bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social dialogue quality and workers’ health as perceived by Belgian trade union representatives during the COVID-19 pandemic
Authors: Wels Jacques , Hamarat Natasia , De Greef Vanessa 
Published: April 2023

AbstractBackgroundBesides major employment disruptions, the COVID-19 pandemic has generated policy responses with specific mechanisms to protect workers’ health. In Belgium, most of these policies were negotiated at national and cross-sectorial level but implemented at company level with company-based collective negotiation playing a key role. This study examines the relationship between trade union representatives’ perception of social dialogue quality and change in workers’ physical and mental health in such a context.MethodsUnion representatives were surveyed throughout Belgium between August and December 2021 through an online questionnaire (N=469). We asked about the way they perceived workers’ physical and mental health within their companies and explain variations with the self-perceived change in quality of social dialogue as an exposure. We use a modified Poisson regression for binary outcomes on four stratified models that additively account for no control, company characteristics, pre-pandemic self-reported health and COVID-19-related measures. Weights are generated to ensure sector representativeness.Results30.1% of the sample reported a worsening social dialogue quality during the pandemic. Relative Risks (RR) of poor physical and mental health when social dialogue has worsened are respectively 1.49 [95%CI:1.03; 2.15] and 1.38 [95%CI= 1.09;1.74] when controlling for company characteristics and pre-pandemic health. Adding pandemic-related measures reduces the risk of both poor mental [RR=1.25; 95%CI: 0.84; 1.87] and physical health [RR=1.18; 95%CI:0.94;1.49].ConclusionsAlthough based on self-reported variables, the study shows an association between poor social dialogue quality and poor physical and mental health during the COVID-19 pandemic that must be explored further in post-pandemic context.
Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment and self-reported side effects in the euthymic phase of bipolar disorders: results from the FACE-BD cohort
Authors: Vidal N , Brunet-Gouet E , Frileux S , Aouizerate B , Aubin V , Belzeaux R , Courtet P , D’Amato T , Dubertret C , Etain B , Haffen E , Januel D , Leboyer M , Lefrere A , Llorca PM , Marlinge E , Olié E , Polosan M , Schwan R , Walter M ,   the FACE-BD (FondaMental Academic Centers of Expertise for Bipolar Disorders) group, Passerieux C , Roux P 
Published: April 2023

AbstractBipolar disorders (BD) are characterized by cognitive impairment during the euthymic phase, to which treatments can contribute. The anticholinergic properties of medications, i.e., the ability of a treatment to inhibit cholinergic receptors, are associated with cognitive impairment in elderly patients and people with schizophrenia but this association has not been well characterized in individuals with remitted bipolar disorders. Moreover, the validity of anticholinergic burden scales designed to assess the anticholinergic load of medications has been scarcely tested in bipolar disorders. We aimed to test the concurrent validity of several scales by assessing their associations with objective cognitive impairment and subjective anticholinergic side-effects in BD. We hypothesized that the scale is valid if its association with cognitive impairment or self-reported anticholinergic side-effects is significant. A sample of 2,031 individuals with euthymic bipolar disorders was evaluated with a neuropsychological battery to identify cognitive impairment. Two scales among 27 were significantly positively associated with cognitive impairment in multiple logistic regressions, whereas chlorpromazine equivalents, lorazepam equivalents, the number of antipsychotics, or the number of treatments were not. The two scales significantly correlated with worse performance in processing speed and verbal memory. In addition, 14 scales showed good concurrent validity to assess self-reported peripheral anticholinergic side-effects and 13 were valid for evaluating self-reported central anticholinergic side-effects. Thus, we identified valid scales to monitor the anticholinergic burden in BD, which may be useful in assessing iatrogenic cognitive impairment in studies investigating cognition in BD.
Generalized mutualisms promote range expansion in both plant and ant partners
Authors: Nathan Pooja , Economo Evan P. , Guénard Benoit , Simonsen Anna , Frederickson Megan E. 
Published: April 2023

