bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity of SARS-CoV-2 Vaccine in Dialysis
Authors: Lacson Eduardo , Argyropoulos Christos P. , Manley Harold J. , Aweh Gideon , Chin Andrew I. , Salman Loay H. , Hsu Caroline M. , Johnson Doug S. , Weiner Daniel E. 
Published: April 2021

AbstractBackgroundPatients receiving maintenance dialysis represent a high risk, immune-compromised population with 15-25% COVID mortality rate who were unrepresented in clinical trials evaluated for mRNA vaccines’ emergency use authorization.MethodAll patients receiving maintenance dialysis that received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021 were included. We report seroresponse based on levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen (seropositive ≥2) using FDA-approved semi-quantitative chemiluminescent assay (ADVIA Centaur® XP/XPT COV2G).ResultsAmong 186 dialysis patients from 32 clinics in 8 states tested 23±8 days after receiving 2 vaccine doses, mean age was 68±12 years, with 47% women, 21% Black, 26% residents in long-term care facilities and 97% undergoing in-center hemodialysis. Overall seropositive rate was 165/186 (88.7%) with 70% at maximum titer and with no significant difference in seropositivity between BNT162b2/Pfizer (N=148) and mRNA-1273/Moderna (N=18) vaccines (88.1% vs. 94.4%, p=0.42). Among patients with COVID-19 history, seropositive rate was 38/38 (100%) with 97% at maximum titer.ConclusionMost patients receiving maintenance dialysis were seropositive after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. Early evidence suggests that vaccinated dialysis patients with prior COVID-19 develop robust antibody response. These results support an equitable and aggressive vaccination strategy for eligible dialysis patients, regardless of age, sex, race, ethnicity, or disability, to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.SignificanceIn this retrospective observational evaluation of SARS-CoV-2 mRNA vaccine response defined by detectable levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen of ≥2 in serum of patients receiving maintenance dialysis, 165/186 (88.7%) were found to be seropositive (with 70% at maximum titer) at least 14 days after completing the second dose. No significant differences were observed by race or other subgroup or by vaccine manufacturer. Therefore, an equitable and aggressive vaccination strategy for all eligible maintenance dialysis patients, regardless of age, sex, race, ethnicity, or disability, is warranted to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.
COVID-19 and mortality risk in patients with psychiatric disorders
Authors: Kirov George , Baker Emily 
Published: April 2021

AbstractCOVID-19 has already caused the deaths of over 2.5 million people worldwide. Patients with certain medical conditions and severe psychiatric disorders are at increased risk of dying from it. However, such people have a reduced life expectancy anyway, raising the question whether COVID-19 incurs a specific risk for such patients for dying, over and above the risk of dying from other causes.We analysed the UK Biobank data of half a million middle-aged participants from the UK. From the start of 2020 up to 24th January 2021, 894 participants had died from COVID-19 and another 4,562 had died from other causes. We demonstrate that the risk of dying from COVID-19 among patients with mental health problems, especially those with dementia, schizophrenia, or bipolar disorder, is increased compared to the risk of dying from other causes. This increase among patients with severe psychiatric disorders cannot be explained solely by the higher rate of diabetes or cardiovascular disorders.
Mental health in the UK Biobank: a roadmap to self-report measures and neuroimaging correlates
Authors: Dutt Rosie , Hannon Kayla , Easley Ty , Griffis Joseph , Zhang Wei , Bijsterbosch Janine 
Published: April 2021

