bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal obesity increases hypothalamic miR-505-5p expression in mouse offspring leading to altered fatty acid sensing and increased intake of high-fat food
Authors: Dearden Laura , Furigo Isadora C. , Pantaleão Lucas C. , Wong L W. P. , Fernandez-Twinn Denise S. , de Almeida-Faria Juliana , Kentistou Katherine A. , Carreira Maria V. , Bidault Guillaume , Vidal-Puig Antonio , Ong Ken K. , Perry John R. B. , Donato Jose , Ozanne Susan E.
Published: June 2022

In uteroexposure to maternal obesity programs increased obesity risk. Animal models show that programmed offspring obesity is preceded by hyperphagia, but the mechanisms that mediate these changes are unknown. Using a mouse model of maternal obesity, we observed increased intake of a high-fat diet in offspring of obese mothers that precedes the development of obesity. Through small RNA sequencing, we identified programmed overexpression of hypothalamic miR-505-5p that is established in the fetus, lasts to adulthood and is maintained in hypothalamic neural progenitor cells culturedin vitro. Metabolic hormones and long-chain fatty acids associated with obesity increase miR-505-5p expression in hypothalamic neuronsin vitro. We demonstrate that targets of miR-505-5p are enriched in fatty acid metabolism pathways and over-expression of miR-505-5p decreased neuronal fatty acid metabolismin vitro. miR-505-5p targets are associated with increased BMI in human genetic studies. Intra-cerebroventricular injection of miR-505-5p in wild-type mice increased high-fat diet intake, mimicking the phenotype observed in offspring exposed to maternal obesity. Conversely, maternal exercise intervention in an obese mouse pregnancy rescued the programmed increase of hypothalamic miR-505-5p in offspring of obese dams and reduced high-fat diet intake to control offspring levels. This study identifies a novel mechanism by which maternal obesity programs obesity in offspring via increased intake of high-fat foods.
Evaluation of training data, ground truth and shape variability in the semantic segmentation of HeLa cells observed with electron microscopy
Authors: Karabağ C. , Reyes-Aldasoro C.C.
Published: June 2022

This paper describes the quantitative and qualitative evaluation of training data, ground truth and the variability of the shape of HeLa cells as observed with electron microscopy in the process of semantic segmentation. HeLa cells are a widely used immortal cell line, but the principles described here could apply to other cells. From a data set of 8, 000×8, 000×517 voxels, a region of interest (ROI) of 2, 000×2, 000×300 was cropped for quantitative evaluation with the qualitative evaluation performed on a larger section of interest. Patches of data and labels were used to train a U-Net architecture from scratch, which was compared also with a traditional image processing algorithm. The correctness of ground truth, that is, the inclusion of one or more nuclei within a region of interest was evaluated with a hand-drawn ground truth of the ROI. The impact of the extent of training data was evaluated by comparing results from 36,000 data and label patches extracted from the odd slices in the central region, to 135,000 patches obtained from every other slice in the set. Accuracy and Jaccard similarity index were higher for the larger training set with multiple nuclei in the ground truth. However, when the U-Nets were used to segment the section of interest beyond the ROI, results were not as good as expected, suggesting that the very complicated nature of the shapes of HeLa cells cannot be learned from a single cell. Data, code and ground truth have been made publicly released through Empair, GitHub and Zenodo.
Sexual selection leads to positive allometry but not sexual dimorphism in the expression of horn shape in the blue wildebeest, Connochaetes taurinus
Authors: Gerstenhaber Chlöe , Knapp Andrew
Published: June 2022

Sexual selection is thought to be an important driver of adaptation, speciation and extinction. Empirically testing these predictions across macroevolutionary timescales first requires an understanding of the morphology of secondary sexual traits in extant taxa. We used three-dimensional geometric morphometrics to analyse a large sample of the skull of the blue wildebeest, Connochaetes taurinus, in which horns are found in both sexes but only used in intrasexual competition in males. We show that the horns fit several predictions of secondary sexual traits; overall skull shape is significantly correlated with size (R2 = 0.38, p = 0.001), and the sexually selected horns show drastically higher growth rates and variation than any other skull element, supporting previous findings. We also find that despite showing significant sexual dimorphism in shape and size (R2 = 0.21, p = 0.001), allometric growth trajectories of sexes are identical (R2 = 0.01, p = 0.635) and dimorphism is not readily detectable without prior knowledge of sex, and is not possible when shape is corrected for size. Our results show that even with strong sexual selection operating in only one sex, the expression of secondary sexual traits may show characteristic and indistinguishable patterns of growth and variance in both sexes.
3D melanoma spheroid model for the development of positronium biomarker
Authors: Karimi Hanieh , Moskal Paweł , Stępień Ewa Ł.
Published: June 2022

It was recently demonstrated that newly invented positronium imaging may be used for improving cancer diagnostics by providing additional information about tissue pathology with respect to the standardized uptake value currently available in positron emission tomography (PET). Positronium imaging utilizes properties of a positronium atoms, which are built from the electron and positron produced in the body during PET examinations.

We hypothesized whether positronium imaging would be sensitive to in vitro discrimination of tumour-like three-dimensional structures (spheroids) build of melanoma cell lines with different cancer activity and biological properties.

