bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphorylation of VapB antitoxins affects intermolecular interactions to regulate VapC toxin activity inMycobacterium tuberculosis
Authors: Malakar Basanti , Barth Valdir , Puffal Julia , Woychik Nancy , Husson Robert N.
Published: May 2024

Toxin-antitoxin modules are present in many bacterial pathogens. The VapBC family is particularly abundant in members of theMycobacterium tuberculosiscomplex, with 50 modules present in theM. tuberculosisgenome. In type IIA modules the VapB antitoxin protein binds to and inhibits the activity of the co-expressed cognate VapC toxin protein. VapB proteins also bind to promoter region sequences and repress expression of thevapB-vapCoperon. Though VapB-VapC interactions can control the amount of free VapC toxin in the bacterial cell, the mechanisms that affect this interaction are poorly understood. Based on our recent finding of Ser/Thr phosphorylation of VapB proteins inM. tuberculosis, we substituted phosphomimetic or phosphoablative amino acids at the phosphorylation sites of two VapB proteins. We found that phosphomimetic substitution of VapB27 and VapB46 resulted in decreased interaction with their respective cognate VapC proteins, whereas phosphoablative substitution did not alter binding. Similarly, we determined that phosphomimetic substitution interfered with VapB binding to promoter region DNA sequences. Both decreased VapB-VapC interaction and decreased VapB repression ofvapB-vapCoperon transcription would result in increased free VapC in theM. tuberculosiscell.M. tuberculosisstrains expressingvapB46-vapC46constructs containing a phosphoablativevapBmutation resulted in lower toxicity compared to a strain expressing nativevapB46, whereas similar or greater toxicity was observed in the strain expressing the phosphomimeticvapBmutation. These results identify a novel mechanism by which VapC toxicity activity can be regulated by VapB phosphorylation, potentially in response to extracytoplasmic as well as intracellular signals.

Importance

Intracellular bacterial toxins are present in many bacterial pathogens and have been linked to bacterial survival in response to stresses encountered during infection. The activity of many toxins is regulated by a co-expressed antitoxin protein that binds to and sequesters the toxin protein. The mechanisms by which an antitoxin may respond to stresses to alter toxin activity are poorly understood. Here we show that antitoxin interactions with its cognate toxin, and with promoter DNA required for antitoxin and toxin expression, can be altered by Ser/Thr phosphorylation of the antitoxin, and thus affect toxin activity. This reversible modification may play an important role in regulating toxin activity within the bacterial cell in response to signals generated during infection.
Structural dynamics of the intrinsically disordered linker region of cardiac troponin T
Authors: Cubuk Jasmine , Greenberg Lina , Greenberg Akiva E. , Emenecker Ryan J. , Stuchell-Brereton Melissa D. , Holehouse Alex S. , Soranno Andrea , Greenberg Michael J.
Published: May 2024

The cardiac troponin complex, composed of troponins I, T, and C, plays a central role in regulating the calcium-dependent interactions between myosin and the thin filament. Mutations in troponin can cause cardiomyopathies; however, it is still a major challenge to connect how changes in sequence affect troponin’s function. Recent high-resolution structures of the thin filament revealed critical insights into the structure-function relationship of troponin, but there remain large, unresolved segments of troponin, including the troponin-T linker region that is a hotspot for cardiomyopathy mutations. This linker region is predicted to be intrinsically disordered, with behaviors that are not well described by traditional structural approaches; however, this proposal has not been experimentally verified. Here, we used a combination of single-molecule Förster resonance energy transfer (FRET), molecular dynamics simulations, and functional reconstitution assays to investigate the troponin-T linker region. We show that in the context of both isolated troponin and the fully regulated troponin complex, the linker behaves as a dynamic, intrinsically disordered region. This region undergoes polyampholyte expansion in the presence of high salt and distinct conformational changes during the assembly of the troponin complex. We also examine the ΔE160 hypertrophic cardiomyopathy mutation in the linker and demonstrate that it does not affect the conformational dynamics of the linker, rather it allosterically affects interactions with other troponin complex subunits, leading to increased molecular contractility. Taken together, our data clearly demonstrate the importance of disorder within the troponin-T linker and provide new insights into the molecular mechanisms driving the pathogenesis of cardiomyopathies.

SIGNIFICANCE STATEMENT

Troponin plays a central role in regulating heart contraction, and mutations in troponin can cause human cardiomyopathies. There are several functionally-significant regions of troponin that have not been structurally resolved, including the troponin T linker region that contains multiple cardiomyopathy mutations. In these unresolved regions, it is not possible to understand how changes in sequence affect function. We used computational and experimental techniques to demonstrate that this linker is dynamic and intrinsically disordered both in isolation and in the fully regulated thin filament. Moreover, we show how a cardiomyopathy mutation in this region affects function via allosteric disruption of intermolecular interactions. Our results highlight the need to consider how key mutations affect troponin disorder rather than the structure-function relationship.
Alpha-defensin binding expands human adenovirus tropism
Authors: Zhao Cheng , Porter Jessica M. , Burke Phillip C. , Arnberg Niklas , Smith Jason G.
Published: May 2024