AbstractMutualism improves organismal fitness, but strong dependence on another species can also limit a species’ ability to thrive in a new range if its partner is absent. We assembled a large, global dataset on mutualistic traits and species ranges to investigate how multiple plant-animal and plant-microbe mutualisms affect the spread of legumes and ants to novel ranges. We found that generalized mutualisms increase the likelihood that a species establishes and thrives beyond its native range, whereas specialized mutualisms either do not affect or reduce non-native spread. This pattern held in both legumes and ants, indicating that specificity between mutualistic partners is a key determinant of ecological success in a new habitat. Our global analysis shows that mutualism plays an important, if often overlooked, role in plant and insect invasions.
Sex-specific developmental changes in spinal cord pain pathways following neonatal inflammation
Authors: Hedley Kateleen E , Cuskelly Annalisa , Quinn Rikki K , Callister Robert J , Hodgson Deborah M , Tadros Melissa A 
Published: April 2023

AbstractEarly-life inflammation can have long lasting impact on pain processing and pain behaviours. For example, we have shown neonatal inflammation can result in changes within spinal neuronal networks and altered flinching of the hind paw following formalin injection three weeks later. This suggests mechanisms for altered pain behaviours lie in first and second order neurons in the pain neuroaxis. Exactly how these changes progress during postnatal development is not known. Accordingly, we investigated neuroinflammatory markers in sensory neurons (dorsal root ganglia; DRGs) and spinal cords of Wistar rats (both sexes) after early life inflammation. Rats were injected with LPS or saline on postnatal days (P) 3 and 5. DRGs and spinal cords (SC) were isolated on P7, 13 and 21, and the expression of six inflammatory mediators were quantified via RT-qPCR. In the DRG, four proinflammatory mediators were elevated in P7 rats exposed to LPS. By P13, only two proinflammatory agents were elevated, whereas at P21 the levels of all six inflammatory mediators were similar between LPS and saline-treated rats. There were no sex-specific differences in the expression profile of any mediator in DRGs. In the spinal cord this expression profile was reversed with no change in inflammatory mediators at P7, elevation of two at P13 and four at P21 in LPS treated rats. Interestingly, these differences were greater in the spinal cords of female rats, indicating sex-specific modulation of neuroinflammation even at these early stages of postnatal development. The increased inflammatory mediator profile in the spinal cords of P21 LPS-treated rats was accompanied by sex-specific modulation of astrocytic (GFAP) activation, with females showing an increase and males a decrease in GFAP following LPS exposure. Together, these data indicate sensory neurons are more susceptible to acute inflammation whereas inflammation in the spinal cord is delayed. The sex-specific modulation of inflammation during critical phases of development may help explain altered pain behaviours in adult males and females.
Ethnic inequalities among NHS staff in England - workplace experiences during the COVID-19 pandemic
Authors: Rhead Rebecca , Harber-Aschan Lisa , Onwumere Juliana , Polling Catherine , Dorrington Sarah , Ehsan Annahita , Stevelink Sharon AM , Khunti Kamlesh , Mir Ghazala , Morriss Richard , Wessely Simon , Woodhead Charlotte , Hatch Stephani L 
Published: April 2023

