bluuebunny/crossref_metadata_2025 huggingface dataset:
PP1 PNUTS binds the “restrictor” and dephosphorylates RNA pol II CTD Ser5 to stimulate transcription termination
Authors: Erickson Benjamin , Fedoryshchak Roman , Fong Nova , Sheridan Ryan , Larson Keira Y. , Saviola Anthony J. , Mouilleron Stephane , Hansen Kirk C. , Treisman Richard , Bentley David L.
Published: July 2024

The restrictor, ZC3H4/WDR82, is the major termination factor for antisense transcription from bidirectional promoters, but its mechanism is poorly understood. We report that ZC3H4/WDR82 co-purifies with PP1 phosphatase and PP1 phosphatase nuclear targeting subunit, PNUTS, which binds directly to the WDR82 subunit of restrictor. AlphaFold predicts a quaternary complex, PPWZ, in whichPP1-associatedPNUTS andZC3H4 both contactWDR82. To investigate the role of protein dephosphorylation in PPWZ activity, we expressed a substrate trap comprising inactive PP1H66Klinked to the PNUTS C-terminus. PP1H66K-PNUTS binds pol II large subunit and nuclear exosome components. PP1H66K-PNUTS, but not PP1WT-PNUTS, functions as a dominant-negative inhibitor of antisense termination and CTD Ser5 dephosphorylation. Both these activities require the PNUTS WDR82 binding domain that interacts with restrictor. We show that CTD Ser5 hyperphosphorylation is associated with higher processivity and reduced pausing that would counteract termination, and propose that Ser5 dephosphorylation by PPWZ is coupled to termination. In summary, we identify the PP1 phosphatase activity of the PPWZ complex as essential for terminator function and propose that this heterotetramer is the physiologically relevant form of restrictor.
RqcH supports survival in the absence of non-stop ribosome rescue factors
Authors: Callan Katrina , Prince Cassidy R. , Feaga Heather A.
Published: July 2024

Ribosomes frequently translate truncated or damaged mRNAs due to the extremely short half-life of mRNAs in bacteria. When ribosomes translate mRNA that lacks a stop codon (non-stop mRNA), specialized pathways are required to rescue the ribosome from the 3’ end of the mRNA. The most highly conserved non-stop rescue pathway istrans-translation, which is found in greater than 95% of bacterial genomes. In all Proteobacteria that have been studied, the alternative non-stop ribosome rescue factors, ArfA and ArfB, are essential in the absence oftrans-translation. Here, we investigate the interaction between non-stop rescue pathways and RqcH, a ribosome quality control factor that is broadly conserved outside of Proteobacteria. RqcH does not act directly on non-stop ribosomes but adds a degron tag to stalled peptides that obstruct the large ribosomal subunit, which allows the stalled peptide to be cleared from the ribosome by peptidyl-tRNA hydrolase (PTH). We show thatBacillus subtiliscan survive withouttrans-translation and BrfA (Bacillus ArfA homolog), due to the presence of RqcH. We also show that expression of RqcH and its helper protein RqcP rescues the synthetic lethality of ΔssrAΔarfAinEscherichia coli. These results suggest that non-stop ribosome complexes can be disassembled and then cleared because of the tagging activity of RqcH, and that this process is essential in the absence of non-stop ribosome rescue pathways. Moreover, we surveyed the conservation of ribosome rescue pathways in >14,000 bacterial genomes. Our analysis reveals a broad distribution of non-stop rescue pathways, especiallytrans-translation and RqcH, and a strong co-occurrence between the ribosome splitting factor MutS2 and RqcH. Altogether, our results support a role for RqcH in non-stop ribosome rescue and provide a broad survey of ribosome rescue pathways in diverse bacterial species.

Importance

Ribosome stalling on damaged mRNA is a major problem in bacteria. It is estimated that 2-4% of all translation reactions terminate with the ribosome stalled on a damaged mRNA lacking a stop codon. Mechanisms that rescue these ribosomes, such astrans-translation, are often essential for viability. We investigated the functional overlap between RqcH and the non-stop ribosome rescue systems (ArfA andtrans-translation) that are present in bothE. coliandB. subtilis. Since these two species are extremely distant relatives, our work is likely to have wider implications for understanding ribosome rescue in bacteria. Furthermore, we used a bioinformatics approach to examine the conservation and overlap of various ribosome rescue systems in >14,000 species throughout the bacterial domain. These results provide key insights into ribosome rescue in diverse phyla.
Measles virus co-opts epithelial-to-mesenchymal transition and live cell extrusion to exit human airway epithelia
Authors: Hippee Camilla E. , Durnell Lorellin A. , Kaufman Justin W. , Murray Eileen , Singh Brajesh K. , Sinn Patrick L.
Published: July 2024

