bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Behavior Atlas: A computational framework for tracking and mapping 3D close interactions of free-moving animals
Authors: Han Yaning , Chen Ke , Wang Yunke , Liu Wenhao , Wang Xiaojing , Liao Jiahui , Huang Yiting , Han Chuanliang , Huang Kang , Zhang Jiajia , Cai Shengyuan , Wang Zhouwei , Wu Yongji , Gao Gao , Wang Nan , Li Jinxiu , Song Yangwangzi , Li Jing , Wang Guodong , Wang Liping , Zhang Yaping , Wei Pengfei
Published: March 2023

The study of social behaviors in animals is essential for understanding their survival and reproductive strategies. However, accurately tracking and analyzing the social interactions of free-moving animals has remained a challenge. Existing multi-animal pose estimation techniques suffer from drawbacks such as the need for extensive manual annotation and difficulty in discriminating between similar-looking animals in close social interactions. In this paper, we present the Social Behavior Atlas (SBeA), a novel computational framework that solves these challenges by employing a deep learning-based video instance segmentation model, 3D pose reconstruction, and unsupervised dynamic behavioral clustering. SBeA framework also involves a multi-camera setup to prevent occlusion, and a novel approach to identify individual animals in close social interactions. We demonstrate the effectiveness of SBeA in tracking and mapping the 3D close interactions of free-moving animals using the example of genetic mutant mice, birds, and dogs. Our results show that SBeA is capable of identifying subtle social interaction abnormalities, and the models and frameworks developed can be applied to a wide range of animal species. SBeA is a powerful tool for researchers in the fields of neuroscience and ecology to study animal social behaviors with a high degree of accuracy and reliability.
Plasma multi-omics outlines association of urobilinogen with corticosteroid non-response, inflammation and leaky gut in Sever Alcoholic Hepatitis
Authors: Yadav Manisha , Mathew Babu , Bhat Sadam H , Sharma Neha , Kumar Jitender , Yadav Pushpa , Tripathi Gaurav , Bindal Vasundhra , Sharma Nupur , Pandey Sushmita , Singh Ravinder , Bhaskar Ashima , Dwivedi Ved Prakash , Trehanpati Nirupama , Sharma Shvetank , Sarin Shiv Kumar , Maras Jaswinder Singh
Published: March 2023

Background and Aims

Severe alcoholic hepatitis (SAH) has a high mortality and corticosteroid therapy is effective in 60% patients. Reliable indicators of response to therapy and mortality in SAH are needed. A total of 223 SAH patients, 70 in derivative [50 responders (R) and 20 non-responders (NR)] and 153 in validation cohort [136R, 17NR] were subjected to plasma metabolic/meta-proteomic analysis using UHPLC-HRMS and validated using Machine-Learning (ML). Temporal metabolic changes were assessed using Weighted Metabolome Correlation Network Analysis (WMCNA). Functionality (inflammatory-nature, effect on membrane integrity and glucocorticoid receptor) of non-response indicator was assessedin-vitroon primary healthy neutrophils or mice enterocytes. Baseline plasma metabolomics and meta-proteomics clearly discriminated NR and showed significant increase in urobilinogen (3.6-fold), cholesterol sulfate (6.9-fold), Adenosine monophosphate (4.7-fold) and others (p<0.05, FC>1.5, FDR<0.01). Increase in alpha/beta diversity, biosynthesis of secondary metabolites was a characteristic feature of NR (p<0.05). NR were metabolically inactive however R showed temporal change in the metabolite expression post-corticosteroid therapy (p<0.05). Plasma urobilinogen predicted non-response [AUC=0.94] with a hazard-ratio of 1.5(1.2-1.6) and cut-off >0.07mg/ml segregated non-survivors (p<0.01) and showed >98% accuracy using ML. Plasma urobilinogen directly correlated with circulating bacterial peptides linked to bilirubin to urobilinogen metabolising bacteria (r2>0.7;p<0.05). Urobilinogen inducedneutrophil activation,oxidative-stressandpro-inflammatory cytokines (CXCR1, NGAL, NOXO1, NOX4, IL15, TNFα and others, p<0.05), promotedcorticosteroid resistanceby increasing the expression of GR-Beta and trans-repression genes under GR-alpha (inflammatory-NFkB, MAPK-MAP) and reducing GR-alpha, and transactivation (anti-inflammatory) gene levels. Urobilinogen also promoted leaky gut by deregulating intestinal membrane junction proteins.

Conclusion

Plasma metabolome/meta-proteome can stratify pre-therapy steroid response. Increase in plasma Urobilinogen pedals a vicious cycle of bacterial translocation and increase in inflammation and corticosteroid non-response in SAH patients.
Crop Filling: a pipeline for repairing memory clinic MRI corrupted by partial brain coverage
Authors: Leal Gonzalo Castro , Whitfield Tim , Praharaju Janaki , Walker Zuzana , Oxtoby Neil P.
Published: March 2023

Data-driven solutions offer great promise for improving healthcare. However standard clinical neuroimaging data is subject to real-world imaging artefacts that can render the data unusable for computational research. T1 weighted structural MRI is used in research to obtain volumetric measurements from cortical and subcortical brain regions. However, clinical radiologists often prioritise T2 weighted or FLAIR scans for visual assessment. As such, T1 weighted scans are often acquired but may not be a priority. This can result in artefacts such as partial brain coverage being systematically present in memory clinic data.

