bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-dependent spatial specificity of high-resolution fMRI: insights into mesoscopic neurovascular coupling
Authors: Fukuda Mitsuhiro , Poplawsky Alexander J. , Kim Seong-Gi 
Published: November 2020

High-resolution functional magnetic resonance imaging (fMRI) is becoming increasingly popular because of the growing availability of ultra-high magnetic fields which are capable of improving sensitivity and spatial resolution. However, it is debatable whether increased spatial resolutions for haemodynamic-based techniques, like fMRI, can accurately detect the true location of neuronal activity. We have addressed this issue in functional columns and layers of animals with haemoglobin-based optical imaging and different fMRI contrasts, such as blood oxygenation level-dependent, cerebral blood flow and cerebral blood volume fMRI. In this review, we describe empirical evidence primarily from our own studies on how well these fMRI signals are spatially specific to the neuronally active site and discuss insights into neurovascular coupling at the mesoscale.
This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
More than just summed neuronal activity: how multiple cell types shape the BOLD response
Authors: Howarth Clare , Mishra Anusha , Hall Catherine N. 
Published: November 2020

Functional neuroimaging techniques are widely applied to investigations of human cognition and disease. The most commonly used among these is blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. The BOLD signal occurs because neural activity induces an increase in local blood supply to support the increased metabolism that occurs during activity. This supply usually outmatches demand, resulting in an increase in oxygenated blood in an active brain region, and a corresponding decrease in deoxygenated blood, which generates the BOLD signal. Hence, the BOLD response is shaped by an integration of local oxygen use, through metabolism, and supply, in the blood. To understand what information is carried in BOLD signals, we must understand how several cell types in the brain—local excitatory neurons, inhibitory neurons, astrocytes and vascular cells (pericytes, vascular smooth muscle and endothelial cells), and their modulation by ascending projection neurons—contribute to both metabolism and haemodynamic changes. Here, we review the contributions of each cell type to the regulation of cerebral blood flow and metabolism, and discuss situations where a simplified interpretation of the BOLD response as reporting local excitatory activity may misrepresent important biological phenomena, for example with regards to arousal states, ageing and neurological disease.
This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Separating vascular and neuronal effects of age on fMRI BOLD signals
Authors: Tsvetanov Kamen A. , Henson Richard N. A. , Rowe James B. 
Published: November 2020

Accurate identification of brain function is necessary to understand the neurobiology of cognitive ageing, and thereby promote well-being across the lifespan. A common tool used to investigate neurocognitive ageing is functional magnetic resonance imaging (fMRI). However, although fMRI data are often interpreted in terms of neuronal activity, the blood oxygenation level-dependent (BOLD) signal measured by fMRI includes contributions of both vascular and neuronal factors, which change differentially with age. While some studies investigate vascular ageing factors, the results of these studies are not well known within the field of neurocognitive ageing and therefore vascular confounds in neurocognitive fMRI studies are common. Despite over 10 000 BOLD-fMRI papers on ageing, fewer than 20 have applied techniques to correct for vascular effects. However, neurovascular ageing is not only a confound in fMRI, but an important feature in its own right, to be assessed alongside measures of neuronal ageing. We review current approaches to dissociate neuronal and vascular components of BOLD-fMRI of regional activity and functional connectivity. We highlight emerging evidence that vascular mechanisms in the brain do not simply control blood flow to support the metabolic needs of neurons, but form complex neurovascular interactions that influence neuronal function in health and disease.This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Levels of biological plausibility
Authors: Love Bradley C. 
Published: November 2020

Notions of mechanism, emergence, reduction and explanation are all tied to levels of analysis. I cover the relationship between lower and higher levels, suggest a level of mechanism approach for neuroscience in which the components of a mechanism can themselves be further decomposed and argue that scientists' goals are best realized by focusing on pragmatic concerns rather than on metaphysical claims about what is ‘real'. Inexplicably, neuroscientists are enchanted by both reduction and emergence. A fascination with reduction is misplaced given that theory is neither sufficiently developed nor formal to allow it, whereas metaphysical claims of emergence bring physicalism into question. Moreover, neuroscience's existence as a discipline is owed to higher-level concepts that prove useful in practice. Claims of biological plausibility are shown to be incoherent from a level of mechanism view and more generally are vacuous. Instead, the relevant findings to address should be specified so that model selection procedures can adjudicate between competing accounts. Model selection can help reduce theoretical confusions and direct empirical investigations. Although measures themselves, such as behaviour, blood-oxygen-level-dependent (BOLD) and single-unit recordings, are not levels of analysis, like levels, no measure is fundamental and understanding how measures relate can hasten scientific progress.This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.
Rude mechanicals in brain haemodynamics: non-neural actors that influence blood flow
Authors: Das Aniruddha , Murphy Kevin , Drew Patrick J. 
Published: November 2020