Measles virus (MeV) is a highly contagious respiratory virus transmitted via aerosols. To understand how MeV exits the airways of an infected host, we use unpassaged primary cultures of human airway epithelial cells (HAE). MeV typically remains cell-associated in HAE and forms foci of infection, termed infectious centers, by directly spreading cell-to-cell. We previously described the phenomenon in which infectious centers detachen massefrom HAE and remain viable. Here we investigate the mechanism of this cellular detachment. Via immunostaining, we observed loss of tight junction and cell adhesion proteins within infectious centers. These morphological changes indicate activation of epithelial-to-mesenchymal transition (EMT). EMT can contribute to wound healing in respiratory epithelia by mobilizing nearby cells. Inhibiting TGF-β, and thus EMT, reduced infectious center detachment. Compared to uninfected cells, MeV-infected cells also expressed increased levels of sphingosine kinase 1 (SK1), a regulator of live cell extrusion. Live cell extrusion encourages cells to detach from respiratory epithelia by contracting the actomyosin of neighboring cells. Inhibition or induction of live cell extrusion impacted infectious center detachment rates. Thus, these two related pathways contributed to infectious center detachment in HAE. Detached infectious centers contained high titers of virus that may be protected from the environment, allowing the virus to live on surfaces longer and infect more hosts. This mechanism may contribute to the highly contagious nature of MeV.

IMPORTANCE

Measles virus (MeV) is an extremely contagious respiratory pathogen that continues to cause large, disruptive outbreaks each year. Here, we examine a phenomenon that may help explain the contagious nature of MeV: detachment of MeV-infected cells. MeV spreads cell-to-cell in human airway epithelial cells (HAE) to form groups of infected cells, termed “infectious centers”. We reported that infectious centers ultimately detach from HAE as a unit, carrying high titers of virus. Viral particles within cells may be more protected from environmental conditions, such as ultraviolet radiation and desiccation. We identified two host pathways, epithelial-to-mesenchymal transition and live cell extrusion, that contribute to infectious center detachment. Perturbing these pathways altered the kinetics of infectious centers detachment. These pathways influence one another and contribute to epithelial wound healing, suggesting infectious center detachment may be a usurped consequence of the host’s response to infection that benefits MeV by increasing its transmissibility between hosts.
Unveiling the role of yeast cytochrome c isoforms in the assembly of mitochondrial supercomplexes and the control of respiratory chain rate
Authors: Guerra-Castellano Alejandra , Aneas Manuel , Tamargo-Azpilicueta Joaquin , Marquez Inmaculada , Olloqui-Sariego Jose Luis , Calvente Juan Jose , De la Rosa Miguel A. , Diaz Moreno Irene
Published: July 2024

Mitochondria play crucial roles as both the powerhouse and signaling center of cells, balancing cell survival and death to maintain homeostasis. Disruption of this balance can lead to various diseases. Therefore, exploring the components involved in mitochondrial metabolism presents a significant challenge. In this context, respiratory supercomplexes are evolutionarily conserved, stable associations between membrane complexes and molecules, including proteins and lipids, within the inner mitochondrial membrane. These supercomplexes dynamically respond to metabolic demands, enhancing the electron transfer rate and reducing the production of reactive oxygen species. Recent research has identified cytochrome c, a mobile electron carrier between complexes III and IV, as a potential key player in the formation of these supercomplexes. This study focuses on elucidating the role of cytochrome c in modulating the assembly of supercomplexes, using the yeast Saccharomyces cerevisiae as a model system for mitochondrial metabolism. Our findings indicate that the viability of Saccharomyces cerevisiae relies on the presence of cytochrome c, with both isoforms playing a role in the assembly of respiratory supercomplexes. Notably, isoform-2 of cytochrome c enhances electron transfer efficiency, resulting in reduced ROS production.
Pseudomonas aeruginosainfection increases palmitoyl carnitine release by host-derived extracellular vesicles
Authors: Ayilam Ramachandran Rajalakshmy , Baniasadi Hamid , Robertson Danielle M.
Published: July 2024

Pseudomonas aeruginosa(PA), an opportunistic gram-negative pathogen, is the most common pathogen identified in all culture positive cases of infectious keratitis. Extracellular vesicles (EVs) are released by most cells in the body and function in intercellular communication. We have previously reported a change in the proteome of host-derived EVs from corneal epithelial cells during PA infection. In the present study, we investigated changes in the metabolome of host-derived EVs from PA infected (PA-C EVs) and non-infected cells (C EVs). We found that one metabolite, palmitoyl carnitine (PAMC), was significantly upregulated in PA-C EVs. To determine the significance of PAMC release, we investigated the effect of PAMC treatment on corneal epithelial cells and neutrophils. EVs were isolated from culture media using size exclusion chromatography. EVs were then characterized using nanoparticle tracking analysis, transmission electron microscopy, and western blot. Metabolomics was performed using an untargeted approach. We found that palmitoyl carnitine (PAMC) was the most abundant metabolite present in PA-C EVs and was increased more than 3 fold compared to C EVs. Treatment of corneal epithelial cells with increasing levels of PAMC increased nuclear translocation of the NF-κB subunit p65. This was associated with an increase in IL-8 production and neutrophil migration. PAMC also increased levels of mitochondrial calcium. Upon inoculation of corneal epithelial cells with PA, 50 μM PAMC completely eradicated intracellular PA, but stimulated growth of extracellular PA. Taken together, these findings suggest that PA exploits EV release by host cells to deplete PAMC from the intracellular environment.
Who’s afraid of AI? socio-technological perspectives on artificial intelligence in the workforce: an Israeli case study
Authors: Vasiliu Vlad , Yavetz Gal
Published: July 2024

Purpose

This study aimed to investigate the perception and acceptance of artificial intelligence (AI) technologies among the Israeli workforce. More specifically, it examined how age, income, and education level are related to employees’ fears of being replaced by AI technologies and their willingness to adopt these technologies in their personal and professional lives.