Here we present a neuroimaging pipeline to ameliorate such situations by filling the missing regions with synthetic data. We validate on artificially cropped scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), showing that our pipeline largely removes the artefact, improving volumetric biomarker accuracy while also retaining statistical differences between diagnostic groups. We demonstrate utility by achieving diagnostic classification performance comparable to uncorrupted data. This is an important contribution towards moving research from the lab into the real world.
The Effects of Prenatal Deaths on National Life Expectancy: Case Study U.S.A
Authors: Hollman Madeleine R. , Pearce Joshua M.
Published: March 2023

It is a positive indicator that human life expectancies calculated from birth have been increasing. The current standards for counting life-years, however, assume social desirability and exclude all prenatal deaths. These assumptions mask low life-year deaths and obscure results of medical and environmental interventions, thus falsely indicating higher life expectancies. This case study investigates 1930 to 2016 using CDC and World Bank data for the U.S. It is evident, published U.S. life expectancies are greatly exaggerated and what would have been short-lived Americans are disproportionately labeled as socially-undesirable and ignored when counting life years, thus presenting an overly-optimistic view of U.S. health. A comprehensive global investigation is needed, and a refinement of life expectancy calculations should be introduced, which does not bias results by only counting life expectancy from the time of live birth.
Preventing production escape during scale-up using an engineered glucose-inducible genetic circuit
Authors: Tavares Leonardo Ferro , Ribeiro Nathan Vinicius , Zocca Vitoria Fernanda Bertolazzi , Correa Graciely Gomes , Amorim Laura Araujo da Silva , Lins Milca Rachel da Costa Ribeiro , Pedrolli Danielle Biscaro
Published: March 2023

A proper balance of metabolic pathways is crucial for engineering microbial strains that can efficiently produce biochemicals at an industrial scale while maintaining cell fitness. High production loads can negatively impact cell fitness and hinder industrial-scale production. To address this, fine-tuning of gene expression using engineered promoters and genetic circuits can offer control over multiple targets in pathways and reduce the burden. We took advantage of the robust carbon catabolite repression system of Bacillus subtilis to engineer a glucose-inducible genetic circuit that supports growth and production. By simulating cultivation scale-up under repressive conditions, we preserved the production capacity of cells, which could be fully accessed by switching to glucose in the final production step. The circuit is also resilient, enabling a quick change in the metabolic status of the culture. Furthermore, the scale-up process selected fast-growing cells without compromising their production capability, leading to higher yields at the end of the production process.
Genomic resources for a historical collection of cultivated two-row European spring barley genotypes
Authors: Schreiber Miriam , Wonneberger Ronja , Haaning Allison M. , Coulter Max , Russell Joanne , Himmelbach Axel , Fiebig Anne , Muehlbauer Gary J. , Stein Nils , Waugh Robbie
Published: March 2023

Barley genomic resources are increasing rapidly, with the publication of a barley pangenome as one of the latest developments. Two-row spring barley cultivars are intensely studied as they are the source of high-quality grain for malting and distilling. Here we provide data from a European two-row spring barley population containing 209 different genotypes registered for the UK market between 1830 to 2014. The dataset encompasses RNA-sequencing data from six different tissues across a range of barley developmental stages, phenotypic datasets from two consecutive years of field-grown trials in the United Kingdom, Germany and the USA; and whole genome shotgun sequencing from all cultivars, which was used to complement the RNA-sequencing data for variant calling. The outcomes are a filtered SNP marker file, a phenotypic database and a large gene expression dataset providing a comprehensive resource which allows for downstream analyses like genome wide association studies or expression associations.
Immunometabolic rewiring in long COVID patients with chronic headache
Authors: Foo Suan-Sin , Chen Weiqiang , Jung Kyle L. , Azamor Tamiris , Choi Un Yung , Zhang Pengfei , Comhair Suzy AA , Erzurum Serpil C. , Jehi Lara , Jung Jae U.
Published: March 2023

Almost 20% of patients with COVID-19 experience long-term effects, known as post-COVID condition or long COVID. Among many lingering neurologic symptoms, chronic headache is the most common. Despite this health concern, the etiology of long COVID headache is still not well characterized. Here, we present a longitudinal multi-omics analysis of blood leukocyte transcriptomics, plasma proteomics and metabolomics of long COVID patients with chronic headache. Long COVID patients experienced a state of hyper-inflammation prior to chronic headache onset and maintained persistent inflammatory activation throughout the progression of chronic headache. Metabolomic analysis also revealed augmented arginine and lipid metabolisms, skewing towards a nitric oxide-based pro-inflammation. Furthermore, metabolisms of neurotransmitters including serotonin, dopamine, glutamate, and GABA were markedly dysregulated during the progression of long COVID headache. Overall, these findings illustrate the immuno-metabolomics landscape of long COVID patients with chronic headache, which may provide insights to potential therapeutic interventions.
Hyperglycemic exacerbation of myocardial infarction through SGLT1 - a glucose paradox
Authors: Almalki Alhanoof , Arjun Sapna , Harding Idris , Jasem Hussain , Kolatsi-Joannou Maria , Jafree Daniyal J , Long David A , Yellon Derek M , Bell Robert M
Published: March 2023

Background

Hyperglycemia is common during acute myocardial infarction, irrespective of diabetic status, and portends excess mortality. The mechanisms of this adverse outcome remain unelucidated.