AbstractObjectivesTo determine how workplace experiences of NHS staff varied by ethnic group during the COVID-19 pandemic and examine how these experiences are associated with mental and physical health at the time of the study.MethodsAn online Inequalities Survey was conducted by the TIDES study (Tackling Inequalities and Discrimination Experiences in health Services) in collaboration with NHS CHECK. This Inequalities Survey collected measures relating to workplace experiences (such as personal protective equipment (PPE), risk assessments, redeployments, and discrimination) as well as mental health, and physical health from NHS staff working in the 18 trusts participating with the NHS CHECK study between February and October 2021 (N=4622).ResultsRegression analysis revealed that staff from Black and Mixed/Other ethnic groups had greater odds of experiencing workplace harassment (adjusted odds ratio (AOR) = 2.43 [1.56-3.78] and 2.38 [1.12-5.07], respectively) and discrimination (AOR = 4.36 [2.73-6.96], and 3.94 [1.67-9.33], respectively) compared to White British staff. Staff from black ethnic groups also had greater odds than White British staff of reporting PPE unavailability (AOR = 2.16 [1.16-4.00]). Such workplace experiences were associated with negative physical and mental health outcomes, though this association varied by ethnicity. Conversely, understanding employment rights around redeployment, being informed about, and having the ability to inform redeployment decisions were associated with lower odds of poor health outcomes.ConclusionsStructural changes to the way staff from ethnically minoritised groups are supported, and how their complaints are addressed by leaders within the NHS are urgently required to address racism and inequalities in the NHS.Policy implicationsMaintaining transparency and implementing effective mechanisms for addressing poor working conditions, harassment, and discrimination is crucial in the NHS. This can be achieved through appointing a designated staff member, establishing a tracking system, and training HR managers in identifying and handling reports of racial discrimination. Incorporating diversity and inclusion considerations into professional development activities and providing staff with opportunities to actively participate in decision-making can also benefit their health. The NHS Workforce Race Equality Standard may need to broaden its scope to assess race equality effectively.
Total cerebral blood volume changes drive macroscopic cerebrospinal fluid flux in humans
Authors: Zimmermann Juliana , Boudriot Clara , Eipert Christiane , Hoffmann Gabriel , Nuttall Rachel , Neumaier Viktor , Bonhoeffer Moritz , Schneider Sebastian , Schmitzer Lena , Kufer Jan , Kaczmarz Stephan , Hedderich Dennis M , Ranft Andreas , Golkowski Daniel , Priller Josef , Zimmer Claus , Ilg Rüdiger , Schneider Gerhard , Preibisch Christine , Sorg Christian , Zott Benedikt 
Published: April 2023

AbstractIn the mammalian brain, the directed motion of cerebrospinal fluid (CSF-flux) is instrumental in the distribution and removal of solutes. Changes in total cerebral blood volume (CBV) have been hypothesized to drive CSF-flux. We tested this hypothesis in two multi-modal brain imaging experiments in healthy humans, in which we drove large changes in total CBV by neuronal burst-suppression under anesthesia, or by transient global vasodilation in a hypercapnic challenge. We developed a technique to monitor CBV changes based on associated changes in total brain volume by functional MRI (fMRI) and measured cerebral blood flow by arterial spin-labeling. Relating CBV-sensitive signals to fMRI-derived measures of macroscopic CSF flow across the basal cisternae, we demonstrate that increasing total CBV extrudes CSF from the skull and decreasing CBV allows its influx. Moreover, CSF largely stagnates when CBV is stable. Together, our results establish the direct coupling between total CBV changes and CSF-flux.
The influence of environment geometry on subiculum boundary vector cells in adulthood and early development
Authors: Muessig Laurenz , Rodrigues Fabio Ribeiro , Bjerknes Tale , Towse Ben , Barry Caswell , Burgess Neil , Moser Edvard I. , Moser May-Britt , Cacucci Francesca , Wills Thomas J. 
Published: April 2023

AbstractBoundaries to movement form a specific class of landmark information used for navigation: Boundary Vector Cells (BVCs) are neurons which encode an animal’s location as a vector displacement from boundaries. Here we report the first objective characterisation of the prevalence and spatial tuning of subiculum BVCs. Manipulations of boundary geometry reveal two novel features of BVC firing. Firstly, BVC directional tunings align with environment walls in squares, but are uniformly distributed in circles, demonstrating that environmental geometry alters BVC receptive fields. Secondly, inserted barriers uncover both excitatory and inhibitory components to BVC receptive fields, demonstrating that inhibitory inputs contribute to BVC field formation. During post-natal development, subiculum BVCs mature slowly, contrasting with the earlier maturation of boundary-responsive cells in upstream Entorhinal Cortex. However, Subiculum and Entorhinal BVC receptive fields are altered by boundary geometry as early as tested, suggesting this is an inherent feature of the hippocampal representation of space.
Oleic acid decouples fecundity and longevity via DAF-12 steroid hormone signaling inC. elegans
Authors: Nichitean Alexandra M. , Compere Frances V. , Hall Sarah E. 
Published: April 2023

