bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mice with humanized livers reveal the involvement of hepatocyte circadian clocks in rhythmic behavior and physiology
Authors: Delbès Anne-Sophie , Quiñones Mar , Gobet Cédric , Castel Julien , Denis Raphaël G. P , Berthelet Jérémy , Weger Benjamin D. , Challet Etienne , Charpagne Aline , Metairon Sylviane , Piccand Julie , Kraus Marine , Rohde Bettina H. , Bial John , Wilson Elizabeth M. , Vedin Lise-Lotte , Minniti Mirko E. , Pedrelli Matteo , Parini Paolo , Gachon Frédéric , Luquet Serge 
Published: September 2022

ABSTRACTThe circadian clock is an evolutionarily acquired gene network that synchronizes physiological processes to adapt homeostasis to the succession of day and night. While most mammalian cells have a circadian clock, their synchronization at the body-level depends on a central pacemaker located in the suprachiasmatic nuclei of the hypothalamus that integrates light signals. However, peripheral organs are also synchronized by feeding cues that can uncoupled them from the central pacemaker. Nevertheless, the potential feedback of peripheral signals on the central clock remains poorly characterized. To discover whether peripheral organ circadian clocks may affect the central pacemaker, we used a chimeric model in which mouse hepatocytes were replaced by human hepatocytes. These human hepatocytes showed a specific rhythmic physiology caused by their blunted response to mouse systemic signals. Strikingly, mouse liver humanization reprogrammed the liver diurnal gene expression and modified the phase of the circadian clock. The phase advance was also reflected in the muscle as well as the entire rhythmic physiology of the animals, indicating an impact on the circadian function of the central clock. Like mice with a deficient central clock, the humanized animals shifted their rhythmic physiology more rapidly to the light phase under day feeding. Our results indicate that peripheral clocks may affect the central pacemaker and offer new perspectives to understand the impact of peripheral clocks on the global circadian physiology.
Digital Spatial Profiling of Intraductal Papillary Mucinous Neoplasms: Towards a Molecular Framework for Risk Stratification
Authors: Iyer Matthew K. , Shi Chanjuan , Eckhoff Austin M. , Fletcher Ashley , Nussbaum Daniel P. , Allen Peter J. 
Published: September 2022

AbstractThe histopathologic heterogeneity of intraductal papillary mucinous neoplasms (IPMN) complicates the prediction of pancreatic ductal adenocarcinoma (PDAC) risk. Intratumoral regions of pancreaticobiliary (PB), intestinal (INT), and gastric foveolar (GF) epithelium may occur with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD). We used digital spatial RNA profiling of dysplastic epithelium (83 regions) from surgically resected IPMN tissues (12 patients) to differentiate subtypes and predict genes associated with malignancy. The expression patterns of PB and GF lesions diverged from INT, suggesting that PB and GF arise from a common lineage. Transcriptional dysregulation within PB lesions mirrored that of PDAC, whereas INT and GF foci did not. Tumor necrosis factor/nuclear factor κB (TNF-NFκB) and cell cycle (cycling-S, cycling-G2/M) programs occurred with relative prominence in PB and INT subtypes, respectively. Taken together, this study delineates markers of high-risk IPMN and insights into malignant progression.One Sentence SummarySpatial profiling of the intratumoral heterogeneity of IPMN yields markers of high-risk disease and insights into malignant progression.
Pyrfume: A Window to the World’s Olfactory Data
Authors: Castro Jason B. , Gould Travis J. , Pellegrino Robert , Liang Zhiwei , Coleman Liyah A. , Patel Famesh , Wallace Derek S. , Bhatnagar Tanushri , Mainland Joel D. , Gerkin Richard C. 
Published: September 2022