Design/methodology/approach

Data were collected by surveying 502 adults from the Jewish population of Israel in February 2023 via an Internet panel. Stratified sampling was performed to ensure a representative cross-section of the population.

Findings

Contrary to the expectations from a technologically advanced society, the findings indicated varied levels of enthusiasm and apprehension. Age was found to be negatively correlated with the fear of being replaced by AI technologies and the willingness to adopt these technologies. Income was negatively correlated with the fear of being replaced by AI technologies. Education level was negatively correlated with the fear of being replaced and positively correlated with the willingness to adopt.

Practical implications

The findings provide valuable guidance for policymakers, educators, and business leaders in shaping AI integration strategies. They emphasize the need for targeted educational and policy initiatives to bridge the gap in AI readiness.

Originality/value

This study offers unique insights into the perceptions toward AI in a leading technological hub, contributing to the understanding of how advanced societies are adapting to rapid AI integration.
Functional heterogeneity in digital entrepreneurial teams and pivoting: the role of digital agility
Authors: Jiao Yishuo , Zhu Renhong , Fu Jialiang , Li Xiaowei , Wang Yichao
Published: July 2024

Purpose

The rapid development of digital technologies drives digital entrepreneurs to pivot, a behavior that allows entrepreneurs to adjust original opportunities and explore new opportunities. This study aims to investigate the effect of the structural characteristics of digital entrepreneurial teams, the functional heterogeneity, on pivoting from the perspective of digital agility. Moreover, this study also examines the moderating effect of knowledge sharing.

Design/methodology/approach

Two-phase survey data were sourced from Chinese digital entrepreneurial teams through the entrepreneurial networks of MBA programs of a Chinese business school and entrepreneurial support organizations in China. The sample of 272 teams with 708 entrepreneurs was collected to test the hypotheses.

Findings

The functional heterogeneity of digital entrepreneurial teams, including industry background heterogeneity and occupational experience heterogeneity, positively impacts pivoting by providing heterogeneous knowledge and resources. Moreover, this relationship is mediated by the digital agility of the digital team, and knowledge sharing moderates the relationship between functional heterogeneity and digital agility.

Originality/value

While existing studies have mainly focused on the external factors, this study empirically investigates the team-level internal factors of digital pivoting in digital entrepreneurial teams, enriching the research perspective of pivoting. Moreover, the current study bridges the literature on digital agility with pivoting, broadening the theoretical mechanism of pivoting and expanding the theoretical boundaries of digital agility.
Smallholder farmers’ vulnerability to climate change in northwest Ethiopia
Authors: Likinaw Aimro , Alemayehu Arragaw , Bewket Woldeamlak
Published: July 2024

Purpose

The purpose of this paper is to investigate the vulnerability of smallholder farmers to climate change in northwest Ethiopia.

Design/methodology/approach

To achieve this aim, data was collected from a survey of 352 households, which were stratified into three groups: Lay Gayint (138 or 39%), Tach Gayint (117 or 33%) and Simada district (97 or 28%). To gain a deeper understanding of the vulnerability of these households, two approaches were used: the livelihood vulnerability index (LVI), consisting of 32 indicators, and the socioeconomic vulnerability index (SeVI), containing 31 indicators. Furthermore, qualitative data was obtained through focus group discussions conducted in six randomly chosen groups from the three districts, which were used to supplement the findings.

Findings

Both methods indicate that Simada is the most vulnerable district, followed by Tach Gayint and Lay Gayint. According to the SeVI approach, Simada district showed the highest level of sensitivity and exposure to climate-related hazards, as well as the lowest score for adaptive capacity. However, using the LVI approach, Simada district was found to have the highest sensitivity to climate effects and exposure to climate-related hazards, along with a higher adaptive capacity than both Lay Gayint and Tach Gayint districts.

Originality/value

Although there are numerous studies available on the vulnerability of farmers to climate change, this particular study stands out by using and contrasting two approaches – the LVI and the SeVI – to assess the vulnerability of households in the study area. Previous research has indicated that no single approach is sufficient to evaluate climate change vulnerability, as each approach has its own strengths and limitations. The findings of this study have significant implications for policymakers and development practitioners, as they can use the results to identify the households that are most vulnerable to climate change. This will enable them to design adaptation options that are tailored to the specific needs of each community and that will effectively address the risks of current and future climate change.
The informational effect of pay for individual performance on intrinsic motivation
Authors: Vilaça Cristiana Rodrigues , Proença Teresa , Carozzo-Todaro Mauro
Published: July 2024

Purpose

This research aims to test the role of the informational effect (IE) on the relationship between pay for individual performance (PFIP) and intrinsic motivation (IM). Special attention is also given to how the supervisor’s positive (PF) and negative feedback (NF) influence workers' perceptions of the informational content of PFIP.

Design/methodology/approach

We used a two-wave online survey among workers covered by a PFIP system and collected a total of 472 answers. To test our hypotheses, we adopted SPSS PROCESS macro Model 9.