AbstractThe UK Biobank (UKB) is a highly promising dataset for brain biomarker research into population mental health due to its unprecedented sample size and extensive phenotypic, imaging, and biological measurements. In this study, we aimed to provide a shared foundation for UKB neuroimaging research into mental health with a focus on anxiety and depression. We compared UKB self-report measures and revealed important timing effects between scan acquisition and separate online acquisition of some mental health measures. To overcome these timing effects, we introduced and validated the Recent Depressive Symptoms (RDS-4) score which we recommend for state-dependent and longitudinal research in the UKB. We furthermore tested univariate and multivariate associations between brain imaging derived phenotypes (IDPs) and mental health. Our results showed a significant multivariate relationship between IDPs and mental health, which was replicable. Conversely, effect sizes for individual IDPs were small. Test-retest reliability of IDPs was stronger for measures of brain structure than for measures of brain function. Taken together, these results provide benchmarks and guidelines for future UKB research into brain biomarkers of mental health.
Early memory deficits and extensive brain network disorganization in theAppNL-F/MAPTdouble knock-in mouse model of familial Alzheimer’s disease
Authors: Borcuk Christopher , Héraud Céline , Herbeaux Karine , Diringer Margot , Panzer Élodie , Scuto Jil , Hashimoto S , Saido T , Saito T , Goutagny Romain , Battaglia Demian , Mathis Chantal 
Published: April 2021

AbstractA critical challenge in current research on AD is to clarify the relationship between early neuropathology and network dysfunction associated to the emergence of subtle memory alterations which announce disease onset. In the present work, the new generationAppNL-F/MAPTdouble knock in (dKI) model was used to evaluate early stages of AD. The initial step of tau pathology was restricted to the perirhinal-entorhinal region, sparing the hippocampus. This discrete neuropathological sign was associated with deficits in the object-place associative memory, one of the earliest recognition memories affected in individuals at risk for developing AD. Analyses of task-dependent c-Fos activation was carried out in 22 brain regions across the medial prefrontal cortex, claustrum, retrosplenial cortex, and medial temporal lobe. Initial hyperactivity was detected in the entorhinal cortex and the claustrum of dKI mice. The retention phase was associated to reduced network efficiency especially across cingulate cortical regions, which may be caused by a disruption of information flow through the retrosplenial cortex. Moreover, the relationship between network global efficiency and memory performance in the WT could predict memory loss in the dKI, further linking reduced network efficiency to memory dysfunction. Our results suggest that early perirhinal-entorhinal pathology is associated with local hyperactivity which spreads towards connected regions such as the claustrum, the medial prefrontal cortex and ultimately the key retrosplenial hub which is needed to relay information flow from frontal to temporal lobes. The similarity between our findings and those reported in the earliest stages of AD suggests that theAppNL-F/MAPTdKI model has a high potential for generating key information on the initial stage of the disease.
Spontaneous visual preference for face-like stimuli is impaired in newly-hatched domestic chicks exposed to valproic acid during embryogenesis
Authors: Adiletta Alice , Pedrana Samantha , Rosa-Salva Orsola , Sgadò Paola 
Published: April 2021

AbstractOne of the most fascinating properties of the human brain is the capacity of newborn babies to recognize and orient to faces and simple schematic face-like patterns since the first hours of life. A striking feature of these social orienting mechanisms is their transversal appearance in remarkably diverse vertebrate species. Similar to newborn babies, also non-human primates and domestic chicks have been shown to express orienting responses to faces and schematic face-like patterns. More importantly, existing studies have hypothesized that early disturbances of these mechanisms represent one of the earliest biomarkers of social deficits in autism spectrum disorders (ASD). Recent data suggest that newborns at high risk for the disorder express altered responses to schematic face-like configurations. Here we modeled ASD in domestic chicks using the anticonvulsant valproic acid (VPA), and tested the animals for their predisposed preference towards schematic face-like configuration stimuli. We found that VPA impairs the chicks’ preference responses to the social stimuli. Based on the results shown here and in previous studies, we propose the domestic chicks as elective animal models to study early-emerging neurobehavioural markers and to investigate the biological mechanisms underlying face processing deficits in ASD.
To buffer or to be labile? A framework to disentangle demographic patterns and evolutionary processes
Authors: Santos Gabriel Silva , Salguero-Gómez Roberto , Dias André Tavares Corrêa , Kajin Maja 
Published: April 2021