The lifetime of ortho-Positronium (o-Ps) was evaluated in melanoma spheroids from two cell lines (WM266-4 and WM115) differing in the stage of malignancy. Additionally, we considered such parameters: as cell size, proliferation rate and malignancy to evaluate their relationship with o-Ps lifetime. We demonstrate the pilot results for the o-Ps lifetime measurement in extracellular matrix free spheroids. With the statistical significance of two standard deviations, we demonstrated that the higher the degree of malignancy and the rate of proliferation of neoplastic cells the shorter the lifetime of ortho-positronium. In particular we observed following indications encouraging further research: (i) WM266-4 spheroids characterized with higher proliferation rate and malignancy showed shorter o-Ps lifetime compared to WM115 spheroids characterized by lower growth rate, (ii) Both cell lines showed a decrease in the lifetime of o-Ps after spheroid generation in 8th day comparing to 4th day in culture and the mean o-Ps lifetime is longer for spheroids formed from WM115 cells than these from WM266-4 cells, regardless spheroid age. The results of these study revealed that positronium is a promising biomarker that may be applied in PET diagnostics for the assessment of the degree of cancer malignancy.
Comparison of Cosine, Modified Cosine, and Neutral Loss Based Spectrum Alignment For Discovery of Structurally Related Molecules
Authors: Bittremieux Wout , Schmid Robin , Huber Florian , van der Hooft Justin JJ , Wang Mingxun , Dorrestein Pieter C
Published: June 2022

Spectrum alignment of tandem mass spectrometry (MS/MS) data using the modified cosine similarity and subsequent visualization as molecular networks have been demonstrated to be a useful strategy to discover analogs of molecules from untargeted MS/MS-based metabolomics experiments. Recently, a neutral loss matching approach has been introduced as an alternative to MS/MS-based molecular networking, with an implied performance advantage in finding analogs that cannot be discovered using existing MS/MS spectrum alignment strategies. To comprehensively evaluate the scoring properties of neutral loss matching, the cosine similarity, and the modified cosine similarity, similarity measures of 955,228 peptide MS/MS spectrum pairs and 10 million small molecule MS/MS spectrum pairs were compared. This comparative analysis revealed that the modified cosine similarity outperformed neutral loss matching and the cosine similarity in all cases. The data further indicated that the performance of MS/MS spectrum alignment depends on the location and type of the modification, as well as the chemical compound class of fragmented molecules.
Methylation in NDUFA13 gene promoter disrupts communication between collaborative transcription factors – potential mechanism for onset of breast cancer
Authors: Johanna Hörberg , Björn Hallbäck , Kevin Moreau , Reymer Anna
Published: June 2022

Selective DNA binding by transcription factors (TFs) is crucial for the correct regulation of DNA transcription. In healthy cells, promoters of active genes are hypomethylated. A single CpG methylation within a TF response element may change the binding preferences of the protein thus causing the dysregulation of transcription programs. Here we investigate a molecular mechanism driving the downregulation of NDUFA13 gene, due to hypermethylation, which is associated with multiple cancers. Using bioinformatic analyses of breast cancer cell line MCF7, we identify a hypermethylated region containing the binding sites of two TFs dimers, CEBPB and E2F1-DP1, located 130 b.p. from the gene transcription start site. All-atom extended MD simulations of wild-type and methylated DNA alone and in complex with either one or both TFs dimers provide mechanistic insights into the cooperative asymmetric binding order of the two dimers; the CEBPB binding should occur first to facilitate the E2F1-DP1-DNA association. The CpG methylation within the E2F1-DP1 response element and the linker decreases the cooperativity effects and renders the E2F1-DP1 binding site less recognizable by the TF dimer. Taken together, the identified CpG methylation site may contribute to the downregulation of NDUFA13 gene and has a potential as a biomarker for breast cancer.
Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97
Authors: Bothe Sebastian , Hänzelmann Petra , Böhler Stephan , Kehrein Josef , Wiedemann Christoph , Hellmich Ute A. , Brenk Ruth , Schindelin Hermann , Sotriffer Christoph
Published: June 2022

Biosensor techniques have become increasingly important for fragment-based drug discovery during the last years. Here, we describe a biolayer interferometry-based fragment screen targeting the AAA+ ATPase p97, an essential protein with key roles in protein homeostasis and a possible target for cancer chemotherapy. Currently available p97 inhibitors target its ATPase activity and globally impair p97-mediated processes. In contrast, inhibition of cofactor binding to the N-domain by a protein-protein-interaction inhibitor would enable the selective targeting of specific p97 functions. We demonstrate that a region known as SHP-motif binding site can be targeted with small molecules. Guided by molecular dynamics simulations, the binding sites of selected screening hits were postulated and experimentally validated using protein- and ligand-based NMR techniques, as well as X-ray crystallography, ultimately resulting in the first structure of a small molecule in complex with the N-domain of p97. The identified fragments provide insights into how this region could be targeted and present first chemical starting points for the development of a protein-protein interaction inhibitor preventing the binding of selected cofactors to p97.
Herpes simplex virus 1 protein pUL21 stimulates cellular ceramide transport by activating CERT
Authors: Benedyk Tomasz H. , Connor Viv , Caroe Eve R. , Shamin Maria , Svergun Dmitri I. , Deane Janet E. , Jeffries Cy M. , Crump Colin M. , Graham Stephen C.
Published: June 2022

