these gaps by providing a comprehensive synthesis of epidemiological evidence related to arsenic exposure during early life, with an emphasis on the underlying mechanisms of arsenic toxicity that contribute to adverse health outcomes, including neurodevelopmental impairments, immune dysfunction, cardiovascular diseases, and cancer. Further, by systematically comparing dietary arsenic exposure in infants across Asia, the Americas, and Europe, our findings reveal that infants in Bangladesh, Pakistan, and India, exposed to levels significantly exceeding the health reference value range of 0.3–8 µg/kg/day, are particularly vulnerable to dietary inorganic arsenic. This comparative analysis not only highlights geographic disparities in exposure but also underscores the variability in regulatory frameworks. Finally, the review identifies early life as a critical window for dietary arsenic exposure and offers evidence‐based recommendations for mitigating arsenic contamination in infant foods. These strategies include improved agricultural practices, dietary modifications, stricter regulatory limits on arsenic in infant products, and encouragement of low‐arsenic dietary alternatives. Our work establishes the framework for future research and policy development aimed at reducing the burden of arsenic exposure from source to table and effectively addressing this significant public health challenge.
Organic acid‐assisted heat treatment enhances the xanthine oxidase inhibitory activity of Flos Sophorae Immaturus tea
Authors: Li Jun , Niu Ben , Wu Peng , Meng Xiangren , Fan Liuping
Published: December 2024

Abundant polyphenols in Flos Sophorae Immaturus tea (FSIt) exhibited xanthine oxidase (XO) inhibitory activity. However, the XO inhibitory activity of FSIt was closely related to the processing methods. Herein, organic acids were employed as catalysts for polyphenol conversion during heat treatment and applied to enhance the XO inhibitory activity of FSIt; the potential mechanisms were clarified by polyphenols degradation and conversion analysis, omission experiment, and interaction assay. Results showed that 10% oxalic acid (OA)‐ or 10% lactic acid (LA)‐assisted heat treatment significantly increased the XO inhibition rate from 26.49% to 84.16% and 75.45%, respectively. OA‐assisted presented the high catalytic efficiency of rutin (31.56%), hyperoside (33.21%), and quercitrin (34.14%) to quercetin during heat treatment, as well as kaempferol‐3‐O‐rutinoside (20.04%) to kaempferol and narcissoside (26.04%) to isorhamnetin. The de‐glycosylation of polyphenols was the predominant reason for the enhancement of XO inhibitory activity. Moreover, the synergistic effect of chlorogenic acid and flavonoids also exhibited the ability to improve the XO inhibitory activity of FSIt.

Practical Application

Improving the polyphenol composition of FSIt through organic acid‐assisted heat treatment, thereby enhancing its XO inhibitory activity, is a promising approach to deeply understand the relationship between processing methods and bioactivities of products, and further promote innovation in specific functional food processing technology.
Untargeted metabolite profiling reveals metabolic disorders in livers of rats with mepiquat exposure
Authors: Hu Chuanqin , Song Xinyu , Wang Jing , Sun Baoguo
Published: December 2024

Mepiquat is a contaminant produced in thermal‐processed food. It can induce spleen and liver injury. However, the mechanism that mepiquat induced hepatotoxicity remains unclear. In this study, a ultra‐performance liquid chromatography‐mass spectrometry (UPLC‐MS/MS)‐based metabolomic analysis of livers in rats was performed to explore metabolic alterations. Our results demonstrated that there were 36 differential metabolites. Eleven major disordered metabolic pathways were found. Network analysis of differential metabolites and metabolic pathways indicated that glutamic acid was a possible key upregulated metabolite. It participated in nine metabolic networks. Glutathione and l‐proline may be key downregulated metabolites. They were involved in eight and seven metabolic pathways, respectively. Compared with the control group, serum concentrations of alanine aminotransferase, aspartate aminotransferase, and total bile acid in high dosage group increased significantly. In addition, histopathological analysis showed liver injury in rats with mepiquat exposure. These data were consistent with results of metabolomics. Our results offered new insights for molecular mechanism of liver toxicity induced by mepiquat.

Practical Application

Mepiquat is a contaminant formed in thermal‐processed food. It can induce spleen and liver injury. Our results offered new insights for molecular mechanism of liver toxicity induced by mepiquat. It will provide important information for official limits of mepiquat in foods.
The fermentation of Cordyceps militaris polysaccharide influenced gut bacterial LPS structure formation and changed its antigenicity
Authors: Zhu Jiahui , Chen Jieming , Chen Jiafeng , Zou Yuan , Ye Zhiwei , Wei Tao , Lin Junfang , Zheng Qianwang
Published: December 2024

Gut bacterial lipopolysaccharide (LPS) could be released into the circulatory system via the gut–liver axis and cause inflammatory immune response, while Cordyceps militaris polysaccharide (CMP40) has been reported to be effective in alleviating this inflammatory response. In this study, the effects of CMP40 gut fermentation on internal LPS structure formation and the subsequent immune response were explored. Results showed that CMP40 could change antigenicity of LPS of Vibrio parahaemolyticus, Salmonella enterica, and enterotoxigenic Escherichia coli, indicated by a reduced level of NO, IL‐1β, IL‐6, and TNF‐α. The LPS structure of these three strains were further elucidated. ESI/MS results revealed that CMP40 fermentation could alter the LPS structure by removing phosphate group from a single Kdo sugar or removing additional sided fatty acid chain. The gene expressions of enzymes that are responsible for group transfer further confirmed this structure modification process. This study focused on the regulation of polysaccharide on gut bacteria LPS and provided a new insight into health effect of CMP40.
Microstructural characterization of a wheat‐based food material using image analysis and pore network modeling during baking
Authors: Nemati Ramin , Takhar Pawan Singh
Published: December 2024

