bluuebunny/crossref_metadata_2025 huggingface dataset:
CryoEM structure of QacA, an antibacterial efflux transporter from Staphylococcus aureus
Authors: Majumder Puja , Ahmed Shahbaz , Ahuja Pragya , Athreya Arunabh , Ranjan Rakesh , Penmatsa Aravind
Published: July 2022

Efflux of antibacterial compounds is a major mechanism for developing antimicrobial resistance. In the Gram-positive pathogen Staphylococcus aureus, QacA, a 14 transmembrane (TM) helix containing major facilitator superfamily antiporter, mediates proton-coupled efflux of mono and divalent cationic antibacterial compounds. In this study, we report the cryoEM structure of QacA, with a single mutation D411N that improves homogeneity and retains efflux activity against divalent cationic compounds like dequalinium and chlorhexidine. The structure of substrate-free QacA, complexed to two single-domain camelid antibodies, was elucidated to a resolution of 3.6 Å. The structure displays an outward-open conformation with an extracellular hairpin loop, which is conserved in a subset of DHA2 transporters and its deletion causes a loss of function in the transporter. Modeling and simulations of QacA’s cytosol-facing and occluded conformations reveal asymmetry in the rocker-switch mode of QacA’s conformational shifts, providing new insights into the organization and structural dynamics of DHA2 members.
Altered visual evoked potentials associated with verbal and nonverbal skills in Fragile X syndrome
Authors: Saoud Elizabeth , Fitzgerald John , Hartney Megan , Wilkinson Carol L.
Published: July 2022

Background

Understanding the neurobiology behind Fragile X syndrome (FXS) is critical in identifying effective therapeutics and improving care for affected individuals.

Electroencephalography (EEG) provides an opportunity to investigate the biological foundations of this disorder. We aimed to characterize the visual evoked potential (VEP) in young children with FXS, and to understand how measures of the VEP are associated with verbal and nonverbal development within FXS.

Methods

VEPs were collected in children between 2-7 years old with FXS (n = 9) as well as corresponding age-(n = 10) and cognitive-matched (n = 9) typically developing children. Additionally, the Mullen Scales of Early Learning and Preschool Language Scales were administered to collect measures of verbal and nonverbal development. Differences in component amplitudes and latencies of the VEP were assessed using ANCOVAs, and associations of VEP measures and verbal and nonverbal development were evaluated using linear regression with age as a covariate.

Results

No differences between groups were observed in N1, P1, or N2 VEP components. However, a consistent and prominent P2 component (latency = 177ms ± 13.7), was observed in children with FXS. The P2 amplitude was significantly increased in FXS children compared to the cognitive-matched group (p = 0.004). For children with FXS, the amplitude of several VEP components were associated with verbal and nonverbal development; larger N1 amplitude and smaller P1 and P2 amplitudes were all associated with better receptive language (all p<0.05) and larger N1 amplitude was also associated with better fine motor skills (p<0.05).

Conclusions

The observed increase in P2 amplitude and its negative association with language development within the FXS group supports the P2 component as a potential biomarker for FXS as a disorder, as well as a pathophysiological marker of verbal impairment that could be used in clinical trials.
Chemokine CXCL4 interactions with extracellular matrix proteoglycans mediate wide-spread non-receptor mediated immune cell recruitment
Authors: Gray Anna L , Karlsson Richard , Roberts Abigail RE , Ridley Amanda JL , Pun Nabina , Hughes Catherine , Medina-Ruiz Laura , Birchenough Holly L , Salanga Catherina L , Yates Edwin A , Turnbull Jeremy E , Handel Tracy M , Graham Gerard J , Jowitt Thomas A , Schiessl Ingo , Richter Ralf P , Miller Rebecca L , Dyer Douglas P
Published: July 2022

Leukocyte recruitment from the vasculature into tissues is a crucial component of the immune system, but is also key to inflammatory disease. Chemokines are central to this process but have yet to be therapeutically targeted during inflammation, due to a lack of mechanistic understanding. Specifically, CXCL4 (PF4) has no established receptor that explains its function. Here we use biophysical, in vitro and in vivo techniques to determine the mechanism underlying CXCL4 mediated leukocyte recruitment. We demonstrate that CXCL4 binds to glycosaminoglycan (GAG) sugars within the endothelial extracellular matrix resulting in increased vascular permeability and non-specific recruitment of a range of leukocytes. Furthermore, GAG sulphation confers selectivity onto chemokine localisation. These findings represent a new understanding of chemokine biology, providing novel mechanisms for future therapeutic targeting.