Herpes simplex virus (HSV)-1 dramatically alters the architecture and protein composition of cellular membranes during infection, but its effects upon membrane lipid composition remain unclear. HSV-1 pUL21 is a virus-encoded protein phosphatase adaptor that promotes dephosphorylation of multiple cellular and virus proteins, including the cellular ceramide transport protein CERT. CERT mediates non- vesicular transport of ceramide from the ER to the trans-Golgi network, whereupon ceramide is converted to sphingomyelin and other sphingolipids that play important roles in cell proliferation, cell signalling and membrane trafficking. Using click chemistry to profile the kinetics of sphingolipid metabolism in cultured cells, we show that pUL21-mediated dephosphorylation activates CERT and increases the rate of ceramide to sphingomyelin conversion. Purified pUL21 and full-length CERT interact with sub-micromolar affinity and we map the domains responsible for the interaction. Solving the solution structure of the pUL21 C-terminal domain in complex with the CERT PH and START domains using small-angle X-ray scattering allows us to identify a single amino acid mutation on the surface of pUL21 that disrupts CERT binding in vitro and in cultured cells. Sphingolipid profiling demonstrates that ceramide to sphingomyelin conversion is severely diminished in the context of HSV- 1 infection, a defect that is compounded when infecting with a virus encoding the mutated form of pUL21 that lacks the ability to activate CERT. However, virus replication and spread are not significantly altered when pUL21-mediated CERT dephosphorylation is abolished, highlighting that dephosphorylation of other cellular and/or viral targets underpins the important role of pUL21 in HSV-1 biology.

Significance

Herpes simplex virus (HSV)-1 causes a life-long dormant infection of neurons, sporadically reactivating to manifest as cold-sores or genital herpes. While the impact of HSV-1 upon the protein content of infected cells has been well studied, we know relatively little about its impact upon cellular lipids. Using bioorthogonal labelling in cultured cells we show that HSV-1 protein pUL21 activates the key cellular lipid transport protein CERT to accelerate the conversion of ceramide to sphingomyelin. HSV-1 infection dramatically alters the kinetics of ceramide metabolism, leading to ceramide accumulation. Mutation of HSV-1 pUL21 to prevent CERT activation further enhances ceramide accumulation but this does not alter the replication or spread of HSV-1, highlighting that other cellular and/or viral proteins represent the critical targets of pUL21-mediated dephosphorylation in cultured cells.
SLAMseq resolves the kinetics of maternal and zygotic gene expression in early zebrafish embryogenesis
Authors: Bhat Pooja , Cabrera-Quio Luis E. , Herzog Veronika A. , Fasching Nina , Pauli Andrea , Ameres Stefan L.
Published: June 2022

The maternal-to-zygotic transition (MZT) is a key developmental process in metazoan embryos that involves the activation of zygotic transcription (ZGA) and degradation of maternal transcripts. We employed metabolic mRNA sequencing (SLAMseq) to deconvolute the compound embryonic transcriptome in zebrafish. While mitochondrial zygotic transcripts prevailed prior to MZT, we uncover the spurious transcription of hundreds of short and intron-poor nuclear genes as early as the 2-cell stage. Upon ZGA, most zygotic transcripts originate from thousands of maternal-zygotic (MZ) genes that are transcribed at rates comparable to those of hundreds of purely zygotic genes and replenish maternal mRNAs at distinct timescales. Rapid replacement of MZ transcripts involves transcript decay features unrelated to major maternal degradation pathways and promotesde novosynthesis of the core gene expression machinery by increasing poly(A)-tail length and translation efficiency. SLAMseq hence provides unprecedented insights into the timescales, molecular features and regulation of MZT during zebrafish embryogenesis.
Reputation and its consequences in Fintech services: the case of mobile banking
Authors: Nguyen Yen Thi Hoang , Tapanainen Tommi , Nguyen Hai Thi Thanh
Published: June 2022

Purpose

Recently, traditional financial institutions are facing strong competition from disruptive innovators (Fintech firms) forcing them to increasingly invest in new IT solutions to maintain their competitive edge. However, there are still advantages that traditional financial institutions enjoy, of which the primary one may be reputation. Surprisingly, the firm reputation link to use intention has not received much attention in the literature, prompting this research. The purpose of this study is to examine the firm reputation link to use intention in the context of mobile banking.

Design/methodology/approach

The results are based on a survey of 783 participants in Vietnam.

Findings

The study confirmed that reputation plays an important role in promoting use intention for mobile banking. Additionally, perceived risk and trust are also linked to perceived usefulness (PU) and perceived ease-of-use (PEOU).

