bluuebunny/crossref_metadata_2025 huggingface dataset:
A Longitudinal Exploration ofCACNA1A-related Hemiplegic Migraine in Children
Authors: Schaare Donna , Lusk Laina , Karlin Alexis , Kaufman Michael C. , Magielski Jan , Sarasua Sara M. , Allison Kendra , Boccuto Luigi , Helbig Ingo
Published: June 2024

Introduction

Since the initial description ofCACNA1A-related hemiplegic migraine (HM), the phenotypic spectrum has expanded from mild episodes in neurotypical individuals to potentially life-threatening events frequently seen in individuals with developmental and epileptic encephalopathies. However, the overall longitudinal course throughout childhood remains unknown.

Methods

We analyzed HM and seizure history in individuals withCACNA1A-related HM, delineating frequency and severity of events in monthly increments through a standardized approach. Combining these data with medication prescription information, we assessed the response of HM to different agents.

Results

Our cohort involved 15 individuals between 3 and 29 years (163 patient years) and included 11 unique and two recurrent variants (p.R1349Q and p.V1393M; bothn=2). The age of first confirmed HM ranged from 14 months to 13 years (average 3 years). 25% of all HM events were severe (lasting >3 days) and 73% of individuals had at least 1 severe occurrence. Spacing of HM events ranged from 1 month to 14 years and changes in HM severity over time of showed increases or decreases of >2 severity levels in 12/122 events. Eight individuals had epilepsy, but severity of epilepsy did not correlate with frequency and severity of HM events. While levetiracetam (n=6) and acetazolamide (n=5) were the most frequently used medications, they did not show efficacy in HM prevention or HM severity reduction. However, verapamil (n=3) showed efficacy in preventing HM episodes (OR 2.68, CI 1.39-5.67).

Significance

The longitudinal course ofCACNA1A-related HM lacks recognizable patterns for timing and severity of HM events or correlation with seizure patterns. Our data underscores the unpredictability ofCACNA1A-related HM, highlighting the need for close surveillance for reoccurring HM events even in individuals with symptom-free periods.

Key points

24% of hemiplegic migraines (HM) inCACNA1A-related disorders are severe, involving cerebral edema and greater than 4 days to recover

Timing and severity of HM are unpredictable, with large changes in severity between events, and age of onset ranging from 1-13 years

Epilepsy occurred in 53% of individuals, with neither the timing nor severity of seizures correlated with HM
The impact of heterogeneous spatial autocorrelation on comparisons of brain maps
Authors: Leech R , Smallwood JS , Moran R , Jones EJH , Vowles N , Leech D , Viegas EM , Turkheimer FE , Alberti F , Margulies D , Jefferies E , Bernhardt B , Váša F
Published: June 2024

It is increasingly common to statistically compare macroscopic brain maps to assess how spatially similar they are. Due to the presence of spatial autocorrelation, statistical inference can be challenging; to address this, random permutation approaches based on null models are widely used. Here, we show how that the presence of heterogeneity in the spatial autocorrelation across brain maps may affect statistical inference in common approaches for spatially correlated maps. In response, we highlight the need to explicitly model spatial processes, including non-stationarity, for more accurate statistical inference. We illustrate how a Bayesian spatial regression approach can be applied to compare functional and structural cortical brain maps, even in the presence of heterogeneity. By explicitly modelling spatial processes underlying the data, a much wider and more sophisticated range of neurobiological questions can be answered about the relationship between brain maps than with current approaches.
Deep learning uncovers histological patterns of YAP1/TEAD activity related to disease aggressiveness in cancer patients
Authors: Schmauch Benoit , Cabeli Vincent , Domingues Omar Darwiche , Douget Jean-Eudes Le , Hardy Alexandra , Belbahri Reda , Maussion Charles , Romagnoni Alberto , Eckstein Markus , Fuchs Florian , Swalduz Aurélie , Lantuejoul Sylvie , Crochet Hugo , Ghiringhelli François , Derangere Valentin , Truntzer Caroline , Pass Harvey , Moreira Andre L. , Chiriboga Luis , Zheng Yuanning , Ozawa Michael , Howitt Brooke E. , Gevaert Olivier , Girard Nicolas , Rexhepaj Elton , Valtingojer Iris , Debussche Laurent , de Rinaldis Emanuele , Nestle Frank , Spanakis Emmanuel , Fantin Valeria R. , Durand Eric Y. , Classe Marion , Loga Katharina Von , Pronier Elodie , Cesaroni Matteo
Published: June 2024

