bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell profiling and zebrafish avatars revealLGALS1as immunomodulating target in glioblastoma
Authors: Finotto Lise , Cole Basiel , Giese Wolfgang , Baumann Elisabeth , Claeys Annelies , Vanmechelen Maxime , Decraene Brecht , Derweduwe Marleen , Lakic Nikolina Dubroja , Shankar Gautam , Kantharaju Madhu Nagathihalli , Albrecht Jan Philipp , Geudens Ilse , Stanchi Fabio , Ligon Keith L. , Boeckx Bram , Lambrechts Diether , Harrington Kyle , Van Den Bosch Ludo , De Vleeschouwer Steven , De Smet Frederik , Gerhardt Holger 
Published: May 2023

AbstractGlioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-timein vivomonitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs – features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identifiedLGALS1as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets.
Bile acids accumulate norovirus-like particles and enhance binding to and entry into human enteric epithelial cells
Authors: Palm Elin , Danskog Katarina , Nord Stefan , Becker Miriam , Tanner Hugh , Sandblad Linda , Öhlund Daniel , Lenman Annasara , Arnberg Niklas 
Published: May 2023

AbstractHuman norovirus (HuNoV) is a leading cause of acute viral gastroenteritis, but despite high impact on public health and health care, the mechanisms of viral attachment to and entry into target cells are not yet fully understood. It is well known that body fluids such as blood can transmit unrelated viruses, but recent reports also indicate that saliva and bile contribute to transmission of HuNoV. For example, human bile acids increase cell surface ceramide levels in human enteroids, which improves norovirus entry into cells resulting in enhanced replication. Bile acids can also interact directly with the norovirus capsid, but it is not known whether bile or other gastrointestinal body fluids directly affect HuNoV attachment to host cells. In this study, we investigated the effects of patient-derived gastric juice, pancreatic juice, and bile on HuNoV GII.4 virus-like particle (VLP) attachment to and entry into a human duodenal cell line, HuTu-80. We show that while gastric juice and pancreatic juice do not affect viral attachment or entry, bile – in particular hydrophobic bile acids – significantly enhance cellular attachment and subsequent entry of GII.4 VLPs into cells. In addition, we show that hydrophobic bile acids induce accumulation of viral particles in the vicinity of cells. Our results suggest the presence of a newen masseinfection mechanism, where bile acids aggregate virions, and allow direct and more efficient attachment to and entry into target cells.ImportanceViruses transmitted by the fecal-oral route encounter secreted host factors in gastrointestinal fluids. Some host factors can be exploited by the virus to facilitate infection. Human bile acids indirectly promote norovirus entry into and infection of human enteroids, but the direct effect of bile acids on attachment and uptake, along with the impact of other gastrointestinal fluids, remain unknown. Here, we investigated the direct effects of human body fluids on cellular attachment of norovirus VLPs. We show that human bile and hydrophobic bile acids induce an accumulation of norovirus VLPs, which is associated with significantly enhanced attachment and entry into human duodenal cell lines. These results highlight the differential effects of gastrointestinal body fluids on viral attachment and entry, while providing useful information into the complex HuNoV-host interactions that facilitate infection.
Fast Cycling Culture of the Marine AnnelidPlatynereis dumerilii
Authors: Legras Mathieu , Ghisleni Giulia , Soilihi Rabouant , Celmar Enzo , Balavoine Guillaume 
Published: May 2023

AbstractPlatynereis dumerilii, a marine annelid, is a model animal that has gained popularity in various fields such as developmental biology, biological rhythms, nervous system organization and physiology, behaviour, reproductive biology, and epigenetic regulation. The transparency ofP. dumeriliitissues at all developmental stages makes it easy to perform live microscopic imaging of all cell types. In addition, the slow-evolving genome ofP. dumeriliiand its phylogenetic position as a representative of the vast branch of Lophotrochozoans add to its evolutionary significance. AlthoughP. dumeriliiis amenable to transgenesis and CRISPR-Cas9 knockouts, its relatively long and indefinite life cycle, as well as its semelparous reproduction have been hindrances to its adoption as a reverse genetics model. To overcome this limitation, an adapted culturing method has been developed allowing much faster life cycling, with median reproductive age at 15 weeks instead of 6-8 months using the traditional protocol. A low worm density in boxes and a strictly controlled feeding regime are important factors for the rapid growth and health of the worms. Moreover, a genetic selection for fast-reproducing individuals has been applied to isolate a “Fast Forward” strain that can be used for egg microinjection. This culture method has several advantages, such as being much more compact, not requiring air bubbling or an artificial moonlight regime for synchronized sexual maturation, and necessitating only limited water change. A full protocol for worm care and handling is provided.
Prolonged body temperature tuning in mice using radio frequency generating electromagnetic resonant circuit-system
Authors: Franck Grégory , Le Borgne Marie , Cazier Hélène , Laignel Patrick , Caligiuri Giuseppina , Nicoletti Antonino 
Published: May 2023