Originality/value

This study is among the first to link perceived risk and trust to PU and PEOU in a mobile banking context. Based on the Theory of Reasoned Action, the study adds to the literature by connecting two separated research themes: technology adoption and reputation. It also suggests avenues for both traditional banks and Fintech firms to set their business strategies to enhance their reputation or collaborate for mutual benefits.
Customers’ perceptions of hotel AI-enabled voice assistants: does brand matter?
Authors: Cai Ruiying , Cain Lisa Nicole , Jeon Hyeongjin
Published: June 2022

Purpose

Extending the technology acceptance model (TAM) to a new context, the purpose of this paper is to propose an integrative model of the brand of artificial intelligence-enabled voice assistants (AI-EVA) and customers’ perceptions and behavioral intentions of using AI-EVA in hotels. Moderating effects of construal levels and hotel scales were examined.

Design/methodology/approach

This paper adopted a mixed method approach. A qualitative and phenomenological methodology was adopted in Study 1 to explore hotel customers’ experience with AI-EVA. Study 2 applied experimental design to investigate the effects of the brand of AI-EVA and construal level on customers’ perceptions and behavioral intentions of using AI-EVA. Based on Studies 1 and 2 results, Study 3 examined how the brand of AI-EVA and hotel scale affect customers’ perceptions and behavioral intentions of using AI-EVA during hotel stays.

Findings

This research found that customers perceive a higher level of perceived usefulness, perceived ease of use and anthropomorphism when AI-EVA is branded (vs off-brand). Perceived usefulness positively affects customers’ intention to use and to spread positive word-of-mouth. Anxiety of using AI-enabled devices and privacy concerns inhibit customers’ intention to use AI-EVA. Anthropomorphism increases customers’ willingness to spread positive word-of-mouth. Construal level moderates the effect of the brand of AI-EVAs on perceived ease of use and anthropomorphism. Hotel scale moderates the effect of brand on perceived usefulness.

Originality/value

This paper is one of the first attempts to uncover and integrate different factors underlying customers’ perceptions of using AI-EVA in an extended TAM in hotel settings. This paper provides an integrative model extending the TAM to a new context by deploying a mixed-method approach across three studies.
Reimagining financial inclusion in the post COVID-19 world: the case of Grameen America
Authors: Mousa Rania , Ozili Peterson K.
Published: June 2022

Purpose

The purpose of this paper is to analyze Grameen America's response to COVID-19 pandemic. This is accomplished by identifying and analyzing the key initiatives implemented by Grameen America within the framework of selected United Nations' Sustainability Development Goals (UN’s SD Goals).

Design/methodology/approach

This study has used qualitative content analysis to analyze financial and nonfinancial information of Grameen Bank.

Findings

This study follows a qualitative content analysis method to precisely gauge the shift in Grameen’s strategy and focus, as well as to assess the impact of its initiatives on the small business community before and after the pandemic. The findings showcase that Grameen’s longstanding mission to alleviate poverty is in line with the UN’s SD Goal 1. Also, Grameen’s commitment to create partnerships with external organizations to offer credit and noncredit services and support is consistent with UN’s SD Goal 17.

Research limitations/implications

Notwithstanding the significant contributions of this case study, the findings are limited in some respects. First, this case study focuses on the Grameen America’s unique experience regarding its response to COVID-19 pandemic. This may affect the interpretation and generalization of the findings of this study. Performing comparative views across wide range of relevant microlending institutions could help improve the generalization of the findings. Also, this case study examines the impact on women and minority groups who were particularly affected by the pandemic. The results should, therefore, be interpreted with care as circumstances may change over time.

Practical implications

The implication for practice is that policymakers should encourage the creation of more member-based financial and non-financial institutions that can help members integrate financially and socially into society. Also, practitioners should increase their ethical duties and responsibilities to their members in society in good and bad times as members tend to value the ethical aspect of financial businesses.

Social implications

The social implication of the findings is that helping members of society to cope with the difficulties brought about by COVID increased the sense of belonging among members and made them feel cared for, thereby increasing financial and social inclusion among underserved people.

Originality/value

Prior literature addressed the initiatives of microlending institutions such as Grameen Bank to achieve financial inclusion among financially vulnerable women. This case study contributes to the literature on financial inclusion and poverty alleviation by examining Grameen America’s response to the pandemic by identifying and assessing Grameen America (GA’s) key initiatives and their impact within the framework of the UN’s SD Goals in the post COVID-19 world.
Alibi corroboration: an examination of laypersons’ expectations
Authors: Warren Kelly , Snow Mark , Abbott Heidi
Published: June 2022

Purpose

The study aims to examine what laypersons expect those corroborating an alibi to remember about an interaction with an alibi provider.

Design/methodology/approach

Participants (N = 314) were presented with a mock crime scenario and answered questions about an alibi provider (i.e. the criminal suspect) and alibi corroborators. Participants also completed a lineup task based on the scenario and rated the likelihood of their own ability to corroborate the suspect’s alibi.

Findings

Overall, participants believed that it was moderately likely that an alibi corroborator with no prior relationship with the suspect would be able to vouch for the suspect, provide a description and to remember his general physical characteristics. Those who were inaccurate in their lineup decision demonstrated lower expectations of their own ability to corroborate the suspect’s alibi relative to those who were accurate in their decision.

