bluuebunny/crossref_metadata_2025_split huggingface dataset:
The experiences of 33 national COVID-19 dashboard teams during the first year of the pandemic in the WHO European Region: a qualitative study
Authors: Barbazza Erica , Ivanković Damir , Davtyan Karapet , Poldrugovac Mircha , Yelgezekova Zhamin , Willmington Claire , Meza-Torres Bernardo , Bos Véronique L.L.C. , Fernandes Óscar Brito , Rotar Alexandru , Nuti Sabina , Vainieri Milena , Carinci Fabrizio , Azzopardi-Muscat Natasha , Groene Oliver , Novillo-Ortiz David , Klazinga Niek , Kringos Dionne 
Published: November 2021

AbstractBackgroundGovernments across the WHO European Region prioritized dashboards for reporting COVID-19 data. The ubiquitous use of dashboards for public reporting is novel. This study explores the development of COVID-19 dashboards during the pandemic’s first year and common barriers, enablers and lessons from the experiences of teams responsible for their development.MethodsMultiple methods were applied to identify and recruit COVID-19 dashboard teams using a purposive, quota sampling approach. Semi-structured group interviews were conducted between April– June 2021. Using elaborative coding and thematic analysis, descriptive and explanatory themes were derived from interview data. A validation workshop with study participants was held in June 2021.ResultsEighty informants, representing 33 national COVID-19 dashboard teams across the WHO European Region participated. Most dashboards were launched swiftly in the first months of the pandemic, between February–May 2020. The urgency, intense workload, limited human resources, data and privacy constraints, and public scrutiny were common to the initial development stage. Themes related to barriers or enablers were identified pertaining to the pre-pandemic context, pandemic itself, people and processes, software, data, and users. Lessons emerged around the themes of simplicity, trust, partnership, software and data, and change.ConclusionsCOVID-19 dashboards were developed in a learning-by-doing approach. The experiences of teams signal initial under-preparedness was compensated by high-level political endorsement, the professionalism of teams, accelerated data improvements, and immediate support of commercial software solutions. To leverage the full potential of dashboards, investments are needed at team-, national- and pan-European-level.
Higher Limbic and Basal Ganglia volumes in surviving COVID-negative patients and the relations to fatigue
Authors: Hafiz Rakibul , Gandhi Tapan Kumar , Mishra Sapna , Prasad Alok , Mahajan Vidur , Di Xin , Natelson Benjamin H. , Biswal Bharat B. 
Published: November 2021

AbstractBackgroundAmong systemic abnormalities caused by the novel coronavirus, little is known about the critical attack on the central nervous system (CNS). Few studies have shown cerebrovascular pathologies that indicate CNS involvement in acute patients. However, replication studies are necessary to verify if these effects persist in COVID-19 survivors more conclusively. Furthermore, recent studies indicate fatigue is highly prevalent among ‘long-COVID’ patients. How morphometry in each group relate to work-related fatigue need to be investigated.MethodCOVID survivors were MRI scanned two weeks after hospital discharge. We hypothesized, these survivors will demonstrate altered gray matter volume (GMV) and experience higher fatigue levels when compared to healthy controls, leading to stronger correlation of GMV with fatigue. Voxel-based morphometry was performed on T1-weighted MRI images between 46 survivors and 30 controls. Unpaired two-sample t-test and multiple linear regression were performed to observe group differences and correlation of fatigue with GMV.ResultsThe COVID group experienced significantly higher fatigue levels and GMV of this group was significantly higher within the Limbic System and Basal Ganglia when compared to healthy controls. Moreover, while a significant positive correlation was observed across the whole group between GMV and self-reported fatigue, COVID subjects showed stronger effects within the Posterior Cingulate, Precuneus and Superior Parietal Lobule.ConclusionBrain regions with GMV alterations in our analysis align with both single case acute patient reports and current group level neuroimaging findings. We also newly report a stronger positive correlation of GMV with fatigue among COVID survivors within brain regions associated with fatigue, indicating a link between structural abnormality and brain function in this cohort.
A RANDOMIZED CLINICAL TRIAL OF 2-WEEK METHOTREXATE DISCONTINUATION IN RHEUMATOID ARTHRITIS PATIENTS VACCINATED WITH INACTIVATED SARS-COV-2 VACCINE
Authors: Araujo Carlo S R , Medeiros-Ribeiro Ana C , Saad Carla G S , Bonfiglioli Karina R , Domiciano Diogo S , Shimabuco Andrea Y , Silva Matheus R , Yuki Emily F N , Pasoto Sandra G , Pedrosa Tatiana N , Kupa Leonard , Zou Gioanna , Pereira Rosa M R , Silva Clovis A , Aikawa Nadia E , Bonfa Eloisa 
Published: November 2021

