bluuebunny/crossref_metadata_2025_split huggingface dataset:
High spatial overlap but diverging age-related trajectories of cortical MRI markers aiming to represent intracortical myelin and microstructure
Authors: Parent Olivier , Olafson Emily , Bussy Aurélie , Tullo Stephanie , Blostein Nadia , Salaciak Alyssa , Bedford Saashi A. , Farzin Sarah , Béland Marie-Lise , Valiquette Vanessa , Tardif Christine L. , Devenyi Gabriel A. , Mallar Chakravarty M. 
Published: January 2022

AbstractCortical thickness (CT), gray-white matter contrast (GWC), boundary sharpness coefficient (BSC), and T1-weighted/T2-weighted ratio (T1w/T2w) are cortical metrics derived from standard T1- and T2-weighted magnetic resonance imaging (MRI) images that are often interpreted as representing or being influenced by intracortical myelin content. However, there is little empirical evidence to justify these interpretations nor have the homologies or differences between these measures been examined. We examined differences and similarities in group mean and age-related trends with the underlying hypothesis that different measures sensitive to similar changes in underlying myelo- and microstructural processes should be highly related. We further probe their sensitivity to cellular organization using the BigBrain, a high-resolution digitized volume stemming from a whole human brain histologically stained for cell bodies with the Merker stain.The measures were generated on both the MRI-derived images of 127 healthy subjects, aged 18 to 81, and on the BigBrain volume using cortical surfaces that were generated with the CIVET 2.1.0 pipeline. Comparing MRI markers between themselves, our results revealed generally high overlap in spatial distribution (i.e., group mean), but mostly divergent age trajectories in the shape, direction, and spatial distribution of the linear age effect. Significant spatial relationships were found between the BSC and GWC and their BigBrain equivalent, as well as a correlation approaching significance between the BigBrain intensities and the T1w/T2w ratio in gray matter (GM) both sampled at half cortical depth.We conclude that the microstructural properties at the source of spatial distributions of MRI cortical markers (e.g. GM myelin) can be different from microstructural changes that affect these markers in aging. While our findings highlight a discrepancy in the interpretation of the biological underpinnings of the cortical markers, they also highlight their potential complementarity, as they are largely independent in aging. Our BigBrain results indicate a general trend of GM T1w signal and myelin being spatially related to the density of cells, which is possibly more pronounced in superficial cortical layers.Highlights–Different MRI cortical markers aim to represent myelin and microstructure–These markers show high spatial overlap, but mostly divergent age trajectories–It is unlikely that myelin changes are the source of the age effect for all markers–Trend of MRI signal being related to cell density in more superficial cortical layers
Structural covariance and heritability of the optic tract and primary visual cortex in living human brains
Authors: Miyata Toshikazu , Benson Noah C. , Winawer Jonathan , Takemura Hiromasa 
Published: January 2022

AbstractIndividual differences among human brains exist at many scales, spanning gene expression, white matter tissue properties, and the size and shape of cortical areas. One notable example is an approximately 3-fold range in the size of human primary visual cortex (V1), a much larger range than is found in overall brain size. A previous study (Andrews et al., 1997) reported a correlation between optic tract cross-section area and V1 size in post-mortem human brains, suggesting that there may be a common developmental mechanism for multiple components of the visual pathways. We evaluated the relationship between properties of the optic tract and V1 in a much larger sample of living human brains by analyzing the Human Connectome Project 7 Tesla Retinotopy Dataset. This dataset includes retinotopic maps measured with functional MRI (fMRI) and fiber tract data measured with diffusion MRI (dMRI). We found a negative correlation between optic tract fractional anisotropy and V1 surface area (r= -0.2). This correlation, though small, was consistent across multiple dMRI datasets differing in acquisition parameters. Further, we found that both V1 size and optic tract properties were correlated among twins, with higher correlations for monozygotic than dizygotic twins, indicating a high degree of heritability for both properties. Together, these results demonstrate covariation across individuals in properties of the retina (optic tract) and cortex (V1) and show that each is influenced by genetic factors.Significance statementThe size of human primary visual cortex (V1) has large inter-individual differences. These differences cannot be explained by differences in overall brain size. A previous post-mortem study reported a correlation between the size of the human optic tract and V1. In this study, we evaluated the relationship between the optic tract and V1 in living humans by analyzing a neuroimaging dataset that included functional and diffusion MRI data. We found a small, but robust correlation between optic tract tissue properties and V1 size, supporting the existence of structural covariance between the optic tract and V1 in living humans. The results suggest that characteristics of retinal ganglion cells, reflected in optic tract measurements, are related to individual differences in human V1.
Cross-modality supervised image restoration enables nanoscale tracking of synaptic plasticity in living mice
Authors: Xu YKT , Graves AR , Coste GI , Huganir RL , Bergles DE , Charles AS , Sulam J 
Published: January 2022