Findings

The results suggest that IE fully mediates the positive impact of PFIP on IM, with this effect diminishing in the presence of NF, while PF shows no significant influence.

Practical implications

Organizations should invest in the development of mechanisms to mitigate perceptions of rewards as behaviour control mechanisms. Instead, PFIP should be perceived as a means to gain valuable insights into performance.

Originality/value

By using a research design allowing external validity in opposition to the widely used experimental one, we contribute to the debate about the relationship between extrinsic rewards and IM. Theoretical and practical implications in the workplace are also discussed.
Artificial intelligence and work transformations: integrating sensemaking and workplace learning perspectives
Authors: Engström Annika , Pittino Daniel , Mohlin Alice , Johansson Anette , Edh Mirzaei Nina
Published: July 2024

Purpose

The purpose of this study is to explore the process of initial sensemaking that organizational members activate when they reflect on AI adoption in their work settings, and how the perceived features of AI technologies trigger sensemaking processes which in turn have the potential to influence workplace learning modes and trajectories.

Design/methodology/approach

We adopted an explorative qualitative and interactive approach to capture free fantasies and imaginative ideas of AI among people within the industry. We adopt a conceptual perspective that combines theories on initial sensemaking and workplace learning as a theoretical lens to analyze data collected during 23 focus groups held at four large Swedish manufacturing companies. The data were analyzed using the Gioia method.

Findings

Two aggregated dimensions were defined and led to the development of an integrated conceptualization of the initial sensemaking of AI technology adoption. Specifically, sensemaking triggered by abstract features of AI technology mainly pointed to an exploitative learning path. Sensemaking triggered by concrete features of the technology mainly pointed to explorative paths, where socio-technical processes appear to be crucial in the process of AI adoption.

Originality/value

This is one of the first studies that attempts to explore and conceptualize how organizations make sense of prospective workplace learning in the context of AI adoption.
The effects of macroprudential policies in the Brazilian banking sector
Authors: Moscareli Lúcio Guimarães , Tessmann Mathias Schneid , Beppler Lucas Souza , Ely Régis Augusto
Published: July 2024

Purpose

This paper aims to investigate the effects of macroprudential policies in Brazil on the banking sector.

Design/methodology/approach

Autoregressive models with distributed lags (ADL) are estimated to verify whether such regulatory measures affected the volume of credit, the banking spread and the concentration index of the five largest Brazilian banks. In addition to the variables of interest, monthly macroeconomic data from 2011 to 2021 are considered.

Findings

Our results suggest that macroprudential policies are effective in reducing credit volume. More importantly, our findings highlight two possible adverse effects of these instruments. Firstly, macroprudential tightenings are associated with increases in bank spread. Secondly, tightening measures contribute to increasing bank market concentration.

Originality/value

These findings are useful for the scientific literature that investigates the regulation of the financial system by providing empirical evidence of the effects of Brazilian macroprudential measures on investors, policymakers and other economic agents whose well-being is associated with economic stability.
Mental health and meaning: a positive autoethnographic case study of Paul Wong
Authors: Wong Paul T.P. , Gonot-Schoupinsky Freda
Published: July 2024

Purpose

The purpose of this article is to meet Professor Paul T.P. Wong, PhD, CPscyh, who is based at the Department of Psychology, Trent University, Peterborough, Ontario, Canada. Wong represents an interesting case of how a racial/cultural minority could achieve success in a hostile environment consisting of the systemic biases of injustice, discrimination and marginalization. His life also epitomizes how one can experience the paradoxical truth of healing and flourishing in an upside-down world through the positive suffering mindset (PSM).

Design/methodology/approach

This case study is presented in two sections: a positive autoethnography written by Wong, followed by his answers to ten questions. The core methodology of positive autoethnography allows people to understand how Wong’s life experience of being a war baby in China, a constant outsider and a lone voice in Western culture, has shaped a very different vision of meaning, positive mental health and global flourishing.

Findings

Wong reveals how to live a life of meaning and happiness for all the suffering people in a difficult world. He has researched the positive psychology of suffering for 60 years, from effective coping with stress and searching for meaning to successful aging and positive death. According to Wong’s suffering hypothesis and the emerging paradigm of existential positive psychology (Wong, 2021), cultivating a PSM is essential for healing and flourishing in all seasons of life.

Research limitations/implications

An expanding literature has been developed to illustrate why the missing link in well-being research is how to transcend and transform suffering into triumph. Wong reveals how this emerging area of research is still not fully embraced by mainstream psychology dominated by the individualistic Euro-American culture, and thus why, in an adversarial milieu, existential positive psychology is limited by its inability to attract more researchers to test out Wong’s suffering hypothesis.

Practical implications

The wisdom and helpful tools presented here may enable people to achieve mature happiness and existential well-being even when they have a very painful past, a very difficult present and a bleak future.

Social implications

This autoethnographic case study offers new grounds for hope for all those who are injured by life, marginalized by systemic biases or tormented by chronic illnesses and disorders. It also provides a road map for a better world with more decent human beings who dare to stand up for justice, integrity and compassion.