ABSTRACTAdvances in theoretical understanding are frequently unlocked by access to large, diverse experimental datasets. Olfactory neuroscience and psychophysics remain years behind the other senses in part because rich datasets linking olfactory stimuli with their corresponding percepts, behaviors, and neural pathways underlying this transformation, remain scarce. Here we present a concerted effort to unlock and unify dozens of stimulus-linked olfactory datasets across species and modalities under a unified framework called Pyrfume. We present examples of how researchers might use Pyrfume to conduct novel analyses uncovering new principles, introduce trainees to the field, or construct benchmarks for machine olfaction.
Malian children infected with Plasmodium ovale and Plasmodium falciparum display very similar gene expression profiles
Authors: Tebben Kieran , Yirampo Salif , Coulibaly Drissa , Koné Abdoulaye K. , Laurens Matthew B. , Stucke Emily M. , Dembélé Ahmadou , Tolo Youssouf , Traoré Karim , Niangaly Amadou , Berry Andrea A. , Kouriba Bourema , Plowe Christopher V. , Doumbo Ogobara K , Lyke Kirsten E. , Takala-Harrison Shannon , Thera Mahamadou A. , Travassos Mark A. , Serre David 
Published: September 2022

AbstractPlasmodium parasites caused 241 million cases of malaria and over 600,000 deaths in 2020. Both P. falciparum and P. ovale are endemic to Mali and cause malaria illness, with P. falciparum infections typically being more severe. Here, we sequenced RNA from nine pediatric blood samples collected during uncomplicated, symptomatic infections with either P. falciparum or P. ovale and characterized the host and parasite gene expression profiles. We found that human gene expression varies more between individuals than according to the parasite species causing the infection, while parasite gene expression profiles cluster by species. Additionally, we characterized DNA polymorphisms of the parasites directly from the RNA-seq reads and found comparable levels of genetic diversity in both species despite dramatic differences in prevalence. Our results provide unique insights into host-pathogen interactions during malaria infections and their variations according to the infecting Plasmodium species, which will be critical to develop better elimination strategies against all human Plasmodium parasites.Author SummaryMultiple species of Plasmodium parasites can cause human malaria. Most studies and elimination efforts target P. falciparum, the most common cause of malaria worldwide and the species responsible for the vast majority of the mortality. Other Plasmodium species, such as P. ovale, typically lead to less severe forms of the disease but little is known about the molecular mechanisms at play during malaria infections with different parasites. We analyzed host and parasite gene expression from children successively infected with P. ovale and P. falciparum and found that, while the parasite gene expression differed significantly, the transcriptional profiles of the host immune cells were similar in P. ovale or P. falciparum infections. This suggests that infected individuals respond to uncomplicated malaria infections similarly, regardless of the Plasmodium species causing the infection, and that alternative immune processes may become important during the progression to severe P. falciparum malaria (rather than being inherent features of P. falciparum infections). Additionally, we observed similar levels of genetic diversity among P. ovale and P. falciparum parasites, suggesting that the P. ovale population might be larger than currently thought, possibly due to extensive misdiagnosis or the existence of hidden reservoirs of parasites.
Localized nanoparticle-mediated delivery of miR-29b normalises the dysregulation of bone homeostasis caused by osteosarcoma whilst simultaneously inhibiting tumour growth
Authors: Freeman Fiona E. , Dosta Pere , Riojas Javelly Cristobal J. , Mahon Olwyn R. , Kelly Daniel J. , Artzi Natalie 
Published: September 2022

