bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of sleep in the human brain and body: insights from multi-organ imaging genetics
Authors: Fan Zirui , Yang Yilin , Guo Yuxin , Li Yujue , Shu Juan , Yang Xiaochen , Li Bingxuan , Lin Jinjie , Wang Qianwen , Gibson Carolyn , Paschou Peristera , Li Tengfei , Gehrman Philip , Zhu Hongtu , Zhao Bingxin
Published: September 2022

Sleep is crucial for overall physical and mental health, concerning organs such as the brain, heart, eye, liver, kidney, and lung. Nonetheless, a thorough understanding of how sleep relates to these organs, as well as their genetic bases, remains elusive. Here we conducted a systematic mapping of sleep-organ connections, focusing on 623 multi-organ imaging biomarkers and 10 sleep traits. Both phenotypic and genetic analyses uncovered robust associations between sleep and the structure and function of multiple organs, such as brain functions measured by functional magnetic resonance imaging (fMRI) and body composition traits in abdominal MRI. Sleep and imaging traits had shared genetic influences in 51 genomic loci, 23 of which had colocalized causal genetic effects. Considering the extensive genetic overlaps between sleep and multi-organ imaging biomarkers, we further described the patterns of genetic similarities between sleep and 50 diseases relevant to these organs. Notably, among all diseases examined, psychiatric disorders consistently exhibited the strongest genetic correlations and causal links with sleep. Mediation analysis further revealed that many of the identified sleep-imaging connections were mediated by intra or inter-organ diseases. Overall, our study demonstrates the broad implications of sleep on brain and body health, influenced in part by shared genetic factors.
Single-Molecule Analysis of DNA Base-Stacking Energetics Using Patterned DNA Nanostructures
Authors: Banerjee Abhinav , Anand Micky , Kalita Simanta , Ganji Mahipal
Published: September 2022

DNA double helix structure is stabilized by the base-pairing and the base-stacking interactions. Base-stacking interactions originating from hydrophobic interactions between the nucleobases predominantly contribute to the duplex stability. A comprehensive understanding of dinucleotide base-stacking interactions is lacking owing to the unavailability of sensitive techniques that can measure these weak interactions. Earlier studies attempting to address this question only managed to estimate the base-pair stacking interactions, however, disentangling individual base-stacking interactions was enigmatic. By combining multiplexed DNA-PAINT imaging with designer DNA nanostructures, we experimentally measure the free energy of dinucleotide base-stacking at the single-molecule level. Multiplexed imaging enabled us to extract binding kinetics of an imager strand with and without additional dinucleotide stacking interactions in a single imaging experiment, abolishing any effects of experimental variations. The DNA-PAINT data showed that a single additional dinucleotide base-stacking results in as much as 250-fold stabilization of the imager strand binding. We found that the dinucleotide base-stacking energies vary from -1.18 ± 0.17 kcal/mol to -3.57 ± 0.08 kcal/mol for C|T and A|C base-stackings, respectively. We demonstrate the application of base-stacking energetics in designing DNA-PAINT probes for multiplexed super-resolution imaging. Our results will aid in designing functional DNA nanostructures, DNA and RNA aptamers, and facilitate better predictions of the local DNA structure.
Semantic-Specific and Domain-General Mechanisms for Integration and Update of Contextual Information
Authors: Branzi Francesca M. , Lambon Ralph Matthew A.
Published: September 2022

Recent research has highlighted the importance of domain-general processes and brain regions for language and semantic cognition. Yet, this has been mainly observed in executively demanding tasks, leaving open the question of the contribution of domain-general processes to natural language and semantic cognition. Using fMRI, we investigated whether neural processes reflecting context integration and context update – two key aspects of naturalistic language and semantic processing – are domain-specific versus domain-general. Thus, we compared neural responses during integration of contextual information across semantic and non-semantic tasks. Whole-brain results revealed both shared (left posterior-dorsal inferior frontal gyrus, left posterior inferior temporal gyrus, and left dorsal angular gyrus/intraparietal sulcus) and distinct (left anterior-ventral inferior frontal gyrus, left anterior ventral angular gyrus, left posterior middle temporal gyrus for semantic control only) regions involved in context integration and update. Furthermore, data-driven functional connectivity analysis clustered domain-specific versus domain-general brain regions into distinct but interacting functional neural networks. These results provide a first characterization of the neural processes required for context-dependent integration during language processing along the domain-specificity dimension, and at the same time, they bring new insights on the role of left posterior lateral temporal cortex and left angular gyrus for semantic cognition.
Dual-Fluorescent Reporter for Live-Cell Imaging of the ER During DENV Infection
Authors: Corliss Lochlain , Holliday Madeline , Lennemann Nicholas J.
Published: September 2022