Objectives

To test the hypothesis that elevated glucose, at the time of reperfusion following myocardial ischemia, is directly injurious to the heart through induction of sodium/glucose-linked transporter 1 (SGLT1) activity.

Methods

Ex-vivo, Langendorff rodent models of 35minute global ischemia and 2hour reperfusion injury were utilised, with variable glucose and reciprocal mannitol concentrations maintaining equivalent osmolarity across groups during reperfusion. Infarct size was assessed by tri-phenyltetrazolium staining. SGLT1 expression was determined in rodents by rtPCR, RNAscope and immunohistochemistry and in human with single-cell transcriptomic analysis.Ex-vivo, functional involvement of SGLT1 was determined using three, structurally distinct pharmacological inhibitors: phlorizin, canagliflozin and mizagliflozin.

Results

In non-diabetic rodent hearts there was a J-shaped dose-response relationship between reperfusion-glucose concentration and infarct size, an association ameliorated in diabetic heart. Single-cell transcriptomic analysis revealed human myocardial SGLT1 expression equivalent to that seen in rodents at both an RNA and protein level. Diabetic rodent heart SGLT1 expression was significantly reduced compared to non-diabetic, and pharmacological SGLT1 inhibition abrogated excess injury associated with high glucose in non-diabetic heart.

Conclusion

Elevated glucose during reperfusion exacerbated myocardial infarction in non-diabetic heart, but this exacerbation was attenuated in diabetic rat heart where SGLT1 expression is suppressed. Inhibiting non-diabetic heart SGLT1 abrogates the excess injury associated with elevated glucose, thus highlighting SGLT1 as a potential clinical translational target to improve outcomes in acute myocardial infarction associated with hyperglycemia.
“How Social Connection and Engagement Relate to Functional Limitations and Depressive Symptoms Outcomes After Stroke”
Authors: Elayoubi Joanne , Haley William E. , Nelson Monica E. , Hueluer Gizem
Published: March 2023

Background

Stroke commonly leads to disability and depression. Social connection and engagement can be protective against functional decline and depression in the general population. We investigated the effects of social connection and engagement on trajectories of function and depressive symptoms in stroke.

Methods

Participants were 898 individuals with incident stroke from the Health and Retirement Study between 1998-2012. Multilevel modeling was used to examine associations of social connection and engagement with changes in functional limitations in instrumental activities of daily living (IADLs) and depressive symptoms over time. Models controlled for age, gender, education, and race/ethnicity. Moderation analyses examined whether high social connection and engagement reduced depressive symptoms for survivors with high IADL impairment.

Results

Social connection and engagement were generally associated with fewer IADL limitations and depressive symptoms at the time of stroke and after stroke. For example, participants who felt lonely and did not provide help to others before stroke had more IADL limitations. Pre-stroke volunteering was associated with less increase in IADL limitations with stroke and increase in having friends and providing help to others compared to one’s pre-stroke status were associated with fewer IADL limitations after stroke. For depressive symptoms, participants who felt lonely and did not have a friend or partner before stroke had more depressive symptoms, and participants who had children residing nearby before stroke showed less increase in depressive symptoms. Moderation effects were not found for social connection and engagement on high IADL impairment and depressive symptoms.

Conclusions

Findings suggest that social connection and engagement may reduce the negative physical and psychological outcomes of stroke, both at baseline and after stroke. Efforts to enhance social engagement and diminish loneliness may both enhance population well-being and enhance resilience and recovery from stroke and other illnesses.
Alterations of the TGFb-sequestration complex member ADAMTSL1 levels are associated with muscular defects and rhabdomyosarcoma aggressiveness
Authors: Bertrand-Chapel Adrien , Meyer Swann , Juban Gaëtan , Kneppers Anita , Huchedé Paul , Gallerne Cindy , Benayoun Ruth , Cohen Enzo , Lopez-Gonzales Alejandro , Larbi Sabrina Ben , Creveaux Marion , Vaille Lucile , Bouvier Amélie , Théodore Marine , Broutier Laura , Dutour Aurélie , Cordier-Bussat Martine , Blay Jean-Yves , Streichenberger Nathalie , Picard Cécile , Corradini Nadège , Allamand Valérie , Mounier Rémi , Castets Perrine , Castets Marie
Published: March 2023

Rhabdomyosarcoma (RMS) is the most frequent form of paediatric soft-tissue sarcoma and remains a medical challenge, holding in failure current therapeutic strategies. RMS shares histological features with cells of the muscle lineage and this cancer is thought to arise from malignant transformation of myogenic precursors. It has been proposed that RMS and myogenesis could represent the “Jekyll and Hyde” of skeletal muscle. The underlying idea is that some early steps of myogenic differentiation are blocked in RMS, and that understanding how the normal process has gone awry could help to decipher the biological underpinnings of tumorigenesis and tumor escape.

It is widely agreed that extracellular matrix (ECM) interferes in skeletal muscle regeneration and that defects in ECM components are clinically significant. The challenge is now to decipher actors and mechanisms responsible for the transmission of signals to muscle cells and the subsequent alterations that could be associated with RMS.