AbstractPatients diagnosed with osteosarcoma undergo extensive surgical intervention and chemotherapy resulting in dismal prognosis and compromised quality of life owing to poor bone regeneration, which is further compromised with chemotherapy delivery. This study aims to investigate if localised delivery of miR-29b—which has been shown to promote bone formation by inducing osteoblast differentiation and also to suppress prostate and glioblastoma tumour growth—would suppress osteosarcoma tumours whilst simultaneously normalising the dysregulation of bone homeostasis caused by osteosarcoma. Thus, we studied the therapeutic potential of miR-29b to promote bone remodelling in an orthotopic model of osteosarcoma (rather than in bone defect models using healthy mice), and in the context of chemotherapy, that is clinically relevant. We developed a formulation of miR-29b:nanoparticles that were delivered via a novel hyaluronic-based hydrogel to enable local and sustained release of the therapy, and to study the potential of attenuating tumour growth whilst normalising bone homeostasis. We found that when miR-29b was delivered along with systemic chemotherapy, compared to chemotherapy alone, our therapy provided a significant decrease in tumour burden, increase in mouse survival, and a significant decrease in osteolysis thereby normalising the dysregulation of bone lysis activity caused by the tumour.
The SARS-CoV-2 Spike Protein Mutation Explorer: Using an Interactive Application to Improve the Public Understanding of SARS-CoV-2 Variants of Concern
Authors: Iannucci Sarah , Harvey William T. , Hughes Joseph , Robertson David L. , Poyade Matthieu , Hutchinson Edward 
Published: September 2022

AbstractSARS-CoV-2 is the virus responsible for the COVID-19 pandemic, which began in late 2019 and has resulted in millions of death globally. The need to understand the pandemic means that detailed descriptions of features of this virus are now of interest to non-expert audiences. In particular, there has been much public interest in the spike protein that protrudes from the surface of the SARS-CoV-2 virus particle. The spike is the major determinant of viral infectivity and the main target for protective immune responses, and included in vaccines, and so its properties influence the impact of the pandemic on people’s lives. This protein is rapidly evolving, with mutations that enhance transmissibility or weaken vaccine protection creating new variants of concern (VOCs) and associated sub-lineages. The spread of SARS-CoV-2 VOCs has been tracked by groups such as the COVID-19 Genomics UK consortium (COG-UK). Their online mutation explorer (COG-UK/ME), which analyses and shares SARS-CoV-2 sequence data, contains information about VOCs that is designed primarily for an expert audience but is potentially of general interest during a pandemic. We wished to make this detailed information about SARS-CoV-2 VOCs more widely accessible. Previously work has shown that visualisations and interactivity can facilitate active learning and boost engagement with molecular biology topics, while animations of these topics can boost understanding on protein structure, function, and dynamics. We therefore set out to develop an educational graphical resource, the SARS-CoV-2 Spike Protein Mutation Explorer (SSPME), which contains interactive 3D molecular models and animations explaining SARS-CoV-2 spike protein variants and VOCs. We performed user-testing of the original COG-UK/ME website and of the SSPME, using a within-groups design to measure knowledge acquisition and a between-groups design to contrast the effectiveness and usability. Statistical analysis demonstrated that, when compared to the COG-UK/ME, the SSPME had higher usability and significantly improved participant knowledge confidence and knowledge acquisition. The SSPME therefore provides an example of how 3D interactive visualisations can be used for effective science communication and education on complex biomedical topics, as well as being a resource to improve the public understanding of SARS-CoV-2 VOCs.
Identifying Pathogen and Allele Type Simultaneously (IPATS) in a single well using droplet digital PCR
Authors: Notsu Kosuke , El Daous Hala , Mitoma Shuya , Wu Xinyue , Norimine Junzo , Sekiguchi Satoshi 
Published: September 2022

AbstractA combined host biomarker and pathogen diagnosis provides insight into disease progression risk and contributes to appropriate clinical decision-making regarding prevention and treatment. In preventive veterinary medicine, such combined diagnosis could improve risk-based livestock herd management. We developed a single-well based test for combined diagnosis of bovine leukemia virus (BLV) and bovine MHC (BoLA)-DRB3alleles. A fourplex droplet digital PCR method targeting the BLVpolgene, BLV-susceptibleDRB3*016:01allele, resistantDRB3*009:02allele, and housekeeping RPP30 gene (IPATS-BLV) successfully measured the percentage of BLV-infected cells and determined allele types precisely. Furthermore, it discriminated homozygous from heterozygous carriers. Using this method to determine the impact of carrying these alleles on the BLV proviral load (PVL), we foundDRB3*009:02-carryingcattle could suppress the PVL to a low or undetectable level, even with the presence of a susceptible allele. Although the population ofDRB3*016:01-carrying cattle showed significantly higher PVLs when compared with cattle carrying other alleles, their individual PVLs were highly variable. Because of the simplicity and speed of this single-well assay, IPATS could be a suitable platform for the combined diagnosis of host biomarkers and pathogens in a wide range of other systems.
Turning Lung Clearance Index on its head. Reference data for SF6 Multiple Breath Washout Derived Ventilation distribution efficiency (VDE)
Authors: Sandvik Rikke Mulvad , Lindblad Anders , Robinson Paul D , Nielsen Kim G , Gustafsson Per 
Published: September 2022