Infection by flaviviruses leads to dramatic remodeling of the endoplasmic reticulum (ER). Viral replication occurs within virus-induced vesicular invaginations in the ER membrane. A hallmark of flavivirus infection is expansion of the ER membrane which can be observed at specific time points post infection. However, this process has not been effectively visualized in living cells throughout the course of infection at the single cell resolution. In this study, we developed a plasmid-based reporter system to monitor flavivirus infection and simultaneous virus-induced manipulation of single cells throughout the course of infection in real-time. This system requires viral protease cleavage to release an ER-anchored fluorescent protein infection reporter that is fused to a nuclear localization signal (NLS). This proteolytic cleavage allows for the translocation of the infection reporter signal to the nucleus while an ER-specific fluorescent marker remains localized in the lumen. Thus, the construct allows for the visualization of virus-dependent changes to the ER throughout the course of infection. In this study, we show that our reporter was efficiently cleaved upon the expression of multiple flavivirus proteases, including dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV). We also found that the DENV protease-dependent cleavage of our ER-anchored reporter exhibited more stringent cleavage sequence specificity than what has previously been shown with biochemical assays. Using this system for long term time-lapse imaging of living cells infected with DENV, we observed nuclear translocation of the reporter signal beginning approximately 8 hours post-infection, which continued to increase throughout the time course. Interestingly, we found that increased reporter signal translocation correlated with increased ER signal intensity, suggesting a positive association between DENV infection and ER expansion in a time-dependent manner. Overall, this report demonstrates that the FlavER platform provides a useful tool for monitoring flavivirus infection and simultaneously observing virus-dependent changes to the host cell ER, allowing for study of the temporal nature of virus-host interactions.
Serial cross-sectional estimation of vaccine and infection-induced SARS-CoV-2 sero-prevalence in children and adults, British Columbia, Canada: March 2020 to August 2022
Authors: Skowronski Danuta M , Kaweski Samantha E , Irvine Michael A , Kim Shinhye , Chuang Erica SY , Sabaiduc Suzana , Fraser Mieke , Reyes Romina C , Henry Bonnie , Levett Paul N , Petric Martin , Krajden Mel , Sekirov Inna
Published: September 2022

Background

We chronicle SARS-CoV-2 sero-prevalence through eight cross-sectional sero-surveys (snapshots) in the Lower Mainland (Greater Vancouver and Fraser Valley), British Columbia, Canada from March 2020 to August 2022.

Methods

Anonymized-residual sera were obtained from children and adults attending an outpatient laboratory network. Sera were tested with at least three immuno-assays per snapshot to detect spike (S1) and/or nucleocapsid protein (NP) antibodies. Sero-prevalence was defined by dual-assay positivity, including any or infection-induced, the latter requiring S1+NP antibody detection from January 2021 owing to vaccine availability. Infection-induced estimates were used to assess the extent to which surveillance case reports under-estimated infections.

Results

Sero-prevalence was ≤1% by the 3rd snapshot in September 2020 and <5% by January 2021 (4th). Following vaccine roll-out, sero-prevalence increased to >55% by May/June 2021 (5th), ∼80% by September/October 2021 (6th), and >95% by March 2022 (7th). In all age groups, infection-induced sero-prevalence remained <15% through September/October 2021, increasing through subsequent Omicron waves to ∼40% by March 2022 (7th) and ∼60% by July/August 2022 (8th). By August 2022, at least 70-80% of children ≤19 years, 60-70% of adults 20-59 years, but ∼40% of adults ≥60 years had been infected. Surveillance case reports under-estimated infections by 12-fold between the 6th-7th and 92-fold between the 7th-8th snapshots.

Interpretation

By August 2022, most children and adults had acquired SARS-CoV-2 vaccine and infection exposures, resulting in more robust hybrid immunity. Conversely the elderly, still at greatest risk of severe outcomes, remain largely-dependent on vaccine-induced protection alone, and should be prioritized for additional doses.
Drosophila Atlastin regulates synaptic vesicle mobilization independent of Bone Morphogenetic Protein signaling
Authors: Bertin Francisca , Jara-Wilde Jorge , Auer Benedikt , Köhler-Solís Andrés , González-Silva Carolina , Thomas Ulrich , Sierralta Jimena
Published: September 2022

Motor neurons are highly dependent on membrane trafficking, in which the endoplasmic reticulum (ER) and its contact sites with endosomes, confer the ER the role of a long-distance communicator. Atlastin (Atl), a large GTPase located on the ER membrane is required for its function and its tubular structural dynamics. Atl also downregulates, by a yet unknown mechanism, the BMP (Bone Morphogenic Protein) pathway. In humans, Atl mutations are the second more common cause of Hereditary Spastic Paraplegia (HSP), a genetic disease characterized by spasticity of the lower extremities. Here, we explore the molecular basis of Atl-dependent defects on synaptic vesicle (SV) traffic in Drosophila under the hypothesis that those defects are the direct consequence of the atl-knock-down and not of the Atl-dependent BMP signaling upregulation.

Motor neuronal knockdown of atl (Atl-KD) leads to an increase in synaptic and satellite bouton number similar to the increase in BMP signaling activity (TKV-CA). Neuronal Atl-KD also associates to a reduction in the boutons of the abundance of the SV markers CSP (Cysteine string protein) and VGLUT (vesicular glutamate transporter) as well as in TKV-CA larvae, both phenotypes are suppressed by decreasing the function of BMP receptor wishful thinking expressing one copy of the mutant receptor (wit /+). Surprisingly, we determined in Atl-KD larvae an increase in the CSP peripheral density and distribution, dependent on synaptic stimulation, that was not replicated in Tkv-CA larvae, suggesting that there could be differences in the mechanisms that underlie the reduction in CSP abundance. Additionally, we determined that Atl-KD associates to an increase in FM 1-43 unload but not in TKV-CA larvae. Moreover, one copy of wit was not able to suppress the FM-143 in Atl-KD larvae (Atl-KD, wit), supporting that BMP signaling does not participate in this phenotype. Together with the stimuli-dependent changes in the SV distribution and dynamics determined in Atl-KD larvae, we measured an increase in Rab11/CSP colocalization, suggesting changes in SV traffic through late recycling endosomes. Together our results suggest a mechanism by which the loss of an ER structuring protein in the motor neuron could, through its role in regulating SV and endosomal trafficking, explain defects in SV accumulation and synaptic dysfunction.
Scalable and model-free detection of spatial patterns and colocalization
Authors: Liu Qi , Hsu Chih-Yuan , Shyr Yu
Published: September 2022