Using an original transgenic mice model, we show here that ADAMTSL1 is involved in skeletal muscle regeneration. As previously reported for other members of its family, ADAMTSL1 is part of the TGF-β-ECM-sequestering complex and likely positively regulates TGF-β-pathway activity. Last, we observed that ADAMTSL1 expression behaves as a strong prognostic factor in the aggressive fusion-positive RMS and correlates with a neural-like phenotype of tumor cells, resulting from gain of SMAD2/3/4 targets.
Molecular Characterization ofFischerella uthpalarensis, the first subsection V cyanobiont from a tropicalAzollaspecies containing dual nitrogenases
Authors: Pushpakumara B.L.D Uthpala , Gunawardana Dilantha
Published: March 2023

There have been theories presented onAzollacyanobionts, known for voracious nitrogen fixation, vertical transmission of cyanobiont and helping transform a greenhouse planet to an icehouse one ~49 Mya. One such theory encapsulates the existence of two cyanobionts, named Major and Minor. We show here the identity of a possible minor cyanobiont ofAzollanamedFischerella uthpalarensis. A likely cyanobiont with straight or curved filaments that were truly branched was isolated. Seven gene fragments, namely 16s rDNA (Forward and Reverse), RNA Polymerase, ITS1 region (Forward and Reverse),nifDand GroEL genes were utilized to identify the isolated cyanobiont. The best match based on BLASTn search tool was found in the RNA Polymerase beta subunit (rpoC) gene fragment, that showed 99.54% identity with 55% coverage toFischerella muscicola. Phylogenetic inferences with therpoCgenetic locus and the GroEL protein sequence suggest a likelyFischerellagenus identity. Furthermore,VnfDGandVnfNfragments too were amplified using PCR and sequenced to demonstrate that this cyanobiont has alternate nitrogenase genes, on top of the molybdenum counterpart, providing an advantage in lifestyle. We encountered a higher level of genomic-level synonymous substitutions, which was not reflected in protein sequences, namelyVnfDGandVnfNgene products, which may be due to codon heterogeneity. We also propose forF. uthpalarensisatypicality in codon usage due to the likely acquisition of the V-nitrogenase operon from a presumed recent horizontal gene transfer (HGT) event. The cyanobiont from this study showcases a higher preference for AT over GC at theVnfDGcomposite locus again hinting at a symbiotic lifestyle.
Inhibitory effect of Ephedra herba on human norovirus infection in human intestinal organoids
Authors: Hayashi Tsuyoshi , Murakami Kosuke , Ando Hirokazu , Ueno Sayuri , Kobayashi Sakura , Muramatsu Masamichi , Tanikawa Takashi , Kitamura Masashi
Published: March 2023

Human norovirus (HuNoV) is a major cause of acute gastroenteritis and foodborne diseases worldwide with public health concern, yet no antiviral therapies have been developed. In this study, we aimed to screen crude drugs, which are components of Japanese traditional medicine, ‘‘Kampo” to see their effects on HuNoV infection using a reproducible HuNoV cultivation system, stem-cell derived human intestinal organoids/enteroids (HIOs). Among the 23 crude drugs tested, Ephedra herba significantly inhibited HuNoV infection in HIOs. A time-of-drug addition experiment indicated that this crude drug likely targets post-entry step for the inhibition. To our knowledge, this is the first anti-HuNoV inhibitor screen targeting crude drugs, and Ephedra herba was identified as a novel inhibitor candidate that merits further study.
Lipid signatures and inter-cellular heterogeneity of naïve and lipopolysaccharide-stimulated human microglia-like cells
Authors: Müller Max A. , Zweig Norman , Spengler Bernhard , Weinert Maria , Heiles Sven
Published: March 2023

Microglia are non-neuronal cells, which are residing in the central nervous system and are known to play an important role in health and disease. We investigated lipidomic phenotypes of human naïve and stimulated microglia-like cells by atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI). With lateral resolutions between 5 μm and 1.5 μm, we were able to chart lipid compositions of individual cells, enabling to differentiate cell lines and stimulation conditions. This allowed us to reveal local lipid heterogeneities in naïve and lipopolysaccharide (LPS)-stimulated cells. We were able to identify individual cells with elevated triglyceride (TG) levels and could show that the number of these TG-enriched cells increased with LPS stimulation as a hallmark for a proinflammatory phenotype. Additionally, observed local abundance alterations of specific phosphatidylinositols (PIs) indicate a cell specific regulation of the PI metabolism.
Super-resolution fluorescence imaging of cryosamples does not limit achievable resolution in cryoEM
Authors: Last Mart G.F. , Noteborn Willem E.M. , Voortman Lenard M. , Sharp Thomas H.
Published: March 2023

Correlated super-resolution cryo-fluorescence and cryo-electron microscopy (cryoEM) has been gaining popularity as a method to investigate biological samples with high resolution and specificity. A concern in this combined method (called SR-cryoCLEM), however, is whether and how fluorescence imaging prior to cryoEM acquisition is detrimental to sample integrity. In this report, we investigated the effect of high-dose laser light irradiation on apoferritin samples prepared for cryoEM with excitation wavelengths commonly used in fluorescence microscopy, and comparing these samples to controls that were kept in the dark. We found that laser illumination, of equal duration and intensity as used in super-resolution cryomicroscopy and in the presence of high concentrations of fluorescent protein, did not affect the achievable resolution in cryoEM, with final reconstructions reaching resolutions of ~1.8 Angstrom regardless of the illumination conditions. The finding that super-resolution fluorescence imaging of cryosamples prior to cryoEM data acquisition does not limit the achievable resolution suggests that super-resolution cryo-fluorescence microscopy and in situ structural biology using cryoEM are entirely compatible.
Development of a Synthetic Biosensor for Chemical Exchange MRI UtilizingIn SilicoOptimized Peptides
Authors: Fillion Adam J. , Bricco Alexander R. , Lee Harvey D. , Korenchan David , Farrar Christian T. , Gilad Assaf A.
Published: March 2023