Over the last decade, Hippo signaling has emerged as a major tumor-suppressing pathway. Its dysregulation is associated with abnormal expression ofYAP1andTEAD-family genes. Recent works have highlighted the role of YAP1/TEAD activity in several cancers and its potential therapeutic implications. Therefore, identifying patients with a dysregulated Hippo pathway is key to enhancing treatment impact. Although recent studies have derived RNAseq-based signatures, there remains a need for a reproducible and cost-effective method to measure the pathway activation. In recent years, deep learning applied to histology slides have emerged as an effective way to predict molecular information from a data modality available in clinical routine. Here, we trained models to predict YAP1/TEAD activity from H&E-stained histology slides in multiple cancers. The robustness of our approach was assessed in seven independent validation cohorts. Finally, we showed that histological markers of disease aggressiveness were associated with dysfunctional Hippo signaling.
uORF-targeting steric block antisense oligonucleotides do not reproducibly activate RNASEH1 expression
Authors: Ahlskog Nina , Svrzikapa Nenad , Abuhamdah Rushdie , Kye Mahnseok , Jad Yahya , Feng Ning , Hanson Britt , Wood Matthew J.A. , Roberts Thomas C.
Published: June 2024

Upstream open reading frames (uORFs) arecis-regulatory motifs that are predicted to occur in the 5ʹ untranslated region (UTR) of the majority of human protein-coding transcripts. uORFs are typically associated with repression of the downstream primary open reading frame (pORF) at either the level of translation, or by promoting mRNA turnover via the nonsense-mediated decay pathway. Interference with uORF activity provides a potential mechanism for targeted upregulation of the expression of specific transcripts. It was recently reported that steric block antisense oligonucleotides (ASOs) can bind to and mask uORF start codons in order to inhibit translation initiation, and thereby disrupt uORF-mediated gene regulation. Given the relative maturity of the oligonucleotide field, such a uORF blocking mechanism might have widespread therapeutic utility. Here, we re-synthesised three of the most potent ASOs targeting theRNASEH1uORF described in the study by Lianget al. and investigated their potential for RNASEH1 protein upregulation. No upregulation (of endogenous or reporter protein expression) was observed with any of the oligonucleotides tested at doses ranging from 25 nM to 300 nM. Conversely, we observed downregulation of expression in some instances, consistent with well-established mechanisms of blocking ribosome procession. Experiments were performed using multiple transfection protocol setups, with care taken to replicate the conditions of the original study. Transfection efficiency was confirmed using aMALAT1-targeting gapmer ASO as a positive control. We conclude that previously-describedRNASEH1uORF-targeting steric block ASOs are incapable of upregulating pORF protein expression in our hands.
Three-dimensional body reconstruction enables quantification of liquid consumption in small invertebrates
Authors: Galante Henrique , Czaczkes Tomer J. , De Agrò Massimo
Published: June 2024

Quantifying feeding patterns provides valuable insights into animal behaviour. However, small invertebrates often consume incredibly small amounts of food. This renders traditional methods, such as weighing individuals before and after food acquisition, either inaccurate or prohibitively expensive. Here, we present a non-invasive method to quantify food consumption of small invertebrates whose body expands during feeding. Using the markerless pose estimation software DeepLabCut, we three-dimensionally track the body of Argentine ants,Linepithema humile. Using these extracted markers, we developed an algorithm which computationally reconstructs the ant’s body, directly measuring volumetric change over time. Moreover, we provide measures of accuracy and quantify the ant’s feeding response to a range of sucrose concentrations, as well as a gradient of caffeine-laced sucrose solutions. Small invertebrates are often prolific invasive species and disease vectors, causing significant ecological and economical damage. Understanding their feeding behaviour could be an important step towards effective control strategies.
Profiling endogenous airway proteases and antiproteases and measuring proteolytic activation of Influenza HA usingin vitroandex vivohuman airway surface liquid samples
Authors: Brocke Stephanie A , Reidel Boris , Ehre Camille , Rebuli Meghan E , Robinette Carole , Schichlein Kevin D , Brooks Christian A , Jaspers Ilona
Published: June 2024

Imbalance of airway proteases and antiproteases has been implicated in diseases such as COPD and environmental exposures including cigarette smoke and ozone. To initiate infection, endogenous proteases are commandeered by respiratory viruses upon encountering the airway epithelium. The airway proteolytic environment likely contains redundant antiproteases and proteases with diverse catalytic mechanisms, however a proteomic profile of these enzymes and inhibitors in airway samples has not been reported. The objective of this study was to first profile extracellular proteases and antiproteases using human airway epithelial cell cultures andex vivonasal epithelial lining fluid (NELF) samples. Secondly, we present an optimized method for probing the proteolytic environment of airway surface liquid samples (in vitroandex vivo) using fluorogenic peptides modeling the cleavage sites of respiratory viruses. We detected 48 proteases in the apical wash of cultured human nasal epithelial cells (HNECs) (n=6) and 57 in NELF (n=13) samples from healthy human subjects using mass-spectrometry based proteomics. Additionally, we detected 29 and 48 antiproteases in the HNEC apical washes and NELF, respectively. We observed large interindividual variability in rate of cleavage of an Influenza H1 peptide in theex vivoclinical samples. Since protease and antiprotease levels have been found to be altered in the airways of smokers, we compared proteolytic cleavage inex vivonasal lavage samples from male/female smokers and non-smokers. There was a statistically significant increase in proteolysis of Influenza H1 in NLF from male smokers compared to female smokers. Furthermore, we measured cleavage of the S1/S2 site of SARS-CoV, SARS-CoV-2, and SARS-CoV-2 Delta peptides in various airway samples, suggesting the method could be used for other viruses of public health relevance. This assay presents a direct and efficient method of evaluating the proteolytic environment of human airway samples in assessment of therapeutic treatment, exposure, or underlying disease.
Membrane binding properties of the cytoskeletal protein bactofilin
Authors: Liu Ying , Karmakar Rajani , Steinchen Wieland , Mukherjee Saumyak , Bange Gert , Schäfer Lars V. , Thanbichler Martin
Published: June 2024

