bluuebunny/crossref_metadata_2025 huggingface dataset:
Burnout in Pediatric Emergency Medicine Physicians
Authors: Kondrich Janienne E. , Han Reintine , Clark Sunday , Platt Shari L.
Published: April 2021

Objectives

This study aims to determine the prevalence of and identify predictors associated with burnout in pediatric emergency medicine (PEM) physicians and to construct a predictive model for burnout in this population to stratify risk.

Methods

We conducted a cross-sectional electronic survey study among a random sample of board-certified or board-eligible PEM physicians throughout the United States and Canada. Our primary outcome was burnout assessed using the Maslach Burnout Inventory on 3 subscales: emotional exhaustion, depersonalization, and personal accomplishment. We defined burnout as scoring in the high-degree range on any 1 of the 3 subscales. The Maslach Burnout Inventory was followed by questions on personal demographics and work environment. We compared PEM physicians with and without burnout using multivariable logistic regression.

Results

We studied a total of 416 PEM board-certified/eligible physicians (61.3% women; mean age, 45.3 ± 8.8 years). Surveys were initiated by 445 of 749 survey recipients (59.4% response rate). Burnout prevalence measured 49.5% (206/416) in the study cohort, with 34.9% (145/416) of participants scoring in the high-degree range for emotional exhaustion, 33.9% (141/416) for depersonalization, and 20% (83/416) for personal accomplishment. A multivariable model identified 6 independent predictors associated with burnout: 1) lack of appreciation from patients, 2) lack of appreciation from supervisors, 3) perception of an unfair clinical work schedule, 4) dissatisfaction with promotion opportunities, 5) feeling that the electronic medical record detracts from patient care, and 6) working in a nonacademic setting (area under the receiver operating characteristic curve, 0.77). A predictive model demonstrated that physicians with 5 or 6 predictors had an 81% probability of having burnout, whereas those with zero predictors had a 28% probability of burnout.

Conclusions

Burnout is prevalent in PEM physicians. We identified 6 independent predictors for burnout and constructed a scoring system that stratifies probability of burnout. This predictive model may be used to guide organizational strategies that mitigate burnout and improve physician well-being.
COVID-19 Presentation in an Acute Motor Incomplete Spinal Cord Injury in Inpatient Rehabilitation
Authors: Khaliq Fareea , Ratnasingam Denesh , Bush-Arnold Michael
Published: April 2021

Spinal cord injuries lead to impairment of the central regulation of respiratory muscle activity. This impairs the cough response, which can increase the risk of complications if infected with coronavirus disease 2019. This case describes a 32-yr-old man with an acute traumatic motor incomplete spinal cord injury, C4 American Spinal cord Injury Association Impairment Scale D D, in an inpatient rehabilitation facility who presented with only a fever. Initial infectious workup was negative, and he continued to have elevated temperatures with no other symptoms. He was then tested for coronavirus disease 2019 and found to be positive. This is the first documented case that identifies this potentially lethal disease in an acute motor incomplete spinal cord injury in an inpatient rehabilitation setting. We further discuss how physiatrists need to be aware of milder presentation of coronavirus disease 2019 in patients with spinal cord injuries. Inability to recognize this disease can lead to delayed diagnosis and asymptomatic spread in an inpatient rehabilitation setting.
Rapid elevation of brain-derived neurotrophic factor production in the bilateral trigeminal ganglia by unilateral transection of the mental nerve in mice
Authors: Yamazaki Maiko , Tsurumaki Tatsuru , Yamada Yurie , Maeda Takeyasu , Seo Kenji
Published: April 2021

Objectives

Previous spinal nerve injury studies have reported brain-derived neurotrophic factor (BDNF) mRNA upregulation in either the ipsilateral dorsal root ganglion (DRG) neurons or both the contralateral and ipsilateral DRG neurons from early period after peripheral nerve injury. This BDNF elevation induces hyperalgesia in the injured and/or uninjured sites, but this detailed mechanism remains unknown. This study aimed to investigate the BDNF mRNA expression in bilateral DRG neurons caused by unilateral nerve injury and to explore the possible mechanisms by which nitric oxide (NO) mediates BDNF production in the DRG, resulting in contralateral hyperalgesia.

Methods

Early changes in BDNF mRNA expression in the bilateral trigeminal ganglia, within 1 day after mental nerve transection, were examined. Additionally, the effects on BDNF production of the NO synthase inhibitor N(ω)-nitro-l-arginine methyl ester (L-NAME) were investigated in the bilateral trigeminal ganglia. The relationship between injured neurons and BDNF production in the trigeminal ganglia was then assessed using immunohistochemical and retrograde tracing methods.