1

Chemical Exchange Saturation Transfer (CEST) magnetic resonance imaging (MRI) has been identified as a novel alternative to classical diagnostic imaging. Over the last several decades, many studies have been conducted to determine possible CEST agents, such as endogenously expressed compounds or proteins, that can be utilized to produce contrast with minimally invasive procedures and reduced or non-existent levels of toxicity. In recent years there has been an increased interest in the generation of genetically engineered CEST contrast agents, typically based on existing proteins with CEST contrast or modified to produce CEST contrast. We have developed anin-silicomethod for the evolution of peptide sequences to optimize CEST contrast and showed that these peptides could be combined to createde novobiosensors for CEST MRI. A single protein, superCESTide 2.0, was designed to be 198 amino acids. SuperCESTide 2.0 was expressed inE. coliand purified with size-exclusion chromatography. The magnetic transfer ratio asymmetry (MTRasym) generated by superCESTide 2.0 was comparable to levels seen in previous CEST reporters, such as protamine sulfate (salmon protamine, SP), Poly-L-Lysine (PLL), and human protamine (hPRM1). This data shows that novel peptides with sequences optimizedin silicofor CEST contrast that utilizes a more comprehensive range of amino acids can still produce contrast when assembled into protein units expressed in complex living environments.
Gasdermin D promotes influenza virus-induced mortality through neutrophil amplification of inflammation
Authors: Speaks Samuel , Zani Ashley , Solstad Abigail , Kenney Adam , McFadden Matthew I. , Zhang Lizhi , Eddy Adrian C. , Amer Amal O. , Robinson Richard , Cai Chuanxi , Ma Jianjie , Hemann Emily A. , Forero Adriana , Yount Jacob S.
Published: March 2023

Influenza virus activates cellular inflammasome pathways, which can be either beneficial or detrimental to infection outcomes. Here, we investigated the role of the inflammasome-activated pore-forming protein gasdermin D (GSDMD) during infection. Ablation of GSDMD in knockout (KO) mice significantly attenuated virus-induced weight loss, lung dysfunction, lung histopathology, and mortality compared with wild type (WT) mice, despite similar viral loads. Infected GSDMD KO mice exhibited decreased inflammatory gene signatures revealed by lung transcriptomics, which also implicated a diminished neutrophil response. Importantly, neutrophil depletion in infected WT mice recapitulated the reduced mortality and lung inflammation observed in GSDMD KO animals, while having no additional protective effects in GSDMD KOs. These findings reveal a new function for GSDMD in promoting lung neutrophil responses that amplify influenza virus-induced inflammation and pathogenesis. Targeting the GSDMD/neutrophil axis may provide a new therapeutic avenue for treating severe influenza.
Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies
Authors: Adell Manuel Alonso Y , Klockner Tamara C. , Höfler Rudolf , Wallner Lea , Schmid Julia , Markovic Ana , Martyniak Anastasiia , Campbell Christopher S.
Published: March 2023

Both the presence of an abnormal complement of chromosomes (aneuploidy) and an increased frequency of chromosome missegregation (chromosomal instability) are hallmarks of cancer. Analyses of cancer genome data have identified certain aneuploidy patterns in tumors; however, the bases behind their selection are largely unexplored. By establishing time-resolved long-term adaptation protocols, we found that human cells adapt to persistent spindle assembly checkpoint (SAC) inhibition by acquiring specific chromosome arm gains and losses. Independently adapted populations converge on complex karyotypes, which over time are refined to contain ever smaller chromosomal changes. Of note, the frequencies of chromosome arm gains in adapted cells correlate with those detected in cancers, suggesting that our cellular adaptation approach recapitulates selective traits that dictate the selection of aneuploidies frequently observed across many cancer types. We further engineered specific aneuploidies to determine the genetic basis behind the observed karyotype patterns. These experiments demonstrated that the adapted and engineered aneuploid cell lines limit CIN by extending mitotic duration. Heterozygous deletions of key SAC and APC/C genes recapitulated the rescue phenotypes of the monosomic chromosomes. We conclude that aneuploidy-induced gene dosage imbalances of individual mitotic regulators are sufficient for altering mitotic timing to reduce CIN.
Anomalous small-angle X-ray scattering analyses on hierarchical structures of rubber–filler systems
Authors: Watanabe Yuki , Nishitsuji Shotaro , Takenaka Mikkihito
Published: March 2023