SUMMARYIn animals, early-life starvation can program gene expression changes that result in profound effects on adult phenotypes. ForC. elegansnematodes, passage through the stress-resistant dauer diapause stage due to early-life starvation establishes a cellular memory that manifests as increased metabolism and decreased fecundity compared to continuously developed adults. To further investigate the connection between metabolism and reproduction, we supplemented the diet of postdauer adults with different fatty acids and examined their life history traits. Here, we show that dietary oleic acid (OA) supplementation uniquely increases the fecundity of both postdauer and continuously developed adults in a DAF-12 steroid signaling dependent manner, potentially through the increased expression offat-7Δ9-desaturase andvit-2vitellogen genes. In addition, OA may rescue increased ferroptosis in postdauer germ lines and has complex effects on adult lifespan depending on the animals’ life history. Together, our results suggest a model where OA modifies DAF-12 activity to positively regulate fecundity, metabolism, and lifespan in adults.
Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors
Authors: Xiao Zebin , Todd Leslie , Huang Li , Noguera-Ortega Estela , Lu Zhen , Huang Lili , Kopp Meghan , Li Yue , Pattada Nimisha , Zhong Wenqun , Guo Wei , Scholler John , Liousia Maria , Assenmacher Charles-Antoine , June Carl H. , Albelda Steven M. , Puré Ellen 
Published: April 2023

AbstractThe desmoplastic stroma in solid tumors presents a formidable challenge to immunotherapies that rely on endogenous or adoptively transferred T cells, however, the mechanisms are poorly understood. To define mechanisms involved, we treat established desmoplastic pancreatic tumors with CAR T cells directed to fibroblast activation protein (FAP), an enzyme highly overexpressed on a subset of cancer-associated fibroblasts (CAFs). Depletion of FAP+CAFs results in loss of the structural integrity of desmoplastic matrix. This renders these highly treatment-resistant cancers susceptible to subsequent treatment with a tumor antigen (mesothelin)-targeted CAR and to anti-PD1 antibody therapy. Mechanisms include overcoming stroma-dependent restriction of T cell extravasation and/or perivascular invasion, reversing immune exclusion, relieving T cell suppression, and altering the immune landscape by reducing myeloid cell accumulation and increasing endogenous CD8+T cell and NK cell infiltration. These data provide strong rationale for combining tumor stroma-and malignant cell-targeted therapies to be tested in clinical trials.
Machine Learning Ensemble Directed Engineering of Genetically Encoded Fluorescent Calcium Indicators
Authors: Wait Sarah J. , Rappleye Michael , Lee Justin Daho , Smith Netta , Berndt Andre 
Published: April 2023

AbstractReal-time monitoring of biological activity can be achieved through the use of genetically encoded fluorescent indicators (GEFIs). GEFIs are protein-based sensing tools whose biophysical characteristics can be engineered to meet experimental needs. However, GEFIs are inherently complex proteins with multiple dynamic states, rendering optimization one of the most challenging problems in protein engineering. Most GEFIs are engineered through trial-and-error mutagenesis, which is time and resource-intensive and often relies on empirical knowledge for each GEFI. We applied an alternative approach using machine learning to efficiently predict the outcomes of sensor mutagenesis by analyzing established libraries that link sensor sequences to functions. Using the GCaMP calcium indicator as a scaffold, we developed an ensemble of three regression models trained on experimentally derived GCaMP mutation libraries. We used the trained ensemble to perform an in silico functional screen on a library of 1423 novel, untested GCaMP variants. The mutations were predicted to significantly alter the fluorescent response, and off-rate kinetics were advanced for verification in vitro. We found that the ensemble’s predictions of novel variants’ biophysical characteristics closely replicated what we observed of the variants in vitro. As a result, we identified the novel ensemble-derived GCaMP (eGCaMP) variants, eGCaMP and eGCaMP+, that achieve both faster kinetics and larger fluorescent responses upon stimulation than previously published fast variants. Furthermore, we identified a combinatorial mutation with extraordinary dynamic range, eGCaMP2+, that outperforms the tested 6th, 7th, and 8th generation GCaMPs. These findings demonstrate the value of machine learning as a tool to facilitate the efficient prescreening of mutants for functional characteristics. By leveraging the learning capabilities of our ensemble, we were able to accelerate the identification of promising mutations and reduce the experimental burden associated with screening an entire library. Machine learning tools such as this have the potential to complement emerging high-throughput screening methodologies that generate massive datasets, which can be tedious to analyze manually. Overall, these findings have significant implications for developing new GEFIs and other protein-based tools, demonstrating the power of machine learning as an asset in protein engineering.
Assisting and Accelerating NMR Assignment with Restrained Structure Prediction
Authors: Liu Sirui , Chu Haotian , Xie Yuhao , Wu Fangming , Ni Ningxi , Wang Chenghao , Mu Fangjing , Wei Jiachen , Zhang Jun , Chen Mengyun , Li Junbin , Yu Fan , Fu Hui , Wang Shenlin , Tian Changlin , Wang Zidong , Gao Yi Qin 
Published: April 2023