Originality/value

Meaning as reflected in suffering is according to Wong the most powerful force to bring out either the worst or the best in people. The new science of suffering shows us how the authors can achieve positive transformation through cultivating a PSM, no matter how harsh one’s fate may be.
A facile approach for fabrication functional finishing and coloring cotton fabrics with haematoxylum campechianum L. Bark
Authors: El-Zawahry Manal , Gamal Hager
Published: July 2024

Purpose

This paper aims to focus on the aqueous extraction of natural dye from haematoxylum campechianum L. bark for finishing the bio-mordant cotton fabrics producing value-added, environment-friendly textile products, for biomedical applications.

Design/methodology/approach

The study focuses on the creation of eco-friendly bio-mordant cotton fabric using gallic acid and gelatin, Al3+ and Fe2+ salts and metal mordant. The optimal pH for extraction, structural characterization and phytochemical analysis of the extracted dye were estimated using UV-visible spectrophotometer, FTIR and qualitative analysis. Variations in electrolyte concentration and pH medium were also considered. The study also examines build-up properties, colorimetric values and fastness characteristics of the colored fabrics.

Findings

All the dyed fabrics exhibit very good to excellent in terms of antimicrobial resistance against S. aureus and C. allbicans.

Practical implications

Pre-mordant cotton fabrics with Fe2+ and a combination of metal and bio-mordant show higher antibacterial resistance against P. aerugionsa. Further, bio-mordant and a combination of both mordant exhibit excellent UV protection and antioxidant activity performance compared to that of undyed fabrics.

Originality/value

This work opens up a huge potential for producing healthy bioactive-colored fabrics used in medical textiles and other usages.
Design for additive manufacturing of topology-optimized structures based on deep learning and transfer learning
Authors: Mohseni Maede , Khodaygan Saeed
Published: July 2024

Purpose

This paper aims to improve the manufacturability of additive manufacturing (AM) for topology-optimized (TO) structures. Enhancement of manufacturability focuses on modifying geometric constraints and classifying the building orientation (BO) of AM parts to reduce stresses and support structures (SSs). To this end, artificial intelligence (AI) networks are being developed to automate design for additive manufacturing (DfAM).

Design/methodology/approach

This study considers three geometric constraints for their correction by convolutional autoencoders (CAEs) and transfer learning (TL). Furthermore, BOs of AM parts are classified using generative adversarial (GAN) and classification networks to reduce the SS. To verify the results, finite element analysis (FEA) is performed to compare the stresses of modified components with the original ones. Moreover, one sample is produced by the laser-based powder bed fusion (LB-PBF) in the BO predicted by the AI to observe its SSs.

Findings

CAE and TL resulted in promoting the manufacturability of TO components. FEA demonstrated that enhancing manufacturability leads to a 50% reduction in stresses. Additionally, training GAN and pre-training the ResNet-18 resulted in 80%, 95% and 96% accuracy for training, validation and testing. The production of a sample with LB-PBF demonstrated that the predicted BO by ResNet-18 does not require SSs.

Originality/value

This paper provides an automatic platform for DfAM of TO parts. Consequently, complex TO parts can be designed most feasibly and manufactured by AM technologies with minimal material usage, residual stresses and distortions.
Sintering parameter optimization by inverse analysis in direct metal deposition of Inconel 718
Authors: Afshari Mahmoud , Khandaei Mehrdad , Shoja Razavi Reza , Barekat Seyed Masoud
Published: July 2024

Purpose

The net power delivered to the surface of parts (i.e. the actual heat flux) is a key parameter in the laser melting process and its exact control has a great impact on the numerical solutions. In this paper, the impact of laser additive manufacturing parameters including laser power, scanning speed and powder injection rate on thermal efficiency, net power delivered to the part and power loss due to powder flow has been investigated.

Design/methodology/approach

The response surface method was applied to measure the net laser power in laser deposited Inconel 718 using k-type thermocouples. The temperature history obtained by thermocouples was used to calculate the net power delivered by inverse analysis method. The applied model is Rosenthal's optimized model, in which all the thermal properties of the material are considered to vary with temperature.

Findings

The results indicated that the thermal efficiency, power delivered to the part and power loss can be optimized simultaneously at laser power of 400 W, scanning speed of 2 mm/s and powder injection rate of 200 mg/s. The microstructure analysis indicated that a high-quality sample without microstructural defects was formed under optimal condition of parameters. Moreover, the primary dendrite arm spacing for the optimal sample was higher than that obtained for other samples.

Originality/value

The novelty of this research summarized as follows: Prediction of the thermal efficiency and power loss during the laser metal deposition of Inconel 718 superalloy using the inverse analysis. Finding the optimal values of thermal efficiency, power delivered to the surface and power loss in the laser metal deposition of Inconel 718 superalloy. Investigating the effect of laser power, powder injection rate and scanning speed on the thermal efficiency and power loss of Inconel 718 superalloy during the laser metal deposition.
Willingness to pay for expanded non‐invasive prenatal screening – An online discrete choice experiment from the perspective of women living in Western Australia
Authors: Long Sarah , O'Leary Peter , Norman Richard , Dickinson Jan E.
Published: July 2024

Introduction

Ongoing advances in genetic technology may soon provide prenatal screening for multiple genetic conditions.

Aims

The aims were to investigate what prenatal screening test characteristics women prioritise and their willingness to pay for these tests.