Originality/value

To the best of the authors’ knowledge, this is the first known study to assess what those judging an alibi expect when making a decision about the outcome of a case. Results demonstrate that laypeople have arguably unrealistic expectations of alibi corroborators, potentially jeopardizing innocent people’s ability to prove their innocence.
Seismic vulnerability analysis of simply supported continuous bridge during construction
Authors: Xiong Huizhong , Jiang Shengtang , Huang Yong , Zhang Jian
Published: June 2022

Purpose

In order to explore the damage probability of bridge engineering in the event of earthquake in the construction stages, the analysis method of seismic vulnerability in the construction stages is proposed in this paper.

Design/methodology/approach

Based on the joint simulation function of construction stage conditions and seismic response conditions of MIDAS/Civil finite element analysis software, combined with the method of IDA analysis and compared the relationship between demand and capacity.

Findings

The research shows that: (1) the average seismic loss in different construction stages varies greatly; (2) the seismic vulnerability varies greatly in different construction stages. The vulnerability of the bridge in stage 6 is determined by the longitudinal direction of bridge. Therefore, during the construction of the whole bridge, we should focus on strengthening the disaster and loss prevention strategy of earthquake insurance in the longitudinal direction of bridge. (3) The application of the secondary dead load mainly affects the fragilityin the longitudinal direction of bridge, but has little effect on the fragility in the transversal direction of bridge.

Originality/value

This paper is to explore the seismic vulnerability of a typical simply supported continuous bridge during the construction stages, and to trace the entire construction stage of a typical simply supported continuous bridge. According to the characteristics of the system transformation in the actual construction steps, demand-capacity ratios were established based on incremental dynamic analysis (IDA) and performance indicators of moment curvature and stability, and the seismic vulnerability research is carried out for the construction stages prone to earthquake damage. Furthermore, it provides a basis for seismic risk assessment of such bridges in different construction stages.
Determinants of adoption of IS-based service innovations in government to create public value
Authors: Duhamel Francois Bernard , Gutiérrez-Martínez Isis , Cordova-Díaz Hugo , Cue-Funes Sergio
Published: June 2022

Purpose

This paper aims to propose a conceptual framework showing factors favoring the adoption of information systems (IS)-based service innovations in the public sector at the organizational level.

Design/methodology/approach

The research design is based on the development of a theoretical framework from the technology–organization–environment framework and from a case study of an outsourced IS-based electronic document management system from six different ministries in the same state in Mexico.

Findings

Strong contrasts in the degree of adoption of the service innovation appeared among various ministries involved in state government, revealing differences in the presence or absence of key variables, integrated into theoretical framework, including perception of external pressure; perception of benefits and risks and organizational readiness; and political, sociotechnical and economical inertia in given institutional conditions, leading to different public value outcomes associated with intraorganizational efficiencies and to the relationship between public administration and politicians.

Practical implications

Public managers must consider process mapping and sources of political, sociotechnical and economical inertia in given institutional conditions, to ensure a satisfactory adoption of service innovations in public administration and create public value. The promotion of a more structured and enduring professional career system in such context is another key to the adoption of innovations.

Originality/value

Based on theoretical and empirical grounds, the main contribution of this paper is to emphasize, through an integrated theoretical framework, the relatively unexplored roles of process mapping in organizational readiness and of political, sociotechnical and economic sources of inertia in relation to specific agents in the adoption of public sector service innovations at the organizational level in the context of the public administration in Mexico to produce public value.
Acute oral toxicity of zinc phosphide: an assessment for wild house mice (Mus musculus)
Authors: HINDS Lyn A. , HENRY Steve , VAN DE WEYER Nikki , ROBINSON Freya , RUSCOE Wendy A. , BROWN Peter R.
Published: June 2022

Irregular plagues of house mice, Mus musculus, incur major economic impacts on agricultural production in Australia. The efficacy of zinc phosphide (ZnP), the only registered broadacre control agent for mice, is reported as increasingly variable. Have mice become less sensitive over time or are they taking a sub‐lethal dose and developing aversion? In this laboratory study, the sensitivity of mice (wild caught; outbred laboratory strain) was assessed using oral gavage of a range of ZnP concentrations. The estimated LD50 values (72–79 mg ZnP/kg body weight) were similar for each mouse group but are significantly higher than previously reported. The willingness of mice to consume ZnP‐coated grains was determined. ZnP‐coated grains (50 g ZnP/kg grain) presented in the absence of alternative food were consumed and 94% of wild mice died. Mice provided with alternative food and ZnP‐coated wheat grains (either 25 or 50 g ZnP/kg grain) consumed toxic and non‐toxic grains, and mortality was lower (33–55%). If a sublethal amount of ZnP‐coated grain was consumed, aversion occurred, mostly when alternative food was present. The sensitivity of wild house mice to ZnP in Australia is significantly lower than previously assumed. Under laboratory conditions, ZnP‐coated grains coated with a new higher dose (50 g ZnP/kg grain) were readily consumed. Consumption of toxic grain occurred when alternative food was available but was decreased. Our unambiguous findings for house mice indicate a re‐assessment of the ZnP loading for baits used for control of many rodents around the world may be warranted.
NF‐κB‐dependent secretome of senescent cells can trigger neuroendocrine transdifferentiation of breast cancer cells
Authors: Raynard Clotilde , Ma Xingjie , Huna Anda , Tessier Nolwenn , Massemin Amélie , Zhu Kexin , Flaman Jean‐Michel , Moulin Florentin , Goehrig Delphine , Medard Jean‐Jacques , Vindrieux David , Treilleux Isabelle , Hernandez‐Vargas Hector , Ducreux Sylvie , Martin Nadine , Bernard David
Published: June 2022