One sentence summary

CXCL4 binds to extracellular matrix proteoglycans resulting in increased vascular permeability and recruitment of a wide range of different leukocytes via a non-canonical mechanism.
Latent Transforming Growth Factor β Binding Protein 3 Controls Adipogenesis
Authors: Singh Karan , Sachan Nalani , Ene Taylor , Dabovic Branka , Rifkin Daniel
Published: July 2022

Transforming growth factor-beta (TGFβ) is released from cells as part of a trimeric latent complex consisting of TGFβ, the TGFβ propeptides, and either a latent TGFβ binding protein (LTBP) or glycoprotein-A repetitions predominant (GARP) protein. LTBP1 and 3 modulate latent TGFβ function with respect to secretion, matrix localization, and activation and, therefore, are vital for the proper function of the cytokine in a number of tissues. TGFβ modulates stem cell differentiation into adipocytes (adipogenesis), but the potential role of LTBPs in this process has not been studied. We observed that 72 h post adipogenesis initiation Ltbp1, 2, and 4 expression levels decrease by 74-84%, whereas Ltbp3 expression levels remain constant during adipogenesis. We found that LTBP3 silencing in C3H/10T1/2 cells reduced adipogenesis, as measured by the percentage of cells with lipid vesicles and the expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). Lentiviral mediated expression of an Ltbp3 mRNA resistant to siRNA targeting rescued the phenotype, validating siRNA specificity. Knockdown (KD) of Ltbp3 expression in 3T3-L1, M2, and primary bone marrow stromal cells (BMSC) indicated a similar requirement for Ltbp3. Epididymal and inguinal white adipose tissue fat pad weights of Ltbp3-/- mice were reduced by 62% and 57%, respectively, compared to wild-type mice. Inhibition of adipogenic differentiation upon LTBP3 loss is mediated by TGFβ, as TGFβ neutralizing antibody and TGFβ receptor I kinase blockade rescue the LTBP3 KD phenotype. These results indicate that LTBP3 has a TGFβ-dependent function in adipogenesis both in vitro and in vivo.

Significance

Understanding the control of mesenchymal stem cell fate is crucial for the potential use of these cells for regenerative medicine.

Highlights

Latent TGFβ binding protein 3 (LTBP3) is required for adipogenesis

LTBP3 mediates TGFβ levels in adipogenesis

Loss of LTBP3 results in enhanced rather than decreased levels of active TGFβ
Dynamics of Borrelia Burgdorferi Invasion and Intravasation in a Tissue Engineered Dermal Microvessel Model
Authors: Guo Zhaobin , Zhao Nan , Chung Tracy D. , Singh Anjan , Pandey Ikshu , Wang Linus , Gu Xinyue , Ademola Aisha , Linville Raleigh M. , Pal Utpal , Dumler J. Stephen , Searson Peter C.
Published: July 2022

Lyme disease is a tick-borne disease prevalent in North America, Europe, and Asia. Dissemination of vector-borne pathogens, such as Borrelia burgdorferi (Bb), results in infection of distant tissues and is the main contributor to poor outcomes. Despite the accumulated knowledge from epidemiological, in vitro, and in animal studies, the understanding of dissemination remains incomplete with several important knowledge gaps, especially related to invasion and intravasation at the site of a tick bite, which cannot be readily studied in animal models or humans. To elucidate the mechanistic details of these processes we developed a tissue-engineered human dermal microvessel model. Fluorescently-labeled Bb (B31 strain) were injected into the extracellular matrix (ECM) of the model to mimic tick inoculation. High resolution, confocal imaging was performed to visualize Bb migration in the ECM and intravasation into circulation. From analysis of migration paths we found no evidence to support adhesin-mediated interactions between Bb and components of the ECM or basement membrane, suggesting that collagen fibers serve as inert obstacles to migration. Transendothelial migration occurred at cell-cell junctions and was relatively fast, consistent with Bb swimming in ECM. In addition, we found that Bb alone can induce endothelium activation, resulting in increased immune cell adhesion but no changes in global or local permeability. Together these results provide new insight into the minimum requirements for dissemination of Bb at the site of a tick bite, and highlight how tissue-engineered models are complementary to animal models in visualizing dynamic processes associated with vector-borne pathogens.

Significance Statement

Using a tissue-engineered human dermal microvessel model we reveal new insight into the invasion and intravasation of Borrelia burgdorferi (Bb), a causative agent of Lyme disease in North America, following a tick bite. These results show how tissue-engineered models enable imaging of dynamic processes that are challenging in animal models or human subjects.
metascreen: A modular tool for the design and analysis of drug combination screens
Authors: Hanes Robert , Ayuda-Durán Pilar , Rønneberg Leiv , Zucknick Manuela , Enserink Jorrit
Published: July 2022

There is a rapidly growing interest in high-throughput drug combination screening to identify synergizing drug interactions for treatment of various maladies, such as cancer and infectious disease. This creates the need for pipelines that can be used to design such screens, perform quality control on the data, and generate data files that can be analyzed by synergy-finding bioinformatics applications. metascreen is an open source, end-to-end modular tool available as an R-package for the design and analysis of drug combination screens. The tool allows for a customized build of pipelines through its modularity and provides a flexible approach to quality control and data analysis. metascreen is adaptable to various experimental requirements with an emphasis on precision medicine. It can be coupled to other R packages, such as bayesynergy, to identify synergistic and antagonistic drug interactions in cell lines or patient samples. metascreen is scalable and provides a complete solution for setting up drug sensitivity screens, read raw measurements and consolidate different datasets, perform various types of quality control, and analyze, report and visualize the results of drug sensitivity screens.