AbstractRationalIn endothermic animals, body temperature (BT) is an evolutionary conserved and well characterized physical parameter that guarantees physiological functioning state. It results from the sum of bioenergetic processes of the body weighted by behavioral strategies, heat loss, and thermolytic processes. However, the intrinsic impact of temperature and temperature changes on the biology is far less understood. To date, the modification of the environmental temperature has constituted the main lever to evaluate the impact of thermic changes in small animal. However, studying intrinsic effect of temperature remains impossible using conventional laboratory equipment, mainly because hypothalamus instructed with information grabbed from the environmental temperature finely regulates and maintain body temperature around 37°C. Numerous pharmacological treatments have been used to block these thermoregulatory mechanisms, but confer high toxicity while dysregulating the central nervous responses and can potentially have confounding direct effects on studied peripheral tissues. Alternatively, physical methods using energy irradiation were reported, but they remain expensive and usually involve animal immobilization. We aimed at designing a simple and affordable device to adjust and maintain body temperature on the long course in conscious and free-moving animals.MethodWe developed an electromagnetic LC resonant circuit (ELM circuit) producing a radio frequency signal (64 kHz) inside a copper coil refrigerated with a water circuit. This setting is powered by a simple a 0-48V AC generator, allowing the use of a domestic electrical network. This setting can accommodate metal-free 3D-printed circular cages, where adult mice, previously implanted with thermometric ID transponders, are monitored remotely for intraperitoneal temperature over time.ResultsThe BT of mice placed in the ELM circuit could be regulated in a reproducible fashion. Healthy mice increased their BT from 37 to 39.8±1°C, upon power supply ranging from 0 to 48V, respectively. In septic mice developing hypothermia (33±1 °C), BT could be either normalized to normothermia (37°C, 24V), or increased to fever-range hyperthermia (40°C, 48V) as a function of radiofrequency energy. BT tuning was accurate and stable for at least 12h. Blood count after 6 or 12 hours showed no modifications between groups, cardiomyocyte displayed heat shock response within the first hour in mice exposed to the maximal dose (BT=41°C). MALDI TOF imaging on brain microsections revealed modifications of the brain proteome, as suggested by differential PKC-theta, and prolactin 7B1 load in heated mice, as compared to controls.ConclusionPrecise body temperature tuning is achievable in small animals, and could be of high interest to understand the impact of temperature in (patho)physiology.
An inverse agonist of orphan receptor GPR61 reveals a novel allosteric mechanism
Authors: Lees Joshua A. , Dias João M. , Rajamohan Francis , Fortin Jean-Philippe , O’Connor Rebecca , Kong Jimmy X. , Hughes Emily , Fisher Ethan L. , Tuttle Jamison B. , Lovett Gabrielle , Kormos Bethany L. , Unwalla Rayomand J. , Zhang Lei , Schmidt Anne-Marie Dechert , Zhou Dahui , Stevens Kimberly A. , Fennell Kimberly F. , Varghese Alison E. , Maxwell Andrew , Cote Emmaline E. , Zhang Yuan , Han Seungil 
Published: May 2023

AbstractGPR61 is a biogenic amine receptor-related orphan GPCR associated with phenotypes relating to appetite and thus, is of interest as a druggable target to treat disorders of metabolism and body weight, such as obesity and cachexia. To date, lack of structural information or a known biological ligand or tool compound has hindered comprehensive efforts to study its structure and function. Here, we report the first ever structural characterization of GPR61, in both its active-like complex with heterotrimeric G protein and in its inactive state. Moreover, we report the discovery of a potent and selective small-molecule inverse agonist against GPR61 and structural elucidation of its unprecedented allosteric site and mode of action. These findings offer key mechanistic insights into an orphan GPCR, while providing both a new structural framework and tool compound to support further studies of GPR61 function and modulation.
Hemin-driven chromatin remodelling by atherosclerotic risk geneSMARCA4switches human blood-derived macrophages from leukocyte disposal to erythrocyte disposal
Authors: Cave Luke , Lodge Katharine M , Chiappo Derick , Sinha Shivani , Chughtai Faiz , Tsao Adam , Haskard Dorian O , Mason Justin C , Humphries Steve E , Boyle Joseph J 
Published: May 2023