Mammalian α-defensins are a family of abundant effector peptides of the mucosal innate immune system. Although primarily considered to be antimicrobial, α-defensins can increase rather than block infection by certain prominent bacterial and viral pathogens in cell culture andin vivo. We have shown previously that exposure of mouse and human adenoviruses (HAdVs) to α-defensins is able to overcome competitive inhibitors that block cell binding, leading us to hypothesize a defensin-mediated binding mechanism that is independent of known viral receptors. To test this hypothesis, we used genetic approaches to demonstrate that none of several primary receptors nor integrin co-receptors are needed for human α-defensin-mediated binding of HAdV to cells; however, infection remains integrin dependent. Thus, our studies have revealed a novel pathway for HAdV binding to cells that bypasses viral primary receptors. We speculate that this pathway functions in parallel with receptor-mediated entry and contributes to α-defensin-enhanced infection of susceptible cells. Remarkably, we also found that in the presence of α-defensins, HAdV tropism is expanded to non-susceptible cells, even when viruses are exposed to a mixture of both susceptible and non-susceptible cells. Therefore, we propose that in the presence of sufficient concentrations of α-defensins, such as in the lung or gut, integrin expression rather than primary receptor expression will dictate HAdV tropismin vivo. In summary, α-defensins may contribute to tissue tropism not only through the neutralization of susceptible viruses but also by allowing certain defensin-resistant viruses to bind to cells independently of previously described mechanisms.

Author Summary

In this study, we demonstrate a novel mechanism for binding of human adenoviruses (HAdVs) to cells that is dependent upon interactions with α-defensin host defense peptides but is independent of known viral receptors and co-receptors. To block normal receptor-mediated HAdV infection, we made genetic changes to both host cells and HAdVs. Under these conditions, α-defensins restored cell binding; however, infection still required the function of HAdV integrin co-receptors. This was true for multiple types of HAdVs that use different primary receptors and for cells that are either naturally devoid of HAdV receptors or were engineered to be receptor deficient. These observations suggest that in the presence of concentrations of α-defensins that would be found naturally in the lung or intestine, there are two parallel pathways for HAdV binding to cells that converge on integrins for productive infection. Moreover, these binding pathways function independently, and both operate in mixed culture. Thus, we have found that viruses can co-opt host defense molecules to expand their tropism.
Dysfunctional S1P/S1PR1 signaling in the dentate gyrus drives vulnerability of chronic pain-related memory impairment
Authors: Cui Mengqiao , Pan Xiaoyuan , Fan Zhijie , Wu Shulin , Ji Ran , Wang Xianlei , Kong Xiangxi , Wu Zhou , Song Lingzhen , Song Weiyi , Yang Jun-Xia , Zhang Hongjie , Zhang Hongxing , Ding Hai-Lei , Cao Jun-Li
Published: May 2024

Memory impairment in chronic pain patients is substantial and common, and few therapeutic strategies are available. Chronic pain-related memory impairment has susceptible and unsusceptible features. Therefore, exploring the underlying mechanisms of its vulnerability is essential for developing effective treatments. Here, combining two spatial memory tests (Y-maze test and Morris water maze), we segregated chronic pain mice into memory impairment-susceptible and -unsusceptible subpopulations in a chronic neuropathic pain model induced by chronic constrictive injury of the sciatic nerve. RNA-seq analysis and gain/loss-of-function study revealed that S1P/S1PR1 signaling is a determinant for vulnerability to chronic pain-related memory impairment. Knockdown of the S1PR1 in the DG promoted a susceptible phenotype and led to structural plasticity changes of reduced excitatory synapse formation and abnormal spine morphology as observed in susceptible mice, while overexpression of the S1PR1 and pharmacological administration of S1PR1 agonist in the DG promoted an unsusceptible phenotype and prevented the occurrence of memory impairment, and rescued the morphological abnormality. Finally, GO enrichment analysis and biochemical evidence indicated that down-regulation of S1PR1 in susceptible mice may impair DG structural plasticity via interaction with actin cytoskeleton rearrangement-related signaling pathways including Itga2 and its downstream Rac1/Cdc42 signaling and Arp2/3 cascade. These results reveal a novel mechanism and provide a promising preventive and therapeutic molecular target for vulnerability to chronic pain-related memory impairment.
STAG3 promotes exit from pluripotency through post-transcriptional mRNA regulation in the cytoplasm
Authors: Weeks Sam , Pezic Dubravka , Dodel Martin , Shah Kunal , Bhamra Amandeep , Henderson Stephen , Surinova Silvia , Sharp Tyson , Mardakheh Faraz , Hadjur Suzana
Published: May 2024