The hierarchical structures of poly(styrene-ran-butadiene) (SBR) rubber/carbon black (CB) systems vulcanized with sulfur and ZnO have been clarified using anomalous small-angle X-ray scattering (ASAXS) near the Zn absorption edge. In the case of SBR/CB systems vulcanized with peroxide, it has been found previously that the hierarchical structures formed by CB consist of aggregates of primary particles and agglomerates of those aggregates with mass-fractal dimensions. However, to date the hierarchical structures in SBR/CB systems vulcanized with sulfur and ZnO have not been well investigated, despite being commonly used. This is because the strong scattering contrast of Zn prevents the quantitative analyses of the hierarchical structures of CB using X-ray scattering. In this study, the effects of Zn on the scattering intensity were eliminated and the structure factors of CB in SBR/CB systems were obtained using the ASAXS method. By extrapolating to the zero volume fraction of CB, the particle structure factor of the CB aggregates was estimated and it was found that the CB aggregates consist of closely packed CB primary particles. The presence of large particles of ZnO and particles of ZnS on the order of 10 nm in size is confirmed.
Public coping discourse in response to government health crisis communication
Authors: Wiese Melanie , Van Der Westhuizen Liezl-Marié
Published: March 2023

Purpose

This study aims to explore public coping strategies with government-imposed lockdown restrictions (i.e. forced compliance) due to a health crisis (i.e. COVID-19). This directly impacts the public's power, as they may feel alienated from their environment and from others. Consequently, this study explores the relationships between the public's power, quality of life and crisis-coping strategies. This is important to help governments understand public discourse surrounding perceived government health crisis communication, which aids effective policy development.

Design/methodology/approach

An online questionnaire distributed via Qualtrics received 371 responses from the South African public and structural equation modelling was used to test the hypotheses.

Findings

The results indicate the public's experience of powerlessness and resulting information-sharing, negative word-of-mouth and support-seeking as crisis coping strategies in response to government-imposed lockdown restrictions.

Originality/value

The public's perspective on health crisis communication used in this study sheds light on adaptive and maladaptive coping strategies that the public employs due to the alienation they feel during a health crisis with government-forced compliance. The findings add to the sparse research on crisis communication from the public perspective in a developing country context and provide insights for governments in developing health crisis communication strategies. The results give insight into developing policies related to community engagement and citizen participation during a pandemic.
Age distribution and prevalence in different age groups of four myositis‐specific autoantibodies, including anti‐ARS, anti‐MDA5, anti‐Mi‐2, and anti‐TIF1γ antibodies
Authors: Ueda‐Hayakawa Ikuko , Tonomura Kyoko , Maekawa Aya , Kaneda Emi , Arase Noriko , Fujimoto Manabu
Published: March 2023

We accumulated the demographic information and analyzed the prevalence of myositis‐specific antibodies (MSAs) in a large cohort across Japan as standard testing for MSAs becomes more widely available. This retrospective, observational, cohort study analyzed the records of individuals aged 0–99 years who are tested for serum MSAs at SRL Incorporation from January 2014 to April 2020 across Japan. An enzyme‐linked immunosorbent assay testing was applied to determine the presence of anti‐aminoacyl tRNA synthetase (anti‐ARS), anti‐Mi‐2, anti‐melanoma differentiation‐associated gene 5 (anti‐MDA5), or anti‐transcriptional intermediary factor 1‐γ (anti‐TIF1γ) (Medical and Biological Laboratories). Anti‐TIF1γ antibody was detected more in male patients than female patients. In contrast, women were predominant in patients with other MSAs. More than half of the anti‐ARS or anti‐TIF1γ antibody‐positive patients were over 60 years old, although anti‐MDA5 or anti‐Mi‐2‐positive patients were mostly under <60 years old. Anti‐MDA5 antibody‐positive patients were mostly aged 40–59 years, while other MSA groups were mostly 60–79 years. Anti‐MDA5 antibody was detected most frequently in the age range of 0–29 years. Anti‐TIF1γ antibody was the second most commonly detected autoantibody in the age range of 0–19 years. Anti‐ARS antibody was the most frequently detected autoantibody after the age of 30 years, and the frequency of anti‐ARS gradually increased at more advanced ages. The second and third most detected autoantibodies were anti‐MDA5 and anti‐TIF1γ, respectively, in ages 30–79 years. We performed a nationwide >3‐year evaluation of MSA detection in a routine diagnostic setting. This paper provides clinical images concerning the relationship between four MSA types and the distribution of sex and age in a large population.
Political ambition and opposition legislative review: Bill scrutiny as an intra‐party signalling device
Authors: BEHRENS LION , NYHUIS DOMINIC , GSCHWEND THOMAS
Published: March 2023

Recent research on executive–legislative relations in parliamentary democracies has shown that members of majority parties submit amendments to government bills to police the coalition compromise and to distinguish themselves from their coalition partners. It is poorly understood, however, what motivates members of the opposition to engage in the resource‐intensive work of proposing changes to government bills. Not only are amendment proposals by the opposition often unsuccessful (lack of policy motivation), they are largely invisible to the electorate (lack of vote motivation). We argue that amendments by the opposition are best understood as reflecting office motivations of legislators. Ambitious legislators draft amendments to signal skill and expertise to their party peers, which is rewarded with promotions to higher office. We confirm our argument with original data from a German state parliament. The findings further our understanding of legislative review, individual legislative efforts and career trajectories.
Improving landscape connectivity through habitat restoration: application for Asian elephant conservation in Xishuangbanna Prefecture, China
Authors: LI Wenwen , LIU Peng , YANG Nian , CHEN Shang , GUO Xianming , WANG Bin , ZHANG Li
Published: March 2023