The expeditious growth in spatial omics technologies enables the profiling of genome-wide molecular events at molecular and single-cell resolution, highlighting a need for fast and reliable methods to characterize spatial patterns. We developed SpaGene, a model-free method to discover spatial patterns rapidly in large-scale spatial omics studies. Analyzing simulation and a variety of spatially resolved transcriptomics data showed that SpaGene is more powerful and scalable than existing methods. Spatial expression patterns identified by SpaGene reconstruct unobserved tissue structures. SpaGene also successfully discovers ligand–receptor interactions through their colocalization.
Perceived barriers and negotiation of using peer-to-peer accommodation by Chinese consumers in the COVID-19 context
Authors: Li Zhiyong , Huang Jiahui , Huang Songshan (Sam) , Huang Dan
Published: September 2022

Purpose

This study aims to understand Chinese consumers’ perceived barriers to using peer-to-peer (P2P) accommodation before and after the outbreak of COVID-19 and the negotiation strategies they applied in overcoming the barriers and enabling consumption.

Design/methodology/approach

A qualitative research design with 28 semi-structured interviews was used. Data were analysed by content analysis.

Findings

Five psychological barriers and four functional barriers were found to inhibit consumers from using P2P accommodation both before and after the COVID-19 outbreak. In overcoming the perceived barriers, consumers applied both behavioural negotiation strategies, including seeking information, behavioural adaptation, selective choice and seeking social support, and cognitive negotiation strategies, including cognitive adaptation and trusting agents. COVID-19 was found to serve as both a barrier and a facilitator for using P2P accommodation. A barriers–negotiation framework was developed in the context.

Research limitations/implications

Theoretically, this study advances consumer resistance and perceived barriers literature by integrating negotiation and developing a barriers–negotiation framework of P2P accommodation usage. This study also offers insights for practitioners in the P2P accommodation industry.

Originality/value

This study showcases the role of negotiation in understanding barriers to using P2P accommodation, paving the way to extend relevant knowledge to advance consumer resistance research, which is an emerging topic in the broader management domain.
Losses because of risk attitudes or time preference: off-farm cold storage and intertemporal marketing of apple growers in China
Authors: Jin Shaoze , Jia Xiangping , James Harvey S.
Published: September 2022

Purpose

This paper aims to explore the relationship between prudence in risk attitudes and patience of time preference of Chinese apple growers regarding off-farm cold storage of production and marketing in non-harvest seasons. The authors also consider the effect of farmer participation in cooperative-like organizations known as Farm Bases (FBs).

Design/methodology/approach

The authors use multiple list methods and elicitation strategies to measure Chinese apple farmers' risk attitudes and time preferences. Because these farmers can either sell their apples immediately to supermarkets or intermediaries or place them in storage, the authors assess correlations between their storage decisions and their preferences regarding risk and time. The authors also differentiate risks involving gains and losses and empirically examine individual risk attitudes in different scenarios.

Findings

Marketing decisions are moderately associated with risk attitudes but not time preference. Farmers with memberships in local farmer cooperatives are likely to speculate more in cold storage. Thus, risk aversion behavioral and psychological motives affect farmers' decision-making of cold storage and intertemporal marketing activities. However, membership in cooperatives does not always result in improved income and welfare for farmers.

Research limitations/implications

The research confirms that behavioral factors may strongly drive vulnerable smallholder farmers to speculate into storage even under seasonal and uncertain marketing volatility. There is the need to think deeper about the rationale of promoting cooperatives and other agricultural forms, because imposing these without careful consideration can have negative impacts.

Originality/value

Do risk and time preferences affect the decision of farmers to utilize storage facilities? This question is important because it is not clear if and how risk preferences affect the tradeoff between consuming today and saving for tomorrow, especially for farmers in developing countries.
Remarkable lives – Laura Scranage in conversation with Robert Hurst
Authors: Scranage Laura , Hurst Robert
Published: September 2022

Purpose

The purpose of this paper is to share Laura Scranage’s story.

Design/methodology/approach

Laura wrote a short piece detailing her journey and was then interviewed by Robert.

Findings

Laura spoke about the difficulties she has faced in life and how her experiences with horses have been deeply therapeutic.

Research limitations/implications

Recovery narratives such as this give us an overview of only a single person’s experiences. However, they allow the person with lived experience to explore their story in depth.

Practical implications

Laura advocates for more research into how horses can be used in therapeutic interventions.

Social implications

There is so much to learn from a story such as Laura’s, for those who have had similar experiences and for those who work in mental health services.