AbstractBackgroundPutative genetic risk loci for atherosclerotic vascular disease includeSMARCA4, a chromatin remodeling gene important for gene activation. Its causal role in atherosclerosis has been uncertain. Intraplaque hemorrhage (IPH) is a late event in atherosclerosis that is linked to plaque destabilisation and increased inflammation. IPH is countered by Mhem macrophages, which are directed by hemin-mediated induction of Heme Oxygenase 1 (HMOX1) via Activating Transcription Factor 1 (ATF1).Atf1deficiencyin vivoimpairs hematoma clearance, promoting inflammation and oxidative stress. Like its homologue cyclic-adenosine monophosphate response element binding protein 1 (CREB1), ATF1 is normally cyclic-AMP activated.HypothesisHemin-directed chromatin remodelling by SMARCA4 regulates specificity of ATF1 gene-binding, thereby switching between leukocyte disposal and erythrocyte disposal, contributing to its role in atherosclerosis.ResultsWe here show thatSMARCA4is genetically independent of the adjacentLDLRlocus (p<0.05). In human blood-derived macrophages, hemin triggered histone acetylation (H3K9Ac) and SMARCA4 recruitment in advance of p-ATF1 recruitment at theHMOX1enhancer. si-RNA-mediatedSMARCA4-knockdown suppressed p-ATF1 binding toHMOX1but increased its binding to cyclic-AMP responsive genesFOSandNR4A2, with corresponding changes in mRNA levels. This functionally correlated withSMARCA4-knockdown switching hemin to mimic prostacyclin (PGI2), for induced genes and phagocytic disposal of leukocytes rather than erythrocytes.ConclusionsThese data establishSMARCA4as an independent atherosclerosis risk gene and reveal a novel mechanism in which it switches between disposal of leukocytes or erythrocytes, with important clinical implications for atherosclerotic inflammation and intraplaque hemorrhage including treatment by histone deacetylase inhibitors.
Trans-scale live imaging of an E5.5 mouse embryo using incubator-type dual-axes light-sheet microscopy
Authors: Shioi Go , Watanabe Tomonobu M , Kaneshiro Junichi , Azuma Yusuke , Onami Shuichi 
Published: May 2023

ABSTRACTWe report our success in simultaneously tracking tissue formation and single-cell migration in a mouse embryo on embryonic day 5.5 for 12 h. The microscope, incubator, and observation protocols were comprehensively specialized and optimized to achieve this. The present system revealed new phenomena that had not previously been observed and promises to elucidate the mechanism of mouse embryonic development in the future.
Building flexible and robust analysis frameworks for molecular subtyping of cancers
Authors: Pedersen Christina Bligaard , Campos Benito , Krishnan Neeraja M. , Panda Binay , Vitting-Seerup Kristoffer , Rossing Maria , Bagger Frederik Otzen , Rønn Olsen Lars 
Published: May 2023

AbstractMolecular subtyping is essential to infer tumor aggressiveness and predict prognosis. In practice, tumor profiling requires in-depth knowledge of bioinformatics tools involved in the processing and analysis of the generated data. Additionally, data incompatibility (e.g., microarray vs. RNA sequencing data) and technical and uncharacterized biological variance between training and test data can pose challenges in classifying individual samples. In this article, we provide a roadmap for implementing bioinformatics frameworks for molecular profiling of human cancers in a clinical diagnostic setting. We describe a framework for integrating several methods for quality control, normalization, batch correction, classification, and reporting and a use case of the framework in breast cancer.
Career shock of hotel employees and their individual resilience: an exploratory study
Authors: Mousa Mohamed , Abdelgaffar Hala 
Published: May 2023

Purpose
This study aims to investigate the extent to which global shocks like Covid-19, climate crisis or war in Ukraine represent a negative career shock for hotel employees and how their individual resilience helps them to mitigate such shock.

Design/methodology/approach
A qualitative research method is used, and semi-structured interviews were conducted with 30 full-time employees working at four hotels in Sharm El-Sheikh, Egypt. Thematic analysis was used to extract the main ideas from the transcripts.

Findings
The findings showed that some of the addressed employees do not perceive the impact of current wicked problems as a negative career shock that would cause them to divert their career paths particularly because of the recent support they receive from their professional and social circles. However, some respondents are worried about their career prospects owing to the dramatic events affecting beach tourism in Egypt this past decade. Findings reveal that managing negative career shocks necessitates institutional support, as well as employee responsibility and the adaptation.