AbstractNMR experiments can detect in situ structures and dynamic interactions, but the NMR assignment process requires expertise and is time-consuming, thereby limiting its applicability. Deep learning algorithms have been employed to aid in experimental data analysis. In this work, we developed a RASP model which can enhance structure prediction with restraints. Based on the Evoformer and structure module architecture of AlphaFold, this model can predict structure based on sequence and a flexible number of input restraints. Moreover, it can evaluate the consistency between the predicted structure and the imposed restraints. Based on this model, we constructed an iterative NMR NOESY peak assignment pipeline named FAAST, to accelerate assignment process of NOESY restraints and obtaining high quality structure ensemble. The RASP model and FAAST pipeline not only allow for the leveraging of experimental restraints to improve model prediction, but can also facilitate and expedite experimental data analysis with their integrated capabilities.
Viral pIC-pocketing: RSV sequestration of eIF4F Initiation Complexes into bi-phasic biomolecular condensates
Authors: Jobe Fatoumatta , Kelly James T. , Simpson Jennifer , Wells Joanna , Armstrong Stuart D , Spick Matt , Lacey Emily , Logan Leanne , Geifman Nophar , Hawes Philippa , Bailey Dalan 
Published: April 2023

AbstractOrthopneumoviruses characteristically form membrane-less cytoplasmic inclusion bodies (IBs) wherein RNA replication and transcription occur. Herein, we report a strategy whereby the orthopneumoviruses sequester various components of the eiF4FInitiationComplex machinery into viral IBs to facilitate translation of their own mRNAs; pIC-pocketing. Mass spectrometry analysis of sub-cellular fractions from RSV-infected cells identified significant modification of the cellular translation machinery; however; interestingly, ribopuromycylation assays showed no changes to global levels of translation. Electron micrographs of RSV-infected cells revealed bi-phasic organisation of IBs; specifically, spherical “droplets” nested within the larger inclusion. Using correlative light and electron microscopy (CLEM), combined with fluorescence in situ hybridisation (FISH), we showed that the observed bi-phasic morphology represents functional compartmentalisation of the IB and that these domains are synonymous with the previously reported inclusion body associated granules (IBAGs). Detailed analysis demonstrated that IBAGs concentrate nascent viral mRNA, the viral M2-1 protein as well as many components of the eIF4F complex, involved in translation initiation. Interestingly, although ribopuromycylation-based imaging indicates the majority of viral mRNA translation likely occurs in the cytoplasm, there was some evidence for intra-IBAG translation, consistent with the likely presence of ribosomes in a subset of IBAGs imaged by electron microscopy. The mechanistic basis for this pathway was subsequently determined; the viral M2-1 protein interacting with eukaryotic translation initiation factor 4G (eIF4G) to facilitate its transport between the cytoplasm and the separate phases of the viral IB. In summary, our data shows that IBs function to spatially regulate early steps in viral translation within a highly selective biphasic liquid organelle.