SummarySynaptic plasticity encodes learning as changes in the strength of synapses, sub-micron structures that mediate communication between brain cells. Due to their small size and high density, synapses are extremely difficult to image in vivo, limiting our ability to directly relate synaptic plasticity with behavior. Here, we developed a combination of computational and biological methods to overcome these challenges. First, we trained a deep learning image restoration algorithm that combines the advantages of ex vivo super-resolution and in vivo imaging modalities to overcome limitations specific to each optical system. Applied to in vivo images from transgenic mice expressing fluorescently labeled synaptic proteins, this restoration algorithm super-resolved diffraction-limited synapses, enabling identification and logitudinal tracking of synaptic plasticity underlying behavior with unprecedented spatial resolution. More generally, our method demonstrates the capabilities of image enhancement to learn from ex vivo data and imaging techniques to improve in vivo imaging resolution.
Anterior insular cortex inputs to the dorsolateral striatum govern the maintenance of binge alcohol drinking
Authors: Haggerty David L. , Muñoz Braulio , Pennington Taylor , Di Prisco Gonzalo Viana , Grecco Gregory G. , Atwood Brady K. 
Published: January 2022

AbstractHow does binge drinking alcohol change synaptic function, and do these changes maintain binge consumption? The anterior insular cortex (AIC) and dorsolateral striatum (DLS) are brain regions implicated in alcohol use disorder. In mice, we found that binge drinking alcohol produced glutamatergic synaptic adaptations selective to AIC inputs within the DLS. Photoexciting AIC→DLS circuitry during binge drinking decreased alcohol, but not water consumption and altered alcohol drinking mechanics. Further, drinking mechanics alone from drinking session data predicted alcohol-related circuit changes. AIC→DLS manipulation did not alter operant, valence, or anxiety-related behaviors. These findings suggest that alcohol-mediated changes at AIC inputs govern behavioral sequences that maintain binge drinking and may serve as a circuit-based biomarker for the development of alcohol use disorder.
Extrinsic mortality and senescence: a guide for the perplexed
Authors: de Vries Charlotte , Galipaud Matthias , Kokko Hanna 
Published: January 2022