AbstractObjectivesTo evaluate the effect on immunogenicity and safety of 2-week methotrexate(MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in rheumatoid arthritis(RA) patients.MethodsThis was a single-center, prospective, randomized, investigator-blinded, intervention study (#NCT04754698, CoronavRheum), including adult RA patients(stable CDAI<10, prednisone<7.5mg/day), randomized(1:1) to withdraw MTX(MTX-hold) for 2 weeks after each vaccine dose or maintain MTX(MTX-maintain), evaluated at D0, D28 and D69. Co-primary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion(SC) and neutralizing antibody(NAb) positivity at D69. Secondary outcomes were GMT and changes in disease activity scores. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and, for safety reasons, those unable to hold MTX twice(CDAI>10 at D28).ResultsRandomization included 138 patients with 9 exclusions(5 COVID-19, 4 protocol violations). Safety evaluation included 60(MTX-hold) and 69(MTX-maintain) patients. Further exclusions consisted of 27 patients[13(21.7%) vs. 14(20.3%),p=0.848] with positive baseline IgG/NAb and 10 patients(21.3%) in MTX-hold with CDAI>10 at D28. At D69, a higher increase in SC[29(78.4%) vs 30(54.5%),p=0.019] was observed in MTX-hold(n=37) in comparison to MTX-maintain(n=55), with parallel augmentation in GMT[34.2(25.2-46.4) vs 16.8(11.9-23.6),p=0.006]. No differences were observed for NAb positivity[23(62.2%) vs 27(49.1%),p=0.217]. Longitudinal variations in disease activity scores were alike in both groups(CDAI,p=0.144; DAS28-CRP,p=0.718).ConclusionWe provided novel data that 2-week MTX withdrawal after each vaccine dose improves anti-SARS-CoV-2 immunogenicity. The comparable longitudinal variations of disease activity in both groups suggest that discontinuation is a feasible and efficient strategy in well-controlled RA patients, and may be even safer for vaccines with longer interval between doses or single dose schedules.FundingFAPESP/CNPq/B3-Bolsa de Valores-Brasil.
Haplotype-resolved powdery mildew resistance loci reveal the impact of heterozygous structural variation on NLR genes inMuscadinia rotundifolia
Authors: Massonnet Mélanie , Vondras Amanda M. , Cochetel Noé , Riaz Summaira , Pap Dániel , Minio Andrea , Figueroa-Balderas Rosa , Walker M. Andrew , Cantu Dario 
Published: November 2021

AbstractMuscadinia rotundifoliacv. Trayshed is a valuable source of resistance to grape powdery mildew. It carries two powdery mildew resistance-associated genetic loci,Run1.2on chromosome 12 andRun2.2on chromosome 18. In this study, we identified, phased, and reconstructed the two haplotypes of each resistance-associated locus. Haplotype phasing allowed the identification of several structural variation events between haplotypes of both loci. Combined with manual refinement of the gene models, we found that the heterozygous structural variants affected the gene content, with some resulting in duplicated or hemizygous nucleotide-binding leucine-rich repeat (NLR) genes. Structural variations also impacted the domain composition of some NLRs. These findings emphasize the need of generating haplotype-resolved sequences instead of using consensus sequences for identifying haplotype-specific candidate genes. Comparison of the NLRs in theRun1.2andRun2.2loci indicated that the two loci are composed of a different number and classes of NLR genes. We provide a list of candidate NLR genes from theRun1.2bandRun2.2loci, whose expression suggests a role in powdery mildew resistance in Trayshed. These first complete and haplotype-resolved resistance-associated loci, and their candidate NLR genes, represent new resources to develop powdery mildew-resistant grape cultivars.
Resting state functional connectivity in relapsing remitting multiple sclerosis with mild disability – a data driven, whole brain multi-voxel pattern analysis study
Authors: Nair Gowthami , Nair Sruthi S. , Arun K. M. , Camacho Paul , Bava Elshal , Ajayaghosh Priya , Menon Ramshekhar N. , Nair Muralidharan , Kesavadas Chandrasekharan , Anteraper Sheeba Arnold 
Published: November 2021