Fluctuations in blood oxygenation and flow are widely used to infer brain activity during resting-state functional magnetic resonance imaging (fMRI). However, there are strong systemic and vascular contributions to resting-state signals that are unrelated to ongoing neural activity. Importantly, these non-neural contributions to haemodynamic signals (or ‘rude mechanicals’) can be as large as or larger than the neurally evoked components. Here, we review the two broad classes of drivers of these signals. One is systemic and is tied to fluctuations in external drivers such as heart rate and breathing, and the robust autoregulatory mechanisms that try to maintain a constant milieu in the brain. The other class comprises local, active fluctuations that appear to be intrinsic to vascular tissue and are likely similar to active local fluctuations seen in vasculature all over the body. In this review, we describe these non-neural fluctuations and some of the tools developed to correct for them when interpreting fMRI recordings. However, we also emphasize the links between these vascular fluctuations and brain physiology and point to ways in which fMRI measurements can be used to exploit such links to gain valuable information about neurovascular health and about internal brain states.
This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Specific immune-regulatory transcriptional signatures reveal sex and age differences in SARS-CoV-2 infected patients
Authors: Freire Paula Paccielli , Marques Alexandre H. C. , Baiocchi Gabriela Crispim , Schimke Lena F. , Fonseca Dennyson Leandro M. , Salgado Ranieri Coelho , Filgueiras Igor Salerno , da Silva Napoleao Sarah Maria , Plaça Desirée Rodrigues , Hirata Thiago Dominguez Crespo , El Khawanky Nadia , Giil Lasse Melvaer , de Miranda Gustavo Cabral , Carvalho Robson Francisco , de Souza Ferreira Luis Carlos , Condino-Neto Antonio , Nakaya Helder Takashi Imoto , Jurisica Igor , Ochs Hans D. , Camara Niels Olsen Saraiva , Calich Vera Lúcia Garcia , Cabral-Marques Otavio 
Published: November 2020

ABSTRACTThe coronavirus disease 2019 (COVID-19) fatality rate varies in different patient groups. However, the underlying mechanisms that explain this variation are poorly understood. Here, we reanalyzed and integrated public RNAseq datasets of nasopharyngeal swabs and peripheral blood leukocytes from patients with SARS-CoV-2, comparing transcription patterns according to sex, age, and viral load. We found that female and young patients infected by SARS-CoV-2 exhibited a similar transcriptomic pattern with a larger number of total (up- and downregulated) differentially expressed genes (DEGs) compared to males and elderly patients. The transcriptional analysis showed a sex-specific profile with a higher transcriptional modulation of immune response-associated genes in female and young subjects against SARS-CoV-2. The functional clustering was characterized by a highly correlated interferome network of cytokine/chemokine- and neutrophil-associated genes that were enriched both in nasopharyngeal cells and peripheral blood of COVID-19 patients. Females exhibited reduced transcriptional levels of key pro-inflammatory/neutrophil-related genes such as CXCL8 receptors (CXCR1/CXCR2), IL-1β, S100A9, ITGAM, and DBNL compared to males, which correlate with a protective gene expression profile against inflammatory damage. Our data indicate specific immune-regulatory pathways associated with sex and age of patients infected with SARS-CoV-2. These results point out therapeutic targets to reduce morbidity and mortality of COVID-19.
Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response
Authors: Shields Adrian M , Faustini Sian E , Perez-Toledo Marisol , Jossi Sian , Allen Joel D , Al-Taei Saly , Backhouse Claire , Dunbar Lynsey , Ebanks Daniel , Emmanuel Beena , Faniyi Aduragbemi A , Garvey Mark I. , Grinbergs Annabel , McGinnell Golaleh , O’Neill Joanne , Watanabe Yasunori , Crispin Max , Wraith David. C , Cunningham Adam F , Drayson Mark T , Richter Alex G 
Published: November 2020