AbstractDo environments or species traits that lower the mortality of individuals create selection for delaying senescence? Reading the literature creates an impression that mathematically oriented biologists cannot agree on the validity of George Williams’ prediction (who claimed ‘yes’). The abundance of models and opinions may bewilder those that are new to the field. Here we provide heuristics as well as simple models that outline when the Williams prediction holds, why there is a ‘null model’ where extrinsic mortality does not change the evolution of senescence at all, and why it is also possible to expect the opposite of William’s prediction, where increased extrinsic mortality favours slower senescence. We hope to offer intuition by quantifying how much delaying the ‘placement’ of an offspring into the population reduces its expected contribution to the gene pool of the future. Our first example shows why sometimes increased extrinsic mortality has no effect (the null result), and why density dependence can change that. Thereafter, a model with ten different choices for population regulation shows that high extrinsic mortality favours fast life histories (Williams) if increasing density harms the production of juveniles or their chances to recruit into the population. If instead increasing density harms the survival of older individuals in a population, then high extrinsic mortality favours slow life histories (anti-Williams). We discuss the possibility that empirically found Williams-like patterns provide indirect evidence for population regulation operating via harming the production or fitness prospects of juveniles, as opposed to the survival of established breeders.
BA.1 and BA.2 sub-lineages of Omicron variant have comparable replication kinetics and susceptibility to neutralization by antibodies
Authors: Singh Janmejay , Panwar Aleksha , Anantharaj Anbalagan , Rani Chitra , Bhardwaj Monika , Kumar Parveen , Pargai Kamal , Chattopadhyay Partha , Devi Priti , Maurya Ranjeet , Mishra Pallavi , Pandey Anil Kumar , Pandey Rajesh , Medigeshi Guruprasad R. 
Published: January 2022

ABSTRACTThe Omicron variant of SARS-CoV-2 is capable of infecting unvaccinated, vaccinated and previously-infected individuals due to its ability to evade neutralization by antibodies. With three sub-lineages of Omicron emerging in the last four months, there is inadequate information on the quantitative antibody response generated upon natural infection with Omicron variant and whether these antibodies offer cross-protection against other sub-lineages of Omicron variant. In this study, we characterized the growth kinetics of Kappa, Delta and Omicron variants of SARS-CoV-2 in Calu-3 cells. Relatively higher amounts infectious virus titers, cytopathic effect and disruption of epithelial barrier functions was observed with Delta variant whereas infection with Omicron variant led to a more robust induction of interferon pathway, lower level of virus replication and mild effect on epithelial barrier. The replication kinetics of BA.1 and BA.2 sub-lineages of the Omicron variant were comparable in cell culture and natural Omicron infection in a subset of individuals led to a significant increase in binding and neutralizing antibodies to both BA.1 and BA.2 sub-lineages but these levels were lower than that produced against the Delta variant. Finally, we show that Cu2+, Zn2+ and Fe2+ salts inhibited in vitro RdRp activity but only Cu2+ and Fe2+ inhibited both the Delta and Omicron variants in cell culture. Thus, our results suggest that high levels of interferons induced upon infection with Omicron variant may counter virus replication and spread. Waning neutralizing antibody titers rendered subjects susceptible to infection by Omicron variant and natural Omicron infection elicits neutralizing antibodies that can cross-react with other sub-lineages of Omicron and other variants of concern.
Investigating the Characteristics of Genes and Variants Associated with Self-Reported Hearing Difficulty in Older Adults in the UK Biobank
Authors: Lewis Morag A. , Schulte Bradley A. , Dubno Judy R. , Steel Karen P. 
Published: January 2022

AbstractBackgroundAge-related hearing loss is a common, heterogeneous disease with a strong genetic component. More than 100 loci have been reported to be involved in human hearing impairment to date, but most of the genes underlying human adult-onset hearing loss remain unknown. Most genetic studies have focussed on very rare variants (such as family studies and patient cohort screens) or very common variants (genome-wide association studies). However, the contribution of variants present in the human population at intermediate frequencies is hard to quantify using these methods, and as a result, the landscape of variation associated with adult-onset hearing loss remains largely unknown.ResultsHere we present a study based on exome sequencing and self-reported hearing difficulty in the UK Biobank, a large-scale biomedical database. We have carried out variant load analyses using different minor allele frequency and impact filters, and compared the resulting gene lists to a manually-curated list of nearly 700 genes known to be involved in hearing in humans and/or mice. An allele frequency cutoff of 0.1, combined with a high predicted variant impact, was found to be the most effective filter settings for our analysis. We also found that separating the participants by sex produced markedly different gene lists. The gene lists obtained were investigated using gene ontology annotation, functional prioritisation and expression analysis, and this identified good candidates for further study.ConclusionsOur results suggest that relatively common as well as rare variants with a high predicted impact contribute to age-related hearing impairment, and that the genetic contributions to adult hearing difficulty may differ between the sexes. Our manually-curated list of deafness genes is a useful resource for candidate gene prioritisation in hearing loss.
Calprotectin and inflammation-associated serum biomarkers determine critical illness in COVID-19
Authors: Kassianides Georgios , Siampanos Athanassios , Poulakou Garyphalia , Adamis George , Rapti Aggeliki , Milionis Haralampos , Dalekos George N. , Petrakis Vasileios , Sympardi Styliani , Metallidis Symeon , Alexiou Zoi , Gkavogianni Theologia , Giamarellos-Bourboulis Evangelos J. , Theoharides Theoharis C. 
Published: January 2022