Originality/value
This paper contributes by filling a gap in hospitality, and human resources management, in which empirical studies on the relationship between career shock of hotel employees and their individual resilience have been limited so far.
Exploring the relationship among ESG, innovation, and economic and financial performance: evidence from the energy sector
Authors: Pinheiro Alan Bandeira , Panza Graziela Bizin , Berhorst Nicolas Lazzaretti , Toaldo Ana Maria Machado , Segatto Andréa Paula 
Published: May 2023

Purpose
This study aims to investigate the effect of innovation on environmental, social and governance (ESG) performance and, consequently, its influence on the economic and financial performance of companies.

Design/methodology/approach
A quantitative and descriptive research was carried out based on secondary data from the Refinitiv Eikon® database, using the panel data regression technique, considering the constructs: innovation, ESG performance and economic and financial performance.

Findings
The results showed that companies that tend to invest more financial resources in R&D are more likely to have higher ESG performance. In addition, companies that have higher ESG performance tend to have higher economic and financial performance.

Practical implications
Managers may consider investing more resources in R&D to achieve superior ESG performance. They should be aware that ESG is a strategic tool for creating financial and nonfinancial value for the organization. More than the traditional preparation of a financial report, stakeholders demand another type of information: ESG information.

Originality/value
The results confirm the basis of Stakeholder Theory, showing that the companies that meet the needs of all stakeholders tend to have greater economic and financial performance. ESG practices can include keeping employees motivated to work, improved corporate image in the eyes of customers, more satisfied suppliers and community and environment aligned with management. Therefore, these ESG initiatives are instrumental in protecting organizational objectives as well as increasing shareholder value.
Occupational health and safety rights of hospital workers in relation to needle stick injuries exposure in Pakistan
Authors: Abbas Mohsin , Rafique Sidra , Asam Zaki-Ul-Zaman 
Published: May 2023

Purpose
The purpose of this study is to explore the determinants of needle stick injuries (NSIs) suffering in terms of occupational health and safety (OHS) coverage critically for health-care workers’ rights in Pakistan.

Design/methodology/approach
This is a qualitative study involving the designing of a questionnaire followed by the World Health Organization’s NSI prevention assessment tool and nationally published reports covering health-care workers’ OHS rights protection. A total of 17 public and private hospitals were surveyed with a two-stage sampling method. Descriptive and inferential statistics (one-way analysis of variance with multiple comparison tests) were applied and significant results were discussed (p = 0.05 & p = 0.01). The results were discussed critically in the context of the OHS rights of health-care workers.

Findings
Analysis revealed the following significant relationships: job type and safety behavior; age group of health-care workers and safety management; injection usage per day and safety behavior; past year’s needle sticks injuries cases with safety behavior and occupational exposure; work shift and work experience with safety knowledge, safety awareness and work experience with safety management. It was also found there is no specific OHS law in the country for health-care workers.

Research limitations/implications
This study is limited in terms of sampling size and quantification of NSI burden among health-care workers.

Practical implications
Improved OHS management practices among health-care workers can control NSIs that ultimately ensure their workplace OHS rights. Health-care workers need OHS coverage in terms of awareness about potential workplace hazards and job training accordingly. Findings from extensive studies of a similar kind can give useful policy directions for workplace health management in health-care setup at the national level.

Originality/value
This study highlights the importance of OHS coverage for health-care workers in hospitals. It reports different determinants of NSIs suffering causing health-care worker’s rights violations at the workplace in Pakistan.
Technology adoption in accounting: the role of staff perceptions and organisational context
Authors: Jackson Denise , Allen Christina 
Published: May 2023

Purpose
Technology is widely recognised to be revolutionising the accounting profession, allowing accountants to focus on professional skills and technical knowledge that deliver value for organisational success. Despite the known benefits, it is reported that accountants are not fully leveraging the potential value of certain technologies. To understand why, this study aims to draw on the technology adoption model (TAM) and investigates accounting professionals’ perceptions towards technology, and how these may influence adoption at work.

Design/methodology/approach
The study gathered online survey data from 585 accounting managers from organisations of varying sizes and in different sectors in Australia and parts of Southeast Asia. Qualitative data were thematically analysed, and quantitative data were analysed using both descriptive and multivariate techniques.

Findings
The study highlighted the pivotal role of staff perceptions on the importance and ease of using technology on the uptake and successful usage. Findings emphasised important opportunities for organisations to educate accounting staff on the value of technology and optimise their confidence and skills through training and support initiatives, particularly smaller businesses. Marked differences in the orientation towards technology among Australian and Southeast Asian participants illuminate how national work culture and practice can influence technology adoption.

Originality/value
The study makes a practical contribution by advancing the understanding of the relative importance and value of certain technologies in different regions and organisation types in the accounting profession. It extends the theoretical understanding of the role of TAM’s core elements to the accounting context, exploring staff’s notions of perceived usefulness and perceived ease of use from the manager’s perspective.