Availability and implementation

The R-package and technical documentation is available at https://github.com/Enserink-lab; the R source code is publicly available at https://github.com/Enserink-lab/metascreen under GNU General Public License v3.0; bayesynergy is accessible at https://github.com/ocbe-uio/bayesynergy/

Selected modules will be available through Galaxy, an open-source platform for FAIR data analysis, Norway: https://usegalaxy.no
Gene co-expression network analysis of the human gut commensal bacterium Faecalibacterium prausnitzii based on WGCNA in R-Shiny
Authors: Auger Sandrine , Mournetas Virginie , Chiapello Hélène , Loux Valentin , Langella Philippe , Chatel Jean-Marc
Published: July 2022

Faecalibacterium prausnitzii is abundant in the healthy human intestinal microbiota, and the absence or scarcity of this bacterium has been linked with inflammatory diseases and metabolic disorders. F. prausnitzii thus shows promise as a next-generation probiotic for use in restoring the balance of the gut microbial flora and, due to its strong anti-inflammatory properties, for the treatment of certain pathological conditions. However, very little information is available about gene function and regulation in this species. Here, we utilized a systems biology approach - weighted gene co-expression network analysis (WGCNA) – to analyze gene expression in three publicly available RNAseq datasets from F. prausnitzii strain A2-165, all obtained in different laboratory conditions. The co-expression network was then subdivided into 24 co-expression gene modules. A subsequent enrichment analysis revealed that these modules are associated with different kinds of biological processes, such as arginine, histidine, cobalamin, or fatty acid metabolism as well as bacteriophage function, molecular chaperones, stress response, or SOS response. Some genes appeared to be associated with mechanisms of protection against oxidative stress and could be essential for F. prausnitzii’s adaptation and survival under anaerobic laboratory conditions. Hub and bottleneck genes were identified by analyses of intramodular connectivity and betweenness, respectively; this highlighted the high connectivity of genes located on mobile genetic elements, which could promote the genetic evolution of F. prausnitzii within its ecological niche. This study provides the first exploration of the complex regulatory networks in F. prausnitzii, and all of the “omics” data are available online for exploration through a graphical interface at https://feaprau.omics.ovh/.
Transgenerational effects of alcohol on intoxication sensitivity in Caenorhabditis elegans
Authors: Guzman Dawn M. , Chakka Keerthana , Shi Ted , Marron Alyssa , Fiorito Ansley E. , Rahman Nima S. , Ro Stephanie , Sucich Dylan G. , Pierce Jonathan T.
Published: July 2022

Alcohol abuse and dependence have a substantial heritable component. Although the genome has been considered the sole vehicle of heritable phenotypes, recent studies suggest that drug or alcohol exposure may induce alterations in gene expression that are transmitted across generations. Still, the transgenerational impact of alcohol use (and abuse) remains largely unexplored in part because multigenerational studies using rodent models present challenges for time, sample size, and genetic heterogeneity. Here, we took advantage of the extremely short generation time, large broods, and clonal form of reproduction of the nematode Caenorhabditis elegans. We developed a model of preconception parental alcohol exposure to test alterations in behavioral responses to acute alcohol treatment (intoxication) in subsequent F1, F2 and F3 generations. We found that a chronic alcohol-treatment paradigm in the parental generation resulted in alcohol-naïve F3 progeny displaying moderate resistance to intoxication. To compare the treatment duration and timing on this transgenerational effect, we repeated the study using an intermittent treatment paradigm. We found that intermittent treatment resulted in alcohol-naïve F3 progeny displaying moderate hypersensitivity to intoxication. Further study of this phenomena using this new C. elegans model may yield mechanistic insights into how transgenerational effects may occur in other animals.
Paving the way for synthetic C1- metabolism in Pseudomonas putida through the reductive glycine pathway
Authors: Bruinsma Lyon , Wenk Sebastian , Claassens Nico J. , Martins dos Santos Vitor A.P.
Published: July 2022

One-carbon (C1) compounds such as methanol, formate, and CO2 are alternative, sustainable microbial feedstocks for the biobased production of chemicals and fuels. In this study, we engineered the carbon metabolism of the industrially important bacterium Pseudomonas putida to assimilate these three substrates through the reductive glycine pathway. First, we demonstrated the functionality of the C1-assimilation module by coupling the growth of auxotrophic strains to formate assimilation. Next, we extended the module from formate to methanol using both NAD and PQQ – dependent methanol dehydrogenases. Finally, we demonstrated CO2-dependent growth through CO2 reduction to formate by the native formate dehydrogenase, which required short-term evolution to rebalance the cellular NADH/NAD+ ratio. This research paves the way to engineer P. putida towards growth on formate, methanol, and CO2 as sole feedstocks, thereby substantially expanding its potential as a sustainable and versatile cell factory.
Machine learning approaches to quantitively predict selectivity of compounds against hDAC1 and hDAC6 isoforms
Authors: Dogan Berna
Published: July 2022