Habitat restoration is an effective method for improving landscape connectivity, which can reduce habitat fragmentation. Maintaining landscape connectivity could promote connections between habitat, which is extremely essential to preserve gene flow and population viability. This study proposes a methodological framework to analyze landscape connectivity for Asian elephant habitat conservation, aiming to provide practical options for reducing habitat fragmentation and improving habitat connectivity. Our approach involved combining a species distribution model using MaxEnt and landscape functional connectivity models using graph theory to assess the impact on connectivity improvement via farmland/plantation restoration as habitat. The results showed that: (1) there were 119 suitable habitat patches of Asian elephant covering a total area of 1952.41 km2. (2) The connectivity between habitats improved significantly after vegetation restoration and the gain first decreased and then increased with the increase of dispersal distance. (3) The first few new habitat patches that were identified played an important role in improving connectivity, and the variation rate of connectivity gradually leveled off as the number of new habitats increased. (4) Prioritization of the 25 best new habitat patches increased connectivity from 0.54% to 5.59% as the dispersal distance increased and mainly was located between two Asian elephant distribution regions and two components. Establishment of new habitat patches was effective for improving or restoring connectivity. Our findings can be used as guidance for improving the studied fragmented Asian elephant habitats, and they can also be used as a reference for the habitat restoration of other endangered species heavily affected by habitat fragmentation.
Genetic predisposition between coronavirus disease 2019 and rheumatic diseases: A 2‐sample Mendelian randomization study
Authors: Quan Liuliu , Tan Jiangshan , Hua Lu , You Xin
Published: March 2023

Objective

The causalities between the coronavirus disease 2019 (COVID‐19) and the risk of rheumatic diseases remain unclear. The purpose of this study was to investigate the causal effect of COVID‐19 on rheumatic disease occurrence.

Methods

Single nucleotide polymorphisms (SNPs), acquired from published genome‐wide association studies, were used to perform 2‐sample Mendelian randomization (MR) on cases diagnosed with COVID‐19 (n = 13 464), rheumatic diseases (n = 444 199), juvenile idiopathic arthritis (JIA, n = 15 872), gout (n = 69  374), systemic lupus erythematosus (SLE, n = 3094), ankylosing spondylitis (n = 75 130), primary biliary cholangitis (PBC, n = 11 375) and primary Sjögren's syndrome (n = 95 046). Three MR methods were used in the analysis based on different heterogeneity and pleiotropy using the Bonferroni correction.

Results

The results revealed a causality between COVID‐19 and rheumatic diseases with an odds ratio (OR) of 1.010 (95% confidence interval [CI], 1.006–1.013; P = .014). In addition, we observed that COVID‐19 was causally associated with an increased risk of JIA (OR 1.517; 95%CI, 1.144–2.011; P = .004), PBC (OR 1.370; 95%CI, 1.149–1.635; P = .005), but a decreased risk of SLE (OR 0.732; 95%CI, 0.590–0.908; P = .004). Using MR, 8 SNPs were identified to associate with COVID‐19 and recognized as significant variables. None of them were previously reported in any other diseases.

Conclusions

This is the first study to use MR to explore the impact of COVID‐19 on rheumatic diseases. From a genetic perspective, we found that COVID‐19 could increase the risk of rheumatic diseases, such as PBC and JIA, but decrease that of SLE, thereby suggesting a potential surge in the disease burden of PBC and JIA following the COVID‐19 pandemic.
Tangible Rewards for More Than Just Productivity: Examining Canadian Public Accounting Firms' Rewards Programs*
Authors: Fiolleau Krista , MacTavish Carolyn , Obendorf Giselle
Published: March 2023

Companies spend significant amounts of money on tangible rewards programs, even during the economic turmoil of the COVID‐19 pandemic. The prevalence, growth, and significance of these expenditures highlight the importance of understanding the purpose and use of these programs by organizations. Research on public accounting (PA) firms' compensation plans has focused on the balance between professional and commercial incentives in partner profit‐sharing schemes but has failed to examine the incentives for nonpartner audit professionals. However, it is exactly these professionals who do a substantial amount of work on audit engagements. This paper has three main purposes. First, we investigate the nature and composition of PA firms' tangible rewards programs and provide a detailed description. Second, we examine the use of firms' tangible rewards programs to provide evidence of what actions are being rewarded. We use Almer et al.'s (2005, Behavioral Research in Accounting 17: 1–22) framework, which presents dimensions of the auditors' professional contribution, and explores whether firms recognize these dimensions using tangible rewards. Third, we develop future research questions to help explore the use of tangible rewards in firms without structured output. We collect archival data on the use of tangible rewards from each of the Big 4 PA firms and three of the next four largest international accounting firms in Canada. We find that firms use their tangible rewards programs for “building a culture of recognition,” for performance incentives, and for employee and firm development, thus rewarding a broad set of measures beyond the incentive measures for hours worked.
Pre‐anaesthetic assessment and related outcome measures in adults undergoing elective surgery—Scoping review protocol
Authors: Brix Lone D. , Gamst‐Jensen Hejdi , Nielsen Anne H. , Thomsen Thordis , Geisler Anja
Published: March 2023

Background

Pre‐anaesthesia assessment is crucial to ensure the quality and safety of anaesthesia and surgery. However, despite being very common and essential for many patients undergoing elective surgery, little is known about the different pre‐anaesthesia assessment approaches. Hence, this article outlines a study protocol for a scoping review aiming to, systematically, map the literature on pre‐anaesthetic assessment approaches and outcomes, synthesise existing evidence, and identify knowledge gaps for future research.