Originality/value

This is the first time that Laura has chosen to share her unique story.
Determinants of intentions to use foodpanda mobile applications in Bangladesh: the role of attitude and fear of COVID-19
Authors: Hasan Abdulla Al-Towfiq
Published: September 2022

Purpose

This study investigates the determinants influencing customers’ intentions of using the foodpanda mobile app during COVID-19 pandemic.

Design/methodology/approach

This study is based on review of the literatures and 388 usable data collection from respondents having prior experiences in online food delivery (OFD) services in Dhaka city in Bangladesh. The subsequent data is analyzed through Structural Equation Modeling using Smart PLS 3.3.3.

Findings

The findings show that perceived usefulness (PU), ease of use, convenience, attitude and fear of COVID-19 significantly impact intentions to use foodpanda mobile app (ITUFPMA) and attitude. Further, attitude partially mediates between PU, ease of use, convenience and ITUFPMA. Moreover, fear of COVID-19 moderates the strength of association between attitude and ITUFPMA.

Practical implications

The findings of the study may be useful to OFD services operators in formulating business strategies for improving customers’ foodpanda mobile app use intentions and coping with competitive business environment of sharing economy sector.

Originality/value

The study presents a unique case highlighting what are influencing customer intentions toward OFD services during COVID-19 context. The current study provides important insights for industry operators by integrating PU, ease of use, convenience, attitude and fear of COVID-19 in examining ITUFPMA during COVID-19 situation.
Illiberal economies: ambivalence and critique in an alternative investment scheme
Authors: Hayden Tiana Bakić , Muir Sarah
Published: September 2022

This article examines practices of critique and ambivalence among participants in a controversial Latin American investment scheme called thetelares de la abundancia(‘looms of abundance’). While the dominant discourses about thetelaresconstrue them as predatory, participants understand themselves as knowing subjects who reject a worldview based on economic rationality and utility in favour of one based on emotional connectedness. While this emphasis on emotional connection is not unique to thetelares, what is remarkable is the central role that doubt plays: thetejedoras(weavers), as they call themselves, assert themselves quite explicitly not only as critical and knowing subjects, but also as profoundly ambivalent subjects who insist upon the incommensurability of emotional connection and financial gain even as they simultaneously pursue both. This article explores howtejedorasconfront and deal with their doubts by cultivating practices of ambivalence. In so doing, it foregrounds the multiplicity of people's allegiances and intuitions in contexts marked by competing epistemologies, as is the case not only in Latin America but also in much of the world where illiberalism has become a central concern. Towards that end, the article develops the concept of ‘illiberal economies’ – spaces in which participants simultaneously pursue contradictory and mutually exclusive forms of value – as a way of shedding light on broader political and economic dynamics that can seem simultaneously (and paradoxically) nonsensical and irrational, on the one hand, and manipulative and instrumental, on the other. In so doing, the article foregrounds the ambivalent dynamics that are at the heart of illiberal economies in order to open up analytic possibilities for grappling with illiberalism more broadly.
Assessment of detection limits for dyed and mounted textile fibers using Raman spectroscopy
Authors: Rydzak Patrick M. , Elwick Kyleen E. , Damaso Natalie , Robertson James M.
Published: September 2022

Trace evidence in the form of textile fibers can be used to link objects and places during an investigation. Raman spectroscopy is a well‐established technique that has been used for the examination of various pigments, paints, inks, and dyes. The objective of this study was to determine the capability of Raman spectroscopy to detect several different dye classes and colors on a variety of textile fibers. To test this, four categories of dyes, reactive, disperse, acid, and direct were examined with Raman microscopy while applied to one of five fiber types (cotton, polyester, nylon, wool, and rayon). Each dye category was tested using four colors, black, blue, red, and yellow, while at four concentrations of dye (w/w), 4% (black only), 1%, 0.5%, and 0.05% (blue, red, and yellow). Finally, each dye, fiber, color, and dye concentration combination were examined with Raman using one of two laser excitation sources (532 nm and 780 nm) while mounted in one of two mounting media, Permount™ and Entellan® new, as well as unmounted. Raman spectroscopy could detect some dyes at low concentrations (0.5% and 0.05%) even when mounted in mounting media and covered with a glass coverslip. Excitation source, dye category, dye concentration, fiber type, and mounting method all influence the ability to detect any given dye. These results support the continued study of Raman as a tool for the examination of fiber dyes as it has shown the potential to be effective even under constraints experienced by forensic examiners.
ECT‐related anxiety during maintenance ECT: A prospective study
Authors: Obbels Jasmien , Gijsbregts Els , Verwijk Esmée , Verspecht Shauni , Lambrichts Simon , Vansteelandt Kristof , Sienaert Pascal
Published: September 2022

Objective

Despite the established safety of electroconvulsive therapy (ECT), ECT‐related anxiety (ERA) remains one of the most distressing complications of ECT. ERA is reported to diminish during an acute course of ECT, but it was never studied during maintenance ECT (M‐ECT). Our aim was to study the trajectories of ERA during M‐ECT and how they differ from trajectories during the acute course.

Methods

Thirty‐nine patients with unipolar or bipolar depression, retained for M‐ECT after an acute ECT course, were included. ERA was assessed the morning before each ECT session using the ECT‐related Anxiety Questionnaire (ERAQ).