Bactofilins are a widespread family of cytoskeletal proteins with important roles in bacterial morphogenesis, chromosome organization and motility. They polymerize in a nucleotide-independent manner, forming non-polar filaments that are typically associated with the cytoplasmic membrane. Membrane binding was suggested to be mediated by a short N-terminal peptide, but the underlying mechanism and the conservation of this interaction determinant among bacteria remain unclear. Here, we use the bactofilin homolog BacA of the stalked bacteriumCaulobacter crescentusas a model to analyze the membranebinding behavior of bactofilins. Based on site-directed mutagenesis of the N-terminal region, we identify the full membrane-targeting sequence of BacA (MFSKQAKS) and identify amino acid residues that are critical for its functionin vivoandin vitro. Molecular dynamics simulations then provide detailed insight into the molecular mechanism underlying the membrane affinity of this peptide. Collectively these analyses reveal a delicate interplay between the water exclusion of hydrophobic N-terminal residues, the arrangement of the peptide within the membrane and the electrostatic attraction between positively charged groups in the peptide and negative charges in the phospholipid molecules. A comprehensive bioinformatic analysis shows that the composition and properties of the membrane-targeting sequence of BacA are conserved in numerous bactofilin homologs from diverse bacterial phyla. Notably, our findings reveal a mutual interdependence between the membrane binding and polymerization activities of BacA. Moreover, we demonstrate that both of these activities have a pivotal role in the recruitment of the BacA client protein PbpC, a membrane-bound cell wall synthase involved in stalk formation whose N-terminal region turns out to associate with the core polymerization domain of BacA. Together, these results unravel the mechanistic underpinnings of membrane binding by bactofilin homologs, thereby illuminating a previously obscure but important aspect in the biology of this cytoskeletal protein family.
Extracellular plant subtilases dampen cold shock peptide elicitor levels
Authors: Chen Changlong , Buscaill Pierre , Sanguankiattichai Nattapong , Huang Jie , Kaschani Farnusch , Kaiser Markus , van der Hoorn Renier A. L.
Published: June 2024

Recognizing pathogen-associated molecular patterns (PAMPs) on the cell surface is crucial for plant immunity. The proteinaceous nature of many of these patterns suggests that secreted proteases play important roles in their formation and stability. Here, we demonstrate that the apoplastic subtilase SBT5.2a inactivates the immunogenicity of cold-shock proteins of the bacterial plant pathogenPseudomonas syringaeby cleaving within the immunogenic csp22 epitope. Consequently, mutant plants lacking SBT5.2a activity retain higher levels of csp22, leading to enhanced immune responses and reduced pathogen growth. SBT5.2 sensitivity is influenced by sequence variation surrounding the cleavage site and likely extends to CSPs from other bacterial species. These findings suggest that variations in csp22 stability among bacterial pathogens are a crucial factor in plant-bacteria interactions and that pathogens might exploit plant proteases to avoid pattern recognition.
Lineage-specific CDK activity dynamics characterize early mammalian development
Authors: Saykali Bechara , Tran Andy D. , Cornwell James A. , Caldwell Matthew A. , Sangsari Paniz Rezvan , Morgan Nicole Y. , Kruhlak Michael J. , Cappell Steven D. , Ruiz Sergio
Published: June 2024

Cyclin-dependent kinases (CDK) are key regulatory enzymes that regulate proliferation dynamics and cell fate in response to extracellular inputs. It remains largely unknown how CDK activity fluctuates and influences cell commitmentin vivoduring early mammalian development. Here, we generated a transgenic mouse model expressing a CDK kinase translocation reporter (KTR) that enabled quantification of CDK activity in live single cells. By examining pre- and post- implantation mouse embryos at different stages, we observed a progressive decrease in CDK activity in cells from the trophectoderm (TE) prior to implantation. This drop correlated with the establishment of an FGF4-dependent signaling gradient through the embryonic-abembryonic axis. Furthermore, we showed that CDK activity levels do not determine cell fate decisions during pre-implantation development. Finally, we uncovered the existence of conserved regulatory mechanisms in mammals by revealing lineage-specific regulation of CDK activity in TE-like human cells.
Genomic characterization ofEscherichia coliharbor a polyketide synthase (pks) island associated with colorectal cancer (CRC) development
Authors: Lv Chao , Abdullah Mohd , Chen Weiye , Zhou Nan , Cheng Zile , Chen Yiwen , Li Min , Simpson Kenneth W. , Elsaadi Ahmed , Zhu Yongzhang , Lipkin Steven M. , Chang Yung-Fu
Published: June 2024