The design of compounds selectively binding to specific isoforms of histone deacetylases (hDAC) is an ongoing research to prevent adverse side effects. Two of the most studied isoforms are hDAC1 and hDAC6 that are important targets to inhibit in various disease conditions. Here, various machine learning approaches were tested with the aim of developing models to predict the bioactivity and selectivity towards specific isoforms. Selectivity models were developed by directly training on the bioactivity differences of tested compounds against hDAC1 and hDAC6. Both classification and regression models were developed and compared to each other by using traditional evaluation metrics.
Dimerization of iLID Optogenetic Proteins Observed Using 3D Single-Molecule Tracking in Live Bacterial Cells
Authors: Achimovich Alecia M. , Yan Ting , Gahlmann Andreas
Published: July 2022

3D single molecule tracking microscopy has enabled measurements of protein diffusion in living cells, offering information about protein dynamics and cellular environments. For example, different diffusive states can be resolved and assigned to protein complexes of different size and composition. However, substantial statistical power and biological validation, often through genetic deletion of binding partners, are required to support diffusive state assignments. When investigating cellular processes, transient perturbation to protein spatial distributions is preferable to permanent genetic deletion of an essential protein. In this context, optogenetic dimerization systems can be used to manipulate protein spatial distributions which could offer a means to deplete specific diffusive states observed in single molecule tracking experiments. Here, we evaluate the performance of the iLID optogenetic system in living E. coli cells using diffraction-limited microscopy and 3D single-molecule tracking. We observed a robust optogenetic response in protein spatial distributions after 488 nm laser activation. Surprisingly, 3D single-molecule tracking results indicate activation of the optogenetic response when illuminating with high intensity light with wavelengths at which there is minimal photon absorbance by the LOV2 domain. The pre-activation can be minimized through the use of iLID system mutants, and titration of protein expression levels.

SIGNIFICANCE STATEMENT

We describe the combination of 3D single-molecule tracking microscopy and optogenetic manipulation of protein spatial distributions in living cells. Such a combination is impactful, because optogenetic systems enable sample perturbation in real time using light, which provides more flexibility than gene deletion and gene editing approaches that result in permanent changes to the specimen. We specifically investigate the performance of the iLID optogenetic system in a knocksideways experiment, in which cytosolic prey proteins (SspB) are sequestered to the membrane by interacting with membrane-anchored bait proteins (iLID). We quantified the magnitude of the optogenetic effect using both diffraction-limited imaging and 3D single-molecule tracking microscopy. We found, surprisingly, that the iLID optogenetic response is activated substantially by high intensity light at wavelengths for which there is negligible photon absorption by the iLID protein. Quantification of this alternative activation mechanism is a necessary component before optogenetic tools, such as iLIDs, are employed in single-molecule knocksideways experiment that are designed to provide new biological insights.
Impact of gradient scheme and shimming on out-of-voxel echo artifacts in edited MRS
Authors: Song Yulu , Zöllner Helge J. , Hui Steve C.N. , Hupfeld Kathleen , Oeltzschner Georg , Edden Richard A.E.
Published: July 2022

Out-of-voxel (OOV) signals are common spurious echo artifacts in magnetic resonance spectroscopy (MRS). These signals often manifest in the spectrum as very strong ‘ripples’ which interfere with spectral quantification by overlapping with targeted metabolite resonances. Dephasing Optimization Through Coherence Order Pathway Selection (DOTCOPS) gradient schemes are algorithmically optimized to suppress all potential alternative coherence transfer pathways (CTPs), and should suppress unwanted OOV echoes. In addition, second-order shimming uses non-linear gradient fields to maximize field homogeneity inside the voxel, which unfortunately increases the diversity of local gradient fields outside of the voxel. Given that strong local spatial B0 gradients can refocus unintended CTPs, it is possible that OOVs are less prevalent when only linear first-order shimming is applied. Here we compare the size of unwanted OOV signals in Hadamard-edited (HERMES) data acquired with either a local gradient scheme (which we refer to here as “Shared”) or DOTCOPS, and with first or second-order shimming. We collected data from 15 healthy volunteers in two brain regions (voxel size 30×26×26mm3) from which it is challenging to acquire MRS data: medial prefrontal cortex (MPFC) and left temporal cortex (LTC). Characteristic OOV echoes were seen in both GABA- and GSH-edited spectra for both brain regions, gradient schemes, and shimming approaches. A linear mixed-effect (LME) model revealed a statistically significant difference in the average residual based on gradient scheme in both GABA-(p < 0.001) and GSH-edited (p < 0.001) spectra; that is, the DOTCOPS gradient scheme resulted in smaller OOV artifacts compared with the Shared scheme. There were no significant differences in OOV artifacts associated with shimming method. Thus, these results suggest that the DOTCOPS gradient scheme for J-difference-edited PRESS acquisitions yields spectra with smaller OOV echo artifacts than the Shared gradient scheme implemented in a widely disseminated editing sequence.
Katdetectr: An R/Bioconductor package utilizing unsupervised changepoint analysis for robust kataegis detection
Authors: Hazelaar Daan M. , van Riet Job , Hoogstrate Youri , van de Werken Harmen J. G.
Published: July 2022

Background

Kataegis refers to the occurrence of regional genomic hypermutation in cancer and is a phenomenon that has been observed in a wide range of malignancies. A kataegis locus constitutes a genomic region with a high mutation rate, i.e., a higher frequency of closely interspersed somatic variants than the overall mutational background. It has been shown that kataegis is of biological significance and possibly clinically relevant. Therefore, an accurate and robust workflow for kataegis detection is paramount.