AbstractIntroductionCystic fibrosis (CF) is characterized by increased ventilation inhomogeneity (VI), as measured by multiple breath washout (MBW), from infancy. Lung clearance index (LCI) is the most reported VI outcome. This study aimed to evaluate historically published reference equations for sulphur hexafluoride (SF6) MBW outcomes, to data collected using updated commercial SF6MBW equipment and to produce device specific equations if necessary.MethodSF6MBW was performed in 327 healthy children aged 0.1-18.4 years (151 [46%] girls), 191 (58.4%) < 3 years. Z-scores were calculated from published reference equations (FRC and LCI) and multivariate linear regression performed to produce device specific reference equations. Due to increasing residual standard deviations with increasing LCI values, investigation of methods for improvement, were investigated, based on the relationship between VI and dead space ventilation (VD/VT; dead space volume/tidal volume) in a cohort of 59 healthy children, 26 children with CF (n=138 test occasions) and 49 adults with lung disease.ResultsHistorical SF6MBW reference equations were unsuitable for Exhalyzer D® data. In contrast to LCI and log10(LCI), 1/LCI (ventilation distribution efficiency; VDE) was linearly related to VD/VT, with z-scores linearly related to its absolute values. Reference equations were reported for VDE and log10(FRC). Significant predictors for VDE and log10(FRC), respectively, were log10(age) and gender, and log10(height), gender and posture.Conclusion1/LCI (e.i., FRC/CEV[%]) reflecting ventilation distribution efficiency (VDE) in the lungs was a superior index of ventilation inhomogeneity compared to LCI and log10(LCI) due to its linear relationship to VD/VT.
Emotional responses in online social interactions: the mediating role of flow
Authors: Herrando Carolina , Jiménez-Martínez Julio , Martín-De Hoyos Maria José , Asakawa Kiyoshi , Yana Kazuo 
Published: September 2022

PurposeDrawing on the three flow-channel model and the stimulus–organism–response model, this research aims to understand how the influence of interactivity on purchase intention is mediated by the state of flow.Design/methodology/approachThis research entails a neurophysiological experiment combined with a survey-based study. This study analyzes, first, participants' heart rate variability through the parasympathetic and sympathetic indexes during five different activities, and, second, the mediating effect of flow through a structural equation model.FindingsThis study contributes to research on the role of flow in interactive marketing. The findings reveal that flow state is associated with less stressful activities, such as navigating highly interactive websites and playing online games. This research confirms the mediating effect of flow between interactivity and purchase intention.Originality/valueThis paper contributes to interactive marketing and flow theory by combining traditional methods with a peripheral physiological technique that draws on neuroscience. In addition, it confirms the positive but indirect effect of interactivity on purchase intention in online contexts.
The effects of executives’ overseas background on enterprise digital transformation: evidence from China
Authors: Hu Dongmei , Peng Yang , Fang Tony , Chen Charles Weizheng 
Published: September 2022

Purpose
The purpose of this study is to examine the effects of executives’ overseas education and work experience on enterprise digital as executives’ overseas background is critical to the development of enterprises. It also explored the mediating role of enterprise digital transformation on the relationship between executives’ overseas background and enterprise growth.