STAG proteins are key regulators of the cohesin complex and are often linked to alterations in cell identity and disease. Among the mammalian STAG paralogs, STAG3 has been less extensively studied beyond its known roles in meiosis. In this work, we demonstrate that STAG3 is expressed in mouse embryonic stem cells (mESCs) and primordial germ cell-like cells (PGCLCs), where it is required for cell fate decisions. Distinct from the other STAG proteins, STAG3 mediates its effects in the cytoplasm, facilitating the post-transcriptional regulation of gene expression. Furthermore, STAG3 localises to the centrosome independently of cohesin and interacts with proteins involved in mRNA localisation and stability. The knockdown of STAG3 in mESCs using siRNAs results in the destabilisation of the centrosome and the key P-body RNA-induced silencing complex (RISC) component TNRC6C, leading to the derepression of P-body localised mRNAs, such as DPPA3. Our results propose a model in which STAG3 collaborates with RNA-binding proteins (RBPs) and specific target mRNAs to control post-transcriptional gene expression and facilitate the transition from pluripotency in mESCs. Given that STAG3 is upregulated in various cancers, our results provide a novel perspective on how STAG proteins might contribute to cell identity and disease.
Structural characterization and inhibition of the interaction between ch-TOG and TACC3
Authors: Shelford James , Burgess Selena G. , Rostkova Elena , Richards Mark W. , Tiede Christian , Fielding Alistair J. , Daviter Tina , Tomlinson Darren C. , Calabrese Antonio N. , Pfuhl Mark , Bayliss Richard , Royle Stephen J.
Published: May 2024

The mitotic spindle is a bipolar array of microtubules, radiating from the poles which each contain a centrosome, embedded in pericentriolar material. Two proteins, ch-TOG and TACC3, have multiple functions at the mitotic spindle due to operating alone, together or in complex with other proteins. To distinguish these activities, we need new molecular tools to dissect their function. Here, we present the structure of theα-helical bundle domain of ch-TOG that mediates its interaction with TACC3 and a structural model describing the interaction, supported by biophysical and biochemical data. We have isolated Affimer tools to precisely target the ch-TOG-binding site on TACC3 in live cells, which displace ch-TOG without affecting the spindle localization of other protein complex components. Inhibition of the TACC3–ch-TOG interaction led unexpectedly to fragmentation of the pericentriolar material in metaphase cells following the formation of a bipolar spindle and delayed mitotic progression; uncovering a novel role of TACC3–ch-TOG in maintaining pericentriolar material integrity during mitosis to ensure timely cell division.
Model-independent predictions for decays of hidden-heavy hadrons into pairs of heavy hadrons
Authors: Braaten E. , Bruschini R.
Published: May 2024

Hidden-heavy hadrons can decay into pairs of heavy hadrons through transitions from confining Born-Oppenheimer potentials to hadron-pair potentials with the same Born-Oppenheimer quantum numbers. The transitions are also constrained by conservation of angular momentum and parity. From these constraints, we derive model-independent selection rules for decays of hidden-heavy hadrons into pairs of heavy hadrons. The coupling potentials are expressed as sums of products of Born-Oppenheimer transition amplitudes and angular-momentum coefficients. If there is a single dominant Born-Oppenheimer transition amplitude, it factors out of the coupling potentials between hidden-heavy hadrons in the same Born-Oppenheimer multiplet and pairs of heavy hadrons in specific heavy-quark-spin-symmetry doublets. If furthermore the kinetic energies of the heavy hadrons are much larger than their spin splittings, we obtain analytic expressions for the relative partial decay rates in terms of Wigner 6j and 9j symbols. We consider in detail the decays of quarkonia and quarkonium hybrids into the lightest heavy-meson pairs. For quarkonia, our model-independent selection rules and relative partial decay rates agree with previous results from quark-pair-creation models in simple cases and give stronger results in other cases. For quarkonium hybrids, we find disagreement even in simple cases.

Published by the American Physical Society
2024
Decay and Fission of Magnetic Quivers
Authors: Bourget Antoine , Sperling Marcus , Zhong Zhenghao
Published: May 2024

In exploring supersymmetric theories with eight supercharges, the Higgs branches present an intriguing window into strong coupling dynamics. Magnetic quivers serve as crucial tools for understanding these branches. Here, we introduce the algorithm for unitary magnetic quivers. It efficiently derives complete phase diagrams (Hasse diagrams) through convex linear algebra. It allows magnetic quivers to undergo or , reflecting Higgs branch RG flows in the theory. Importantly, the algorithm generates magnetic quivers for the RG fixed points and simplifies the understanding of transverse slice geometry with no need for a list of minimal transitions. In contrast, the algorithm hints to the existence of a new minimal transition, whose geometry and physics need to be explored.