Findings

Here we presentKatdetectr, an open-source R/Bioconductor-based package for the robust yet flexible and fast detection of kataegis loci in genomic data. In addition,Katdetectrhouses functionalities to characterize and visualize kataegis and provides results in a standardized format useful for subsequent analysis. In brief,Katdetectrimports industry-standard formats (MAF, VCF, and VRanges), determines the intermutation distance of the genomic variants and performs unsupervised changepoint analysis utilizing the Pruned Exact Linear Time search algorithm followed by kataegis calling according to user-defined parameters.

We used synthetic data and ana priorilabeled pan-cancer dataset of Whole Genome Sequenced malignancies for the performance evaluation of Katdetectr and five publicly available kataegis detection packages. Our performance evaluation shows that Katdetectr is robust regarding tumor mutational burden (TMB) and shows the fastest mean computation time. Additionally, Katdetectr reveals the highest accuracy (0.99, 0.99) and normalized Matthews Correlation Coefficient (0.98, 0.92) of all evaluated tools for both datasets.

Conclusions

Katdetectris a robust workflow for the detection, characterization, and visualization of kataegis and is available on Bioconductor:https://doi.org/doi:10.18129/B9.bioc.katdetectr
Synthesis, crystal structure determination and Hirshfeld surface analysis of three new salt forms of creatinine with hydrobromic acid, 3-aminobenzoic acid and 3,5-dinitrobenzoic acid
Authors: Jeyaraman Selvaraj Nirmalram , Sathya Udhayasuriyan , Gomathi Sundaramoorthy , Jegan Jennifer Samson , Mathivathanan Logesh , Abdul Razak Ibrahim
Published: July 2022

Creatinine, a biologically important compound, is used to analyze kidney function and kidney diseases in the human body. The salt form of creatinine is used in the formation of drug materials like anti-HIV, antifungal, antiprotozoal, antiviral and antitumour compounds. Here we report the solid-state structures of three new crystalline salts, namely, creatininium (2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-3-ium) bromide, C4H8N3O+·Br−, (I), creatininium 3-aminobenzoate, C4H8N3O+·C7H6NO2
−, (II), and creatininium 3,5-dinitrobenzoate, C4H8N3O+·C7H3N2O6
−, (III). These salts have been synthesized and characterized by single-crystal X-ray diffraction and Hirshfeld surface analysis. The structural chemistry of salts (I)–(III) and their crystal packing are discussed in detail. The primary interaction between the creatinine cation and the acid anion in the three salts is N—H...Br/O hydrogen bonds. In salt (I), the creatinine cation and bromide anion are connected through a pair of N—H...Br hydrogen bonds forming R
4
2(8) and R
4
2(12) ring motifs. In salts (II) and (III), the creatinine cation interacts with the corresponding anion via a pair of N—H...O hydrogen bonds. The crystal structure is further stabilized by C—H...O and O—H...O hydrogen bonds with the ring motifs R
2
2(8), R
2
1(7) and R
2
1(6). Furthermore, the crystal structures are stabilized by π–π, C—H...π, C—O...π and N—O...π stacking interactions. The contributions made by each hydrogen bond in maintaining the crystal structure stability has been quantified by Hirshfeld surface analysis.
Digital artefacts of rural tourism: the case study of Poland
Authors: Król Karol , Zdonek Dariusz
Published: July 2022

Purpose

Rural tourism facilities in Poland were very keen on amateur websites to promote their hospitality services from 2000 to 2018. In most cases, the websites were nonprofessional, hosted on free servers and made by family members or friends of the holding. After search engine algorithms changed in 2015–2019, the websites started to go extinct on a large scale; they were deleted and often replaced with a more modern design and a commercial domain. These resources offered a rare opportunity to gain insight into rural tourism, rural changes and socioeconomic and cultural phenomena.

Design/methodology/approach

The paper’s objective is to demonstrate with an analysis of archived Polish rural tourism websites that digital cultural artefacts are generated in rural areas. The study was an analysis of selected development attributes of rural tourism websites found in the Internet Archive. The analysis involved those attributes that are important for determining whether a website or content can be considered digital cultural heritage assets.

Findings

The conclusions demonstrate that rural digital cultural heritage is a set of digital artefacts created in rural areas with their characteristics. Rural digital artefacts are records of ICT, infrastructure, environmental, cultural and socioeconomic changes.