ABSTRACTBackgroundMultivoxel pattern analysis (MVPA) has emerged as a powerful unbiased approach for generating seed regions of interest (ROIs) in resting-state functional connectivity (RSFC) analysis in a data-driven manner. Studies exploring RSFC in multiple sclerosis have produced diverse and often incongruent results.ObjectivesThe aim of the present study was to investigate RSFC differences between persons with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC).MethodsWe performed a whole-brain connectome-wide MVPA in 50 RRMS patients with expanded disability status scale ≤4 and 50 age and gender-matched HCs.ResultsSignificant group differences were noted in RSFC in three clusters distributed in the following regions; anterior cingulate gyrus, right middle frontal gyrus, and frontal medial cortex. Whole-brain seed-to-voxel RSFC characterization of these clusters as seed ROIs revealed network-specific abnormalities, specifically in the anterior cingulate cortex and the default mode network.ConclusionsThe network-wide RSFC abnormalities we report agree with the previous findings in RRMS, the cognitive and clinical implications of which are discussed herein.IMPACT STATEMENTThis study investigated resting state functional connectivity (RSFC) in relapsing remitting multiple sclerosis (RRMS) persons with mild disability (expanded disability status scale ≤4). Whole-brain connectome-wide multivoxel pattern analysis (MVPA) was used for assessing RSFC. Compared to healthy controls (HC), we were able to identify three regions of interest for significant differences in connectivity patterns, which were then extracted as a mask for whole-brain seed-to-voxel analysis. A reduced connectivity was noted in the RRMS group, particularly in the anterior cingulate cortex and the default mode network regions, providing insights into the RSFC abnormalities in RRMS.
Chemo-mechanical Diffusion Waves Orchestrate Collective Dynamics of Immune Cell Podosomes
Authors: Gong Ze , van den Dries Koen , Cambi Alessandra , Shenoy Vivek B. 
Published: November 2021

AbstractImmune cells, such as macrophages and dendritic cells, can utilize podosomes, actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. In these cells, individual podosomes exhibit periodic protrusion and retraction cycles (vertical oscillations) to probe their microenvironment, while multiple podosomes arranged in clusters demonstrate coordinated wave-like spatiotemporal dynamics. However, the mechanisms governing both the individual vertical oscillations and the coordinated oscillation waves in clusters remain unclear. By integrating actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling, we develop a chemo-mechanical model for both the oscillatory growth of individual podosomes and wave-like dynamics in clusters. Our model reveals that podosomes show oscillatory growth when the actin polymerization-associated protrusion and the signaling-associated myosin contraction occur at similar rates, while the diffusion of actin monomers within the cluster drives mesoscale coordination of individual podosome oscillations in an apparent wave-like fashion. Our model predicts the influence of different pharmacological treatments targeting myosin activity, actin polymerization, and mechanosensitive pathways, as well as the impact of the microenvironment stiffness on the wavelengths, frequencies, and speeds of the chemo-mechanical waves. Overall, our integrated theoretical and experimental approach reveals how collective wave dynamics arise due to the coupling between chemo-mechanical signaling and actin diffusion, shedding light on the role of podosomes in immune cell mechanosensing within the context of wound healing and cancer immunotherapy.
A family of cell wall transglutaminases is essential for appressorium development and pathogenicity in Phytophthora infestans
Authors: Brus-Szkalej Maja , Andersen Christian B. , Vetukuri Ramesh R. , Grenville-Briggs Laura J. 
Published: November 2021

