bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare workers’ perceptions and medically approved COVID-19 infection risk: understanding the mental health dimension of the pandemic. A German hospital case study
Authors: Kuhlmann Ellen , Behrens Georg M. N. , Cossmann Anne , Homann Stefanie , Happle Christine , Dopfer-Jablonka Alexandra 
Published: March 2022

AbstractIntroductionThis study analyses how healthcare workers (HCWs) perceived risks, protection and preventive measures during the COVID-19 pandemic in relation to medically approved risks and organisational measures. The aim is to explore ‘blind spots’ of pandemic protection and make mental health needs of HCWs visible.MethodsWe have chosen an ‘optimal-case’ scenario of a high-income country with a well-resourced hospital sector and low HCW infection rate at the organisational level to explore governance gaps in HCW protection. A German multi-method hospital study at Hannover Medical School served as empirical case; document analysis, expert information and survey data (n=1163) were collected as part of a clinical study into SARS-CoV-2 serology testing during the second wave of the pandemic (November 2020-February 2021). Selected survey items included perceptions of risks, protection and preventive measures. Descriptive statistical analysis and regression were undertaken for gender, profession and COVID-19 patient care.ResultsThe results reveal a low risk of 1% medically approved infections among participants, but a much higher mean personal risk estimate of 15%. The majority (68.4%) expressed ‘some’ to ‘very strong’ fear of acquiring infection at the workplace. Individual protective behaviour and compliance with protective workplace measures were estimated as very high. Yet only about half of the respondents felt strongly protected by the employer; 12% even perceived ‘no’ or ‘little’ protection. Gender and contact with COVID-19 patients had no significant effect on the estimations of infection risks and protective workplace behaviour, but nursing was correlated with higher levels of personal risk estimations and fear of infection.ConclusionsA strong mismatch between low medically approved risk and personal risk perceptions of HCWs brings stressors and threats into view, that may be preventable through better information and risk communication and through investment in mental health and inclusion in pandemic preparedness plans.
COVID-19 mortality among working-age Americans in 46 states, by industry and occupation
Authors: Chen Yea-Hung , Chen Ruijia , Charpignon Marie-Laure , Kiang Mathew V , Riley Alicia R , Glymour M Maria , Bibbins-Domingo Kirsten , Stokes Andrew C 
Published: March 2022

AbstractIntroductionA small body of epidemiological research suggests that working in an essential sector is a risk factor for SARS-CoV-2 infection or subsequent disease or mortality. However, there is limited evidence to date on the US, or on how the risks associated with essential work differ across demographic subgroups defined by age, sex, and race/ethnicity.MethodsUsing publicly available data from the National Center for Health Statistics on deaths occurring in the US in 2020, we calculated per-capita COVID-19 mortality by industry and occupation. We additionally calculated per-capita COVID-19 mortality by essential industry—essential or not—by age group, sex, and race/ethnicity.ResultsAmong non-military individuals and individuals with a known industry or occupation, there were 48,030 reported COVID-19 deaths, representing 25.1 COVID-19 deaths per 100,000 working-age individuals after age standardization. Per-capita age-standardized COVID-19 mortality was 1.96 times higher among essential workers than among workers in non-essential industries, representing an absolute difference of 14.9 per 100,000. Across industry, per-capita age-standardized COVID-19 mortality was highest in the following industries: accommodation and food services (45.4 per 100,000); transportation and warehousing (43.4); agriculture, forestry, fishing and hunting (42.3); mining (39.6); and construction (38.7).DiscussionGiven that SARS-CoV-2 is an airborne virus, we call for collaborative efforts to ensure that workplace settings are properly ventilated and that workers have access to effective masks. We also urge for paid sick leave, which can help increase vaccine access and minimize disease transmission.
Severe outcomes in unvaccinated COVID-19 cases <18 years during different variant waves in Norway
Authors: Whittaker Robert , Greve-Isdahl Margrethe , Bøås Håkon , Suren Pål , Buanes Eirik Alnes , Veneti Lamprini 
Published: March 2022