TheE. colistrain harboring the polyketide synthase(Pks)island encodes the genotoxin colibactin, a secondary metabolite reported to have severe implications for human health and for the progression of colorectal cancer. The present study involved whole-genome-wide comparison and phylogenetic analysis ofpksharboringE. coliisolates to gain insight into the distribution and evolution of these organism. FifteenE. colistrains isolated from patients with ulcerative colitis were sequenced, 13 of which harbored pks islands. In addition, 2,654 genomes from the public database were also screened forpksharboringE. coligenomes, 158 of which werepks-positive isolates. Whole-genome-wide comparison and phylogenetic analysis revealed that 171 (158+13)pks-positive isolates belonged to phylogroup B2, and most of the isolates associated to sequence types ST73 and ST95. One isolate from an ulcerative colitis (UC) patient was of the sequence type ST8303. The maximum likelihood tree based on the core genome ofpks-positive isolates revealed horizontal gene transfer across sequence types and serotypes. Virulome and resistome analyses revealed the preponderance of virulence genes and a reduced number of antimicrobial genes inPks-positive isolates. This study strongly contributes to understanding the evolution ofpksislands inE. coli.
A phosphorylation signal activates genome-wide transcriptional control by BfmR, the global regulator ofAcinetobacterresistance and virulence
Authors: Raustad Nicole , Dai Yunfei , Iinishi Akira , Mohapatra Arpita , Soo Mark W. , Hay Everett , Hernandez Gabrielle M. , Geisinger Edward
Published: June 2024

The nosocomial pathogenAcinetobacter baumanniiis a major threat to human health. The sensor kinase-response regulator system, BfmS-BfmR, is essential to multidrug resistance and virulence in the bacterium and represents a potential antimicrobial target. Important questions remain about how the system controls resistance and pathogenesis. Although BfmR knockout alters expression of >1000 genes, its direct regulon is undefined. Moreover, how phosphorylation controls the regulator is unclear. Here, we address these problems by combining mutagenesis, ChIP-seq, and in vitro phosphorylation to study the functions of phospho-BfmR. We show that phosphorylation is required for BfmR-mediated gene regulation, antibiotic resistance, and sepsis development in vivo. Consistent with activating the protein, phosphorylation induces dimerization and target DNA affinity. Integrated analysis of genome-wide binding and transcriptional profiles of BfmR led to additional key findings: (1) Phosphorylation dramatically expands the number of genomic sites BfmR binds; (2) DNA recognition involves a direct repeat motif widespread across promoters; (3) BfmR directly regulates 303 genes as activator (eg, capsule, peptidoglycan, and outer membrane biogenesis) or repressor (pilus biogenesis); (4) BfmR controls several non-coding sRNAs. These studies reveal the centrality of a phosphorylation signal in drivingA. baumanniidisease and disentangle the extensive pathogenic gene-regulatory network under its control.
Credit rating of family farms based on optimal assignment of credit indicators by BP neural network
Authors: Fu Wenluhan , Li Zhanjiang
Published: June 2024

Purpose

In order to solve the problems of difficulty in lending to family farms and the lack of credit products, it is necessary to classify the credit rating of family farms and determine the credit risk level of different family farms, so that agriculture-related financial institutions can implement different credit strategies.

Design/methodology/approach

A method based on BP neural network model is proposed to measure the weights of credit evaluation indicators of family farms and the linear weighting method and the fuzzy comprehensive evaluation method are used to establish the final credit rating system for family farms.

Findings

The empirical results show that the majority of the 246 family farms in Inner Mongolia have a low CC rating.

Originality/value

By constructing a sound and reasonable credit rating system for family farms, thus providing an objective evaluation of the credit rating of family farms, the credit granting status of agriculture-related financial institutions will be adapted to the reasonable loan demand status of family farm owners, and the quality and level of their credit approval will be continuously enhanced.
Tech-ready teachers for Agriculture 4.0: a teacher–industry partnership case study
Authors: Cosby Amy , Sullivan Melissa Ann , Manning Jaime , Harreveld Bobby
Published: June 2024

Purpose

This case study is based on the Women in Agri-Tech programme, a teacher professional development programme that aimed to build teachers’ capabilities to use Agri-Tech in their agriculture/STEM classes to increase student awareness of agriculture technology and its associated career paths. Teachers and agriculture industry partners co-created Agri-Tech modules, which were implemented and evaluated from teachers’ and students’ perspectives. This paper demonstrates how work-related learning that emphasises technology can increase the visibility of career pathways and how multi-stakeholder benefits can evolve from teacher–industry partnerships.

Design/methodology/approach

An action research design using quantitative and qualitative methods was used to construct this case study. Data collection methods included surveys, interviews, peer evaluation and teacher reflections.

Findings

Teacher professional development that incorporates teacher-industry partnerships can increase teachers’ self-efficacy and build confidence to support authentic work-related learning in their classes. Integrating technology into agriculture/STEM classes can increase the visibility of agriculture career paths for students, which is critical given the serious skills shortage in this sector.