Originality/value

The “digital assets” of rural areas are yet to be discussed in the context of rural cultural heritage, as a set of artefacts created in these areas and characteristic of them.
Information sharing on social media pages related to wildlife conservation in a South African national game reserve
Authors: Schellnack-Kelly Isabel Stella
Published: July 2022

Purpose

Social media sites contribute significantly to nature conservation in, that they enlighten and educate those members of the public who would ordinarily not be in a position, or would not be fortunate enough to visit the park and experience the various aspects first-hand. The purpose of this paper is to showcase social media pages related to a national game reserve in South Africa. This game reserve is the largest in the country and has a wide variety of conserved fauna and flora.

Design/methodology/approach

The theoretical framework used is the SCOPE framework that streamlines strategy development, content choice, refinement of online engagement, choice of social media platform and evaluations of social media campaigns.

Findings

The findings relate to the content found on these social media pages, as well as how members of the public interact with each other and officials from the game reserve in sharing experiences related to this wilderness area.

Research limitations/implications

The research is related to the Kruger National Park in South Africa and is limited to three social media sites.

Originality/value

Through its social media presence, this South African game reserve is able to share experiences from what is effectively a living museum, as well as from its library and archives, with members of the public and allowing individual members to share their encounters with wildlife and their historical memories of this wilderness area.
Experiencing time elapse phenomenon in nostalgia: effect on consumption behavior in adulthood
Authors: Sotelo-Duarte Manuel , Rajagopal
Published: July 2022

Purpose

This paper aims to understand how mental time traveling impacts consumption by triggering nostalgia. The effects of nostalgic behavior are explored further in regards of its impact on dears and nears.

Design/methodology/approach

This study is based on qualitative information from in-depth interviews. In total, 30 parents with children form Chihuahua, Mexico, answer to a semi-structured interview. Participants presented nostalgic orientation.

Findings

Nostalgic individual move back and forward in time through memory retrieval. Retrieval's quality is related to social impact during memory creation and retrieval process. Nostalgia is not only a cognitive process, but it manifests on behaviors that affects people around the nostalgic individuals. In the context of parent–child relationship, sharing nostalgia is useful for creating new bond across participants.

Research limitations/implications

Contributions toward theory of memory, nostalgia and social learning were made. Result suggests social implications on nostalgic behavior because social interaction is important for quality of memory retrieval. Behavioral implications are discussed in the context of parent–child relationship and the use of nostalgia to develop new and stronger bonds. Companies should develop strategies that privilege social moments around brands to increase memory retrieval quality and nostalgia.

Practical implications

Companies should develop strategies that create social moments around brands to increase memory retrieval quality and nostalgia. Additionally, using social moments on communications could trigger nostalgia and detonates consumption behavior.

Originality/value

The research builds on previous studies about nostalgia. However, this research focusses on mental time travel along nostalgic memories that individuals perform every day to take decisions that affects them and their loved ones. The value of nostalgia on building relationships through consumption is analyzed. The results were obtained from the Mexican context that has not been explored before on nostalgia research.
Assessment and treatment of pectus deformities: a review of reverse engineering and 3D printing techniques
Authors: Mussi Elisa , Servi Michaela , Facchini Flavio , Furferi Rocco , Volpe Yary
Published: July 2022

Purpose

Among thoracic malformations, pectus deformities have the highest incidence and can result in a wide range of severe and mild clinical manifestations. Recently, the treatment of pectus deformities is shifting from traditional approaches toward customized solutions. This occurs by leveraging innovative rapid prototyping tools that allow for the design and fabrication of patient-specific treatments and medical devices. This paper aims to provide a comprehensive view of the growing literature in this area to analyze the progress made in this direction.

Design/methodology/approach

The search was performed on major search engines through keywords inherent to reverse engineering (RE) and additive manufacturing (AM) technologies applied to pectus deformities and related treatments, selecting 54 papers. These were analyzed according to the addressed pathology, the hardware and software tools used and/or implemented and their integration within the clinical pathway.

Findings

First, the analysis led to analyze and divide the papers according to how RE and AM technologies are applied for surgical and non-surgical treatments, pathological assessment and preoperative simulation and planning. Second, all papers were considered within the typical rapid prototyping framework consisting of the three phases of three-dimensional (3D) scanning, 3D modelling and 3D printing.

Originality/value

To the best of the authors’ knowledge, to date, no survey has provided a comprehensive view of innovative and personalized treatment strategies for thoracic malformations; the present work fills this gap, allowing researchers in this field to have access to the most promising findings on the treatment and evaluation of pathology.
Bodily health and bodily integrity capabilities of students with autism spectrum disorder
Authors: Mousavi Seyedeh Tahmineh
Published: July 2022

The purpose of this study was to explore the views of school staff about the bodily health and bodily integrity capabilities of students with autism spectrum disorder (ASD). These capabilities refer to being healthy and moving freely from place to place. Semi‐structured interviews with 12 school staff (teaching and non‐teaching staff) in Tehran, Iran, were carried out and thematically analyzed. ‘Nutritional education’ and ‘sexual health education’ emerged as two major themes. The findings revealed that children with ASD struggle to maintain excellent physical health and bodily integrity. The findings underscore the need for having an interprofessional approach to develop students' bodily health and bodily integrity capabilities. Although it is critical to improve these capabilities, the existing curriculum, time management and workload priorities may conflict with this goal.
Knowing receipt: continuing trusts and conscionability Byers v Saudi National Bank
Authors: Georgiou Alexander
Published: July 2022