AbstractObjectivesWe used linked individual-level data from national registries to compare the risk of severe outcomes among unvaccinated COVID-19 cases <18 years between waves of the SARS-CoV-2 Alpha, Delta and Omicron variants in Norway.MethodsOur outcomes were hospitalisation with acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C). We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable log-binomial regression, adjusting for variant wave, demographic characteristics and underlying comorbidities.ResultsWe included 10,538 Alpha (21 hospitalised with acute COVID-19, 7 MIS-C), 42,362 Delta (28 acute COVID-19, 14 MIS-C) and 82,907 Omicron wave cases (48 acute COVID-19, 7 MIS-C). The risk of hospitalisation with acute COVID-19 in cases <1 year was lower in the Delta (aRR: 0.28, 95% CI: 0.16–0.89) and Omicron wave (aRR: 0.41, 95% CI: 0.20–0.81), compared to the Alpha wave. We found no difference in the risk for this outcome for Omicron compared to Delta in any age group. The risk of MIS-C was lower in the Omicron wave compared to the Alpha (aRR: 0.09, 95% CI: 0.03–0.27) and Delta wave (aRR: 0.26, 95% CI: 0.10–0.63).ConclusionsWe found no evidence of a difference in the risk of hospitalisation due to acute COVID-19 among unvaccinated cases <18 years for Omicron compared to Delta, but a reduced risk among cases <1 year in Omicron and Delta waves, compared to Alpha. Results also suggest a decrease in the risk of MIS-C in the Omicron wave compared to the Alpha and Delta waves.Article SummaryWe compare the risk of severe outcomes in unvaccinated COVID-19 cases <18 years between waves of the SARS-CoV-2 Alpha, Delta and Omicron variant in Norway.What’s Known on This SubjectCurrently, limited evidence suggests no clear difference in the risk of severe disease outcomes among children infected with different SARS-CoV-2 variants. The risk of multisystem inflammatory syndrome in children following infection with the Omicron variant has not been quantified.What This Study AddsWe find a lower risk of hospitalisation due to acute COVID-19 among cases <1 year in the Delta and Omicron waves compared to the Alpha wave, and a lower risk of multisystem inflammatory syndrome in the Omicron wave, in Norway.
NOMe-HiC: joint profiling of genetic variants, DNA methylation, chromatin accessibility, and 3D genome in the same DNA molecule
Authors: Fu Hailu , Zheng Haizi , Chen Xiaoting , Weirauch Matthew T. , Muglia Louis J. , Wang Li , Liu Yaping 
Published: March 2022

AbstractCis-regulatory elements coordinate the regulation of their targeted genes’ expression. However, the joint measurement of cis-regulatory elements’ activities and their interactions in spatial proximity is limited by the current sequencing approaches. We describe a method, NOMe-HiC, which simultaneously captures single nucleotide polymorphisms, DNA methylation, chromatin accessibility (GpC methyltransferase footprints), and chromosome conformation changes from the same DNA molecule, together with the transcriptome, in a single assay. NOMe-HiC shows high concordance with state-of-the-art mono-omic assays across different molecular measurements and reveals coordinated chromatin accessibility at distal genomic segments in spatial proximity and novel types of long-range allele-specific chromatin accessibility.
Memory reactivation in slow wave sleep enhances relational learning
Authors: Santamaria Lorena , Kashif Ibad , McGinley Niall , Lewis Penelope A. 
Published: March 2022

AbstractSleep has been shown to boost the integration of memories, and thus to facilitate relational learning. This benefit is thought to rely upon memory reactivation during non-REM sleep. We set out to test this possibility by explicitly cueing such reactivation using a technique called targeted memory reactivation (TMR), in which sounds are paired with learned material in wake and then softly played back to the participant in sleep, triggering reactivation of the associated memories. Specifically, we tested whether TMR during slow wave sleep leads to enhancements in inferential thinking in a transitive inference task. Because the Up-phase of the slow oscillation is more responsive to external cues than the Down-phase, we also asked whether stimulation at this specific phase is more beneficial for such integration. Our data show that Up-phase TMR boosts the ability to make inferences, but only for the most distant inferential leaps. Such stimulation was also associated with detectable memory reinstatement, whereas Down-phase stimulation produced no such trace and led to below-chance performance. These findings demonstrate that cueing memory reactivation at the right time points in sleep can provide a direct benefit to difficult relational learning problems.Significance StatementMemory reactivation in sleep is thought to be important for integrative thinking. We examined this by explicitly cueing reactivation of a transitive inference task during slow wave sleep using Targeted Memory Reactivation (TMR). Because TMR at different phases of the slow oscillation has different impacts, we cued different hierarchies at Up and Down phases. Up-phase TMR enhanced inferential performance and was associated with classifiable memory reactivation. Conversely, Down-phase TMR lead to a short-term impairment in inferential thinking and no detectable reactivation. These findings provide the first evidence that TMR can boost transitive inference and is thus important for integration and reasoning.
Protein language models trained on multiple sequence alignments learn phylogenetic relationships
Authors: Lupo Umberto , Sgarbossa Damiano , Bitbol Anne-Florence 
Published: March 2022