Research limitations/implications

This study is limited in that the Women in Agri-Tech professional development programme was one standalone programme tailored specifically for women agriculture/STEM teachers through a competitive process. However, the beneficial implications of such programmes that support teacher–industry engagement have far-reaching benefits. Teacher professional development programmes that provide opportunities to partner with industry can support improvements in integrating career-aligned learning into the curriculum and can specifically address industry skills and knowledge gaps by addressing school-based learning requirements for the future workforce.

Originality/value

This paper contributes to the literature on education–industry partnerships and considers how teachers can contribute to an early intervention sector workforce development strategy for future industry sustainability.
Tales of luxury: unveiling gender-based insights into hotel brands’ Instagram marketing
Authors: Chalke Anuja , Cheng Boon Liat , Dent Michael
Published: June 2024

Purpose

Storytelling-driven messaging for luxury hotels is a robust social media marketing strategy to boost electronic word of mouth (e-WOM) and induce visit intention. This paper focuses on individual-related characteristics related to imagery processing and explores their relationship with brand trust and narrative transportation. Gender is examined for its potential moderating impact on relationships revolving around e-WOM intent formation.

Design/methodology/approach

This study employs the partial least squares-structural equations modelling (SEM) and multi-group analyses (MGA) approaches to examine consumer responses to luxury hotel brands’ Instagram marketing. Data from 268 responses to an online survey was analyzed on Smart PLS4.

Findings

Results confirm that comprehension fluency, imagery fluency and narrative transportation are predictors of brand trust. Additionally, brand trust and narrative transportation impact e-WOM intention. The impact of narrative transportation on e-WOM intention is relatively stronger in men; while women exhibit a stronger impact of brand trust on e-WOM intention.

Practical implications

It is recommended that luxury hotel brands create content which is easy to comprehend and also capable of inducing mental imagery, to boost the narrative transportation effect. Content should be tailored to target specific gender segments to enhance e-WOM effectiveness. Detailed strategies for segment-specific content are discussed in the paper.

Originality/value

This study demonstrates how gender differences shape consumer responses to brand storytelling on Instagram, particularly for luxury hotels, filling a notable gap in extant literature.
Toward disaster resilience in property management: the nomenclature of structural and non-structural building adaptation measures relative to flood exposure
Authors: Amadi Alolote
Published: June 2024

Purpose

The study aims to investigate the nomenclature of structural versus non-structural building adaptation measures taken by occupants of residential properties located in flood-prone areas of Port Harcourt, Nigeria, to verify whether they are adapted or maladapted relative to their level of flood exposure and underscore the role of disaster resilience in property management.

Design/methodology/approach

Using the survey research strategy, the uptake of structural and non-structural adaptation measures in spatially distributed areas of Port Harcourt was descriptively analyzed and tested to identify significant variation in the uptake of adaptation measures relative to increasing flooding levels, using a one-way ANOVA.

Findings

The study outcome reveals that there are some distinctive features of buildings in Port Harcourt which provide wet-proofing structural adaptation qualities while dry-proofing structural adaptation measures are not adequate. However, although some key structural adaptation measures were adapted relative to the levels of flood exposure, most structural features of the buildings do not vary relative to flooding levels, indicating maladaptation even with increasing flood risk. The uptake of non-structural measures is also inadequate and maladapted relative to changes in the level of flood exposure, despite their non-intrusive and low-cost nature. Overall, the findings imply that maladaptation is more prevalent.

Originality/value

The study provides a descriptive snapshot of the nomenclature of property-level flood risk adaptation in residential buildings, while highlighting the maladaptive tendencies/behavior of property occupants, within a metropolitan setting in the developing world, necessary to inform policy and provide sensitization for fostering disaster resilience in property management.
Resource manipulation reveals interactive phenotype‐dependent foraging in free‐ranging lizards
Authors: Spiegel Orr , Michelangeli Marcus , Sinn David L. , Payne Eric , Klein Janine‐Rose V. , Kirkpatrick Jamie , Harbusch Marco , Sih Andrew
Published: June 2024

Recent evidence suggests that individuals differ in foraging tactics and this variation is often linked to an individual's behavioural type (BT). Yet, while foraging typically comprises a series of search and handling steps, empirical investigations have rarely considered BT‐dependent effects across multiple stages of the foraging process, particularly in natural settings.

In our long‐term sleepy lizard (Tiliqua rugosa) study system, individuals exhibit behavioural consistency in boldness (measured as an individual's willingness to approach a novel food item in the presence of a threat) and aggressiveness (measured as an individual's response to an ‘attack’ by a conspecific dummy). These BTs are only weakly correlated and have previously been shown to have interactive effects on lizard space use and movement, suggesting that they could also affect lizard foraging performance, particularly in their search behaviour for food.

To investigate how lizards' BTs affect their foraging process in the wild, we supplemented food in 123 patches across a 120‐ha study site with three food abundance treatments (high, low and no‐food controls). Patches were replenished twice a week over the species' entire spring activity season and feeding behaviours were quantified with camera traps at these patches. We tracked lizards using GPS to determine their home range (HR) size and repeatedly assayed their aggressiveness and boldness in designated assays.