Results

Reverse transcription-PCR analysis demonstrated that unilateral transection of the mental nerve induced a rapid elevation of BDNF mRNA expression, which was inhibited by the intracerebroventricular administration of L-NAME prior to nerve transection. This effect was observed in both the ipsilateral and contralateral sides to the nerve transection. BDNF immunostaining combined with FluoroGold retrograde tracing revealed two types of BDNF-reactive neurons, FluoroGold-labelled and non-FluoroGold-labelled neurons, in the ipsilateral and contralateral sides of the trigeminal ganglia. BDNF-positive cells were also observed in the trigeminal ganglia of other trigeminal nerve branches.

Conclusions

Unilateral nerve injury upregulates BDNF production in the bilateral trigeminal ganglia by NO-mediated and/or indirect activation of afferent neurons, resulting in contralateral hyperalgesia.
Prospective evaluation of ID NOW COVID-19 assay used as point-of-care test in an Emergency Department
Authors: Nguyen Van Jean-Claude , Gerlier Camille , Pilmis Benoît , Mizrahi Assaf , Péan de Ponfilly Gauthier , Khaterchi Amir , Enouf Vincent , Ganansia Olivier , Le Monnier Alban
Published: April 2021

Background

Rapid testing for COVID-19 has been clearly identified as an essential component of the strategy to control the SARS-CoV-2 epidemic, worldwide. The ID NOW COVID-19 assay is a simple, user-friendly, rapid molecular biology test based on nicking and extension amplification reaction (NEAR).

Objectives

The aim of this study was to evaluate the ID NOW COVID-19 assay when used as a point-of-care test (POCT) in our Emergency Department (ED).

Type of study

This prospective study enrolled 395 consecutive patients; paired nasopharyngeal swabs were collected from each study participant. The first swab was tested with the ID NOW COVID-19 assay at the point-of-care by ED nurses. The second swab was diluted in viral transport medium (VTM) and sent to the clinical microbiology department for analysis by both the RT-PCR Simplexa test COVID-19 Direct assay as the study reference method, and the ID NOW COVID-19 assay performed in the laboratory.

Results

Nasopharyngeal swabs directly tested with the ID NOW COVID-19 assay yielded a sensitivity, specificity, PPV and NPV of 98.0%, 97.5%, 96.2% and 98.7%, respectively, in comparison with the RT-PCR study reference assay. When the ID NOW COVID-19 assay was performed in the laboratory using the VTM samples, the sensitivity decreased to 62.5% and the NPV to 79.7%. Three false negative test results were reported with the ID NOW COVID-19 assay when performed using undiluted swabs directly in the ED; these results were obtained from patients with elevated CT values (>30).

Conclusion

We demonstrated that the ID NOW COVID-19 assay, performed as a point of care test in the ED using dry swabs, provides a rapid and reliable alternative to laboratory-based RT-PCR methods
Food Insecurity in Households of People with Autism Spectrum Disorder during the COVID-19 Pandemic
Authors: Vasudevan Vijay , Karpur Arun , Shih Andy , Frazier Thomas
Published: April 2021

Objectives

To explore differences in food insecurity for individuals and families of people with autism spectrum disorder (ASD) during the COVID-19 pandemic by individual, family, and neighborhood characteristics.

Methods

We surveyed a convenience sample of households of people with ASD. We calculated food insecurity using items from the US Census Bureau’s Household Pulse Survey..

Results

Over half of all respondents reported being food insecure (51.8%). Respondents who reported being food insecure were more likely to be minority, have a high school education or less, be on public insurance or uninsured, live in urban/rural communities, and say that their community is not supportive. The majority of respondents did not get free food or groceries (53.2%). Food insecure respondents who got free food was most likely to get them from schools (34.2%).

Conclusion

This is the first study of its kind to explore food security in households of people with ASD. The pandemic has exacerbated existing neighborhood disparities. The federal response to food insecurity caused by the pandemic needs to be further explored especially for preferred and medically necessary foods for people with ASD.
Thyroid dysfunction diagnosis from routine laboratory tests based on machine learning
Authors: Hu Min , Asami Chikashi , Iwakura Hiroshi , Nakajima Yasuyo , Sema Ryousuke , Kikuchi Tsuyoshi , Miyata Tsuyoshi , Sakamaki Koji , Kudo Takumi , Yamada Masanobu , Akamizu Takashi , Sakakibara Yasubumi
Published: April 2021

Approximately 2.4 million patients in Japan need treatment for thyroid disease, including Graves’ disease and Hashimoto’s disease. However, only 450,000 of them are receiving treatment, and many patients with thyroid dysfunction remain largely overlooked. In this retrospective study, we aimed to screen patients with hyperthyroidism and hypothyroidism who would greatly benefit from prompt medical treatment. We examined routine laboratory finding data and machine learning algorithms to investigate whether such accurate and robust screening is possible to prevent overlooking and misdiagnosing thyroid dysfunction. We succeeded in developing a machine learning method to construct a classification model for detecting hyperthyroidism and hypothyroidism in patients using 11 routine laboratory tests. We collected electronic health records and medical checkup data from four hospitals in Japan. As a result of cross-validation and external evaluation, we achieved a high classification accuracy for the hyperthyroidism and hypothyroidism models.
Functional amyloids in the microbiomes of a rat Parkinson’s disease model and wild-type rats
Authors: Christensen Line Friis Bakmann , Alijanvand Saeid Hadi , Burdukiewicz Michał , Herbst Florian-Alexander , Kjeldal Henrik , Dueholm Morten Simonsen , Otzen Daniel E.
Published: April 2021