AbstractSelf-supervised neural language models with attention have recently been applied to biological sequence data, advancing structure, function and mutational effect prediction. Some protein language models, including MSA Transformer and AlphaFold’s EvoFormer, take multiple sequence alignments (MSAs) of evolutionarily related proteins as inputs. Simple combinations of MSA Transformer’s row attentions have led to state-of-the-art unsupervised structural contact prediction. We demonstrate that similarly simple, and universal, combinations of MSA Transformer’s column attentions strongly correlate with Hamming distances between sequences in MSAs. There-fore, MSA-based language models encode detailed phylogenetic relationships. We further show that these models can separate coevolutionary signals encoding functional and structural constraints from phylogenetic correlations reflecting historical contingency. To assess this, we generate synthetic MSAs, either without or with phylogeny, from Potts models trained on natural MSAs. We find that unsupervised contact prediction is substantially more resilient to phylogenetic noise when using MSA Transformer versus inferred Potts models.
Measurement of plant water status via static uniaxial compression of the leaf lamina
Authors: Fuenzalida Tomás I. , Binks Oliver , Bryant Callum J. , Wolfe Joe , Ball Marilyn C. 
Published: March 2022

AbstractTurgor pressure is an essential, but difficult to measure indicator of plant water status. Turgor has been quantified by localised compression of cells or tissues, but a simple method to perform these measurements is lacking. We hypothesized that changes in leaf turgor pressure can be monitored by uniaxially compressing the leaf lamina and measuring the mechanical stress under a constrained thickness (stress relaxation); and that changes in leaf water content can be monitored by measuring the thickness of the leaf lamina compressed under a constant force (creep). Using a custom-built leaf squeeze-flow rheometer, we performed different compression tests on leaves from thirteen plant species. The equilibrium mechanical stress measured during stress relaxation was correlated with leaf turgor pressure (R2 > 0.95) and thus with leaf water potential (R2 > 0.94); the equilibrium leaf thickness measured during creep was correlated with relative water content (R2 > 0.74). The coefficients of these relationships were related to the leaf osmotic pressure at the turgor-loss point. An idealised average-cell model suggests that, under isothermal conditions, the bulk cell stiffness during compression is largely determined by the leaf osmotic pressure. Our study presents an inexpensive, accessible and automatable method to monitor plant water status non-invasively.
Inhibiting presynaptic calcium channel mobility in the auditory cortex suppresses synchronized input processing
Authors: Deane Katrina E. , Klymentiev Ruslan , Heck Jennifer , Mark Melanie D. , Ohl Frank W. , Heine Martin , Happel Max F. K. 
Published: March 2022