We hypothesised that bolder lizards would be more efficient foragers while aggressive ones would be less attentive to the quality of foraging patches. We found an interactive BT effect on overall foraging performance. Individuals that were both bold and aggressive ate the highest number of food items from the foraging array. Further dissection of the foraging process showed that aggressive lizards in general ate the fewest food items in part because they visited foraging patches less regularly, and because they discriminated less between high and low‐quality patches when revisiting them. Bolder lizards, in contrast, ate more tomatoes because they visited foraging patches more regularly, and ate a higher proportion of the available tomatoes at patches during visits.

Our study demonstrates that BTs can interact to affect different search and handling components of the foraging process, leading to within‐population variation in foraging success. Given that individual differences in foraging and movement will influence social and ecological interactions, our results highlight the potential role of BT's in shaping individual fitness strategies and population dynamics.
‘If my boss wasn't so accommodating, I don't know what I would do’: Workplace supports for carers and the role of line managers and co‐workers in mediating informal flexibility
Authors: Fahy M. , Dowling‐Hetherington L. , Phillips D. , Moloney B. , Duffy C. , Paul G. , Fealy G. , Kroll T. , Lafferty A.
Published: June 2024

Most employees will experience at least one episode of caregiving during their working lives. While work is important for carers' identity and well‐being, the increasing complexity of caregiving situations and the often unpredictable needs of care recipients means that working carers may need to informally adjust when, where and how they work. The manner in which this informal flexibility is enacted is not well understood. Using a qualitative research design, this paper provides an insight into employees' experiences of combining work and caregiving and gives voice to working carers and the daily struggles they face. Drawing on the literature on work‐family conflict (WFC) theory, signalling theory and flexible working, our research highlights the importance of informal flexibility, and the mediating role of line managers and co‐workers in providing access to this flexibility. We identify the enabling mechanisms, or explicit signals of support, through which carer‐friendly informal flexibility is enacted, namely: reassurance and pre‐emptive support; carer advocacy; and idiosyncratic deal‐making (i‐deals). We argue that when these enabling mechanisms are in place, WFC is alleviated and attachment to the workforce is facilitated. Where the enabling mechanisms are not accessible, WFC increases and attachment to the workforce is hindered.
Association between prenatal glucocorticoid exposure and adolescent neurodevelopment: An observational follow‐up study
Authors: Rakers Florian , Schleussner Ekkehard , Cornelius Amani , Kluckow Steffen , Muth Isabel , Hoyer Dirk , Rupprecht Sven , Schultze Torsten , Schiecke Karin , Ligges Carolin , Schwab Matthias , Hoyer Heike
Published: June 2024

Introduction

Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long‐lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8–9 years. This follow‐up study aimed to examine whether these findings persisted into adolescence.

Material and Methods

Prospective observational follow‐up study involving twenty‐one 14‐ to 15‐year‐old adolescents born to mothers who received betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty‐five children not exposed to betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention‐deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus–pituitary–adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm.

Results

No statistically significant group difference was observed in global IQ (adjusted mean: betamethasone 103.9 vs references 105.9, mean difference −2.0, 95% confidence interval [CI]: −7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress‐induced activity of the HPAA and the ANS did not differ significantly between groups. However, the betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency–adjusted means: 16.0 Hz vs 17.8 Hz, mean difference −1.83 Hz, 95% CI: −3.21 to −0.45, p = 0.01).

Conclusions

In 14‐ to 15‐year‐old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow‐up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions.
Emotion regulation styles and the tendency to learn from academic failures
Authors: Sharabi Yonatan , Roth Guy
Published: June 2024

Background

Research on learners' reactions to failure finds negative emotions may present an obstacle for learning; a painful experience of failure may result in disengagement and avoidance. However, research on styles of emotion regulation and learning from failure is scarce. Self‐determination theory's (SDT) conception of adaptive and maladaptive emotion regulation differentiates among three styles of regulation: integrative emotion regulation (IER), suppressive emotion regulation (SER) and amotivated emotion regulation.

Aims

Two studies were conducted, one cross‐sectional and one longitudinal, to test the associations between IER and learning from failure among adolescents.

Sample

Study 1 comprised 184 adolescents (mean age = 16.55; SD = 1.2). Study 2 comprised 565 adolescents (8–12 graders). The main analysis was based on 192 adolescents' perceptions of failing math grades.

Method

Study 1 surveyed adolescents on their emotion regulation styles, adaptive and maladaptive coping practices when dealing with failure and tendency to learn from failure. Study 2 was longitudinal and focused on failure in math. We approached participants twice, before and after the math test.

Conclusions

In both studies, IER was related to adaptive coping practices and the tendency to learn from failure. In Study 2, adaptive coping practices mediated relations between IER and learning from failure in math and learning from failure mediated relations between IER and future engagement. These findings suggest that styles of emotion regulation play an important role in learning from failure.
A high‐precision view of intercompartmental drug transport via simultaneous, seconds‐resolved, in situ measurements in the vein and brain
Authors: Gerson Julian , Erdal Murat Kaan , Dauphin‐Ducharme Philippe , Idili Andrea , Hespanha Joao P. , Plaxco Kevin W. , Kippin Tod E.
Published: June 2024

Background and Purpose

The ability to measure specific molecules at multiple sites within the body simultaneously, and with a time resolution of seconds, could greatly advance our understanding of drug transport and elimination.