Published by the American Physical Society
2024
Synthesis and crystal structure of the cluster (Et4N)[(Tp*)MoFe3S3(μ3-NSiMe3)(N3)3]
Authors: Li Yue , Wei Jia , Han Jie , Chen Xu-Dong
Published: May 2024

The title compound, tetraethylammonium triazidotri-μ3-sulfido-[μ3-(trimethylsilyl)azanediido][tris(3,5-dimethylpyrazol-1-yl)hydroborato]triiron(+2.33)molybdenum(IV), (C8H20N)[Fe3MoS3(C15H22BN6)(C3H9NSi)(N3)3] or (Et4N)[(Tp*)MoFe3S3(μ3-NSiMe3)(N3)3] [Tp* = tris(3,5-dimethylpyrazol-1-yl)hydroborate(1−)], crystallizes as needle-like black crystals in space group P\overline{1}. In this cluster, the Mo site is in a distorted octahedral coordination model, coordinating three N atoms on the Tp* ligand and three μ3-bridging S atoms in the core. The Fe sites are in a distorted tetrahedral coordination model, coordinating two μ3-bridging S atoms, one μ3-bridging N atom from Me3SiN2−, and another N atom on the terminal azide ligand. This type of heterometallic and heteroleptic single cubane cluster represents a typical example within the Mo–Fe–S cluster family, which may be a good reference for understanding the structure and function of the nitrogenase FeMo cofactor. The residual electron density of disordered solvent molecules in the void space could not be reasonably modeled, thus the SQUEEZE [Spek (2015). Acta Cryst. C71, 9–18] function was applied. The solvent contribution is not included in the reported molecular weight and density.
The crystal structures and Hirshfeld surface analysis of three new bromo-substituted 3-methyl-1-(phenylsulfonyl)-1H-indole derivatives
Authors: Madhan S. , NizamMohideen M. , Harikrishnan K. , MohanaKrishnan Arasambattu K.
Published: May 2024

Three new 1H-indole derivatives, namely, 2-(bromomethyl)-3-methyl-1-(phenylsulfonyl)-1H-indole, C16H14BrNO2S, (I), 2-[(E)-2-(2-bromo-5-methoxyphenyl)ethenyl]-3-methyl-1-(phenylsulfonyl)-1H-indole, C24H20BrNO3S, (II), and 2-[(E)-2-(2-bromophenyl)ethenyl]-3-methyl-1-(phenylsulfonyl)-1H-indole, C23H18BrNO2S, (III), exhibit nearly orthogonal orientations of their indole ring systems and sulfonyl-bound phenyl rings. Such conformations are favourable for intermolecular bonding involving sets of slipped π–π interactions between the indole systems and mutual C—H...π hydrogen bonds, with the generation of two-dimensional monoperiodic patterns. The latter are found in all three structures, in the form of supramolecular columns with every pair of successive molecules related by inversion. The crystal packing of the compounds is additionally stabilized by weaker slipped π–π interactions between the outer phenyl rings (in II and III) and by weak C—H...O, C—H...Br and C—H...π hydrogen bonds. The structural significance of the different kinds of interactions agree with the results of a Hirshfeld surface analysis and the calculated interaction energies. In particular, the largest interaction energies (up to −60.8 kJ mol−1) are associated with pairing of antiparallel indole systems, while the energetics of weak hydrogen bonds and phenyl π–π interactions are comparable and account for 13–34 kJ mol−1.
An intelligent framework for rework risk identification in prefabricated construction processes based on compliance checking
Authors: Meng Fanfan , Cao Xinying
Published: May 2024

Purpose

This study establishes an ontology-based framework for rework risk identification (RRI) by integrating heterogeneous data from the information flow of the prefabricated construction (PC) process. The main objective is to enhance the automation level of rework management and reduce the degree of reliance on human factors and manual operations.

Design/methodology/approach

The proposed framework comprises four levels aimed at managing dispersed rework risk knowledge and integrating heterogeneous data. The functionalities were realised through an integrated ontology that aligned the rework risk ontology with the PC ontology. The ontologies were developed and edited with Protégé. Ultimately, the potential benefit of the framework was validated through a case study and an expert questionnaire survey.

Findings

The framework is proven to effectively manage rework risk knowledge and can identify risk objects, clarify risk factors, determine risk events, and retrieve risk measures, thereby enabling the pre-identification of prefabricated rework risk (PRR) and improving the automation level. This study is meaningful and lays the foundation for the application of other computer methods in rework management research and practice in the future.

Originality/value

This research provides insights into the application of ontology to solve rework risk issues in the PC process and introduces a novel risk management method for future prefabricated project research and practice. The findings have significant theoretical value in terms of enriching the methods of risk assessment and control and the information management system of prefabricated projects.
Information sharing and feeling of competency at work: a proactive training seeking perspective
Authors: Cangialosi Nicola , Odoardi Carlo , Déprez Guillaume R.M.
Published: May 2024

Purpose

This study aims to investigate the mediating role of challenging tasks, organizational identification and technological training seeking behavior in the relationship between information sharing as a human resource practice and employees’ feelings of competency at work.

Design/methodology/approach

Structural equation modeling was used to analyze data collected from a three-wave online survey conducted in an Italian aerospace manufacturing company (n = 294).

Findings

The results reveal an indirect path between information sharing and feelings of competence, mediated by organizational identification and training seeking behavior. However, no total indirect path was observed between feelings of competency and information sharing through challenging tasks and training seeking.