Methods

We designed an online survey incorporating a series of discrete choice scenarios. Dimensions and levels were selected based on existing prenatal tests and a hypothetical prenatal test that could non‐invasively detect multiple genetic disorders in pregnancy. Participants were recruited from social media platforms. Data were analysed using conditional logistic regression and latent class analysis (LCA).

Results

A total of 219 women completed the survey. Women with higher incomes and those with a tertiary education were willing to pay more than other groups. The maximum willingness to pay was AUD1870 (95% confidence interval: 1630, 2112) for a hypothetical non‐invasive test to detect multiple genetic conditions in early pregnancy. An LCA demonstrated considerable heterogeneity in preferences, differing in both overall preference for testing and test characteristics considered most attractive. Among the participants, decision factors cited by 14.5% of participants were the risk of pregnancy loss, making them less likely to undergo testing; for 32.1% participants, accuracy was a major factor, and they were very likely to have testing; for 12.9%, test availability early in pregnancy was a decision factor.

Conclusions

If a non‐invasive test that could detect the greatest number of genetic disorders in pregnancy was available, the priorities were test accuracy, risk of pregnancy loss and a test available early in pregnancy.
Differential decline of SARS‐CoV‐2‐specific antibody levels, innate and adaptive immune cells, and shift of Th1/inflammatory to Th2 serum cytokine levels long after first COVID‐19
Authors: Kratzer Bernhard , Gattinger Pia , Trapin Doris , Ettel Paul , Körmöczi Ulrike , Rottal Arno , Stieger Robert B. , Sehgal Al Nasar Ahmed , Feichter Melanie , Borochova Kristina , Tulaeva Inna , Grabmeier‐Pfistershammer Katharina , Tauber Peter A. , Perkmann Thomas , Fae Ingrid , Wenda Sabine , Kundi Michael , Fischer Gottfried F. , Valenta Rudolf , Pickl Winfried F.
Published: July 2024

Background

SARS‐CoV‐2 has triggered a pandemic and contributes to long‐lasting morbidity. Several studies have investigated immediate cellular and humoral immune responses during acute infection. However, little is known about long‐term effects of COVID‐19 on the immune system.

Methods

We performed a longitudinal investigation of cellular and humoral immune parameters in 106 non‐vaccinated subjects ten weeks (10 w) and ten months (10 m) after their first SARS‐CoV‐2 infection. Peripheral blood immune cells were analyzed by multiparametric flow cytometry, serum cytokines were examined by multiplex technology. Antibodies specific for the Spike protein (S), the receptor‐binding domain (RBD) and the nucleocapsid protein (NC) were determined. All parameters measured 10 w and 10 m after infection were compared with those of a matched, noninfected control group (n = 98).

Results

Whole blood flow cytometric analyses revealed that 10 m after COVID‐19, convalescent patients compared to controls had reduced absolute granulocyte, monocyte, and lymphocyte counts, involving T, B, and NK cells, in particular CD3+CD45RA+CD62L+CD31+ recent thymic emigrant T cells and non‐class‐switched CD19+IgD+CD27+ memory B cells. Cellular changes were associated with a reversal from Th1‐ to Th2‐dominated serum cytokine patterns. Strong declines of NC‐ and S‐specific antibody levels were associated with younger age (by 10.3 years, p < .01) and fewer CD3−CD56+ NK and CD19+CD27+ B memory cells. Changes of T‐cell subsets at 10 m such as normalization of effector and Treg numbers, decline of RTE, and increase of central memory T cell numbers were independent of antibody decline pattern.

Conclusions

COVID‐19 causes long‐term reduction of innate and adaptive immune cells which is associated with a Th2 serum cytokine profile. This may provide an immunological mechanism for long‐term sequelae after COVID‐19.
Effect of time since vasectomy on live birth rate of TESE‒ICSI egg donation cycles and male‐related prognostic factors
Authors: Hervas Irene , Pellegrini Livia , Valls Lorena , Gil Julia Maria , Navarro‐Gomezlechon Ana , Rivera‐Egea Rocio , Mossetti Laura , Jabaloyas Jose Maria Martinez , Garrido Nicolas
Published: July 2024

Background

Vasectomy is a widely used method of contraception. However, some men may have the desire to become biological fathers again after a period.

Objective

To explore the effect of time since vasectomy and different male comorbidities on live birth rates from intracytoplasmic sperm injection cycles using donated oocytes by using testicular spermatozoa obtained by testicular sperm extraction.

Materials and methods

This was a retrospective study of 123 couples who underwent a testicular sperm extraction‒intracytoplasmic sperm injection cycle after vasectomy using donated oocytes. Subjects were divided into groups according to time since vasectomy and the male risk factor evaluated. The main outcomes measured were live birth rate per embryo transfer, per oocyte donation cycle, and per couple. We assessed the cumulative live birth rate according to the time since vasectomy and considered male comorbidities: body mass index, hypertension, diabetes mellitus, dyslipidemia, and smoking.