Experimental Approach

As a proof‐of‐principle demonstration, here we describe the use of electrochemical aptamer‐based (EAB) sensors to measure transport of the antibiotic vancomycin from the plasma (measured in the jugular vein) to the cerebrospinal fluid (measured in the lateral ventricle) of live rats with temporal resolution of a few seconds.

Key Results

In our first efforts, we made measurements solely in the ventricle. Doing so we find that, although the collection of hundreds of concentration values over a single drug lifetime enables high‐precision estimates of the parameters describing intracranial transport, due to a mathematical equivalence, the data produce two divergent descriptions of the drug's plasma pharmacokinetics that fit the in‐brain observations equally well. The simultaneous collection of intravenous measurements, however, resolves this ambiguity, enabling high‐precision (typically of ±5 to ±20% at 95% confidence levels) estimates of the key pharmacokinetic parameters describing transport from the blood to the cerebrospinal fluid in individual animals.

Conclusions and Implications

The availability of simultaneous, high‐density ‘in‐vein’ (plasma) and ‘in‐brain’ (cerebrospinal fluid) measurements provides unique opportunities to explore the assumptions almost universally employed in earlier compartmental models of drug transport, allowing the quantitative assessment of, for example, the pharmacokinetic effects of physiological processes such as the bulk transport of the drug out of the CNS via the dural venous sinuses.
Development of phenyl‐urea‐based small molecules that target penicillin‐binding protein 4
Authors: Gondil Vijay S. , Butman Hailey S. , Young Mikaeel , Walsh Danica J. , Narkhede Yogesh , Zeiler Michael J. , Crow Andrew H. , Carpenter Morgan E. , Mardikar Aashay , Melander Roberta J. , Wiest Olaf , Dunman Paul M. , Melander Christian
Published: June 2024

Staphylococcus aureus has the ability to invade cortical bone osteocyte lacuno‐canalicular networks (OLCNs) and cause osteomyelitis. It was recently established that the cell wall transpeptidase, penicillin‐binding protein 4 (PBP4), is crucial for this function, with pbp4 deletion strains unable to invade OLCNs and cause bone pathogenesis in a murine model of S. aureus osteomyelitis. Moreover, PBP4 has recently been found to modulate S. aureus resistance to β‐lactam antibiotics. As such, small molecule inhibitors of S. aureus PBP4 may represent dual functional antimicrobial agents that limit osteomyelitis and/or reverse antibiotic resistance. A high throughput screen recently revealed that the phenyl‐urea 1 targets PBP4. Herein, we describe a structure–activity relationship (SAR) study on 1. Leveraging in silico docking and modeling, a set of analogs was synthesized and assessed for PBP4 inhibitory activities. Results revealed a preliminary SAR and identified lead compounds with enhanced binding to PBP4, more potent antibiotic resistance reversal, and diminished PBP4 cell wall transpeptidase activity in comparison to 1.
Who let the dog out? Dog owner attitudes and economics regulate the potential negative impact of domestic dogs on wildlife in a reserve network
Authors: Weng Yue , McShea William Joseph , Yang Hongbo , Zhang Zhuojin , Lin Weiming , Wang Fang
Published: June 2024

Many domestic animals have a profound impact on endangered species through complex interactions and spillover effects in and between coupled human and natural systems. A thorough understanding of the driving forces of human decisions regarding how domestic animals are kept is therefore critical to promote the synergy of human livelihood and biodiversity conservation. Working in the Qinling Mountains of China, we conducted a multidisciplinary study using a structural equation model (SEM) to link households' demographic and economic conditions, peoples attitudes and activities with their decisions, and further investigated how such process influences the potential negative impact of free‐ranging dogs on wildlife. Among 139 blood and saliva samples collected from dogs that were owned by local villagers but allowed to roam freely, 33.3% were positive for at least one of three viral infections, including canine distemper (28.2%), canine parvovirus (25.6%), and rabies virus prevalence (10.3%). SEM modeling revealed that human activity (β = 0.27, p = .012) has significantly increased dogs' potential negative impacts on wildlife by increasing the number of dogs and their direct contact with wildlife, as well as their larger movement range. Conversely, improvement in demographic and economic conditions (β = −0.22, p = .011) and human attitudes (β = −0.51, p = .013) suppresses the influence of free roaming dogs on wildlife. Meanwhile, livelihoods dependent on natural resources increased the likelihood of owners having dog practice that may negatively impact wildlife (β = 0.54, p < .001), without improving the economic conditions of the residents (β = −0.26, p < .001). Based on the above results, we recommend a program that combines educational and conservation efforts to encourages local residents in more responsible dog ownership and recommend reserve managers provide financial incentives to mitigate human‐wildlife conflicts.
Ulcerated CRTC1::TRIM11 cutaneous tumor with metastases
Authors: Tseng Calvin , Hein Erica C. Koch , Smith Stephen M. , King Ian , Saibil Sam , Saeed Kamil Zaid
Published: June 2024