SummaryTransglutaminases (TGases) are enzymes highly conserved among prokaryotic and eukaryotic organisms, where their role is to catalyse protein cross-linking. One of the putative TGases of Phytophthora infestans has previously been shown to be localised to the cell wall. Based on sequence similarity we were able to identify six more genes annotated as putative TGases and show that these seven genes group together in phylogenetic analysis. All of the seven proteins are predicted to contain transmembrane helices and both a TGase domain and a MANSC domain, the latter of which was previously shown to play a role in protein stability. Chemical inhibition of transglutaminase activity and silencing of the entire family of the putative cell wall TGases are both lethal to P. infestans indicating the importance of these proteins in cell wall formation and stability. The intermediate phenotype obtained with lower drug concentrations and less efficient silencing displays a number of deformations to germ tubes and appressoria. Both chemically treated and silenced lines show lower pathogenicity than the wild type in leaf infection assays. Finally, we show that appressoria of P. infestans possess the ability to build up turgor pressure and that this ability is decreased by chemical inhibition of TGases.
Alpha oscillations and stimulus-evoked activity dissociate metacognitive reports of attention, visibility and confidence in a rapid visual detection task
Authors: Davidson Matthew J , Macdonald James S.P. , Yeung Nick 
Published: November 2021

AbstractVariability in the detection and discrimination of weak visual stimuli has been linked to oscillatory neural activity. In particular, the amplitude of activity in the alpha-band (8-12 Hz) has been shown to impact upon the objective likelihood of stimulus detection, as well as measures of subjective visibility, attention, and decision confidence. We aimed to clarify how preparatory alpha influences performance and phenomenology, by recording simultaneous subjective measures of attention and confidence (Experiment 1), or attention and visibility (Experiment 2) on a trial-by-trial basis in a visual detection task. Across both experiments, alpha amplitude was negatively and linearly correlated with the intensity of subjective attention. In contrast to this linear relationship, we observed a quadratic relationship between the strength of alpha oscillations and subjective ratings of confidence and visibility. We find that this same quadratic relationship links alpha amplitude to the strength of stimulus evoked responses. Visibility and confidence judgements corresponded to the strength of evoked responses, but confidence, uniquely, incorporated information about attentional state. As such, our findings reveal distinct psychological and neural correlates of metacognitive judgements of attentional state, stimulus visibility, and decision confidence.
Transection injury differentially alters the proteome of the human sural nerve
Authors: Chau Monica J. , Quintero Jorge E. , Blalock Eric , Samaan Christopher , Gerhardt Greg , van Horne Craig 
Published: November 2021

AbstractRegeneration after severe peripheral nerve injury is often poor. Knowledge of human nerve regeneration and the growth microenvironment is greatly lacking. We aimed to identify the regenerative proteins in human peripheral nerve by comparing the proteome before and after a transection injury. In a unique study design, we collected from the same participants, samples from naïve and degenerating sural nerve. Naïve and degenerating (two weeks after injury) samples were analyzed using mass spectrometry and immunoassays. Using a correlation matrix, we found significantly altered levels following the nerve injury. Mass spectrometry revealed that post-injury samples had 672 proteins significantly upregulated and 661 significantly downregulated compared to naïve samples (q < 0.05, |FC| > 2). We used Gene Ontology pathways to highlight groups of proteins that were significantly upregulated or downregulated with injury-induced degeneration and regeneration. Significant protein changes in key pathways were identified including growth factor levels, Schwann cell de-differentiation, myelination downregulation, epithelial-mesenchymal transition, and axonal regeneration pathways. Having proteome signatures of human peripheral nerves of both the uninjured and the degenerating/regenerating state may serve as biomarkers to aid in the future development of repair strategies and in monitoring neural tissue regeneration.
Tom70-based transcriptional regulation of mitochondrial biogenesis and aging
Authors: Liu Qingqing , Chang Catherine E. , Wooldredge Alexandra C. , Fong Benjamin , Kennedy Brian K. , Zhou Chuankai 
Published: November 2021