Originality/value

This research contributes to the understanding of the impact of information sharing on individuals’ feelings of competency in the context of organizational change, particularly through the introduction of the concept of proactive training seeking as a novel dimension of proactive behavior.
Perceptions of organizational politics and organizational commitment: role of personal motive and ability
Authors: Lee Jun-hyuk
Published: May 2024

Purpose

This study expanded previous studies on the relationship between POP (Perceptions of Organizational Politics) and OC (Organizational Commitment); and it examined the mediating effect of OCM (Organizational Concern Motive) and the moderated mediating effect of PS (Political Skills). Based on the uncertainty management and expectancy theories, the mediating role of OCM was assumed; also, the moderated mediating effect of PS was assumed, because of the effect of the POP on members' motives would vary depending on each individual's ability to respond.

Design/methodology/approach

To collect the required data for analyzing the research model of this study, a questionnaire was conducted on employees of South Korean companies and institutions. To verify the hypothesis of this study, the measurement and hypothesized models were analyzed sequentially.

Findings

The results of this study indicated that the OCM mediates the relationship between POP and OC. Furthermore, the mediating effect of OCM is moderated by PS. Specifically the negative effect of the POP on the OCM was mitigated in the group with proficient PS.

Research limitations/implications

To mitigate the negative effects of POP, this study suggests that managers should provide fair evaluation and reward based on performance, and consider PS as an important factor in employee selection and education/training.

Originality/value

This study is original in that it presents the mechanisms of both variables in terms of an individual's motive towards the organization. Furthermore, this study is valuable in that it suggests ways to mitigate the negative effects of POP through PS.
Impact of small-scale irrigation on the income of rural farm households: empirical evidence from Ethiopia
Authors: Jatana Desta , Tesfahun Azmeraw Ayehu
Published: May 2024

Purpose

Agricultural production in Ethiopia is largely dependent on seasonal rainfall. This has made the agriculture-based economy of the country extremely vulnerable to the impacts of climatic change. To reduce this risk, the government has introduced strategies that promote irrigation as a key policy priority. Despite this, there has been limited empirical evidence on the impact of practicing small-scale irrigation on household income. This study was, therefore, conducted to examine the impact of access to small-scale irrigation on farm-household income in GannaBossa district, Ethiopia.

Design/methodology/approach

A multistage stratified random sampling technique was adopted to select 289 study participants. The data were analysed using both descriptive and inferential data analysis techniques. Propensity score matching (PSM) and logit regression were applied to analyse the impact of irrigation utilization on farm households’ income and identify factors influencing farm households’ decisions about irrigation-utilization, respectively.

Findings

The results of the study indicated that access to irrigation has a positive and significant impact on farm-household income. Estimates of the PSM model also confirmed that the mean income of irrigating households is significantly higher than that of non-irritating households. Further analysis of the results of the regression model revealed that amongst the hypothesized predictors of irrigation utilization, family size, soil fertility status, access to credit, access to extension services and access to the market were found to be positive and significant determinants of irrigation utilization, while distance to a water source was found to be a negative and significant predictor of irrigation utilization.

Practical implications

The results of the study can inform development practitioners on how expanding access to irrigation can serve as one key driver in enhancing growth in agricultural productivity, increasing household income and contributing to the alleviation of rural poverty in areas with irregular rainfall and a high risk of drought.

Originality/value

Given the country’s irrigation potential and policy priorities, such empirical evidence informs decision-makers to make informed decisions regarding prioritizing irrigation interventions and expanding access and management in Ethiopia.
Ecologically‐related variation of digit morphology in Cyrtodactylus (Gekkota, Squamata) reveals repeated origins of incipient adhesive toepads
Authors: Riedel Jendrian , Eisele Katrin , Gabelaia Mariam , Higham Timothy E. , Wu Joseph , Do Quyen Hanh , Nguyen Truong Quang , Meneses Camila G. , Brown Rafe M. , Ziegler Thomas , Grismer L. Lee , Russell Anthony P. , Rödder Dennis
Published: May 2024

Exploitation of different locomotor substrates in different ecological niches has driven the evolution of specialized morphological structures, and similar ecological demands, such as the structure of the microhabitat, often lead to convergent or parallel evolution.

The evolution of adhesive toepads in geckos remains understudied because of the paucity of phylogenetically‐informed investigations of candidate clades exhibiting purported incipient expression of these (i.e. species having evolved some, but not all, parts of the complex adhesive system of pad‐bearing geckos).

Using Cyrtodactylus, a speciose genus with well‐established ecotypes, we tested the hypothesis that microhabitats that require more climbing will lead to the acquisition of incipient adhesive morphology.

We measured subdigital scale area, a proxy for adhesive toepad evolution, and quantified subdigital scale shape for 77 of the 354 described species, including at least one representative of each ecotype.

Subdigital scale area increased from terrestrial through generalist and saxicoline (rock‐dwelling) to arboreal ecotypes, with subdigital scale shape evolving from ancestral conditions for padless lizards to lateromedially expanded lamella‐like scales only in the arboreal ecotypes.

This significant link between phenotype and environment supports the contention that scansorial, and particularly arboreal, Cyrtodactylus ecotypes have evolved incipiently expressed adhesive toepads. This highlights the suitability of this genus as a model system for studying the ecology and evolution of adhesive toepads as well as being a promising candidate for research on adaptive radiations.