AbstractUntil recently, natural selection was assumed to reduce temporal fluctuation in vital rates due to its negative effects on population dynamics – the so-called Demographic Buffering Hypothesis (DBH). After several failures to support the DBH in the two decades since it was first posited, an alternative hypothesis was suggested; the Demographic Lability Hypothesis (DLH), where population vital rates should track rather than buffer the environmental conditions. Despite the huge contribution of both hypotheses to comprehend the demographic strategies to cope the environmental stochasticity, it remains unclear if they represent two competing patterns or the extreme ends of a continuum encompassing all demographic strategies. To solve this historical debate, we unify several methods with an integrative theoretical approach where: i) using the sum of stochastic elasticity with respect to mean and variance – a first-order derivative approach – we rank species on a Buffering-Lability (DB-DL) continuum and ii) using the second-order derivative, we examine how vital rates are shaped by natural selection. Our framework, applied to 40 populations of 34 mammals, successfully placed the species on the DB-DL continuum. We could also link the species' position on the DB-DL continuum to their generation time and time to recovery. Moreover, the second-order derivative unveiled that vital rates with lower temporal variation are not necessarily under a strong pressure of stabilizing selection, as predicted by DBH and DLH. Our framework provides an important step towards unifying the different perspectives of DBH and DLH with key evolutionary concepts.
Clustering single-cell RNA-seq data by rank constrained similarity learning
Authors: Mei Qinglin , Li Guojun , Su Zhengchang 
Published: April 2021

AbstractMotivationRecent breakthroughs of single-cell RNA sequencing (scRNA-seq) technologies offer an exciting opportunity to identify heterogeneous cell types in complex tissues. However, the unavoidable biological noise and technical artifacts in scRNA-seq data as well as the high dimensionality of expression vectors make the problem highly challenging. Consequently, although numerous tools have been developed, their accuracy remains to be improved.ResultsHere, we introduce a novel clustering algorithm and tool RCSL (Rank Constrained Similarity Learning) to accurately identify various cell types using scRNA-seq data from a complex tissue. RCSL considers both local similarity and global similarity among the cells to discern the subtle differences among cells of the same type as well as larger differences among cells of different types. RCSL uses Spearman’s rank correlations of a cell’s expression vector with those of other cells to measure its global similarity, and adaptively learns neighbour representation of a cell as its local similarity. The overall similarity of a cell to other cells is a linear combination of its global similarity and local similarity. RCSL automatically estimates the number of cell types defined in the similarity matrix, and identifies them by constructing a block-diagonal matrix, such that its distance to the similarity matrix is minimized. Each block-diagonal submatrix is a cell cluster/type, corresponding to a connected component in the cognate similarity graph. When tested on 16 benchmark scRNA-seq datasets in which the cell types are well-annotated, RCSL substantially outperformed six state-of-the-art methods in accuracy and robustness as measured by three metrics.AvailabilityThe RCSL algorithm is implemented in R and can be freely downloaded athttps://github.com/QinglinMei/RCSL.Contactguojunsdu@gmail.com,zcsu@uncc.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
Network dynamics scale with levels of awareness
Authors: Coppola Peter , Spindler Lennart R.B. , Luppi Andrea I. , Adapa Ram , Naci Lorina , Allanson Judith , Finoia Paola , Williams Guy B. , Pickard John D. , Owen Adrian M. , Menon David K. , Stamatakis Emmanuel A. 
Published: April 2021

AbstractSmall world topologies are thought to provide a valuable insight into human brain organisation and consciousness. However, functional magnetic resonance imaging studies in consciousness have not yielded consistent results. Given the importance of dynamics for both consciousness and cognition, here we investigate how the diversity of brain dynamics pertaining to small world topology (quantified by sample entropy; dSW-E) scales with decreasing levels of awareness (i.e., sedation and disorders of consciousness). Paying particular attention to result reproducibility, we show that dSW-E is a consistent predictor of levels of awareness even when controlling for the underlying functional connectivity dynamics. We find that dSW-E of subcortical and cortical areas are predictive, with the former showing higher and more robust effect sizes across analyses. Consequently, we propose that the dynamic reorganisation of the functional information architecture, in particular of the subcortex, is a characteristic that emerges with awareness and has explanatory power beyond that of the complexity of dynamic functional connectivity.
The reserve of joint torque determines movement coordination
Authors: Faity Germain , Mottet Denis , Pla Simon , Froger Jérôme 
Published: April 2021