Cross-seeding between amyloidogenic proteins in the gut is receiving increasing attention as a possible mechanism for initiation or acceleration of amyloid formation by aggregation-prone proteins such as αSN, which is central in the development of Parkinson’s disease. This is particularly pertinent in view of the growing number of functional (i.e.benign and useful) amyloid proteins discovered in bacteria. Here we identify two functional amyloid proteins, Pr12 and Pr17, in fecal matter from Parkinson’s disease transgenic rats and their wild type counterparts, based on their stability against dissolution by formic acid. Both proteins show robust aggregation into ThT-positive aggregates that contain higher-order β-sheets and have a fibrillar morphology, indicative of amyloid proteins. In addition, Pr17 aggregates formedin vitroshowed significant resistance against formic acid, suggesting an ability to form highly stable amyloid. Treatment with proteinase K revealed a protected core of approx. 9 kDa. Neither Pr12 nor Pr17, however, affected αSN aggregationin vitro. Thus, amyloidogenicity does notper selead to an ability to cross-seed fibrillation of αSN. Our results support the use of proteomics and formic acid to identify amyloid protein in complex mixtures and indicates the existence of numerous functional amyloid proteins in microbiomes.

IMPORTANCE

The bacterial microbiome in the gastrointestinal tract is increasingly seen as important for human health and disease. One area of particular interest is that of neurodegenerative diseases such as Parkinson’s which involve pathological aggregation into amyloid of human proteins such as α- synuclein (αSN). Bacteria are known to form benign or functional amyloid, some of which may initiate unwanted aggregation ofe.g.αSN in the enteric nervous system through cross-seeding via contact with the microbiome. Here we show that the rat microbiome contains several proteins which form this type of amyloid aggregate bothin vivoandin vitro. Although the two proteins we investigate in depth do not directly promote αSN aggregation, our work shows that the microbiome potentially harbors a significant number of bacterial amyloid which could play a role in human physiology at various levels.
Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination
Authors: Loyal Lucie , Braun Julian , Henze Larissa , Kruse Beate , Dingeldey Manuela , Reimer Ulf , Kern Florian , Schwarz Tatjana , Mangold Maike , Unger Clara , Dörfler Friederike , Kadler Shirin , Rosowski Jennifer , Gürcan Kübrah , Uyar-Aydin Zehra , Frentsch Marco , Kurth Florian , Schnatbaum Karsten , Eckey Maren , Hippenstiel Stefan , Hocke Andreas , Müller Marcel A. , Sawitzki Birgit , Miltenyi Stefan , Paul Friedemann , Mall Marcus A. , Wenschuh Holger , Voigt Sebastian , Drosten Christian , Lauster Roland , Lachman Nils , Sander Leif-Erik , Corman Victor M. , Röhmel Jobst , Meyer-Arndt Lil , Thiel Andreas , Giesecke-Thiel Claudia ,   the Charité Corona Cross Study Group
Published: April 2021

While evidence for pre-existing SARS-CoV-2-cross-reactive CD4+ T cells in unexposed individuals is increasing, their functional significance remains unclear. Here, we comprehensively determined SARS-CoV-2-cross-reactivity and human coronavirus-reactivity in unexposed individuals. SARS-CoV-2-cross-reactive CD4+ T cells were ubiquitous, but their presence decreased with age. Within the spike glycoprotein fusion domain, we identified a universal immunodominant coronavirus-specific peptide epitope (iCope). Pre-existing spike- and iCope-reactive memory T cells were efficiently recruited into mild SARS-CoV-2 infections and their abundance correlated with higher IgG titers. Importantly, the cells were also reactivated after primary BNT162b2 COVID-19 mRNA vaccination in which their kinetics resembled that of secondary immune responses. Our results highlight the functional importance of pre-existing spike-cross-reactive T cells in SARS-CoV-2 infection and vaccination. Abundant spike-specific cross-immunity may be responsible for the unexpectedly high efficacy of current vaccines even with single doses and the high rate of asymptomatic/mild infection courses.
Rapid, Affordable and Scalable SARS-CoV-2 Detection from Saliva
Authors: Hayden Andrew , Kuentzel Marcy , Chittur Sridar V.
Published: April 2021