Cellular senescence is characterized by a stable proliferation arrest in response to stresses and the acquisition of a senescence‐associated secretory phenotype, called SASP, composed of numerous factors including pro‐inflammatory molecules, proteases, and growth factors. The SASP affects the environment of senescent cells, especially during aging, by inducing and modulating various phenotypes such as paracrine senescence, immune cell activity, and extracellular matrix deposition and organization, which critically impact various pathophysiological situations, including fibrosis and cancer. Here, we uncover a novel paracrine effect of the SASP: the neuroendocrine transdifferentiation (NED) of some epithelial cancer cells, evidenced both in the breast and prostate. Mechanistically, this effect is mediated by NF‐κB‐dependent SASP factors, and leads to an increase in intracellular Ca2+ levels. Consistently, buffering Ca2+ by overexpressing the CALB1 buffering protein partly reverts SASP‐induced NED, suggesting that the SASP promotes NED through a SASP‐induced Ca2+ signaling. Human breast cancer dataset analyses support that NED occurs mainly in p53 WT tumors and in older patients, in line with a role of senescent cells and its secretome, as they are increasing during aging. In conclusion, our work, uncovering SASP‐induced NED in some cancer cells, paves the way for future studies aiming at better understanding the functional link between senescent cell accumulation during aging, NED and clinical patient outcome.
Association between antenatal glucocorticoid exposure and the activity of the stress system, cognition, and behavior in 8‐ to 9‐year‐old children: A prospective observational study
Authors: Rakers Florian , Schleußner Ekkehard , Muth Isabel , Hoyer Dirk , Rupprecht Sven , Schiecke Karin , Groten Tanja , Dreiling Michelle , Kozik Valeska , Schwab Matthias , Hoyer Heike , Ligges Carolin
Published: June 2022

Introduction

Glucocorticoid (GC) ‐induced fetal programming of the activity of the hypothalamus–pituitary–adrenal axis (HPAA) and its associated cognitive and behavioral consequences in later life have been well characterized in several animal species. However, information on humans is scarce. In this study, we examined HPAA activity markers and associated outcomes at 8 to 9 years of age among children prenatally exposed to GC for suspected preterm birth. Our hypothesis was that antenatal exposure to the betamethasone (BM) is associated with exacerbation of HPAA activity in childhood.

Material and methods

Prospective observational study in 31 children whose mothers received single (n = 19) or multiple (n = 12) courses of BM for threatened preterm birth but born with normal weight appropriate for the gestational age (median 37+6 weeks of gestation) compared with 38 non‐exposed, age‐matched children. Primary end point was the activity of the HPAA in response to the Trier Social Stress Test. Secondary end points were changes in autonomic nervous system (ANS) activity, cognitive performance (IQ), attention‐deficit/hyperactivity disorder (ADHD) symptoms, and electrocortical activity (EEG).

Results

There was no statistically significant difference in HPAA activity markers between antenatal BM exposed and unexposed groups. ANS activity in BM‐exposed children shifted towards a higher parasympathetic tone reflected by a higher overall high‐frequency band power of heart rate variability. IQ scores were within normal limits for both groups; however, BM‐exposed children had lower IQ scores than the unexposed group. BM‐exposed group had marginally more ADHD core symptoms and increased electrocortical activity in the occipital brain region compared with controls. A monotonic dose–response relation between BM exposure and activity of the ANS and IQ was estimated in post‐hoc analyses.

Conclusions

Antenatal exposure to BM in the context of threatened preterm birth was not associated with changes in HPAA activity in childhood. However, BM exposure may be associated with changes in ANS activity. Antenatal GC prophylaxis is a valuable and often life‐saving therapy, but its prescription may warrant a well‐balanced risk–benefit assessment.
Achieving high coverage of Kangaroo mother care practice is possible: Lessons from implementation research for accelerating scale‐up in Tigray Region, Ethiopia
Authors: Beyene Selemawit Asfaw , Hadush Marta Yemane , Gebregizabher Fisseha Ashebir , Gebremariam Dawit Seyoum , Asmelash Tirhas , Zelelow Yibrah Berhe , Amare Samson Yohannes , Abay Tedros Hailu , Medhanyie Araya Abrha
Published: June 2022

Aim

To evaluate coverage of effective Kangaroo mother care (KMC) by developing a model that would result in high coverage (≥80%) of KMC for newborn weighing less than 2000 g at birth in Tigray region, Ethiopia.

Methods

The study used formative research and continuous programme learning in iterative cycles of model development and modification conducted in close collaboration with the Tigray Regional Health Bureau. Quantitative methods were used to evaluate the various models. All study facilities were enrolled simultaneously, and hospitals and health centres were considered to become KMC‐providers.

Results

The final scalable model implemented in two rural districts and one special urban zone of Tigray region attained the desired objective, with coverage of effective KMC of 82.3% at discharge.