AbstractObjectiveTo determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19.DesignA retrospective cohort study of healthcare workers who had self-isolated due to COVID-19.SettingUniversity Hospitals Birmingham NHS Foundation Trust, UK (UHBFT).Participants956 health care workers were recruited by open invitation via UHBFT trust email and social media.InterventionParticipants volunteered a venous blood sample that was tested for the presence of anti-SARS-CoV-2 spike glycoprotein antibodies. Results were interpreted in the context of the symptoms of their original illness and ethnodemographic variables.ResultsUsing an assay that simultaneously measures the combined IgG, IgA and IgM response against the spike glycoprotein (IgGAM), the overall seroprevalence within this cohort was 46.2% (n=442/956). The seroprevalence of immunoglobulin isotypes was 36.3%, 18.7% and 8.1% for IgG, IgA and IgM respectively. IgGAM identified serological responses in 40.6% (n=52/128) of symptomatic individuals who reported a negative SARS-CoV-2 PCR test. Increasing age, non-white ethnicity and obesity were independently associated with greater IgG antibody response against the spike glycoprotein. Self-reported fever and fatigue were associated with greater IgG and IgA responses against the spike glycoprotein. The combination of fever and/or cough and/or anosmia had a positive predictive value of 92.3% for seropositivity.Conclusions and relevanceAssays employing combined antibody detection demonstrate enhanced seroepidemiological sensitivity and can detect prior viral exposure even when PCR swabs have been negative. We demonstrate an association between known ethnodemographic risk factors associated with mortality from COVID-19 and the magnitude of serological responses in mild-to-moderate disease. The combination of cough, and/or fever and/or anosmia identifies the majority of individuals who should self-isolate for COVID-19.
The prevalence of psychological distress and relationships with social fragmentation and isolation: a geospatial study and survey in rural Australia
Authors: Forcadela Victor , Bagheri Nasser , Slimings Claudia 
Published: November 2020

AbstractPurposeThere is limited data on the effects of social isolation on rural mental health. The aim of this study was to describe the prevalence of psychological distress in a rural area of Australia while exploring the association between psychological distress and social isolation at the individual and area level.MethodsAn online cross-sectional survey of 408 adult volunteers was conducted across rural south-eastern New South Wales from October 2019 to April 2020. The Kessler 10 was used to measure psychological distress, while area-level social fragmentation was assessed using the family (ANSFIfam) and mobility (ANSFImob) components of the Australian Neighbourhood Social Fragmentation Index. The number of different occupations of people known socially was used to assess individual-level social isolation. Spatial analysis was performed to identify any spatial autocorrelation.ResultsThe prevalence of high psychological distress in the sample was 29%. Using logistic regression models, there was little evidence of a relationship between high psychological distress and ANSFIfam (odds ratio (OR)=0.98, 95% confidence interval (CI)=0.93–1.03), or ANSFImob (OR=1.04, 95%CI=0.99–1.09). High psychological distress also did not appear to be associated with number of occupations known socially (OR=1.00, 95%CI=0.99–1.00). There was no significant spatial autocorrelation of psychological distress or social fragmentation at the postal area level.ConclusionThe results suggest that social fragmentation or isolation may not have a significant effect on psychological distress in a rural setting. Nevertheless, further investigation of the effects of social isolation on mental health in rural areas is warranted.
High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease
Authors: Soria María Eugenia , Cortón Marta , Martínez-González Brenda , Lobo-Vega Rebeca , Vázquez-Sirvent Lucía , López-Rodríguez Rosario , Almoguera Berta , Mahillo Ignacio , Mínguez Pablo , Herrero Antonio , Taracido Juan Carlos , Macías-Valcayo Alicia , Esteban Jaime , Fernandez-Roblas Ricardo , Gadea Ignacio , Ruíz-Hornillos Javier , Ayuso Carmen , Perales Celia 
Published: November 2020

AbstractCOVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work is to determine a possible association between the viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we have clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or exitus. Here we report a statistically significant correlation between viral load and disease severity, being high viral load associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity, and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce the viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.
Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection
Authors: Mpande Cheleka A.M. , Rozot Virginie , Mosito Boitumelo , Musvosvi Munyaradzi , Dintwe One B , Bilek Nicole , Hatherill Mark , Scriba Thomas J. , Nemes Elisa ,   the ACS Study Team
Published: November 2020