Methods

We will conduct a scoping review of all study designs following the Preferred Reporting Items for Systematic and Meta‐Analyses (PRISMA) statement. Moreover, the five steps set forth by Arksey and O'Malley and refined by Levac will guide the review process. Studies with adults (≥18 years) scheduled for elective surgery are included. Data regarding trial characteristics, patients, clinicians performing the pre‐anaesthetic assessment, interventions and outcomes are included using a combination of Covidence and Excel. Quantitative data are summarised using descriptive statistics, and qualitative data are presented through a descriptive synthesis.

Conclusion

The outlined scoping review will provide a synthesis of the literature, which can support the development of new evidence‐based practices for safe perioperative management of adult patients undergoing elective surgery.
Effects of preconception exposure to phthalates on mouse sperm capacitation parameters
Authors: Mohanty Gayatri , Tourzani Darya A. , Gervasi María G. , Houle Emily , Oluwayiose Oladele , Suvorov Alexander , Pilsner J. Richard , Visconti Pablo E.
Published: March 2023

Background

Phthalates have been linked to adverse male reproductive health, including poor sperm quality and embryo quality as well as a longer time to pregnancy (months of unprotected intercourse before conception occurs). The present study aimed to evaluate the effect of preconception exposure to two ubiquitous phthalate chemicals, di(2‐ethylhexyl) phthalate (DEHP), di‐n‐butyl phthalate (DBP), and their mixture on sperm function, fertilization, and embryo development in mice.

Materials and methods

Adult male C57BL/6J mice aged 8–9 weeks were exposed to di(2‐ethylhexyl) phthalate, di‐n‐butyl phthalate, or their mixture (di‐n‐butyl phthalate + di(2‐ethylhexyl) phthalate) at 2.5 mg/kg/day or vehicle for 40 days (equivalent to one spermatogenic cycle) via surgically implanted osmotic pumps. Caudal epididymal spermatozoa were extracted and analyzed for motility using computer‐assisted sperm analyses. Sperm phosphorylation of protein kinase A substrates and tyrosine phosphorylation, markers of early and late capacitation events, respectively, were analyzed by Western blots. In vitro fertilization was used to evaluate the sperm fertilizing capacity.

Results

While the study did not reveal any significant differences in sperm motility and fertilization potential, abnormal sperm morphology was observed in all phthalate exposures, particularly in the phthalate mixture group. In addition, the study revealed significant differences in sperm concentration between control and exposed groups. Moreover, protein phosphorylation of protein kinase A substrates was decreased in the di(2‐ethylhexyl) phthalate and mixture exposure groups, while no significant changes in protein tyrosine phosphorylation were observed in any of the groups. Assessment of the reproductive functionality did not reveal significant effects on in vitro fertilization and early embryo development rates but showed wide variability in the phthalate mixture group.

Conclusion

Our findings suggest that preconception phthalate exposure affects sperm numbers and phosphorylation of protein kinase A substrates involved in capacitation. Future research is warranted to examine the associations between phthalate exposure and capacitation in human spermatozoa.
Post‐percutaneous coronary intervention CYP2C19 genotyping in an Irish population: The potential role in identifying clopidogrel therapy‐related bleeding risks
Authors: Soh Bing Wei Thaddeus , Cusack Ronan , Waters Max , O'Connor Cormac , Arnous Samer , Kiernan Thomas
Published: March 2023

Aims

Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains the standard of care. CYP2C19 genetic polymorphisms cause variable clopidogrel bioactivation. Increased function (CYP2C19*17) allele carriers (rapid metabolizers [RM] or ultrarapid metabolizers [UM]) are clopidogrel hyper‐responders, hence are more susceptible to clopidogrel‐related bleeding. Since current guidelines recommend against routine genotyping following PCI, data on the clinical utility of CYP2C19*17 genotype guided strategy are sparce. Our study provides real‐world data on the 12‐month follow‐up of CYP2C19 genotyping in patients post‐PCI.

Methods

This is a cohort study within an Irish population receiving 12‐month DAPT following PCI. It identifies the prevalence of CYP2C19 polymorphisms within an Irish population and describes the ischaemic and bleeding outcomes after 12 months of DAPT.

Results

A total of 129 patients were included with the following CYP2C19 polymorphism prevalence: 30.2% hyper‐responders (26.4% RM [1*/17*], 3.9% UM [17*/17*]) and 28.7% poor‐responders (22.5% IM [1*/2*], 3.9% IM [2*/17*], 2.3% PM [2*/2*]). A total of 53 and 76 patients received clopidogrel and ticagrelor, respectively. At 12 months, total bleeding incidence within the clopidogrel group was positively correlated with CYP2C19 activity: IM/PM (0.0%), NM (15.0%) and RM/UM (25.0%). The positive relationship showed a moderate association that was statistically significant: rτ = 0.28, P = 0.035.

Conclusions

The prevalence of CYP2C19 polymorphisms in Ireland is 58.9% (30.2% CYP2C19*17, 28.7% CYP2C19*2) with an approximately one in three chance of being a clopidogrel hyper‐responder. Positive correlation between bleeding and increasing CYP2C19 activity within the clopidogrel group (n = 53) suggests possible clinical utility of a genotype‐guided strategy identifying high bleeding risk with clopidogrel in CYP2C19*17 carriers, but further studies are required.