Here we present an inexpensive, rapid, and robust RT-LAMP based SARS-CoV-2 detection method that is easily scalable, enabling point of care facilities and clinical labs to determine results from patients’ saliva directly in 30 minutes for less than $2 a sample. The method utilizes a novel combination of widely available reagents that can be prepared in bulk, plated and frozen and remain stable until samples are received. This innovation dramatically reduces preparation time, enabling high-throughput automation and testing with time to results (including setup) in less than one hour for 96 patient samples simultaneously when using a 384 well format. By utilizing a dual-reporter (phenol red pH indicator for end-point detection and SYTO-9 fluorescent dye for real-time), the assay also provides internal validation of results and redundancy in the event of an instrument malfunction.
A Rapid SARS-CoV-2 Variant Detection by Molecular-Clamping Based RT-qPCR
Authors: Shen Shuo , Fu Andrew Y. , Jamba Maidar , Li Jonathan , Powell Mike J. , Zhang Aiguo , Lu Chuanyi M. , Sha Michael Y.
Published: April 2021

We applied XNA-based Molecular Clamping Technology to develop a multiplex qPCR assay for rapid and accurate detection of SARS-CoV-2 mutations. A total of 278 previously tested SARS-COV-2 positive samples originating primarily from San Francisco Bay Area were tested, including 139 Samples collected in middle January and 139 samples collected at the end of February 2021, respectively. The SARS-CoV-2 Spike-gene D614G mutation was detected from 58 samples (41.7%) collected in January 2021 and, 78 samples (56.1%) collected in February. Notably, while there were no N501Y mutation detected in samples from January, seven of the February samples were tested positive for the N501Y and D614G mutations. The results suggest a relatively recent and speedy spreading of the UK variant (B.1.1.7) in Northern California. This new Molecular Clamping technology-based multiplex RT-qPCR assay is highly sensitive and specific and can help speed up large scale testing for SARS-CoV-2 variants.
Altered metal distribution in thesr45-1Arabidopsis mutant causes developmental defects
Authors: Fanara Steven , Schloesser Marie , Hanikenne Marc , Motte Patrick
Published: April 2021

The plant SR (serine/arginine-rich) splicing factor SR45 plays important roles in several biological processes, such as splicing, DNA methylation, innate immunity, glucose regulation and ABA signaling. A homozygous Arabidopsissr45-1null mutant is viable, but exhibits diverse phenotypic alterations, including delayed root development, late flowering, shorter siliques with fewer seeds, narrower leaves and petals, and unusual numbers of floral organs. Here, we report that thesr45-1mutant presents an unexpected constitutive iron deficiency phenotype characterized by altered metal distribution in the plant. RNA-Sequencing highlighted severe perturbations in metal homeostasis, phenylpropanoid pathway, oxidative stress responses, and reproductive development. Ionomic quantification and histochemical staining revealed strong iron accumulation in thesr45-1root tissues accompanied by an iron starvation in aerial parts. We showed that somesr45-1developmental abnormalities can be complemented by exogenous iron supply. Our findings provide new insight into the molecular mechanisms governing the phenotypes of thesr45-1mutant.

One sentence summary

Thesr45-1mutation affects Fe homeostasis, which results in reproductive defects
One dose of COVID-19 nanoparticle vaccine REVC-128 provides protection against SARS-CoV-2 challenge at two weeks post immunization
Authors: Gu Maggie , Torres Jonathan L. , Greenhouse Jack , Wallace Shannon , Chiang Chi-I , Jackson Abigail M. , Porto Maciel , Kar Swagata , Li Yuxing , Ward Andrew B. , Wang Yimeng
Published: April 2021

A COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain subunits with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results show that vaccination protects hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage (lung and nares) for protected animals, compared with ~10% weight loss, higher viral loads and tissue damage in unprotected animals. Furthermore, the data show that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a long history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.
Driving potent neutralization of a SARS-CoV-2 Variant of Concern with a heterotypic boost
Authors: Sheward Daniel J. , Mandolesi Marco , Urgard Egon , Kim Changil , Hanke Leo , Vidakovics Laura Perez , Pankow Alec , Smith Natalie L. , Dopico Xaquin Castro , McInerney Gerald , Coquet Jonathan M. , Hedestam Gunilla B. Karlsson , Murrell Ben
Published: April 2021

The emergence of SARS-CoV-2 Variants of Concern (VOCs) with mutations in key neutralizing antibody epitopes threatens to undermine vaccines developed against the pandemic founder variant (Wu-Hu-1). Widespread vaccine rollout and continued transmission are creating a population that has antibody responses of varying potency to Wu-Hu-1. Against this background, it is critical to assess the outcomes of subsequent immunization with variant antigens. It is not yet known whether heterotypic vaccine boosts would be compromised by original antigenic sin, where pre-existing responses to a prior variant dampen responses to a new one, or whether the primed memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. Here, we show that a single adjuvanted dose of receptor binding domain (RBD) protein from VOC 501Y.V2 (B.1.351) drives an extremely potent neutralizing antibody response capable of cross-neutralizing both Wu-Hu-1 and 501Y.V2 in rhesus macaques previously immunized with Wu-Hu-1 spike protein. Passive immunization with plasma sampled following this boost protected K18-hACE2 mice from lethal challenge with a 501Y.V2 clinical isolate, whereas only partial protection was afforded by plasma sampled after two Wu-Hu-1 spike immunizations.
Deep Generative Analysis for Task-Based Functional MRI Experiments
Authors: de Albuquerque Daniela , Goffinet Jack , Wright Rachael , Pearson John
Published: April 2021