AbstractBackgroundRecent Mycobacterium tuberculosis (M.tb) infection is associated with a higher risk of progression to tuberculosis disease, compared to persistent infection after remote exposure. However, current immunodiagnostic tools fail to distinguish between recent and remote infection. We aimed to characterise the immunobiology associated with acquisition of M.tb infection and identify a biomarker that can distinguish recent from remote infection.MethodsHealthy South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion <6 months) and persistent (QuantiFERON-TB+ for >1.5 year) infection. We characterized M.tb-specific CD4 T cell functional (IFN-γ, TNF, IL-2, CD107, CD154), memory (CD45RA, CCR7, CD27, KLRG-1) and activation (HLA-DR) profiles by flow cytometry after CFP-10/ESAT-6 peptide pool or M.tb lysate stimulation. We then assessed the diagnostic performance of immune profiles that were differentially expressed between individuals with recent or persistent QuantiFERON-TB+.FindingsCFP-10/ESAT-6-specific CD4 T cell activation but not functional or memory phenotypes distinguished between individuals with recent and persistent QuantiFERON-TB+. In response to M.tb lysate, recent QuantiFERON-TB+ individuals had lower proportions of highly differentiated IFN-γ+TNF+ CD4 T cells expressing a KLRG-1+ effector phenotype and higher proportions of early differentiated IFN-γ-TNF+IL-2+ and activated CD4 T cells compared to persistent QuantiFERON-TB+ individuals. Among all differentially expressed T cell features CFP-10/ESAT-6-specific CD4 T cell activation was the best performing diagnostic biomarker of recent infection.InterpretationRecent M.tb infection is associated with highly activated and moderately differentiated functional M.tb-specific T cell subsets, that can be used as biomarkers to distinguish between recent and remote infection.
Quantitative Assessment of Chest CT Patterns in COVID-19 and Bacterial Pneumonia patients: A Deep Learning Perspective
Authors: Kang Myeongkyun , Chikontwe Philip , Luna Miguel , Hong Kyung Soo , Jang Jong Geol , Park Jongsoo , Shin Kyeong-Cheol , Ahn June Hong , Park Sang Hyun 
Published: November 2020

ABSTRACTAs the number of COVID-19 patients has increased worldwide, many efforts have been made to find common patterns in CT images of COVID-19 patients and to confirm the relevance of these patterns against other clinical information. The aim of this paper is to propose a new method that allowed us to find patterns which observed on CTs of patients, and further we use these patterns for disease and severity diagnosis. For the experiment, we performed a retrospective cohort study of 170 confirmed patients with COVID-19 and bacterial pneumonia acquired at Yeungnam University hospital in Daegu, Korea. We extracted lesions inside the lungs from the CT images and classified whether these lesions were from COVID-19 patients or bacterial pneumonia patients by applying a deep learning model. From our experiments, we found 20 patterns that have a major effect on the classification performance of the deep learning model. Crazy-paving was extracted as a major pattern of bacterial pneumonia, while Ground-glass opacities (GGOs) in the peripheral lungs as that of COVID-19. Diffuse GGOs in the central and peripheral lungs was considered to be a key factor for severity classification. The proposed method achieved an accuracy of 91.2% for classifying COVID-19 and bacterial pneumonia with 95% reported for severity classification. Chest CT analysis with constructed lesion clusters revealed well-known COVID-19 CT manifestations comparable to manual CT analysis. Moreover, the constructed patient level histogram with/without radiomics features showed feasibility and improved accuracy for both disease and severity classification with key clinical implications.
Racial and ethnic differentials in COVID-19-related job exposures by occupational standing in the US
Authors: Goldman Noreen , Pebley Anne R. , Lee Keunbok , Andrasfay Theresa , Pratt Boriana 
Published: November 2020

AbstractResearchers and journalists have argued that work-related factors may be partly responsible for disproportionate COVID-19 infection and death rates among vulnerable groups. We evaluate these claims by examining racial and ethnic differences in the likelihood of work-related exposure to COVID-19. We extend previous studies by considering 12 racial and ethnic groups and five types of potential occupational exposure to the virus: exposure to infection, physical proximity to others, face-to-face discussions, interactions with external customers and the public, and working indoors. Most importantly, we stratify our results by occupational standing, defined as the proportion of workers within each occupation with at least some college education. This measure serves as a proxy for whether workplaces and workers employ significant COVID-19-related risk reduction strategies. We use the 2018 American Community Survey to identify recent workers by occupation, and link 409 occupations to information on work context from the Occupational Information Network to identify potential COVID-related risk factors. We then examine the racial/ethnic distribution of all frontline workers and frontline workers at highest potential risk of COVID-19, by occupational standing and by sex. The results indicate that, contrary to expectation, White frontline workers are often overrepresented in high-risk jobs while Black and Latino frontline workers are generally underrepresented in these jobs. However, disaggregation of the results by occupational standing shows that, in contrast to Whites and several Asian groups, Latino and Black frontline workers are overrepresented in lower status occupations overall and in lower status occupations associated with high risk, and are thus less likely to have adequate COVID-19 protections. Our findings suggest that greater work exposures likely contribute to a higher prevalence of COVID-19 among Latino and Black adults and underscore the need for measures to reduce potential exposure for workers in low status occupations and for the development of programs outside the workplace.