Read the free Plain Language Summary for this article on the Journal blog.
Research on the influence of emergency rescue information importance on emergency decisions
Authors: Jiang Wei , Zhou Jiankai , Ma Shengxiang , Wu Zonghao , Cui Xiaoyuan , Yang Chaofan
Published: May 2024

Emergency rescue information is a significant factor affecting emergency decisions in the accident process, and determining the content and importance of this information can greatly assist emergency decisions and improve their effectiveness. For this reason, this paper combines decision‐making trial and evaluation laboratory (DEMATEL) with a backpropagation (BP) neural network and uses the Levenberg‒Marquardt (LM) algorithm to optimize it, builds the LM‐BP‐DEMATEL model, and investigates the contents and importance of emergency rescue information with hazardous chemical spills as an illustrative case. First, the meaning of emergency rescue information was defined using national laws and regulations and academic research. Second, using hazardous chemical spills as an example, 62 hazardous chemical spills were collected, and 7 categories with a total of 32 emergency rescue information were extracted. Third, the constructed LM‐BP‐DEMATEL model was utilized to analyse the importance of 14 types of common emergency rescue information in 62 cases. Last, the centrality and causality of 14 types of emergency rescue information were obtained and then classified into four categories according to centrality and causality. The research results show that deaths (U8) and leakage information (U6) are the most critical emergency rescue information, that more attention should be given to emergency decision‐making and that targeted strategies should be formulated to improve the effect of emergency decisions.
Spermatocytes are the terminals of germ cell differentiation in plateau zokor (Eospalax baileyi) during the non‐breeding season
Authors: AN Kang , YAO Baohui , TAN Yuchen , KANG Yukun , WANG Zhicheng , SU Junhu
Published: May 2024

Plateau zokor (Eospalax baileyi) is a subterranean rodent and seasonal breeder. During the non‐breeding season, the testicles regress, leading to the arrest of spermatogenesis and loss of fertility. The identification of the specific germ cell type at which spermatogenesis is arrested, as well as potential regulatory factors during the non‐breeding season, is important for understanding seasonal spermatogenesis in subterranean species. This study analyzed genes in spermatocytes of plateau zokor by referring to single‐cell RNA results in mice. We discovered that spermatogenesis is arrested at the spermatocyte during the non‐breeding season, which was corroborated via immunofluorescence staining results. The analysis of gene expression during different stages of meiotic prophase I has revealed that germ cell development may be arrested, starting from zygonema, during the non‐breeding season. Meanwhile, we discovered that the apoptosis genes were up‐regulated, leading to apoptosis in spermatocytes. To confirm that the germ cell differentiation was blocked during the non‐breeding season due to a decrease in the androgen level, we used androgen receptor antagonist (flutamide) to intervene in the breeding season and found that the inner diameter of the seminiferous tubules was significantly reduced, spermatogenesis was arrested, and spermatocytes underwent apoptosis. This study revealed that spermatocytes are the terminal of germ cell differentiation in plateau zokor during the non‐breeding season and that the arrest of differentiation is attributed to a decline in androgen levels. Our results complement the theoretical basis of seasonal reproduction in plateau zokor.
Place of death among children from 0 to 17 years of age: A population‐based study from Sweden
Authors: Nilsson Stefan , Öhlén Joakim , Nyblom Stina , Ozanne Anneli , Stenmarker Margaretha , Larsdotter Cecilia
Published: May 2024

Aim

The aim of this study is to contribute to the development of paediatric palliative care by investigating, on a population basis, where children in Sweden died, from 2013 to 2019. A particular focus was on comparing two groups: children who died during their first year of life with children who died at 1–17 years of age.

Methods

We hypothesised that there might be variations in place of death between the defined groups. Utilising national registry data, descriptive statistics were used to assess the distribution and variations in the place of death. Logistic regression analyses were conducted to ascertain the impact of associated factors.

Results

Most children died in hospitals (74.7%). The hypothesis postulating divergences in the place of death between age groups was not substantiated. Sex and birthplace showed no significant differences in home deaths. Deaths due to malignancies had a relatively high likelihood of occurring at home (39.0%). For perinatal diagnoses, the incidence of home deaths was relatively low (1.5%).

Conclusion

Children who received support from a specialist palliative service in their own homes were notably less likely to die in a hospital setting compared to those who did not receive such support. An unplanned hospital visit increased the likelihood of hospital death.
Thrombocytopenia 4 (THC4): Six novel families with mutations of the cytochrome c gene
Authors: Marzollo Antonio , Zampieri Stefania , Barozzi Serena , Yousaf Muhammad Abrar , Quartararo Jade , De Rocco Daniela , Faleschini Michela , Marconi Caterina , Ceccatelli Berti Camilla , Bozzi Valeria , Russo Giovanna , Giordano Paola , Goffrini Paola , Bresolin Silvia , Pastore Annalisa , Savoia Anna , Pecci Alessandro
Published: May 2024