Results

ERA remained stable during M‐ECT (RC = −0.05 (SE = 0.06), t(8.35) = −0.86, p = 0.42), while ERA declined significantly during the acute course (RC = −0.85 (SE = 0.30), t(33.6) = −2.81, p = 0.0082). During the acute course, patients with a psychotic depression were more anxious at baseline (t(32)= −2.42, p = 0.02), and showed a significant decline in ERAQ scores (RC = −1.65 (SE = 0.46), t(31.6) = −3.56, p = 0.0012), whereas patients with a non‐psychotic depression were less anxious at baseline and retained stable ERAQ scores during the acute course (RC = −0.06 (SE = 0.41), t(32.1) = −0.14, p = 0.89). Whereas a correlation (r = 0.48) was noticed between the decline of depression severity and ERA during the acute course, this was not the case during M‐ECT.

Conclusion

ERA runs a stable course during M‐ECT, after having decreased during the acute course. During the acute course, ERA trajectories differed significantly between patients with a psychotic and non‐psychotic depression. Decline of depression severity and ERA are significantly connected during the acute course of ECT. Both depression severity and ERA remain stable during M‐ECT.
‘I hate sand … it gets everywhere’—Phanerozoic sedimentary recycling from NW Africa
Authors: Lovell‐Kennedy James , Roquette Emmanuel , Schröder Stefan , Redfern Jonathan
Published: September 2022

Over 10,000 published detrital zircon ages have been reprocessed (applying a +10% normal and reverse concordance range) and analysed to understand the evolution of the detrital zircon record of north‐west Africa during the Phanerozoic. Using dissimilarity and clustering analysis, shifts in detrital zircon populations allow interpretation of the evolution of source regions and source to sink systems throughout the Phanerozoic within the West Gondwana superfan. Previous thermochronology and field studies conducted across north‐west Africa indicate significant and sustained shifts in source regions in Meso‐Cenozoic times which are not recorded in the detrital zircon geochronology record. This discrepancy is most notable for Mesozoic to modern source to sink studies focused on the evolution of the Atlasic rift and opening of the Atlantic and Tethyan Oceans to the west and north respectively. Our results indicate a high degree of similarity between samples from Cambrian times onwards due to successive phases of sediment recycling. This highlights the need to integrate detrital zircon analysis with other techniques to provide confident reconstruction of sediment routing systems across Morocco. This systematic review also reveals the ubiquitous occurrence of Mesoproterozoic zircons within Moroccan sediment. No basement of this age is known from north‐west Africa—often described as the ‘Mesoproterozoic Gap’, which was thought to be a diagnostic feature of sediment derived from the West African Craton. However, zircons of this age form 7% of all analysed zircons and are present in sediments from at least 700 Ma. The presence of this population is interpreted as strongly diagnostic of provenance from either the Amazonian Craton or the Eastern Gondwana Orogen within Central Africa. Their presence in the Moroccan detrital record from the Neoproterozoic onwards raises questions about the position of the West African Craton in the Proterozoic, and for the spatial extent of Mesoproterozoic orogeny within north Africa.
Carcinogenesis resistance in the longest‐lived rodent, the naked mole‐rat
Authors: Yamamura Yuki , Kawamura Yoshimi , Oka Kaori , Miura Kyoko
Published: September 2022

Certain mammalian species are resistant to cancer, and a better understanding of how this cancer resistance arises could provide valuable insights for basic cancer research. Recent technological innovations in molecular biology have allowed the study of cancer‐resistant mammals, despite the fact that they are not the classical model animals, which are easily studied using genetic approaches. Naked mole‐rats (NMRs; Heterocephalus glaber) are the longest‐lived rodent, with a maximum lifespan of more than 37 years, and almost never show spontaneous carcinogenesis. NMRs are currently attracting much attention from aging and cancer researchers, and published studies on NMR have continued to increase over the past decade. Cancer development occurs via multiple steps and involves many biological processes. Recent research on the NMR as a model for cancer resistance suggests that they possess various unique carcinogenesis‐resistance mechanisms, including efficient DNA repair pathways, cell‐autonomous resistance to transformation, and dampened inflammatory response. Here, we summarize the molecular mechanisms of carcinogenesis resistance in NMR, which have been uncovered over the past two decades, and discuss future perspectives.
BRCA1 transports the DNA damage signal for CDDP‐induced centrosome amplification through the centrosomal Aurora A
Authors: Qi Huicheng , Kikuchi Megumi , Yoshino Yuki , Fang Zhenzhou , Ohashi Kazune , Gotoh Takato , Ideta Ryo , Ui Ayako , Endo Shino , Otsuka Kei , Shindo Norihisa , Gonda Kohsuke , Ishioka Chikashi , Miki Yoshio , Iwabuchi Tokuro , Chiba Natsuko
Published: September 2022