In Byers v Saudi National Bank [2022] EWCA Civ 43 the Court of Appeal examined a seemingly straightforward question: where rights are dissipated in breach of trust, is it a necessary condition of the recipient being liable for ‘knowing receipt’ that the dissipation did not extinguish the beneficiary's rights? The answer sheds considerable light on the juridical nature of liability for ‘knowing receipt’. This note argues that the Court of Appeal's analysis correctly supports the theory that so‐called ‘recipient’ liability is in fact a species of liability for breach of trust. It also examines the implications of that conclusion for the elements of, and remedies for, ‘knowing receipt’.
Driving Global Convergence in Green Financial Policies: China as Policy Pioneer and the EU as Standard Setter
Authors: Larsen Mathias Lund
Published: July 2022

Although policies for green financial systems are proliferating across the globe, the dynamics shaping such policies remain inadequately understood. With China and the EU at the global forefront of green financial policies, this paper demonstrates how they each influence global policy norms through their distinct policy models. This contributes to the literature, first, by improving our understanding of the global green financial policy processes and, second, by challenging current expectations from the literature. Analysing three central policy areas (information disclosure, taxonomies, and central banking) from an institutional approach, the paper, first, finds that green financial policies are both proliferating and converging globally. Second, the paper finds that China pioneered policy types around 2015, creating an Overton Window. Subsequently, since 2018, the EU has been standardising policy contents within the policy types that China pioneered. The findings suggest that China acts as a policy pioneer through its top–down policy approach, whereas the EU acts as a standard setter through its bottom–up approach. Although this confirms the literature's expectation that the EU creates global standards, it challenges the expectation that China is both primarily a recipient of policy practice and too unique for other countries to learn from directly. In the broader context, the findings imply that the current global situation of competing political models may be an advantage as countries complement each other through both competition and collaboration. Efforts to align financial systems with sustainable development have moved from industry‐led initiatives to state‐led green financial policies, which are now proliferating and converging across the globe. China and the EU are the most influential actors in shaping how countries across the world use green financial policy because China acts as a policy pioneer based on its top–down policymaking model and the EU acts as a standard setter based on its bottom–up model. Although China and the EU have competing governance and policymaking models, their differences may have been an advantage to scaling up green financial policies as they complement each other through different roles. Awareness of their roles and different approaches should inform future China‐EU policy coordination because harmonisation of practice remains a barrier to mainstreaming green finance. Other countries can benefit from awareness of policy developments in the EU and China to support their own policy development in terms of future scope and contents.
ITCH facilitates proteasomal degradation of TXNIP in hypoxia‐ induced lung cancer cells
Authors: Sun Qian , Wang Bi‐Bo , Wei Wei , Huang Gui‐Chun , Liu Lei‐Lei , Chen Wei‐Wei , Wang Jing , Zhao Xiao‐Yue , Lu Lu , Fang Rong , Zhu Chun‐Yan , Chu Xiao‐Yuan
Published: July 2022

Background

Lung cancer (LC) is one of the most common cancers and a leading cause of cancer‐related deaths worldwide. In many pathological conditions, particularly in the tumor microenvironment, cells and tissues frequently exist in a hypoxic state.

Here, we evaluated Itchy E3 ubiquitin protein ligase (ITCH) expression in LC cells following hypoxia treatment.

Methods

LC cell lines were treated with hypoxic condition. Cell migration, invasion, inflammation, reactive oxygen species (ROS) production, and apoptosis of LC cells were determined by wound healing assay, Transwell invasive assay, ELISA, DCFH‐DA staining, and flow cytometry, respectively. qPCR and WB were used to determine the expression of ITCH and TXNIP. Co‐IP was performed to assess the interaction between ITCH and TXNIP.

Results

ITCH expression was downregulated in LC cells under hypoxic conditions. Next, LC cells were subjected to hypoxic conditions and changes in cell viability and metastasis were determined. Hypoxic conditions resulted in increased migration and invasion abilities of LC cells. Intracellular reactive oxygen species (ROS) production, inflammation, and apoptosis were also promoted by hypoxia. We found that ITCH overexpression led to the proteasomal degradation of thioredoxin‐interacting protein (TXNIP), whereas the expression of the ITCH C830A mutant did not affect TXNIP levels in LC cells. The gain‐of‐function experiment demonstrated that migration, invasion, ROS generation, inflammation, and apoptosis of hypoxia‐conditioned LC cells were ameliorated by ITCH overexpression, whereas the ITCH C830A mutant did not cause any changes in these phenotypes. Furthermore, the contribution of TXNIP knockdown and ITCH overexpression to the hypoxia‐induced features in LC cells with ITCH C830A was found to be similar.