AbstractLittle is known on the key contributing factors towards progression into acute respiratory distress syndrome (ARDS) necessitating mechanical ventilation (MV) in COVID-19. We determined serum levels, within 24 hours of diagnosis, of alarmins, as well as pro- and anti-inflammatory molecules in asymptomatic, moderate, severe and intubated patients compared to non-infected comparators. Levels of the pro-inflammatory interleukin (IL)-8, IL-18, matrix metalloproteinase-9, platelet-derived growth factor (PDGF)-B and calprotectin (S100A8/A9) were specific drivers of ARDS. Levels of the anti-inflammatory IL-1ra and IL-33r were increased; IL-38 was increased only in asymptomatic patients, but significantly decreased in the more severe COVID-19 cases. Multivariate ordinal regression showed that pathways of IL-6, IL-33 and calprotectin gave significant probability for worse outcome. These results indicate a dysfunctional response to the presence of alarmins that may be used for prognosis and development of effective treatments.
The progressive loss of brain network fingerprints in Amyotrophic Lateral Sclerosis predicts clinical impairment
Authors: Romano Antonella , Lopez Emahnuel Trosi , Liparoti Marianna , Polverino Arianna , Minino Roberta , Trojsi Francesca , Bonavita Simona , Mandolesi Laura , Granata Carmine , Amico Enrico , Sorrentino Giuseppe , Sorrentino Pierpaolo 
Published: January 2022

ABSTRACTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by functional connectivity alterations in both motor and extra-motor brain regions. In network analysis, fingerprint represent a valid approach able to assess the subject-specific connectivity features of a given population. Here, we applied the Clinical Connectome Fingerprint (CCF) analysis to source-reconstructed magnetoencephalography (MEG) signals in a cohort of seventy-eight subjects: thirty-nine ALS patients and thirty-nine healthy controls. We set out to develop an identifiability matrix to assess the extent to which each subject was recognisable based on his/her connectome. The analysis was performed in all five canonical frequency bands. Then we built a multilinear regression model to test the ability of “clinical fingerprint” to predict the clinical evolution of disease assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-r), the King’s disease staging system and the Milano-Torino Staging (MiToS) disease staging system. We found a drop in patients’ identifiability in the alpha band compared to the healthy controls. Furthermore, the “clinical fingerprint” was predictive of ALSFRS-r (p=0.0397; β=32.8), King’s (p=0.0001; β= -7.40) and MiToS (p=0.0025; β= -4.9) scores and negatively correlated with King’s and MiToS scales according to Spearman’s correlation. Our results demonstrated the ability of the CCF approach in assessing the individual motor condition and its relationship with ALS disease. Thanks to the subject-specific characteristic of this approach, we hope that further exploration related to its clinical application may help improve the management of disease.
Critical success factors for high routine immunization performance: A case study of Nepal
Authors: Hester Kyra A , Sakas Zoe , Ellis Anna S. , Bose Anindya Sekhar , Darwar Roopa , Gautam Jhalak , Jaishwal Chandni , James Hanleigh , Keskinocak Pinar , Nazzal Dima , Ogutu Emily Awino , Rodriguez Katie , Zunino Francisco Castillo , Dixit Sameer , Bednarczyk Robert A. , Freeman Matthew C. ,   the Vaccine Exemplars Research Consortium
Published: January 2022