Breast cancer gene 1 (BRCA1) plays roles in DNA repair and centrosome regulation and is involved in DNA damage‐induced centrosome amplification (DDICA). Here, the centrosomal localization of BRCA1 and the kinases involved in centrosome duplication were analyzed in each cell cycle phase after treatment with DNA crosslinker cisplatin (CDDP). CDDP treatment increased the centrosomal localization of BRCA1 in early S–G2 phase. BRCA1 contributed to the increased centrosomal localization of Aurora A in S phase and that of phosphorylated Polo‐like kinase 1 (PLK1) in late S phase after CDDP treatment, resulting in centriole disengagement and overduplication. The increased centrosomal localization of BRCA1 and Aurora A induced by CDDP treatment involved the nuclear export of BRCA1 and BRCA1 phosphorylation by ataxia telangiectasia mutated (ATM). Patient‐derived variants and mutations at phosphorylated residues of BRCA1 suppressed the interaction between BRCA1 and Aurora A, as well as the CDDP‐induced increase in the centrosomal localization of BRCA1 and Aurora A. These results suggest that CDDP induces the phosphorylation of BRCA1 by ATM in the nucleus and its transport to the cytoplasm, thereby promoting the centrosomal localization Aurora A, which phosphorylates PLK1. The function of BRCA1 in the translocation of the DNA damage signal from the nucleus to the centrosome to induce centrosome amplification after CDDP treatment might support its role as a tumor suppressor.
Information needs of patients considering oral immunotherapy for food allergy
Authors: Mack Douglas Paul , Greenhawt Matthew , Turner Paul J. , Wasserman Richard L. , Hanna Mariam A. , Shaker Marcus , Hughes Sarah W. , Rodríguez del Río Pablo
Published: September 2022

While the historic management of food allergy includes avoidance strategies and allergic reaction treatment, oral immunotherapy (OIT) approaches have become more commonly integrated into therapeutic approaches. International guidelines, phase 3 trials and real‐world experience have supported the implementation of this procedure. However, OIT is an elective, rarely curative procedure with inherent risks that necessitates an increased degree of health literacy for the patients and families. Families assume the responsibility of amateur healthcare providers to ensure the daily safe administration of the allergenic food. As such, it is incumbent upon physicians to ensure that families are prepared for this role. A thorough educational and shared decision‐making approach is necessary during the counselling and consent process to adequately inform the families. Educated discussion about the efficacy and patient‐centred effectiveness, therapeutic alternatives and family goals is required to align physician and patient expectations. A frank discussion about the struggles, practical challenges, risks and contraindications can help to develop an understanding of the risk mitigation strategies employed to maintain safety. Physicians should develop a proactive approach to educate families about this, at times, burdensome procedure. This educational approach should encourage ongoing support starting prior to consent through the maintenance visits. By preparing families for their unique management role, physicians can help ensure the safe and successful integration of OIT into the therapeutic offering for the management of food allergies.
Drift as a Driver of Language Change: An Artificial Language Experiment
Authors: Ventura Rafael , Plotkin Joshua B. , Roberts Gareth
Published: September 2022

Over half a century ago, George Zipf observed that more frequent words tend to be older. Corpus studies since then have confirmed this pattern, with more frequent words being replaced and regularized less often than less frequent words. Two main hypotheses have been proposed to explain this: that frequent words change less because selection against innovation is stronger at higher frequencies, or that they change less because stochastic drift is stronger at lower frequencies. Here, we report the first experimental test of these hypotheses. Participants were tasked with learning a miniature language consisting of two nouns and two plural markers. Nouns occurred at different frequencies and were subjected to treatments that varied drift and selection. Using a model that accounts for participant heterogeneity, we measured the rate of noun regularization, the strength of selection, and the strength of drift in participant responses. Results suggest that drift alone is sufficient to generate the elevated rate of regularization we observed in low‐frequency nouns, adding to a growing body of evidence that drift may be a major driver of language change.
Mechanisms of cerebral vasospasm and cerebral ischaemia in subarachnoid haemorrhage
Authors: Viderman Dmitriy , Tapinova Karina , Abdildin Yerkin G.
Published: September 2022

Subarachnoid haemorrhage (SAH) is a cerebrovascular emergency associated with significant morbidity and mortality. SAH is characterized by heterogeneity, interindividual variation and complexity of pathophysiological responses following extravasation of blood from cerebral circulation. The purpose of this review is to integrate previously established pre‐existing factors, pathophysiological pathways and to develop a concept map of mechanisms of SAH‐induced cerebral vasospasm and delayed cerebral ischaemia using a systematic approach. We conducted an extensive mapping of a hypothesized sequence of pathophysiological events. Documentation of supporting evidence was done alongside a concept map building. After finalizing the model, we conducted an analysis of the consequences and connections of pathophysiological events. We included the findings of experimental research, focusing on pathophysiological processes. We focused on SAH‐induced cerebral vasospasm and delayed cerebral ischaemia as a component of cerebral injury and potential systemic consequences. SAH‐induced brain injury occurs within 72 h following haemorrhage. Pathophysiology of cerebral vasospasm may include reduction in NO production, direct activation of calcium channels, upregulating genes involved with inflammation and extracellular matrix remodelling, triggering oxidative stress and free radical damage to smooth muscle and lipid peroxidation of cell membranes, cortical spreading depolarizations, sympathetic activation, finally resulting in the failure of cerebral autoregulation, microthrombosis and cerebral ischaemic injury. This cascade of events might explain why medical therapy often fails to reverse resistant cerebral vasospasm and to prevent cerebral ischaemia.
Prospective study on the risk of transmission due to droplets and aerosols during an endoscopic procedure and the usefulness of extraoral suction devices
Authors: Sunakawa Hironori , Yoda Yusuke , Takahashi Mari , Arai Keisuke , Kano Yuki , Yamashita Hiroki , Aoyama Naoki , Mitsui Tomohiro , Inaba Atsushi , Takashima Kenji , Nakajo Keiichiro , Murano Tatsuro , Kadota Tomohiro , Shinmura Kensuke , Ikematsu Hiroaki , Yano Tomonori
Published: September 2022