Conclusion

Our results suggest a novel mechanism underlying the changes in ITCH‐mediated malignant phenotypes of hypoxia‐conditioned LC cells via TXNIP.
A rare presentation of anaplastic large cell lymphoma as a cavitary pulmonary mass with hypercalcemia
Authors: Chen Hsu‐Yuan , Kuo Yu‐Chu , Cheng Wen‐Chien , Chen Wei‐Cheng
Published: July 2022

Cavitary lung lesions found on chest imaging may point to various diseases. These lesions may be caused by numerous etiologies, such as infection, inflammatory diseases, or malignancy. Thus, its etiology may be challenging to differentiate using imaging alone. Differential diagnoses are created using a combination of clinical symptoms, medical history, laboratory results, and physical examination. Primary pulmonary lymphoma and anaplastic large cell lymphoma (ALCL) are rare differentials. Here, we report a case of ALCL that initially presented with back pain, intermittent fever, hemoptysis, hypercalcemia, and bilateral multiple cavitary lung nodules. Because a cavitary pulmonary mass with sustained hypercalcemia is commonly seen in patients with squamous cell carcinomas or pulmonary tuberculosis, patients with ALCL may be misdiagnosed and undergo delayed treatment. This study highlights that ALCL should be considered in patients presenting with a cavitary pulmonary mass and hypercalcemia.
99mTc bone scintigraphy does not affect preoperative workup for patients with potentially resectable esophageal squamous cell carcinoma
Authors: Wei Xiu‐feng , Chen Xian‐kai , Lu Lu , Luo Peng , Xu Lei , Xie Hou‐nai , Yang Ya‐fan , Yu Yong‐kui , Li Hao‐miao , Liu Qi , Zhang Rui‐xiang , Qin Jian‐jun , Li Yin
Published: July 2022

Background

99mTc bone scintigraphy (BS) is the mainstay and most widely used technique in evaluation of bone metastasis (BM) in China. This study aimed to investigate the value of 99mTc BS in preoperative workup for patients with potentially resectable (cT1−4aN0−3) esophageal squamous cell carcinoma (ESCC).

Methods

This prospective cross‐section clinical trial (ChiCTR1800020304) enrolled a total of 385 patients with ESCC diagnosed at thoracic surgery clinic from October 2018 to September 2020. All patients were diagnosed with stage cT1−4aN0−3 and were potential candidates for surgical resection. BS was performed preoperatively and the treatment strategy was changed after confirmation of BM. The primary endpoint was the rate of change of the treatment regimen because of BM, while the secondary endpoint was the rate of positive BS findings.

Results

Out of the 385 patients, only two (0.5%) changed their treatment regimen because of BM. The rate of positive BS findings was 1%, while two patients (0.5%) had false‐positive or false‐negative results. The BS diagnostic performance for BM was sensitivity 50%, specificity 99.5%, positive predictive value 50%, negative predictive value 99.5%, and accuracy 99.0%. There was no significant difference in BM in relation to age, sex, tumor location or clinical stage.

Conclusion

Our data demonstrated that 99mTc bone scintigraphy does not significantly affect the preoperative workup in patients with potentially resectable ESCC, especially in early clinical stage patients.
Adolescent substance use and high school noncompletion: exploring the nature of the relationship using a discordant twin design
Authors: Davis Christal N. , Gizer Ian R. , Lynskey Michael T. , Statham Dixie J. , Heath Andrew C. , Martin Nicholas G. , Slutske Wendy S.
Published: July 2022

Background and Aims

Previous studies have demonstrated associations between substance use and reduced educational attainment; however, many were unable to account for potential confounding factors like genetics and the rearing environment. In the few studies that controlled for these factors, the substances assessed were limited to alcohol, cannabis, and tobacco. To address these limitations, we examined the relationship between adolescent use of seven kinds of substances, the number of additional substances used, and high school noncompletion within a large sample of Australian twins.

Design

A series of two‐level generalized mixed effects logistic regressions were conducted to examine associations between adolescent substance use and high school noncompletion.

Setting

Australia.

Participants

A total of 9579 adult Australian twins from two cohorts of the Australian Twin Registry.

Measurements

Assessments of high school completion, childhood major depression, conduct disorder symptoms, substance use initiation, demographics, and parental educational attainment using the Australian version of the Semi‐Structured Assessment for the Genetics of Alcoholism.

Findings

There were unique within‐twin‐pair effects of use of sedatives (odds ratio [OR] = 22.39 [95% confidence interval (CI) = 1.18–423.48]) and inhalants/solvents (OR = 10.46 [95% CI = 1.30–84.16]) on high school noncompletion. The number of substances used in adolescence was strongly associated with high school noncompletion across all discordant twin models (ORs from 1.50–2.32, Ps < 0.03).

Conclusions

In Australia, adolescent substance use appears to be associated with early school dropout, with the effects of any given substance largely because of the confounding factors of parental education, childhood conduct disorder symptoms, and use of other substances. Sedatives and inhalants/solvents have effects on high school noncompletion that cannot be explained by polysubstance use or familial factors.