Thrombocytopenia 4 (THC4) is an autosomal‐dominant thrombocytopenia caused by mutations in CYCS, the gene encoding cytochrome c (CYCS), a small haeme protein essential for electron transport in mitochondria and cell apoptosis. THC4 is considered an extremely rare condition since only a few patients have been reported so far. These subjects presented mild thrombocytopenia and no or mild bleeding tendency. In this study, we describe six Italian families with five different heterozygous missense CYCS variants: p.Gly42Ser and p.Tyr49His previously associated with THC4, and three novel variants (p.Ala52Thr, p.Arg92Gly, and p.Leu99Val), which have been classified as pathogenic by bioinformatics and segregation analyses. Moreover, we supported functional effects of p.Ala52Thr and p.Arg92Gly on oxidative growth and respiratory activity in a yeast model. The clinical characterization of the 22 affected individuals, the largest series of THC4 patients ever reported, showed that this disorder is characterized by mild‐to‐moderate thrombocytopenia, normal platelet size, and function, low risk of bleeding, and no additional clinical phenotypes associated with reduced platelet count. Finally, we describe a significant correlation between the region of CYCS affected by mutations and the extent of thrombocytopenia, which could reflect different degrees of impairment of CYCS functions caused by different pathogenetic variants.
18F‐fluoro‐ethyl‐tyrosine PET co‐registered with MRI in patients with persisting acromegaly
Authors: Bakker Leontine E. H. , Verstegen Marco J. T. , Manole Diandra C. , Lu Huangling , Decramer Thomas J. M. , Pelsma Iris C. M. , Kruit Mark C. , Verbist Berit M. , van de Ven Annenienke , Gurnell Mark , Ghariq Idris , van Furth Wouter R. , Biermasz Nienke R. , Pereira Arias‐Bouda Lenka M.
Published: May 2024

Objective

To report our experience with 18F‐fluoro‐ethyl‐tyrosine (FET) positron emission tomography‐computed tomography (PET‐CT) co‐registered with magnetic resonance imaging (MRI) (FET‐PET/MRICR) in the care trajectory for persistent acromegaly.

Design

Prospective case series.

Patients

Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options.

Measurements

FET‐PET/MRICR was used to support decision‐making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery.

Results

FET‐PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET‐PET/MRICR was fully concordant with conventional MRI, and in one patient partially concordant. FET‐PET/MRICR identified suggestive new foci in four other patients. Surgical re‐exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET‐PET/MRICR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF‐1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients.

Conclusions

In patients with persisting acromegaly without a clear surgical target on MRI, FET‐PET/MRICR is a new tracer to provide additional information to aid decision‐making by the multidisciplinary pituitary team.
CCR6+ T helper cells and regulatory T cells in the blood and gastric mucosa during Helicobacter pylori infection
Authors: Talayev Vladimir , Svetlova Maria , Zaichenko Irina , Voronina Elena , Babaykina Olga , Neumoina Natalia , Perfilova Ksenia
Published: May 2024

Background

Helicobacter pylori (H. pylori) can evade the host's immune response and persist for a long time on the gastric mucosa. T helper (Th) cells appear to be involved in the control of H. pylori bacteria but promote mucosal inflammation. In contrast, regulatory T cells (Tregs) may reduce inflammation but promote H. pylori persistence. CC motif chemokine receptor 6 (CCR6) is involved in the migration of various cells into inflamed gastric mucosa. In this study, we examined CCR6+ Th cells and CCR6+ Tregs during H. pylori infection in humans.

Materials and Methods

Isolation of cells from blood and mucosal biopsies, magnetic separation of В cells, CD4+ and CD4+CCR6+CD45RO+ T cells, antigen‐specific activation, B cell response in vitro, flow cytometry, determination of CD4+CD25hiFoxP3+ Tregs and various groups of Th cells.

Results

CD4+CCR6+ blood lymphocytes from healthy donors included Th cells and Tregs. These CCR6+ Th cells produced proinflammatory cytokines and also stimulated plasma cell maturation and antibody production in vitro. H. pylori gastritis and peptic ulcer disease were associated with an increase in the number of circulate CD4+CCR6+CD45RO+ cells and the percentage of Th1, Th17 and Th1/17 cells in this lymphocyte subgroup. In H. pylori‐positive patients, circulating CD4+CCR6+ cells contained a higher proportion of H. pylori‐specific cells compared with their CD4+CCR6− counterparts. H. pylori infection strongly increased the content of CD4+ lymphocytes in the inflamed gastric mucosa, with the majority of these CD4+ lymphocytes expressing CCR6. CD4+CCR6+ lymphocytes from H. pylori‐infected stomach included Tregs and in vivo activated T cells, some of which produced interferon‐γ without ex vivo stimulation.