Conclusion

Achieving high coverage of KMC is possible through the design of context‐specific implementation strategies. The key factors for success were the commitment and strong leadership from the regional health bureau, strong linkages within the health system and between different departments within health facilities, improved health worker knowledge, skills and attitudes, hospitals and health centres that supported KMC performance, and systematic generation and use of data for continuous quality improvement.
Pernio and early SARS-CoV-2 variants: natural history of a prospective cohort and the role of interferon
Authors: Ng Ashley T. , Moon John J. , Steidl Olivia R. , Bussan Hailey , Tran Jennifer M. , Luong George , Nihal Aman , Kenfield Meaghan , Frere Justin , TenOever Benjamin R. , Costa da Silva Ana C. , Mays Jacqueline W. , Cowen Edward W. , Drolet Beth A. , Singh Anne Marie , Arkin Lisa M.
Published: June 2022

Cases of new-onset pernio and recurrences in our cohort align tightly with trends in mean 7-day COVID-19 positivity in Wisconsin and mean temperature in Madison, Wisconsin by month.
Healing of ExcisionAl wounds on Lower legs by Secondary intention (HEALS) cohort study. Part 1: a multicentre prospective observational cohort study in patients without planned compression
Authors: Pynn Emma V. , Ransom Myka , Walker Benjamin , McGinnis Elizabeth , Brown Sarah , Gilberts Rachael , Trehan Pooja , Jayasekera Prativa S. A. , Veitch David , Hussain Walayat , Collins Jemma , Abbott Rachel Angharad , Chen Kun Sen , Nixon Jane
Published: June 2022

Background

There is no agreed treatment pathway following excision of keratinocyte cancer (KC). Compression therapy is considered beneficial for secondary intention healing on the lower leg; however, there is a lack of supportive evidence. To plan a randomized controlled trial (RCT), suitable data are needed. We report a multicentre prospective observational cohort study in this patient population with the intention of informing a future trial design.

Aim

To estimate the time to healing in wounds healing by secondary intention without planned postoperative compression, following excision of KC on the lower leg; to characterize the patient population, including factors affecting healing; and to assess the incidence of complications.

Methods

This was a multicentre prospective observational cohort study. Inclusion criteria were age ≥ 18 years with planned excision of KC on the lower leg and healing by secondary intention, an ankle–brachial pressure index (ABPI) of ≥ 0.8; and written informed consent. Exclusion criteria included planned excision with primary closure, skin graft or flap; compression therapy for another indication; planned compression; inability of patient to receive, comply with or tolerate high compression; or a suspected diagnosis other than KC.

Results

This study recruited 58 patients from 9 secondary care dermatology clinics. In the analysis population (n = 53), mean age was 81 years (range 25–97 years), median time to healing was 81 days (95% CI 73–92) and 45 patients (84.9%) had healing of the wound at the 6-month follow-up. The healing prognostic factors were wound parameters and ABPI. Wound infections occurred in 16 participants (30.2%). Four patients (7.5%) were admitted to hospital; three because of an infection and one because of a fall.

Conclusions

The collected data have informed the RCT preparation. A relatively high proportion (7.5–15%) of unhealed wounds, infection and hospital admissions demonstrate the need for clearly establishing potentially effective treatments to improve outcomes for this population.
Familiarity with the internet and health apps, and specific topic needs are amongst the factors that influence how online health information is used for health decisions amongst adolescents
Authors: Gazibara Tatjana , Cakic Milica , Cakic Jelena , Grgurevic Anita , Pekmezovic Tatjana
Published: June 2022

Background

Many adolescents believe that online health information is reliable, particularly when they are familiar with the source of information.

Objective

To analyse the degree of influence of online health information on high school students' health decisions and examine whether socio‐demographic characteristics, digital literacy, use of different websites and interest in specific health topics are associated with a stronger influence of online health information on adolescents' health‐related decisions.

Methods

Participants were students from four public high schools in Belgrade, Serbia. Socio‐demographic and behavioural questionnaire as well as the e‐health literacy scale (eHEALS) were used to collect data.

Results

The study sample comprised 702 students. A total of 79.6% of students reported that online health information influenced their health decisions to a certain extent (from ‘a little’ to ‘a lot’). Being a boy, using the internet since younger age, better self‐perceived e‐health literacy, using health apps, Google, health forums, websites of health institutions, social media and YouTube, being interested in diet/nutrition, sexually transmitted infections and cigarettes were the characteristics associated with a stronger influence of online health information on students' health decisions.

Conclusion

This study provides clues about how online health‐related information can be used to adjust and enhance health promotion amongst adolescents.
Digital skin imaging applications, part I: Assessment of image acquisition technique features
Authors: Sun Mary D. , Kentley Jonathan , Wilson Britney W. , Soyer H. Peter , Curiel‐Lewandrowski Clara N. , Rotemberg Veronica , Halpern Allan C. ,   ISIC Technique Working Group
Published: June 2022

Background

The rapid adoption of digital skin imaging applications has increased the utilization of smartphone‐acquired images in dermatology. While this has enormous potential for scaling the assessment of concerning skin lesions, the insufficient quality of many consumer/patient‐taken images can undermine clinical accuracy and potentially harm patients due to lack of diagnostic interpretability. We aim to characterize the current state of digital skin imaging applications and comprehensively assess how image acquisition features address image quality.