AbstractHumans coordinate biomechanical degrees of freedom to perform tasks at minimum cost. When reaching a target from a seated position, the trunk-arm-forearm coordination moves the hand to the well-defined spatial goal, while typically minimising hand jerk and trunk motion. However, due to fatigue or stroke, people visibly move the trunk more, and it is unclear what cost can account for this. Here we show that people recruit their trunk when the torque at the shoulder is too close to the maximum. We asked 26 healthy participants to reach a target while seated and we found that the trunk contribution to hand displacement increases from 11% to 27% when an additional load is handled. By flexing and rotating the trunk, participants spontaneously increase the reserve of anti-gravitational torque at the shoulder from 25% to 40% of maximal voluntary torque. Our findings provide hints on how to include the reserve of torque in the cost function of optimal control models of human coordination in healthy fatigued persons or in stroke victims.
Adaptive mossy cell circuit plasticity after status epilepticus
Authors: Butler Corwin R. , Westbrook Gary L. , Schnell Eric 
Published: April 2021

SummaryHilar mossy cells control network function in the hippocampus through both direct excitation and di-synaptic inhibition of dentate granule cells (DGCs). Substantial mossy cell loss occurs after epileptic seizures; however the contribution of surviving mossy cells to network activity in the reorganized dentate gyrus is unknown. To examine functional circuit changes after pilocarpine-induced status epilepticus, we optogenetically stimulated mossy cells in acute hippocampal slices. In control mice, activation of mossy cells produced monosynaptic excitatory and di-synaptic GABAergic currents in DGCs. In pilocarpine-treated mice, mossy cell density and excitation of DGCs were reduced in parallel, with only a minimal reduction in feedforward inhibition, enhancing the inhibition:excitation ratio. Surprisingly, mossy cell-driven excitation of parvalbumin-positive basket cells, the primary mediators of feed-forward inhibition, was maintained, indicating increased connectivity between surviving mossy cells and these targets. Our results suggest that mossy cell outputs reorganize following seizures, increasing their net inhibitory effect in the hippocampus.
Influence of Mpv17 on hair-cell mitochondrial homeostasis, synapse integrity, and vulnerability to damage in the zebrafish lateral line
Authors: Holmgren Melanie , Sheets Lavinia 
Published: April 2021

AbstractNoise exposure is particularly stressful to hair-cell mitochondria, which must produce enough energy to meet high metabolic demands as well as regulate local intracellular Ca2+concentrations. Mitochondrial Inner Membrane Protein 17 (Mpv17) functions as a non-selective channel and plays a role in maintaining mitochondrial homeostasis. In zebrafish, hair cells inmpv17a9/a9mutants displayed elevated levels of reactive oxygen species (ROS), elevated mitochondrial calcium, hyperpolarized transmembrane potential, and greater vulnerability to neomycin, indicating impaired mitochondrial function. Using a strong water current to overstimulate hair cells in the zebrafish lateral line, we observedmpv17a9/a9mutant hair cells were more vulnerable to morphological disruption and hair-cell loss than wild type siblings simultaneously exposed to the same stimulus. To determine the role of mitochondrial homeostasis on hair-cell synapse integrity, we surveyed synapse number inmpv17a9/a9mutants and wild type siblings as well as the sizes of presynaptic dense bodies (ribbons) and postsynaptic densities immediately following stimulus exposure. We observed mechanically injuredmpv17a9/a9neuromasts, while they lost a greater number of hair cells, lost a similar number of synapses per hair cell relative to wild type. Additionally, we quantified the size of hair cell pre- and postsynaptic structures and observed significantly enlarged wild type postsynaptic densities, yet relatively little change in the size ofmpv17a9/a9postsynaptic densities following stimulation. These results suggest impaired hair-cell mitochondrial activity influences synaptic morphology and hair-cell survival but does not exacerbate synapse loss following mechanical injury.
Evidence provided by high-impact cell culture studies does not support authors’ claims
Authors: Özkaya Ali Burak , Geyik Caner 
Published: April 2021