Results

The overall live birth rate per couple was 59.3% (50.6–68.0). Considering the number of embryo transfer and oocyte donation cycle, the live birth rates were 34.1% (27.8–40.4) and 44.5% (36.9–52.1), respectively. The live birth rate according to time since vasectomy was not statistically different between groups. Consequently, the cumulative live birth rate was similar between the different interval times when considering one to eight embryo transfers (p = 0.74). No statistical differences in live birth rate and cumulative live birth rate were found between groups clustered according to male body mass index, smoking, hypertension, and dyslipidemia. However, diabetic male patients had a significantly lower rate of live birth rate per couple (22.2% [4.94–49.4]) than non‐diabetic patients did (62.7% [53.7–71.8]) (p = 0.03), but not in their cumulative live birth rate.

Conclusions

The time since vasectomy seems to have no detrimental effects on the live birth rate and cumulative live birth rate in testicular sperm extraction‒intracytoplasmic sperm injection cycles with donated oocytes. Male diabetes negatively affects the overall live birth rate per couple, but not the cumulative live birth rate. These results could be useful for multidisciplinary patient‐tailored counseling, regarding the chance of having a pregnancy and facilitating the decision‐making process of the fertility specialists.
The effect of vitamin E and docosahexaenoic acid ethyl ester on Metabolic Dysfunction‐Associated steatotic Liver Disease (MASLD)—A randomised, double‐blind, placebo‐controlled, parallel‐group clinical trial (PUVENAFLD)
Authors: Alkhouri Naim , McCarthy Deanna , Bayne Anne‐Cécile V. , Blonquist Traci , Yurko‐Mauro Karin , Vuppalanchi Raj , Lawitz Eric , Chalasani Naga
Published: July 2024

Aims

We conducted a clinical trial to determine the efficacy of the combination of vitamin E and/or docosahexaenoic acid (DHA) versus placebo in reducing liver fat content after 6 months of intervention in adults with MASLD.

Methods

Adults with MASLD were randomised to one of four treatment arms (vitamin E 1000 mg/daily + DHA 1.89 g/daily or combination arm, vitamin E 1000 mg alone, DHA 1.89 g alone or placebo) following a 2:1:1:2 randomisation. The primary objective was to determine the efficacy of DHA + vitamin E versus placebo in reducing hepatic fat fraction (%) relative to baseline after 6 months of intervention. Secondary objectives were to determine the effect of vitamin E or DHA alone versus placebo on reducing liver fat at 6 months.

Results

Our cohort consisted of 203 subjects with a mean age of 51 years, 53% female, 91% White, 59% Hispanic ethnicity. The combination of vitamin E + DHA had no effect on the primary endpoint of reducing hepatic steatosis as determined by MRI‐PDFF (p = 0.98). Neither vitamin E alone (p = 0.91) nor DHA alone (p = 0.14) significantly reduced hepatic steatosis compared to placebo. However, the trial was not powered adequately for this analysis. Compared with placebo, no statistically significant differences were detected in the 3‐month or 6‐month levels for ALT (U/L) or AST (U/L) in all three intervention groups.

Conclusions

The combination of DHA + vitamin E or either agent alone did not demonstrate efficacy on reducing liver fat or aminotransferases in the studied population.
Novel phenylpiperazine derivatives as potent transient receptor potential vanilloid 1 antagonists
Authors: Jing Lina , Liu Chunxia
Published: July 2024

Transient receptor potential vanilloid 1 (TRPV1) is a non‐selective cation channel, which is considered a highly validated target for pain perception. Repeated activation with agonists to desensitize receptors or use the antagonists can both exert analgesic effects. In this work, two series of novel phenylpiperazine derivatives were designed, synthesized, and evaluated for the in vitro receptor inhibitory activity and in vivo analgesic activity. Among them, L‐21 containing sulfonylurea group was identified with potent TRPV1 antagonistic activity and analgesic activity in various pain models. At the same time, L‐21 exhibited low risk of hyperthermia side effect. These results indicated that L‐21 is a promising candidate for further development of novel TRPV1 antagonist to treat pain.
Compound heterozygous variants in SLC45A1 might cause syndromic intellectual disability by localization failure and activity attenuation in cells
Authors: Zhou Chiyan , Zhu Jianjun , Tang Ping , Zhu Jingkang , Zhu Xinyi , Yang Li , Bian Wei , Zhao Wei , Liu Xiaodan
Published: July 2024

Intellectual disability (ID) is a kind of nervous developmental disorder and affects more than 1% of people worldwide. SLC45A1 as a transmembrane protein is implicated in the regulation of glucose homoeostasis. Through trio‐based exome sequencing, the missense mutations of SLC45A1 c.103G>A (p.V35M) and c.1211T>G (p.F404C) were identified in the proband with syndromic ID. The distribution, expression and activity of SLC45A1 wild‐type (WT) and variants were assayed in transfected COS7 cells. In SLC45A1 variants, the hydrogen bonds surrounding the 35th and 404th amino acid were changed, location on the cytomembrane was failed, their activity to transport glucose was also significantly decreased to contrast with SLC45A1‐WT. No difference was observed at the mRNA and protein level. In conclusion, the compound heterozygous variants of SLC45A1 might be the genetic etiology for syndromic ID. These novel mutations probably attenuated its activity to transport glucose by the alteration of tertiary structure and failure of intracellular location.
Risk factors for complications following sacral neuromodulation for faecal incontinence: Long‐term follow‐up
Authors: Gefen Rachel , Strassmann Victor , Stefano Hernandez Felice De , Garoufalia Zoe , Horesh Nir , Emile Sameh Hany , Da Silva Giovanna , Wexner Steven
Published: July 2024

Aim

Sacral neuromodulation (SNM) has become a standard surgical treatment for faecal incontinence (FI). Prior studies have reported various adverse events of SNM, including suboptimal therapeutic response, infection, pain, haematoma, and potential need for redo SNM. The aim of this study was to identify the risk factors associated with long‐term complications of SNM.