Objectives

Endoscopy poses a high risk of severe acute respiratory syndrome coronavirus 2 infection for medical personnel due to the dispersal of aerosols from the patient. We investigated the location and size of droplets generated during esophagogastroduodenoscopy (EGD) and endoscopic submucosal dissection (ESD), the contamination of the surrounding area before and after the procedures, and the effectiveness of using an extraoral suction device (Free arm arteo; TOKYO GIKEN, Inc., Tokyo, Japan).

Methods

Patients who consented to the study and underwent EGD or ESD between December 8, 2020, and April 15, 2021, at the National Cancer Center East Hospital were included. Adenosine triphosphate (ATP) hygiene monitoring tests and a particle counter were used for measurements.

Results

Assessments were performed on 22 EGD and 15 ESD cases. ATP hygiene monitoring tests showed significant elevations at three sites near the patient, and two sites 1.5 m away, for EGD, and at four sites near the patient and 1.5 m away for ESD. In both ESD and EGD, extraoral suction devices reduced the extent of the contamination. Particles <5 μm in size were generated during endoscopic procedures and dispersed from both the forceps hole and the patient's mouth. The extraoral suction device did not reduce the number of particles generated.

Conclusions

During endoscopic procedures, cleaning the surrounding environment is important in addition to standard precautions the endoscopist and caregivers take. The use of extraoral suction devices can also potentially reduce contamination of the surrounding environment.
Tibetan Buddhist belief and disaster resilience: a qualitative exploration of the Yushu area, China
Authors: Sun Lei , Qi Wenhua
Published: September 2022

The role of religious belief in disasters has attracted increased scholarly interest in recent years. This paper shows that religious belief can generate disaster resilience through the pathways of disaster framing, mental health, and disaster behaviours. Drawing on interviews conducted with Tibetan Buddhist believers in the Yushu earthquake area of China, this study indicates that notions of Tibetan Buddhism, as well as religious practices, helped locals to make sense of the 2010 event, obtain spiritual support in its aftermath, foster a sense of community, and develop a prosocial post‐earthquake environment. These religious notions and practices also assisted in sustaining a faith‐based network composed of two kinds of important local social relationships, layperson–layperson and layperson–monk, which increased local disaster resilience at the level of response behaviour. The findings enrich our understanding of the religious source of disaster resilience and yield insights into disaster risk reduction in religious regions, especially where Buddhist belief is prevalent.
Latitudinal but not elevational variation in blood glucose level is linked to life history across passerine birds
Authors: Tomášek Oldřich , Bobek Lukáš , Kauzálová Tereza , Kauzál Ondřej , Adámková Marie , Horák Kryštof , Kumar Sampath Anandan , Manialeu Judith Pouadjeu , Munclinger Pavel , Nana Eric Djomo , Nguelefack Télesphore Benoît , Sedláček Ondřej , Albrecht Tomáš
Published: September 2022

Macrophysiological research is vital to our understanding of mechanisms underpinning global life history variation and adaptation to diverse environments. Here, we examined latitudinal and elevational variation in a key substrate of energy metabolism and an emerging physiological component of pace‐of‐life syndromes, blood glucose concentration. Our data, collected from 61 European temperate and 99 Afrotropical passerine species, revealed that baseline blood glucose increases with both latitude and elevation, whereas blood glucose stress response shows divergent directions, being stronger at low latitudes and high elevations. Low baseline glucose in tropical birds, compared to their temperate counterparts, was mainly explained by their low fecundity, consistent with the slow pace‐of‐life syndrome in the tropics. In contrast, elevational variation in this trait was decoupled from fecundity, implying a unique montane pace‐of‐life syndrome combining slow‐paced life histories with fast‐paced physiology. The observed patterns suggest that pace‐of‐life syndromes do not evolve along the single fast‐slow axis.
Early cost–utility analysis of genetically guided therapy for patients with drug‐resistant epilepsy
Authors: Gordon Louisa G. , Elliott Thomas M. , Bennett Carmen , Hollway Georgina , Waddell Nicola , Vadlamudi Lata
Published: September 2022

Objective

Existing gene panels were developed to understand the etiology of epilepsy, and further benefits will arise from an effective pharmacogenomics panel for personalizing therapy and achieving seizure control. Our study assessed the cost‐effectiveness of a pharmacogenomics panel for patients with drug‐resistant epilepsy, compared with usual care.

Methods

A cost–utility analysis was employed using a discrete event simulation model. The microsimulation model aggregated the costs and benefits of genetically guided treatment versus usual care for 5000 simulated patients. The 10‐year model combined data from various sources including genomic databases on prevalence of variants, population‐level pharmaceutical claims on antiseizure medications, published long‐term therapy retention rates, patient‐level cost data, and systematic reviews. Incremental cost per quality‐adjusted life‐year (QALY) gained was computed. Deterministic and probabilistic sensitivity analyses were undertaken to address uncertainty in model parameters.