CRTC1::TRIM11 cutaneous tumor (CTCT) is a rare skin tumor of uncertain differentiation. In the 49 reported cases, only four cases showed regional or distant metastasis, but follow‐up remains limited. Herein, we present a case of metastatic CTCT with ulceration, a histological feature that has not been previously described. A 75‐year‐old male with a 2‐month history of toe ulceration underwent a shave biopsy, which showed a dermal nodular neoplasm that was immunoreactive for SOX10 and S100, negative for Melan‐A, and was initially diagnosed as melanoma. Upon pathology review at our institution, the tumor was composed of intersecting fascicles and nests of epithelioid and spindle cells. Additional immunohistochemistry revealed immunoreactivity of the tumor for MiTF and NTRK and negativity for HMB‐45 and PRAME. Next‐generation sequencing identified CRTC1::TRIM11 fusion, leading to a revised diagnosis of CTCT. The patient proceeded to a toe amputation and sentinel lymph node (SLN) biopsy 5 months after the shave biopsy. The amputation showed residual CTCT and a focus on lymphovascular invasion. The SLN revealed multifocal subcapsular metastases. The patient was started on adjuvant nivolumab and showed biopsy‐proven recurrence in the right inguinal lymph nodes and imaging findings suspicious for pulmonary metastases 8 months after the excision. In summary, we present a case of CTCT with ulceration and lymphovascular invasion. We also provide additional evidence that a subset of CTCT behaves aggressively. The optimal surgical and medical treatments are unknown.
Cutaneous metastases: From epidemiology to therapy
Authors: Gschnell Martin , Volberg Christian , Hauser Christina , Krönig Lisa
Published: June 2024

Cutaneous metastases are seen in up to 10% of all oncology patients and can occur in different locations depending on the entity. Cutaneous metastases are often associated with a high psychological burden and, especially in the case of exulceration, with shame and social withdrawal. This review discusses the diagnostic and therapeutic options. The most common tumor entities in which cutaneous metastases are observed are discussed, and local and systemic treatment options are presented according to the current state of research.
Long daytime napping: A silent danger for hypertensive individuals
Authors: Wu Jinhong , Liu Lishun , Huang Zena , Wang Li , Cai Fengjiao , Li Aimin , Sun Yong , Wang Binyan , Li Jianping , Huo Yong , Lu Yan
Published: June 2024

Background and purpose

Hypertension significantly contributes to stroke. Previous research has indicated a connection between daytime napping and stroke. Research on the connection between daytime napping duration and first stroke in hypertensive individuals is lacking nevertheless.

Methods

This research, which ran from 24 August 2013 to 31 December 2022, recruited 11,252 individuals with hypertension and without a history of stroke from the China Stroke Primary Prevention Trial. To determine the relationship between daytime napping duration and stroke onset in hypertensive individuals, we conducted analyses for threshold effects, multivariate‐adjusted Cox proportional hazard regression models, and Kaplan–Meier survival curves.

Results

The duration of daytime napping (<75 min) was positively correlated with stroke risk; beyond 75 min, the risk did not increase further. When compared to hypertensive individuals who napped for 1–30 min, daytime napping 31–60 min (hazard ratio [HR] = 1.27, 95% confidence interval [CI] = 1.06–1.53) and >60 min (HR = 1.37, 95% CI = 1.14–1.65) were substantially related with a greater risk of first stroke. Additionally, this correlation was absent in cases of hemorrhagic stroke, but present in cases of ischemic stroke, specifically for hypertensive individuals who napped for 31–60 min or >60 min (p < 0.05). Kaplan–Meier survival curves displayed that hypertensive individuals who extended daytime napping had an elevated incidence of stroke.

Conclusions

Hypertensive individuals who take longer daytime naps (>30 min) are at an elevated risk of stroke onset, particularly ischemic stroke, irrespective of other factors.
Burying in lake sediments: A potential tactic used by female northern map turtles to avoid male harassment
Authors: Bulté Grégory , Robichaud Jessica A. , Cooke Steven J. , MacMillan Heath A. , Blouin‐Demers Gabriel
Published: June 2024

How often males and females need to mate to maximize their fitness is a source of sexual conflict in animals. Sexual conflict over mating frequency can lead to antagonistic coevolution in which males employ tactics to coerce females into mating, while females resist or evade mating attempts by males. Here, we report on a novel burying behavior observed in female northern map turtles (Graptemys geographica) in Opinicon Lake, Ontario, Canada that appears to function as a tactic to avoid male detection during the mating season. Underwater videos indicated that females are heavily solicited during the mating season with over half the females being actively pursued by males. Biologgers indicated that females are less active and remain deeper than males during the mating season. Our data strongly suggest that female northern map turtles avoid intense solicitation and potential harassment by males by burying themselves in lake sediments. This behavior appears to be a low‐cost solution for females to reduce the costs of resistance and mating while they are constrained to habitats with high male densities for overwintering.