Method

This retrospective cohort reviewed patients who underwent two‐stage SNM for FI at our institution between 2011–2021. Preoperative baseline characteristics and follow‐up were obtained from the medical record and/or by telephone interview. Management and outcome of each postoperative event were evaluated by univariate and multivariate regression analyses.

Results

A total of 291 patients (85.2% female) were included in this study. Postoperative complications were recorded in 219 (75.2%) patients and 154 (52.9%) patients required surgical intervention to treat complications. The most common postoperative event was loss of efficacy (46.4%). Other common adverse events were problems at the implant site (pain, infection, etc.) in 16.5% and pain during stimulation in 11.7%. Previous vaginal delivery (OR 2.74, p = 0.003) and anal surgery (OR = 2.46, p = 0.039) were independent predictors for complications. Previous colorectal (OR = 2.04, p = 0.026) and anal (OR = 1.98, p = 0.022) surgery and history of irritable bowel syndrome (IBS) (OR = 3.49, p = 0.003) were independent predictors for loss of efficacy.

Conclusion

Postoperative adverse events are frequently recorded after SNM. Loss of efficacy is the most common. Previous colorectal or anal surgery, vaginal delivery, and IBS are independent risk factors for complications.
Indications of Helicobacter pylori Eradication Treatment and Its Influence on Prescriptions and Effectiveness (Hp‐EuReg)
Authors: Martínez‐Domínguez Samuel J. , Nyssen Olga P. , Lanas Ángel , Alfaro Enrique , Jonaitis Laimas , Mahmudov Umud , Voynovan Irina , Gülüstan Babayeva , Rodrigo Luis , Fiorini Giulia , Perez‐Aisa Ángeles , Tejedor‐Tejada Javier , Tepes Bojan , Vologzanina Ludmila , Mammadov Emin , Lerang Frode , Oğlu Quliyev Fərid Vidadi , Bakulina Natalia V. , Abdulkhakov Rustam , Tatiana Ilchishina , Butler Thomas J. , Sarsenbaeva Aiman Silkanovna , Bumane Renate , Lucendo Alfredo J. , Romano Marco , Bujanda Luis , Abdulkhakov Sayar R. , Zaytsev Oleg , Pabón‐Carrasco Manuel , Keco‐Huerga Alma , Denkovski Maja , Huguet Jose M. , Perona Monica , Núñez Óscar , Pavoni Matteo , Fadieienko Galyna , Alekseenko Sergey , Smith Sinead M. , Hernández Luis , Kupcinskas Juozas , Bordin Dmitry S. , Leja Mārcis , Gasbarrini Antonio , Gridnyev Oleksiy , Cano‐Català Anna , Parra Pablo , Moreira Leticia , Mégraud Francis , O'Morain Colm , Gisbert Javier P. ,   the Hp‐EuReg Investigators
Published: July 2024

Background

The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance.

Methods

International, prospective, non‐interventional registry of the management of H. pylori infection by European gastroenterologists (Hp‐EuReg). Treatment‐näive patients registered from 2013 to 2023 at e‐CRF AEG‐REDCap were analyzed. The effectiveness was assessed by modified intention‐to‐treat analysis.

Results

Overall, 53,636 treatment‐naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non‐investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non‐investigated dyspepsia (87%). Bismuth‐metronidazole‐tetracycline and clarithromycin‐amoxicillin‐bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin‐amoxicillin‐tinidazole/metronidazole reached 90% cure rates except in patients with non‐investigated dyspepsia; whereas sequential clarithromycin‐amoxicillin‐tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001).

Conclusion

In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non‐bismuth quadruple therapies achieved optimal results in almost all indications.

Trial Registration

ClinicalTrials.gov identifier: NCT02328131.
Effect of Fe2O3 on the structure and properties of Mo‐containing borosilicate glasses for nuclear waste immobilization
Authors: Xu Youli , Liao Qilong , Wang Fu , Gu Yuxin , Pu Boyang , Zhu Hanzhen
Published: July 2024

As a fission product in high‐level radioactive nuclear waste, Mo has low solubility in borosilicate glass. Fe2O3 is not only a prevalent transition metal element but also a major corrosion product in high‐level radioactive nuclear waste. Against this backdrop, the effect of Fe2O3 content on the structure and chemical durability of typical molybdenum‐containing sodium borosilicate glasses for nuclear waste immobilization are studied. The results show that the samples containing more than 3.85 mol% Fe2O3, a completely homogenous amorphous glass sample is obtained. Moreover, the mechanism of the effect of Fe2O3 on the solubility of Mo is discussed in detail. In this work, a portion of Fe3+ is reduced to Fe2+ and enters into the glasses as a charge compensation ion as Fe2+O6. Concurrently, Fe3+ ions contribute to the formation of the glass networks as Fe3+O4. Iron incorporation can improve the chemical durability of the sample.