Microstructural properties of wheat‐based food materials change during baking. These alterations affect the final product's mechanical properties, physical attributes, and consumer satisfaction. Image processing and pore network modeling were used to analyze the variations in a cookie's microstructural properties during baking. Cookies were baked in an oven set at 184 ± 2°C for 10–60 min and then freeze‐dried. Over 1500 two‐dimensional images were collected for each sample using X‐ray micro‐computed tomography. Image processing and pore network modeling were utilized to obtain porosity, pore size distribution, tortuosity, pore coordination number, permeability, and other properties. A gas pycnometer was used to validate the obtained porosity values and calculate the solid density. Three stages of expansion, shrinkage, and subsequent expansion were observed during baking. The total porosity ranged between 0.145 and 0.373. The largest pores were observed in the 20‐min baked sample, which had a moisture content of 8.53 g/100 g solids. Cookies baked longer had more interconnected pores than the 10‐min sample, enabling them to conduct fluid at a higher rate. The absolute permeability values were between 1.75 × 10−11 m2 and 4.68 × 10−11 m2. The results suggested that porosity and pore coordination number had a similar trend as cookie permeability. Both heat and mass transfer during baking are expected to influence the development of the porous structure.

Practical Application

Understanding the microstructural properties of wheat‐based food materials is expected to help the baking industry control processing conditions, final product quality, and visual texture by adjusting the baking parameters.
Indocyanine Green Fluorescence Plus Blue Dye for Sentinel Lymph Node Biopsy in Patients Undergoing Neoadjuvant Chemotherapy for Breast Cancer: A Multicenter, Prospective Cohort Study
Authors: Liu Miao , Yang Yang , Hua Bin , Feng Rui , Xu Tianyu , Wang Mengyuan , Qi Xiaowei , Cao Yingming , Zhou Bo , Tong Fuzhong , Liu Peng , Liu Hongjun , Cheng Lin , Yang Houpu , Xie Fei , Wang Siyuan , Wang Chaobin , Peng Yuan , Shen Danhua , Chen Lei , Jiang Jun , Wang Shu
Published: December 2024

Background

Sentinel lymph node biopsy (SLNB) using radioisotope tracer plus blue dye is the gold standard after neoadjuvant chemotherapy (NAC) in initially cN1 breast cancer patients, but clinical use still has limitations. This study aims to examine diagnostic performance of dual indocyanine green (ICG) and methylene blue tracing for SLNB in patients who have completed NAC for breast cancer with initially cN1 disease.

Methods

Adult women (20–80 years of age) scheduled to undergo NAC for biopsy‐proven cT0‐3N1M0 primary invasive breast cancer were consecutively enrolled in this prospective, multicenter, cohort study. Upon the completion of NAC, SLNB was conducted using ICG and methylene blue, followed by axillary lymph node dissection. The primary outcome was the detection rate (DR); secondary outcomes included the false‐negative rate (FNR) and adverse events associated with the use of tracers.

Results

A total of 156 patients were enrolled; all underwent SLNB after NAC. The median number of lymph nodes retrieved during SLNB was 3 (range: 0–11). The DR was 97.4% (152/156; 95% CI, 93.6%–99.0%). The FNR was 6.7% (4/60; 95% CI, 2.6%–15.9%). Negative predictive value was 95.7% (88/92; 95% CI, 89.4%–98.3%). In the subgroup analysis stratified by ycN status, FNR was 4.0% (1/25; 95% CI, 0.7%–19.5%) and 8.6% (3/35; 95% CI, 3.0%–22.4%) in the ycN0 and ycN+ subgroups, respectively. No allergic reaction was reported.

Conclusions

SLNB with ICG plus methylene blue achieved a high DR and a very low FNR in breast cancer patients with initially cN1 disease.

Trial Registration

ClinicalTrials.gov (https://www.clinicaltrials.gov/), NCT02869815
A Case of Primary Lung Adenocarcinoma With Recurrent Brain Metastasis due to Transformation to Small Cell Carcinoma During Adjuvant Atezolizumab Therapy
Authors: Kobayashi Nao , Sunaga Noriaki , Yatomi Masakiyo , Wakamatsu Ikuo , Muto Sohei , Ikota Hayato , Yamaguchi Rei , Ohtaki Yoichi , Nagashima Toshiteru , Kubo Nobuteru , Masuda Tomomi , Miura Yosuke , Tsurumaki Hiroaki , Sakurai Reiko , Koga Yasuhiko , Hisada Takeshi , Maeno Toshitaka
Published: December 2024

Histologic transformation from non‐small cell to small cell lung cancer (SCLC) is a resistance mechanism to immune checkpoint inhibitors. We report herein a case of lung adenocarcinoma who developed liver and brain metastases during adjuvant atezolizumab therapy. The patient underwent a craniotomy to resect a brain metastasis, which was pathologically diagnosed as SCLC. He subsequently received platinum‐based chemotherapy with durvalumab, resulting in sustained regression of the liver metastases. This case demonstrates a metastatic brain tumor‐acquired resistance to atezolizumab through histologic transformation from adenocarcinoma to SCLC. Therefore, rebiopsy is needed if recurrent disease appears during immune checkpoint inhibitor treatment in patients with non‐small cell lung cancer.