While functional magnetic resonance imaging (fMRI) remains one of the most widespread and important methods in basic and clinical neuroscience, the data it produces—time series of brain volumes—continue to pose daunting analysis challenges. The current standard (“mass univariate”) approach involves constructing a matrix of task regressors, fitting a separate general linear model at each volume pixel (“voxel”), computing test statistics for each model, and correcting for false positivespost hocusing bootstrap or other resampling methods. Despite its simplicity, this approach has enjoyed great success over the last two decades due to: 1) its ability to produce effect maps highlighting brain regions whose activity significantly correlates with a given variable of interest; and 2) its modeling of experimental effects as separable and thus easily interpretable. However, this approach suffers from several well-known drawbacks, namely: inaccurate assumptions of linearity and noise Gaussianity; a limited ability to capture individual effects and variability; and difficulties in performing proper statistical testing secondary to independently fitting voxels. In this work, we adopt a different approach, modeling entire volumes directly in a manner that increases model flexibility while preserving interpretability. Specifically, we use a generalized additive model (GAM) in which the effects of each regressor remain separable, the product of a spatial map produced by a variational autoencoder and a (potentially nonlinear) gain modeled by a covariate-specific Gaussian Process. The result is a model that yields group-level effect maps comparable or superior to the ones obtained with standard fMRI analysis software while also producing single-subject effect maps capturing individual differences. This suggests that generative models with a decomposable structure might offer a more flexible alternative for the analysis of task-based fMRI data.
Differential neural activity patterns mediate learning across contexts in a social cichlid fish
Authors: Rodriguez-Santiago Mariana , Jordan Alex , Hofmann Hans A.
Published: April 2021

Learning and decision-making are greatly influenced by the social context surrounding individuals. When navigating a complex social world, individuals must quickly ascertain where to gain important resources and which group members are useful sources of such information. Such dynamic behavioral processes require neural mechanisms that are flexible across contexts. Here we examined how the social context influences the learning response during a visual cue discrimination task and the neural activity patterns that underlie acquisition of this novel information. Using the cichlid fish,Astatotilapia burtoni, we show that learning of the task is faster in social groups than in a non-social context. We quantified the expression of Fos, an immediate-early gene, across candidate brain regions known to play a role in social behavior and learning, such as the putative teleost homologues of the mammalian hippocampus, basolateral amygdala, and medial amygdala/BNST complex. We found that neural activity patterns differ between social and non-social contexts. Our results suggest that while the same brain regions may be involved in the learning of a discrimination task independent of social context, activity in each region encodes specific aspects of the task based on context.
PRMT5 regulates ovarian follicle development by facilitatingWt1translation
Authors: Chen Min , Dong Fangfang , Chen Min , Shen Zhiming , Wu Haowei , Cen Changhuo , Cui Xiuhong , Bao Shilai , Gao Fei
Published: April 2021

Protein arginine methyltransferase 5 (Prmt5) is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found PRMT5 was expressed at high level in ovarian granulosa cells of growing follicles. Inactivation ofPrmt5in granulosa cells resulted in aberrant follicle development and female infertility. InPrmt5-knockout mice, follicle development was arrested with disorganized granulosa cells in which WT1 expression was dramatically reduced and the expression of steroidogenesis-related genes was significantly increased. The premature differentiated granulosa cells were detached from oocytes and follicle structure was disrupted. Mechanism studies revealed thatWt1expression was regulated by PRMT5 at the protein level. PRMT5 facilitated IRES-dependent translation ofWt1mRNA by methylating HnRNPA1. Moreover, the upregulation of steroidogenic genes inPrmt5-deficient granulosa cells was repressed byWt1overexpression. These results demonstrate PRMT5 participates in granulosa cell lineage maintenance by inducingWt1expression. Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development.
MetaMutationalSigs: Comparison of mutational signature refitting results made easy
Authors: Pandey Palash , Arora Sanjeevani , Rosen Gail
Published: April 2021

The analysis of mutational signatures is becoming increasingly common in cancer genetics, with emerging implications in cancer evolution, classification, treatment decision and prognosis. Recently, several packages have been developed for mutational signature analysis, with each using different methodology and yielding significantly different results. Because of the nontrivial differences in tools’ refitting results, researchers may desire to survey and compare the available tools, in order to objectively evaluate the results for their specific research question, such as which mutational signatures are prevalent in different cancer types. There is a need for a software that can aggregate results from different refitting packages and present them in a user-friendly way to facilitate effective comparison of mutational signatures.