Conclusion

H. pylori infection causes an increase in the number of mature CD4+CCR6+ lymphocytes in the blood, with a pro‐inflammatory shift in their composition and enrichment of the gastric mucosa with CD4+CCR6+ lymphocytes, including CCR6+ Th1 cells and Tregs.
Agricultural crisis, refugee crisis, or health crisis? Migrant seasonal workers in Italian agriculture during the COVID pandemic
Authors: Cingolani Pietro
Published: May 2024

The concept of crisis has been widely used to describe European social phenomena which have become acute and unmanageable in recent years. Exceptionality and emergency have become attributes of the political strategies developed to address the economic, social, and environmental unsustainability of industrial farming; the flow of forced migrants; and the COVID‐19 pandemic. This article is based on ethnographic data collected over more than 2 years among immigrant workers and their employers in northern Italy, before and during the spread of the pandemic. By relating the experience of the people involved and analysis of the structural dimensions, I show how the “refugeeization of the agricultural workforce” and the “normalization of precarity” are two interconnected and interdependent processes. My study contributes to the recent scientific debate on the “polycrisis” by highlighting how the agricultural crisis generated a demand for vulnerable migrant labour and this situation was exacerbated by the health crisis.
Switching to a 100% remote follow‐up of implantable cardiac electronic devices: Organizational model and results of a single center experience
Authors: Miracapillo Gennaro , Addonisio Luigi , De Sensi Francesco , Orselli Paolo , Piccinetti Elena , Aramini Carla , Limbruno Ugo
Published: May 2024

Introduction

During the SARS‐CoV‐2 COVID‐19 pandemic, the global health system needed to review important processes involved in daily routines such as outpatient activities within the hospital, including follow‐up visits of implantable cardiac electronic devices (CIEDs) carried out in office. The aim of this study is to describe our 3.5 years of real‐world experience of a full remote CIED follow‐up, evaluate the success rate of remote transmissions, and verify the adopted organizational model.

Methods

From April 2020 to November 2023, all patients with an activated and well‐functioning remote monitoring (RM) system and automatic algorithms, like autocapture and autosensing, underwent exclusive RM follow‐up. Unscheduled in‐office visits were only prompted by remote yellow or red alerts. Patients were divided into two groups, based on available technology: Manual Transmission System (MTS) and Automatic Transmission System (ATS). The ATS group, in addition to ensuring a daily transmission of any yellow or red alerts, was checked at least every 15 days to ensure a valid connection. An automatic transmission was scheduled once a year, irrespective of alerts occurred. The MTS group provided a manual transmission every 6 months.

Results

One thousand nine hundred thirty‐seven consecutive patients were included in the study. By the end of November 2023, a total of 1409 patients (1192 in the ATS and 217 in the MTS group) were still actively followed by our remote clinic (384 expired, 137 dismissed, 7 transferred). The overall success rate of transmissions with the adopted organizational model was 96.6% in the ATS group (connection index) and 87% in the MTS group. Conventional in‐hospital follow‐up visits decreased by 44%. Total clinic working time, resulting from the sum of the time spent during in‐hospital and remote follow‐up, after an initial increase, was progressively reduced to the actual −25%. Mortality rate for any cause was 7.5% per year in remote follow‐up patients and 8.3% (p=NS) in in‐office patients. In the ATS group, no device malfunctions were notified to our remote clinic, before we had already realized it through appropriate alerts.

Conclusions

The available technology makes moving to a 100% remote clinic possible, without overwhelming clinic workflow, safely. Adopting an appropriate organizational model, it is possible to maintain high transmission success rates. The automatic transmissions allow a more frequent control of patients with CIED.
Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid‐induced myopathy
Authors: He A. , Koszegi B. , Uzun S. , Bilgic A. , Bozca B. C. , Yang B. , Daneshpazhooh M. , Boziou M. , Patsatsi A. , Kakuta R. , Takahashi H. , Nery D. , Mundin C. , Ramirez‐Quizon M. , Culton D. , McAlpine S. , Johal J. , Shulruf B. , Stone J. H. , Murrell D. F.
Published: May 2024

Background

Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid‐induced myopathy (GIM) is a well‐established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time.

Objectives

This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors.

Methods

This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit.

Results

The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM.

Conclusions

GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered.
Feedback‐based learning from viewpoints of surgical nursing students: A mixed‐method study
Authors: Keshmiri Fatemeh , Javadi Alireza
Published: May 2024

Background

Feedback‐based learning (FBL) focuses on guiding the learning process according to educational objectives and the student's needs. This study aimed to investigate surgical nursing students' perceptions and explore their experiences of FBL.

Method

The present study used a mixed‐methods sequential explanatory design that was conducted in the quantitative and qualitative phases. Surgical nursing students participated in the quantitative phase (n = 105). In the first phase, students completed two questionnaires about FBL and clinical feedback. Semi‐structured face‐to‐face interviews were used to collect qualitative data in the second phase. Graneheim and Lundman's inductive approaches were used to analyse the qualitative data.

Results

The mean (SD) score for students' perception of FBL was 3.99 ± 0.70. The qualitative results were explored in two themes, “motivational support for improvement” and “unpleasant learning”.

Conclusion

In this study, the positive and negative aspects of FBL were explained. FBL is perceived as a motivational support mechanism to improve students' capabilities during their academic courses and also prepare them for future careers. Conversely, FBL may experience unpleasant learning due to negative feedback and negative emotions.