AbstractThe emergent coherent population activity from thousands of stochastic neurons in the brain is believed to constitute a key neuronal mechanism for salient processing of external stimuli and its link to internal states like attention and perception. In the sensory cortex, functional cell assemblies are formed by recurrent excitation and inhibitory influences. The stochastic dynamics of each cell involved is largely orchestrated by presynaptic CAV2.1 voltage-gated calcium channels (VGCCs). Cav2.1 VGCCs initiate the release of neurotransmitters from the presynaptic compartment and are therefore able to add variability into synaptic transmission which can be partly explained by their mobile organization around docked vesicles. To investigate the relevance of Cav2.1 channel surface mobility for the input processing in the primary auditory cortex (A1) in vivo, we make use of a new optogenetic system which allows us to acutely cross-link Cav2.1 VGCCs via a photo-cross-linkable cryptochrome mutant, CRY2olig. In order to map neuronal activity across all cortical layers of the A1, we performed laminar current-source density (CSD) recordings with varying auditory stimulus sets in transgenic mice with a citrine tag on the N-terminus of the VGCCs. Clustering VGCCs suppresses overall sensory-evoked population activity, particularly when stimuli lead to a highly synchronized distribution of synaptic inputs. Our findings reveal the importance of membrane dynamics of presynaptic calcium channels for sensory encoding by dynamically adjusting network activity across a wide range of synaptic input strength.Statement of SignificanceVoltage Gated Calcium Channel (VGCC) mobility plays an important role in neuronal firing dynamics. Failure of these channels to function or be regulated has been linked to migraine and ataxia. We here link the microscopic process of VGCC mobility to the mesoscopic population dynamics as a mechanism to regulate and appropriately amplify synaptic inputs of different strengths to the mouse primary auditory cortex. We also demonstrate a novel and effective technique with which VGCC function can be further explored in meso- or macroscopic scales and with behaving subjects. We believe that this is of importance to the broader scientific community in aspects of non-linear scaling in the brain, potential translational applications, and basic research on cortical mechanisms of physiological function.
Mechanism and consequence of daily modulation of cortical parvalbumin-positive inhibitory neurons
Authors: Zong Fang-Jiao , Zhang Xue-Ting , Zhang Yan , Min Xia , Liu Yang , He Kai-Wen 
Published: March 2022

AbstractParvalbumin-positive (PV) neurons, the main class of inhibitory neurons in the neocortex, play critical roles in maintaining normal brain function and are implicated in a variety of brain disorders. Here we found that their function is modulated in a time- and sleep-dependent manner naturally during the day. We first show that PV-evoked inhibition is stronger by the end of the light (ZT12) compared to the end of dark (ZT0) cycle. In addition, both PV’s excitatory and inhibitory synaptic transmission slowly oscillate but in the opposite directions during the light/dark cycle. Whereas excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep. Mechanistically, we found that the daily regulation of PV’s inhibitory synapses is mediated by acetylcholine activating M1 receptors. Consistent with our ex vivo findings, we show in vivo that PV’s spontaneous activity display clear oscillation, which is opposite to that of the pyramidal neurons. Finally, we demonstrate that the daily changes in PV neural activity negatively correlate with the dLGN-evoked responses in V1, underscoring the physiological significance of PV’s daily regulation.
Intracellular Aβ42 aggregation leads to cellular thermogenesis
Authors: Chung Chyi Wei , Stephens Amberley D. , Konno Tasuku , Ward Edward , Avezov Edward , Kaminski Clemens F. , Hassanali Ali , Kaminski Schierle Gabriele S. 
Published: March 2022

AbstractThe aggregation of Aβ42 is a hallmark of Alzheimer’s disease. It is still not known what the biochemical changes are inside a cell which will eventually lead to Aβ42 aggregation. Thermogenesis has been associated with cellular stress, the latter of which may promote aggregation. We perform intracellular thermometry measurements using fluorescent polymeric thermometers (FPTs) to show that Aβ42 aggregation in live cells leads to an increase in cell-averaged temperatures. This rise in temperature is mitigated upon treatment with an aggregation inhibitor of Aβ42 and is independent of mitochondrial damage that can otherwise lead to thermogenesis. With this, we present a diagnostic assay which could be used to screen small-molecule inhibitors to amyloid proteins in physiologically relevant settings. To interpret our experimental observations and motivate the development of future models, we perform classical molecular dynamics of model Aβ peptides to examine the factors that hinder thermal disspation. We observe that this is controlled by the presence of ions in its surrounding environment, the morphology of the amyloid peptides and the extent of its hydrogen-bonding interactions with water. We show that aggregation and heat retention by Aβ peptides are favoured under intracellular-mimicking ionic conditions, which could potentially promote thermogenesis. The latter will, in turn, trigger further nucleation events that accelerate disease progression.
Influenza A virus RNA Polymerase targets the chromatin of innate immune response genes
Authors: Yi Jia , Morel Jessica , Costallat Mickaël , Lejal Nathalie , Delmas Bernard , Muchardt Christian , Batsché Eric 
Published: March 2022