Availability and implementation

MetaMutationalSigs is implemented using R and python and is available for installation using Docker and available at:https://github.com/EESI/MetaMutationalSigs

Contact

Gail Rosen (glr26@drexel.edu).

Supplementary information

More information about the package including test data and results are available athttps://github.com/EESI/MetaMutationalSigs
COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women
Authors: Atyeo Caroline , DeRiso Elizabeth A. , Davis Christine , Bordt Evan A. , DeGuzman Rose M. , Shook Lydia L. , Yonker Lael M. , Fasano Alessio , Akinwunmi Babatunde , Lauffenburger Douglas A. , Elovitz Michal A. , Gray Kathryn J. , Edlow Andrea G. , Alter Galit
Published: April 2021

Significant immunological changes occur throughout pregnancy to tolerize the mother and allow growth of the fetal graft. However, additional local and systemic immunological adaptations also occur, allowing the maternal immune system to continue to protect the dyad against foreign invaders both during pregnancy and after birth through lactation. This fine balance of tolerance and immunity, along with physiological and hormonal changes, contribute to increased susceptibility to particular infections in pregnancy, including more severe COVID-19 disease. Whether these changes also make pregnant women less responsive to vaccination or induce altered immune responses to vaccination remains incompletely understood. To holistically define potential changes in vaccine response during pregnancy and lactation, we deeply profiled the humoral vaccine response in a group of pregnant and lactating women and non-pregnant age-matched controls. Vaccine-specific titers were comparable, albeit slightly lower, between pregnant and lactating women, compared to non-pregnant controls. Among pregnant women, we found higher antibody titers and functions in those vaccinated with the Moderna vaccine. FcR-binding and antibody effector functions were induced with delayed kinetics in both pregnant and lactating women compared to non-pregnant women. Antibody boosting resulted in high FcR-binding titers in breastmilk. These data point to an immune resistance to generate highly inflammatory antibodies during pregnancy and lactation, and a critical need to follow prime/boost timelines in this vulnerable population to ensure full immunity is attained.
Bipartite functional fractionation within the neural system for social cognition supports the psychological continuity of selfvs.other
Authors: Chiou Rocco , Cox Christopher R. , Lambon Ralph Matthew A.
Published: April 2021

Research of social neuroscience establishes that regions in the brain’s default network (DN) and semantic network (SN) are engaged by socio-cognitive tasks. Research of the human connectome shows that DN and SN regions are both situated at the high-order end of cortical gradient but differ in their positions on this gradient. In the present study, we integrated these two bodies of research, used the psychological continuity of selfvs.other as a ‘test-case’, and used fMRI to investigate whether these networks would encode social concepts differently. We found a robust dissociation between the DN and SN – while both networks contained sufficient information for decoding broad-stroke distinction of social categories, the DN carried more generalisable information for cross-classifying across social distance and emotive valence than did the SN. We also found that the overarching distinction of selfvs.other was a principal divider of the representational space while social distance was an auxiliary factor (subdivision, nested within the principal dimension), and this representational landscape was more manifest in the DN than in the SN. Taken together, our findings demonstrate how insights from connectome research can benefit social neuroscience, and have implications for clarifying the two networks’ differential contributions to social cognition.
Species boundaries among extremely diverse and sexually dimorphicArrenuruswater mites (Acariformes: Hydrachnidiae: Arrenuridae)
Authors: Więcek Mariusz , Broda Łukasz , Proctor Heather , Dabert Miroslawa , Smith Bruce P. , Dabert Jacek
Published: April 2021

Arrenurus(Arrenuridae) is the most species-rich genus of mites with about 950 named species that inhabit standing, and to a lesser extent, running water habitats around the world. To date, distinguishing species ofArrenurushas been based on male reproductive morphology. Here, we use morphological and molecular approaches to examine species boundaries among 42 named species ofArrenurus, including four named species that have colour variants (red and greenA. americanus, and red and blueA. intermedius, A. manubriatorandA. apetiolatus), and two unnamed morphospecies. In this study, we examine male genital structures with the use of SEM techniques, and apply mitochondrial (COI barcode region) and nuclear (28S rRNA) gene fragments to test whether male morphology reflects species boundaries inArrenurusassessed by molecular analyses. Our results reveal that male reproductive morphology parallels species boundaries as judged by molecular data. We discuss the cases of genetically poorly diversified, yet morphologically clearly defined named species. Moreover, we show that based on the species we examined, colour morphs within otherwise morphologically similar specimens represent within-species variation and, in the absence of other diagnostic traits, colour itself can be misleading in distinguishing species. Our outcomes on molecular taxonomy ofArrenurusprovide a background for testing hypotheses about speciation rate in water mites.
Substitutions and codon usage in SARS-CoV-2 in mammals indicate natural selection and host adaptation
Authors: Lei Zhixiong , Zhang Dan , Yang Ruiping , Li Jian , Du Weixing , Liu Yanqing , Tan Huabing , Liu Zhixin , Liu Long
Published: April 2021

The outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, rapidly spread to create a global pandemic and has continued to spread across hosts from humans to animals, transmitting particularly effectively in mink. How SARS-CoV-2 evolves in animals and humans and the differences in the separate evolutionary processes remain unclear. We analyzed the composition and codon usage bias of SARS-CoV-2 in infected humans and animals. Compared with other animals, SARS-CoV-2 in mink had the most substitutions. The substitutions of cytidine in SARS-CoV-2 in mink account for nearly 50% of the substitutions, while those in other animals represent only 30% of the substitutions. The incidence of adenine transversion in SARS-CoV-2 in other animals is threefold higher than that in mink-CoV (the SARS-CoV-2 virus in mink). A synonymous codon usage analysis showed that SARS-CoV-2 is optimized to adapt in the animals in which it is currently reported, and all the animals showed decreased adaptability relative to that of humans, except for mink. A binding affinity analysis indicated that the spike protein of the SARS-CoV-2 variant in mink showed a greater preference for binding with the mink receptor ACE2 than with the human receptor, especially as the mutation Y453F and F486L in mink-CoV lead to improvement of binding affinity for mink receptor. Our study focuses on the divergence of SARS-CoV-2 genome composition and codon usage in humans and animals, indicating possible natural selection and current host adaptation.
Localizing Brain Function Based on Full Multivariate Activity Patterns: The Case of Visual Perception and Emotion Decoding
Authors: David Isaac , Barrios Fernando A.
Published: April 2021

Multivariate statistics and machine learning methods have become a common tool to extract information represented in the brain. What is less recognized is that, in the process, it has become more difficult to perform data-driven discovery and functional localization. This is because multivariate pattern analysis (MVPA) studies tend to restrict themselves to a subset of the available data, or because sound inference to map model parameters back to brain anatomy is lacking. Here, we present a high-dimensional (including brain-wide) multivariate classification pipeline for the detection and localization of brain functions during tasks. In particular, we probe it at visual and socio-affective states in a task-oriented functional magnetic resonance imaging (fMRI) experiment. Classification models for a group of human participants and existing rigorous cluster inference methods are used to construct group anatomical-statistical parametric maps, which correspond to the most likely neural correlates of each psychological state. This led to the discovery of a multidimensional pattern of macroscale brain activity which reliably encodes for the perception of happiness in the visual cortex, lingual gyri and the posterior perivermian cerebellum. We failed to find similar evidence for sadness and anger. Anatomical consistency of discriminating features across subjects and contrasts despite the high number of dimensions suggests MVPA is a viable tool for a complete functional mapping pipeline, and not just the prediction of psychological states.

Abstract Figure
Cytoplasmic pressure maintains epithelial integrity and inhibits cell motility
Authors: Chengappa Pragati , Jones Tia M. , Cowan James M. , Kainth Devneet , Petrie Ryan J.
Published: April 2021

Cytoplasmic pressure, a function of actomyosin contractility and water flow, can regulate cellular morphology and dynamics. In mesenchymal cells, cytoplasmic pressure powers cell protrusion through physiological three-dimensional extracellular matrices. However, the role of intracellular pressure in epithelial cells is relatively unclear. Here we find that high cytoplasmic pressure is necessary to maintain barrier function, one of the hallmarks of epithelial homeostasis. Further, our data show that decreased cytoplasmic pressure facilitates lamellipodia formation during the epithelial to mesenchymal transition (EMT). Critically, activation of the actin nucleating protein Arp2/3 is required for the reduction in cytoplasmic pressure and lamellipodia formation in response to treatment with hepatocyte growth factor (HGF) to induce EMT. Thus, elevated cytoplasmic pressure functions to maintain epithelial tissue integrity, while reduced cytoplasmic pressure triggers lamellipodia formation and motility during HGF-dependent EMT.
Distilling agency in BIM-induced change in work practices
Authors: Akintola Adeyemi Ayodele , Venkatachalam Senthilkumar , Root David , Oti Akponanabofa Henry
Published: April 2021

Purpose

Critics of claims about building information modeling’s (BIM’s) capability to revolutionize construction industry practices describe it as overhyped, fallacious and therefore suggest that there is need for a more critical examination of its change impacts. Others have posited that the changes BIM induces are evolutionary rather than revolutionary. In this vein, the purpose of this paper was to undertake a careful analysis of the nature of such changes to distil actual changes that happened, and the type of agency that brings such changes about.

Design/methodology/approach

Drawing from appropriate qualitative research strategies, data was collected through key informant interviews from consulting organizations in South Africa that have implemented BIM within their organizations and on projects.

Findings

Changes in organizations’ work practices were evident in their workflows, formal/informal methods of interaction, norms, leadership and authority structures, remuneration and the way work was conceived or conceptualized. Furthermore, changes in organizational work practices do not solely occur through the direct agency of the BIM tool’s implementation. Instead, BIM-induced change occurs by delegated, conditional and needs-based agency – which are not mutually exclusive.