Design/methodology/approach
Chinese A-share companies listed on the Shanghai and Shenzhen Stock Exchanges for the period 2018–2020 were analyzed using regression analysis and bootstrapping to verify hypothesized relationships.

Findings
Executives’ overseas study and work experience both enhanced enterprise digital transformation significantly, thus improving enterprise growth. The level of employee education moderated the mediating role proposed in the theoretical model. Moreover, the promoting effect of executives’ overseas background on enterprise digital transformation was more significant for non-state-owned enterprises and those in eastern China.

Practical implications
The findings provide reference for the formulation and optimization of companies’ human resource structure and have implications on the improvement of enterprise digital transformation and enterprise growth.

Originality/value
This study explored the factors influencing enterprise digital transformation at the microlevel of corporate human capital, thereby providing microlevel empirical evidence for research on the factors influencing enterprise digital transformation. Its findings shed light on the mechanism and context under which executives with overseas backgrounds may enhance enterprise digital transformation and growth.
It’s not whether you win or lose, it’s how you play: customer delight in unpredictable experiential encounters
Authors: Barnes Donald C. , Pelletier Mark J. , Collier Joel E. , Beatty Sharon E. 
Published: September 2022

Purpose
The purpose of this paper is to investigate if customer delight is possible when the service encounter result may not be successful. Such a scenario is increasingly likely with the experiential, sticky and unpredictable nature of many competitively based experiential encounters where one side wins and the other loses.

Design/methodology/approach
Across four studies using both field and panel data, this research provides a framework to evaluate how firms can still create customer delight even if the result of the encounter is unpredictable or possibly negative. Further, the authors combine qualitative data, structural equation modeling and experimental design to test the models across four competitively based experiential contexts.

Findings
Findings indicate that firms can create delight through a variety of antecedent variables, including employee expertise, servicescape, social congruence and atmosphere. Neither importance of winning nor expectations for a win significantly alter the relationships of these antecedents in creating delight. Further, evidence from this research indicates that both feelings of nostalgia and geographic self-identity enhance delight’s effect on behavioral intentions, while geographic self-identity also enhances delight’s effect on customers’ evangelizing to others.

Research limitations/implications
This research extends the field’s understanding of the customer delight construct, sticky vs smooth encounters, as well as providing guidance to both practitioners and academics on new possibilities in the delight realm.

Practical implications
This research provides insights for practitioners on how to maximize customer emotions aside from surprisingly disconfirming customer expectations, as well as leaning into different tactics to influence the customer that are not outcome based.

Originality/value
To the best of the authors’ knowledge, this is the first research to evaluate customer delight in competitively based experiential encounters where the encounter result is unpredictable and possibly negative.
Social factors impacting student’s choice of institution for higher studies in India
Authors: Srivastava Khusboo , Dhamija Somesh 
Published: September 2022

PurposeThis study intends to build up a thorough understanding of social factors that largely influence students’ decision-making to opt institution for higher studies in India.Design/methodology/approachThis descriptive research follows two sequential phases consisting of the literature review to identify social factors and validate the factors through the questionnaire method. Factor analysis was applied to identify the various factors that influence the student’s institution choice.FindingsThe research work explores and identified four factors and their associated attributes that impact students’ decision-making to opt institution for higher studies. It was found that the career advisor influence variable has the highest level of variance, followed by societal norms, social platform and cohort influence.Research limitations/implicationsThe present study is limited to social factors only. Therefore, many other determinants which may influence the student’s decision-making to opt the institute for higher studies remain unaddressed in this study.Practical implicationsThe findings of the study can guide the institutions' admission management in underpinning the acceptance of social factors to observe their influence on student’s choice of an institution. An important implication is the identification of career advisor influence as the strongest social factor which may bridge the student's career fit in the institution and social platform influence which may help higher education institutions to redesign their marketing strategies to augment students’ enrolment.Originality/valueThis study provides insight into the important role of social factors that impact the student's decision-making regarding institution choice in India.