Results

The mean cost of the genetically guided treatment option was AU$98 199 compared with AU$95 386 for usual care. Corresponding mean QALYs were 4.67 compared with 4.28 for genetically guided and usual care strategies, respectively. The incremental cost per QALY gained was AU$7381. In probabilistic sensitivity analyses, the incremental cost per QALY gained was AU$6321 (95% uncertainty interval = AU$3604–AU$9621), with a 100% likelihood of being cost‐effective in the Australian health care system. The most influential drivers of the findings were the monthly health care costs associated with reduced seizures, costs when seizures continued, and the quality‐of‐life estimates under genetically guided and usual care strategies.

Significance

This early economic evaluation of a pharmacogenomics panel to guide treatment for drug‐resistant epilepsy could potentially be cost‐effective in the Australian health care system. Clinical trial evidence is necessary to confirm these findings.
Experiences of fathers caring for children with neurodevelopmental disorders: A meta‐synthesis
Authors: Shorey Shefaly , Pereira Travis Lanz‐Brian
Published: September 2022

Parents raising children with neurodevelopmental disorders (NDD) experience greater family, health, and psychosocial dysfunction due to the compounding nature of children's NDD and disease manifestations. Furthermore, the experiences of fathers and mothers are significantly different, and there is a paucity of consolidated evidence on fathers' experiences. A systematic review and meta‐synthesis were conducted using Sandelowski and Barroso's approach. Six electronic databases were searched for relevant articles published between November 2011 and November 2021. Thirty‐eight studies were included in this review. An overarching theme “Out of the Shadows, and Into the Sunshine” emerged along with four main themes: (a) “The Illness Is All the Time”: An Overwhelming Experience, (b) “Navigating health care and Education Systems,” (c) “Strong Alone, Stronger Together,” and (d) “My Child Is Different Not Less: A Different Perspective.” This meta‐synthesis analyzed the facilitators and barriers married fathers of children with NDD faced and suggested a paradigm shift where these fathers are becoming more actively involved in the care of their children. There is a need for family clinicians and therapists and health care, education, and workforce policymakers to collaborate to tackle the current and potential unique barriers faced by fathers of children with NDD.
The endoglycosidase activity of Dispersin B is mediated through electrostatic interactions with cationic poly‐β‐(1→6)‐N‐acetylglucosamine
Authors: Breslawec Alexandra P. , Wang Shaochi , Monahan Kathleen N. , Barry Lucas L. , Poulin Myles B.
Published: September 2022

Bacterial biofilms consist of bacterial cells embedded within a self‐produced extracellular polymeric substance (EPS) composed of exopolysaccharides, extra cellular DNA, proteins and lipids. The enzyme Dispersin B (DspB) is a CAZy type 20 β‐hexosaminidase enzyme that catalyses the hydrolysis of poly‐N‐acetylglucosamine (PNAG), a major biofilm polysaccharide produced by a wide variety of biofilm‐forming bacteria. Native PNAG is partially de‐N‐acetylated, and the degree of deacetylation varies between species and dependent on the environment. We have previously shown that DspB is able to perform both endo‐ and exo‐glycosidic bond cleavage of PNAG depending on the de‐N‐acetylation patterns present in the PNAG substrate. Here, we used a combination of synthetic PNAG substrate analogues, site‐directed mutagenesis and in vitro biofilm dispersal assay to investigate the molecular basis for the endo‐glycosidic cleavage activity of DspB and the importance of this activity for dispersal of PNAG‐dependent Staphylococcus epidermidis biofilms. We found that D242 contributes to the endoglycosidase activity of DspB through electrostatic interactions with cationic substrates in the −2 binding site. A DspBD242N mutant was highly deficient in endoglycosidase activity while maintaining exoglycosidase activity. When used to disperse S. epidermidis biofilms, this DspBD242N mutant resulted in an increase in residual biofilm biomass after treatment when compared to wild‐type DspB. These results suggest that the de‐N‐acetylation of PNAG in S. epidermidis biofilms is not uniformly distributed and that the endoglycosidase activity of DspB is required for efficient biofilm dispersal.
Use of sensory rooms in adult psychiatric inpatient settings: A systematic review and narrative synthesis
Authors: Haig Stephanie , Hallett Nutmeg
Published: September 2022

Reducing the use of restrictive interventions within psychiatric inpatient settings is a global priority. There are many strategies which may support the prevention of violence before escalation into more severe incidences. Sensory rooms have been identified as one such intervention, aiding patients to emotionally regulate and reduce distress, with a growing body of academic literature interested in whether sensory rooms can ultimately impact incidences of patient violence and the use of restraint, seclusion, and other restrictive practices. A systematic literature review was conducted to identify how effective sensory rooms are at reducing patient violence and restrictive interventions within adult psychiatric inpatient settings. Eighteen studies met the eligibility criteria and were included in the review. There is a lack of evidence as to whether sensory rooms are effective at reducing seclusion, restraint, or violence. They are, however, likely to support a reduction in patient distress. Patient and staff experiences suggest sensory rooms support emotional regulation, promote self‐management, and positively impact the overall patient admission experience and ward environment. Further research is needed to identify what works, for who and in what circumstances in relation to the design of sensory rooms.