AbstractThe influenza A virus (IAV) profoundly affects host cell nuclear processes to accommodate for its transcription. In particular, the IAV RNA polymerase (FluPol) associates with host genes to snatch capped 5’-ends from nascent messenger RNAs, that are then used to prime viral transcription. The extend of FluPol-host gene interaction and its actual consequence on host transcription are still poorly characterized. We show here, using genome-wide approaches, that the PA, PB1, and PB2 subunits of FluPol establish contacts with both chromatin and RNA transcripts at promoters, but also within the coding region of genes. These interactions also reach into downstream regions where recruitment of FluPol subunits correlates with previously reported transcription termination defects induced by IAV, indicative of an implication of the FluPol in this viral strategy to limit host cell defense by interfering with transcription re-initiation. The latter is further suggested by a bias in the FluPol genomic targets, enriched in genes associated with anti-viral defense. Together, our observations suggest that FluPol-chromatin binding contributes to targeted dampening of host immune response pathways.
CRISPRi screen for enhancing heterologous α-amylase yield in Bacillus subtilis
Authors: Geissler Adrian Sven , Fehler Annaleigh Ohrt , Poulsen Line Dahl , González-Tortuero Enrique , Kallehauge Thomas Beuchert , Alkan Ferhat , Anthon Christian , Seemann Stefan Ernst , Rasmussen Michael Dolberg , Breüner Anne , Hjort Carsten , Vinther Jeppe , Gorodkin Jan 
Published: March 2022

AbstractEnhancing yield during bacterial enzyme production could have positive economic and environmental impacts. For cell factories, such improvements in yields could potentially be obtained by fine-tuning the metabolic processes and their regulatory mechanisms for gene candidates. In pursuit of such candidates, we performed RNA-sequencing of two α-amylase producing Bacillus strains and predict hundreds of putative novel non-coding transcribed regions. Complex operons that are regulated by a wide variety of transcription factors, non-coding and structured RNAs add to the challenge of finding yield-affecting candidates. Surprisingly, we found that non-coding genomic regions are proportionally undergoing the highest changes in expression during fermentation (75% of novel RNA predictions had absolute logFC > 2). Since these classes of RNA are also understudied, we targeted the corresponding genomic regions with CRIPSRi knockdown to test for any potential impact on the yield. From differentially expressed annotations, including both novel candidate and prior annotated ncRNAs, we selected 53 non-coding candidates. The targeting with CRISPRi knockdowns transcription in a genomic region on both the sense and the antisense strand. Thus, the CRISPRi experiment cannot link causes for yield changes to the sense or antisense disruption. Nevertheless, we observed on several instances with strong changes in enzyme yield. The knockdown targeting the genomic region for a putative antisense RNA of the 3’ UTR of the skfA-skfH operon led to a 21% increase in yield. In contrast, the knockdown targeting the genomic regions of putative antisense RNAs of the cytochrome c oxidase subunit 1 (ctaD), the sigma factor sigH, and the uncharacterized gene yhfT decreased yields by 31 to 43%.
S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress
Authors: Godbole Adwait A. , Gopalan Sneha , Nguyen Thien-Kim , Munden Alexander , Vo Paula , Lewis Caroline A. , Spinelli Jessica B. , Fazzio Thomas G. , Walker Amy K. 
Published: March 2022

AbstractMethylation is a widely occurring modification that requires the methyl donor S-adenosylmethionine (SAM) and acts in regulation of gene expression and other processes. SAM is synthesized from methionine, which is imported or generated through the 1-carbon cycle (1CC). Alterations in 1CC function have clear effects on lifespan and stress responses, but the wide distribution of this modification has made identification of specific mechanistic links difficult. Exploiting a dynamic stress-induced transcription model, we find that two SAM synthases inCaenorhabditis elegans, SAMS-1 and SAMS-4, contribute differently to modification of H3K4me3, gene expression and survival. We find thatsams-4enhances H3K4me3 in heat shocked animals lackingsams-1, however,sams-1cannot compensate forsams-4, which is required to survive heat stress. This suggests that the regulatory functions of SAM depend on its enzymatic source and that provisioning of SAM may be an important regulatory step linking 1CC function to phenotypes in aging and stress.