AbstractIntroductionThe essential components of a vaccine delivery system are well-documented, but robust evidence on how and why the related processes and implementation strategies drive catalytic improvements in vaccination coverage are not well established. To address this gap, we identified critical success factors that may have led to substantial improvements in routine childhood immunization coverage in Nepal from 2000 through 2019.MethodsWe identified Nepal as an exemplar in the delivery of early childhood vaccines through analysis of DTP1 and DTP3 coverage data. Through interviews and focus group discussions at the national, regional, district, health post, and community level, we investigated factors that contributed to high and sustained vaccine coverage. We conducted a thematic analysis through application of implementation science frameworks to determine critical success factors. We triangulated these findings with quantitative analyses using publicly available data.ResultsThe following success factors emerged: 1) Codification of health as a human right, along with other vaccine-specific legislation, ensured the stability of vaccination programming; 2) National and multi-national partnerships supported information sharing, division of labor, and mutual capacity building; 3) Pro-vaccine messaging through various mediums, which was tailored to local needs, generated public awareness; 4) Female Community Health Volunteers educated community members as trusted and compassionate neighbors; and 5) Cultural values fostered collective responsibility and community ownership of vaccine coverage.ConclusionThis case study of Nepal suggests that the success of its national immunization program relied on the engagement and understanding of the beneficiaries. The immunization program was supported by consistent and reliable commitment, collaboration, awareness, and collective responsibility between the government, community, and partners. These networks are strengthened through a collective dedication to vaccination programming and a universal belief in health as a human right.
Collaborative research methods and best practice with children and young people: Protocol for a mixed-method review of the health and social sciences literature
Authors: Nowland R. , Robertson L. , Farrelly N. , Roy A. , Sharpe D. , Harris C. , Morocza N. , Larkins C. 
Published: January 2022

AbstractIntroductionChildren and young people have the right to participate in research on matters that affect them, and their contribution improves research quality and insights from findings. Discrete participatory approaches are used across different disciplines. This review will provide a synthesis of existing literature from different disciplines by working with young people and adults experienced in participatory research to develop a broad definition of child and youth led research and to identify best practice.Methods and AnalysisComprehensive searches will be conducted in eight electronic databases (PsycINFO, Medline, CINAHL, Embase, SocINDEX, ASSIA: Applied Social Sciences Index and Abstracts (Proquest), Social Care Online and SCOPUS). Grey literature reports will also be sourced using Google searching. Eligible studies will be English language primary studies and reviews on collaborative research with children and young people (aged 5-25 years). Qualitative and quantitative data will be integrated in a single qualitative synthesis following the JBI convergent integrated approach. Study quality will be assessed by developed checklists based on existing participation tools co-created with the project steering group and co-creation activities with young people.Ethics and DisseminationEthical approval is not required as no primary data will be collected. The review will develop guidance on best practice for collaborative research with children and young people, synthesising learnings from a wide variety of disciplines. Dissemination will be via peer-reviewed publications, presentations at academic conferences and lay summaries for various stakeholders. Opportunities for co-creation of outputs will be sought with the young researchers and the project steering committee.PROSPERO registration number: CRD42021246378Article SummaryStrengths and limitations of the studyFirst systematic review to synthesise findings across different approaches to collaborative research with children and young peopleResearch focus, questions and analysis framework have been co-designed with young researchers experienced in participatory researchMixed method review methodology will enable an in-depth evidence synthesis across a disparate evidence baseProvides an interdisciplinary perspective on best practice for collaborative research with children and young people