Originality/value

The nature of changes in professional work practices could be misconstrued as being solely because of the actions of agents who actively participate in implementing BIM. The discussion in the literature has, therefore, been advanced from general to specific theoretical understandings of BIM-induced change, which emphasize the need for construction stakeholders to actively participate in developing the innovations that drive change in the industry rather than hand the power to drive change to BIM authoring and management application developers who have less stake in the industry.
From Ebola to COVID-19: what explains institutionalized manias and the ultimate preference for non-optimal solutions in global health governance?
Authors: Ahen Frederick
Published: April 2021

Purpose

The purpose of this paper is to investigate how “manias” in global health governance lead to health inequalities even before, during and in the aftermath of acute health crises such as the COVID-19 pandemic. “Manias” as used here refer to obsessive ir/rational behaviors, misguided policy/strategic choices and the exercise of power that benefit the major global health actors at the expense of stakeholders.

Design/methodology/approach

From post-colonial and historical perspectives, this study delineates how the major global health actors influence outcomes in global health governance and international business when they interact at the national–global level using an illustration from an emerging economy.

Findings

Power asymmetry in global health governance is constructed around the centralization of economic influence, medico-techno-scientific innovation and the geopolitical hegemony of a conglomerate of super-rich/powerful actors. They cluster these powers and resources in the core region (industrialized economies) and use them to influence the periphery (developing economies) through international NGOs, hybrid organizations, MNCs and multilateral/bilateral agreements. The power of actors to maintain manias lies in not only how they influence the periphery but also the consequences of the periphery’s “passivity” and “voluntary” renunciation of sovereignty in medical innovations and global health policies/politics.

Social implications

As a quintessential feature of manias, power asymmetry makes it harder for weaker actors to actually change the institutional conditions that produce structural inequalities in global health.

Originality/value

This timely and multidisciplinary study calls for a novel architecture of global health governance. Thus, democratizing global health governance with sufficiently foresighted investments that prioritize equitable access by and the inclusiveness of vulnerable stakeholders will help dismantle institutionalized manias while decreasing health inequalities.
Reversal of language hierarchy and the politics of translation in a multinational corporation
Authors: Ristolainen Jonna , Outila Virpi , Piekkari Rebecca
Published: April 2021

Purpose

The purpose of this paper is to explain the reversal of language hierarchy in a Finnish multinational corporation (MNC) from a political perspective. This paper situated the language hierarchy in the historical context of the colonial-style relationship between Finland and Russia. From a post-colonial perspective, the colonial legacy of Russia has had an influence on language strategy and everyday translation work in the Finnish multinational until the present day.

Design/methodology/approach

This paper undertook a case study based on qualitative secondary analysis of existing data sets. These data sets originated from two previously conducted studies of the same Finnish MNC.

Findings

The findings revealed a reversal of the traditional corporate language hierarchy. Russian, as the host country language of powerful local subsidiaries, rose to the top of the hierarchy at the expense of English, the common corporate language, and other languages. The colonial-style relationship was enacted by professional and paraprofessional translators who collaborated by using “the master’s language and imitating the master’s voice” to reap the strategic benefits of local responsiveness.

Originality/value

In contrast to previous work drawing on post-colonial theory in the study of MNCs, this paper represents the headquarters in Finland as the “colonised” party and the Russian subsidiaries as the “coloniser.” Owing to its colonial legacy, Russian, the host country language, became very powerful and influenced the language strategy of the entire MNC. This paper conceptualized translation as a multilevel phenomenon and offers a holistic explanation of why the language hierarchy in the Finnish MNC was reversed.
When and how does perceived overqualification lead to turnover intention? A moderated mediation model
Authors: Vinayak Riya , Bhatnagar Jyotsna , Agarwal Madhushree Nanda
Published: April 2021

Purpose

The study is aimed at developing and testing a theoretical model where psychological capital acts as the intervening mechanism explicating the relationship between perceived overqualification (POQ) and turnover intention. It also explores how perceived supervisor support (PSS) influences the mediating role of psychological capital in the perceived overqualification and turnover intention association.

Design/methodology/approach

The authors test the model through a sample data of 314 workers employed in the Indian IT service sector. IBM SPSS and SPSS AMOS software were utilized for conducting analysis and testing the model involving first-stage moderated mediation.

Findings

The study confirms that perceptions of overqualification have a positive relationship with turnover intentions. Further, it finds that the positive association between POQ and turnover intention will be mediated by psychological capital. The results reflected that perceived supervisor support shall weaken the relationship between perceptions of overqualification and psychological capital.

Originality/value

The research is amongst the limited researches which look at the influence of psychological capital and perceived supervisor support with regards to POQ. It attempts to lay down the underlying psychological mechanism of POQ and highlight the role played by perceived supervisor support.