Materials and methods

Publicly discoverable mobile, web, and desktop‐based skin imaging applications, identified through keyword searches in mobile app stores, Google Search queries, previous teledermatology studies, and expert recommendations were independently assessed by three reviewers. Applications were categorized by primary audience (consumer‐facing, nonhospital‐based practice, or enterprise/health system), function (education, store‐and‐forward teledermatology, live‐interactive teledermatology, electronic medical record adjunct/clinical imaging storage, or clinical triage), in‐app connection to a healthcare provider (yes or no), and user type (patient, provider, or both).

Results

Just over half (57%) of 191 included skin imaging applications had at least one of 14 image acquisition technique features. Those that were consumer‐facing, intended for educational use, and designed for both patient and physician users had significantly greater feature richness (p < 0.05). The most common feature was the inclusion of text‐based imaging tips, followed by the requirement to submit multiple images and body area matching.

Conclusion

Very few skin imaging applications included more than one image acquisition technique feature. Feature richness varied significantly by audience, function, and user categories. Users of digital dermatology tools should consider which applications have standardized features that improve image quality.
DYW deaminase domain has a distinct preference for neighboring nucleotides of the target RNA editing sites
Authors: Maeda Ayako , Takenaka Sachi , Wang Tenghua , Frink Brody , Shikanai Toshiharu , Takenaka Mizuki
Published: June 2022

C‐to‐U RNA editing sites in plant organelles show a strong bias for neighboring nucleotides. The nucleotide upstream of the target cytidine is typically C or U, whereas A and G are less common and rare, respectively. In pentatricopeptide repeat (PPR)‐type RNA editing factors, the PPR domain specifically binds to the 5′ sequence of target cytidines, whereas the DYW domain catalyzes the C‐to‐U deamination. We comprehensively analyzed the effects of neighboring nucleotides of the target cytidines using an Escherichia coli orthogonal system. Physcomitrium PPR56 efficiently edited target cytidines when the nucleotide upstream was U or C, whereas it barely edited when the position was G or the nucleotide downstream was C. This preference pattern, which corresponds well with the observed nucleotide bias for neighboring nucleotides in plant organelles, was altered when the DYW domain of OTP86 or DYW1 was adopted. The PPR56 chimeric proteins edited the target sites even when the −1 position was G. Our results suggest that the DYW domain possesses a distinct preference for the neighboring nucleotides of the target sites, thus contributing to target selection in addition to the existing selection determined by the PPR domain.
An Analysis of the Load Distribution Characteristics of a Cylindrical Roller Bearing Including the Component Deformation and Waviness
Authors: Liu Jing , Xu Zidan , An Chenyu
Published: June 2022

Cylindrical roller bearings (CRBs) are key components of mechanical transmission systems. The internal load distribution and stiffness (LDAS) have significant effects on the bearing fatigue life and vibrations. It can also affect the precision, reliability, and service life of mechanical transmission systems. Due to the external loads applied on the bearing, the flexible deformations of rings and rollers would be produced, which will change the LDAS. To study the LDAS of CRB, an improved quasi-static model of CRB is established. The flexible deformations and waviness of rings and rollers are considered. An analytical calculation method based on the Newton–Raphson method is conducted to obtain the LDAS. The results show that the radial force, speed, and waviness can greatly affect the LDAS; the flexible deformations of rings and rollers increase with the increments of radial force and speed; the internal load distribution is also greatly affected by the waviness, which leads to the uneven load distribution; the radial stiffness decreases with the increment of waviness amplitude; and the waviness order has a slight effect on the radial stiffness.
Polytriazole membranes with ultrathin tunable selective layer for crude oil fractionation
Authors: Chisca Stefan , Musteata Valentina-Elena , Zhang Wen , Vasylevskyi Serhii , Falca Gheorghe , Abou-Hamad Edy , Emwas Abdul-Hamid , Altunkaya Mustafa , Nunes Suzana P.
Published: June 2022

The design of materials and their manufacture into membranes that can handle industrial conditions and separate complex nonaqueous mixtures are challenging. We report a versatile strategy to fabricate polytriazole membranes with 10-nanometer-thin selective layers containing subnanometer channels for the separation of hydrocarbons. The process involves the use of the classical nonsolvent-induced phase separation method and thermal cross-linking. The membrane selectivity can be tuned to the lower end of the typical nanofiltration range (200 to 1000 gram mole
−1
). The polytriazole membrane can enrich up to 80 to 95% of the hydrocarbon content with less than 10 carbon atoms (140 gram mole
−1
). These membranes preferentially separate paraffin over aromatic components, making them suitable for integration in hybrid distillation systems for crude oil fractionation.
Immune memory to SARS-CoV-2 Omicron BA.1 breakthrough infections: To change the vaccine or not?
Authors: van Zelm Menno C.
Published: June 2022

Analysis of memory B cell responses to Spike antigen after Omicron BA.1 breakthrough infections suggests that “original antigenic sin” is in play.