AbstractMitochondrial biogenesis has two major steps: the transcriptional activation of nuclear genome-encoded mitochondrial proteins and the import of nascent mitochondrial proteins that are synthesized in the cytosol. These nascent mitochondrial proteins are aggregation-prone and can cause cytosolic proteostasis stress. The transcription factor-dependent transcriptional regulations and the TOM-TIM complex-dependent import of nascent mitochondrial proteins have been extensively studied. Yet, little is known regarding how these two steps of mitochondrial biogenesis coordinate with each other to avoid the cytosolic accumulation of these aggregation-prone nascent mitochondrial proteins. Here we show that in budding yeast, Tom70, a conserved receptor of the TOM complex, moonlights to regulate the transcriptional activity of mitochondrial proteins. Tom70’s transcription regulatory role is conserved in Drosophila. The dual roles of Tom70 in both transcription/biogenesis and import of mitochondrial proteins allow the cells to accomplish mitochondrial biogenesis without compromising cytosolic proteostasis. The age-related reduction of Tom70, caused by reduced biogenesis and increased degradation of Tom70, is associated with the loss of mitochondrial membrane potential, mtDNA, and mitochondrial proteins. While loss of Tom70 accelerates aging and age-related mitochondrial defects, overexpressing TOM70 delays these mitochondrial dysfunctions and extends the replicative lifespan. Our results reveal unexpected roles of Tom70 in mitochondrial biogenesis and aging.
Categorical encoding of voice in human superior temporal cortex
Authors: Rupp Kyle , Hect Jasmine , Remick Madison , Ghuman Avniel , Chandrasekaran Bharath , Holt Lori L. , Abel Taylor J. 
Published: November 2021

AbstractThe ability to recognize abstract features of voice during auditory perception is a complex, yet poorly understood, feat of human audition. For the listener, this occurs in near-automatic fasion to seamlessly extract complex cues from a highly variable auditory signal. Voice perception depends on specialized regions of auditory cortex, including superior temporal gyrus (STG) and superior temporal sulcus (STS). However, the nature of voice encoding at the cortical level remains poorly understoood. We leverage intracerebral recordings across human auditory cortex during presentation of voice and non-voice acoustic stimuli to examine voice encoding in auditory cortex, in eight patient-participants undergoing epilepsy surgery evaluation. We show that voice-selectivity increases along the auditory hierarchy from supratemporal plane (STP) to the STG and STS. Results show accurate decoding of vocalizations from human auditory cortical activity even in the complete absence of linguistic content. These findings show an early, less-selective temporal window of neural activity in the STG and STS followed by a sustained, strongly voice-selective window. We then developed encoding models that demonstrate divergence in the encoding of acoustic features along the auditory hierarchy, wherein STG/STS responses were best explained by voice category as opposed to the acoustic features of voice stimuli. This is in contrast to neural activity recorded from STP, in which responses were accounted for by acoustic features. These findings support a model of voice perception that engages categorical encoding mechanisms within STG and STS.Significance StatementVoice perception occurs via specialized networks in higher order auditory cortex, yet how voice features are encoded remains a central unanswered question. With human intracerebral recordings of auditory cortex, we provide evidence for categorical encoding of voice in STG and STS and occurs in the absence of linguistic content. This selectivity strengthens after an initial onset response and cannot be explained by simple acoustic features. Together, these data support the existence of sites within STG and STS that are specialized for voice perception.
A target expression threshold dictates invader defense and autoimmunity by CRISPR-Cas13
Authors: Vialetto Elena , Yu Yanying , Collins Scott P. , Wandera Katharina G. , Barquist Lars , Beisel Chase L. 
Published: November 2021

SUMMARYImmune systems must recognize and clear foreign invaders without eliciting autoimmunity. CRISPR-Cas immune systems in prokaryotes manage this task by following two criteria: extensive guide:target complementarity and a defined target-flanking motif. Here we report an additional requirement for RNA-targeting CRISPR-Cas13 systems: expression of the target transcript exceeding a threshold. This finding is based on targeting endogenous non-essential transcripts, which rarely elicited dormancy through collateral RNA degradation. Instead, eliciting dormancy required over-expressing targeted transcripts above a threshold. A genome-wide screen confirmed target expression levels as the principal determinant of cytotoxic autoimmunity and revealed that the threshold shifts with the guide:target pair. This expression threshold ensured defense against a lytic bacteriophage yet allowed tolerance of a targeted beneficial gene expressed from an invading plasmid. These findings establish target expression levels as a third criterion for immune activation by RNA-targeting CRISPR-Cas systems, buffering against autoimmunity and distinguishing pathogenic and benign invaders.HIGHLIGHTSCas13-induced dormancy requires RNA target levels to exceed an expression thresholdThe expression threshold can prevent cytotoxic self-targeting for endogenous transcriptsThe threshold shifts depending on the CRISPR RNA guide:target pairThe threshold allows cells to distinguish pathogenic and benign infections