ABSTRACTBackgroundReliability of preclinical research is of critical concern. Previous studies demonstrate the low reproducibility in research and recommend raising standards to improve reproducibility and robustness. One understudied aspect of this quality issue is the harmony between the hypotheses and the experimental design in published work.Methods and findingsIn this study we focused on highly cited cell culture studies and investigated whether the claims of the study are backed with sufficient experimental evidence or not. We created an open access database containing all 282 claims asserted by 103 different high-impact articles as well as the results of this study. Our findings revealed that only 64% of all claims were sufficiently supported by evidence and there were concerning misinterpretations such as considering the results of tetrazolium salt reduction assays as indicators of cell death or apoptosis.ConclusionsOur analysis revealed an alarming discordance between the actual experimental findings and the way that the manuscript is written to discuss them in highly cited cell culture studies. In order to improve quality of pre-clinical research, we require a clear nomenclature by which different cell culture claims are distinctively categorized, materials and methods sections to be written more meticulously and cell culture techniques to be selected and utilized more carefully.
fMRI Informed Montage Selection for Transcranial Electrical Stimulation: Frontoparietal Synchronization for Drug Cue Reactivity
Authors: Soleimani Ghazaleh , Kupliki Rayus , Bodurka Jerzy , Paulus Martin , Ekhtiari Hamed 
Published: April 2021

AbstractBackgroundFrontoparietal network (FPN) with multiple cortical nodes is involved in executive functions. Transcranial electrical stimulation (tES) can potentially modulate interactions between these nodes using frontoparietal synchronization (FPS). Here we used fMRI and computational head models (CHMs) to inform electrode montage and dosage selection in FPS.MethodsSixty methamphetamine users completed an fMRI drug cue-reactivity task. Two sets of 4×1 HD electrodes with anode over F3 and F4 were simulated and spheres around maximum electric field in each hemisphere were defined as frontal seeds. Using frontal seeds, a task-based functional connectivity analysis was conducted based on a seed-to-whole brain generalized psychophysiological interaction (gPPI). Electrode placement for parietal sites was selected based on gPPI results. Task-based and resting-state connectivity were compared between fMRI-informed and classic F3-P3/F4-P4 montages.ResultsWhole-brain gPPI showed two significant clusters (left: 506 voxels P=0.006, right: 455 voxels P=0.016), located in the inferior parietal lobule under the CP5 and CP6 electrode location. Pair-wise ROI-based gPPI comparing informed (F3-CP5/F4-CP6) and classic (F3-P3/F4-P4) montages showed significant increased PPI and resting-state connectivity only in the informed montage. Cue-induced craving score was also correlated with left (F3-CP5) frontoparietal connectivity in the fMRI-informed montage.ConclusionThis study proposes an analytic pipeline to select electrode montage and dosage in dual site tES using CHMs and task-based connectivity. Stimulating F3-F4 can tap into both FPN and saliency network (SN) based on the montage selection. Using CHM and fMRI will be essential to navigating ample parameter space in the stimulation protocols for future tES studies.HighlightsWe demonstrated a methodology for montage selection in network-based tESTask-based functional connectivity can inform dual-site tES montage selectionHead models can help to induce balance tES dose in targeted brain regionsTargeting DLPFC with tES can tap into both saliency and frontoparietal networksLower resting-state frontoparietal connectivity before cue exposure followed by a greater craving