bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial Allocation of Scarce COVID-19 Vaccines*†‡
Authors: Castonguay François M. , Blackwood Julie C. , Howerton Emily , Shea Katriona , Sims Charles , Sanchirico James N. 
Published: December 2020

AbstractThe COVID-19 Vaccines Global Access (COVAX) is an initiative led by the World Health Organization (WHO) and other partners that aims for an equitable access of COVID-19 vaccines. Despite a potential heterogeneous disease burden across space, countries receiving allotments of vaccines via COVAX may want to follow WHO’s allocation rule and distribute vaccines to their jurisdictions based on the jurisdictions’ relative population size. Utilizing economic–epidemiological modeling, we benchmark the performance of thisad hocallocation rule by comparing it to the rule that minimizes the economic damages and expenditures over time, including a penalty cost representing the social costs of deviating from thead hocallocation. Under different levels of vaccine scarcity and different demographic characteristics, we consider scenarios where length of immunity and compliance to travel restrictions vary, and consider the robustness of the rules when assumptions regarding these factors are incorrect. The benefits from deviating are especially high when immunity is permanent, when there is compliance to travel restrictions, when the supply of vaccine is low, and when there is heterogeneity in demographic characteristics. Interestingly, a lack of compliance to travel restrictions pushes the optimal allocations of vaccine towards thead hocand improves the relative robustness of thead hocrule, as the mixing of the populations reduces the spatial heterogeneity in disease burden.JEL ClassificationC61, H12, H84, I18, Q54
The impact of the first UK Covid-19 lockdown on carers and people living with low prevalence dementia: results from the Rare Dementia Support survey
Authors: Suárez-González Aida , Harding Emma , Zimmerman Nikki , Hoare Zoe , Brotherhood Emilie , Crutch Sebastian 
Published: December 2020

AbstractIntroductionThe public health measures imposed to contain Covid-19 during the first UK lockdown resulted in significant changes in the provision of community support and care for people with dementia. People with low prevalence and young-onset dementias often experience non-memory, behavioural or neuropsychiatric symptoms that require specialised support.ObjectiveWe explored the impact of the first Covid-19 lockdown on people living with low prevalence and young-onset dementia and their carers in the UK.MethodAn online survey, including eleven questions about the impact of the lockdown on both the person with dementia and their family caregivers was conducted. Participants were people living with dementia and caregivers who are members of the UK national-reach organisation Rare Dementia Support.Results184 carers and 24 people with dementia completed the survey. People with dementia experienced worsening of cognitive symptoms (70%), ability to do things (62%) and well-being (57%) according to their carers. Carers also reported a reduction in the support received for caring (55%). 93% of carers of people living in care homes reported a reduction in their ability to provide care. 26% of carers reported changes in the medication of the person with dementia during the lockdown. 74% of people with dementia reported decreased ability to connect with people socially.ConclusionsPeople with dementia experienced a worsening of dementia symptoms, removal of support and increased difficulty to connect with other people socially during the 1st wave of Covid-19. Carers encountered barriers to both receiving and providing support and a decline in their own mental health and well-being.Key points70 % of carers reported cognitive symptoms getting worse during the lockdown (e.g., the person with dementia being more disoriented and finding it more difficult to communicate).26 % of carers reported a change (initiation or increase) in medication in the person with dementia during the lockdown.79 % carers reported their own physical or mental health getting worse due to the lockdown. This increased to 93% when considering responses only from family carers of people living in care homes.93 % of family carers of people living in care homes found it harder to continue providing care and support for their relative due to Covid-19.
Common X-chromosome variants are associated with Parkinson’s disease risk
Authors: Guen Yann Le , Napolioni Valerio , Belloy Michael E. , Yu Eric , Krohn Lynne , Ruskey Jennifer A. , Gan-Or Ziv , Kennedy Gabriel , Eger Sarah J. , Greicius Michael D. 
Published: December 2020

AbstractObjectiveIdentify genetic variants on the X-chromosome associated with Parkinson’s disease (PD) risk.MethodsWe performed an X-chromosome-wide association study (XWAS) of PD risk by meta-analyzing results from sex-stratified analyses. To avoid spurious associations, we designed a specific harmonization pipeline for the X-chromosome and focused on a European ancestry sample. We included 11,324 cases, 280,060 controls, and 5,379 proxy cases, based on parental history of PD. Additionally, we tested the association of significant variants with: (i) PD risk in an independent replication with 1,564 cases and 2,467 controls, and (ii) putamen volume in 33,360 individuals from the UK Biobank.ResultsIn the discovery meta-analysis, we identified: rs7066890 (OR=1.10 [1.06-1.14]; P=2.2×10−9) intron of GPM6B, and rs28602900 (OR=1.10 [1.07-1.14]; P=1.6×10−8) in a high gene density region including RPL10, ATP6A1, FAM50A, PLXNA3. The rs28602900 association with PD was replicated (OR=1.16 [1.03-1.30]; P=0.016) and shown to colocalize with a significant expression quantitative locus (eQTL) regulating RPL10 expression in the putamen and other brain tissues in GTEx. Additionally, the rs28602900 locus was found to be associated with reduced brain putamen volume. No results reached genome-wide significance in the sex-stratified analyses.InterpretationWe report the first XWAS of PD and identify two genome-wide significant loci. The rs28602900 association replicated in an independent PD dataset and showed concordant effects in its association with putamen volume. Critically, rs26802900 is a significant eQTL of RPL10.These results support a role for ribosomal proteins in PD pathogenesis and show that the X-chromosome contributes to PD genetic risk.
Common variants at 21q22.3 locus influenceMX1gene expression and susceptibility to severe COVID-19
Authors: Andolfo Immacolata , Russo Roberta , Lasorsa Alessandro Vito , Cantalupo Sueva , Rosato Barbara Eleni , Bonfiglio Ferdinando , Frisso Giulia , Pasquale Abete , Cassese Gian Marco , Servillo Giuseppe , Esposito Gabriella , Gentile Ivan , Piscopo Carmelo , Villani Romolo , Fiorentino Giuseppe , Cerino Pellegrino , Buonerba Carlo , Pierri Biancamaria , Zollo Massimo , Iolascon Achille , Capasso Mario 
Published: December 2020

AbstractThe COVID-19 disease, caused by the SARS-Cov-2, presents a heterogeneous clinical spectrum. The risk factors do not fully explain the wide spectrum of disease manifestations, so it is possible that genetic factors could account for novel insights into its pathogenesis.In our previous study, we hypothesized that common variants on chromosome 21, nearTMPRSS2andMX1genes, may be genetic risk factors associated to the different clinical manifestations of COVID-19. Here, we performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms (SNPs) withinTMPRSS2and nearMX1gene show suggestive associations (P≤1×10−5) with severe COVID-19. All five SNPs replicated the association in two independent cohorts of Asian subjects while two and one out of the 5 SNPs replicated in African and Italian populations, respectively (P≤0.05). The minor alleles of these five SNPs correlated with a reduced risk of developing severe COVID-19 and increased level ofMX1expression in blood.Our findings provide further evidence that host genetic factors can contribute to determine the different clinical presentations of COVID-19 and that MX1, an antiviral effector of type I and III interferon pathway, may be a potential therapeutic target.
Effects of obesity on serum levels of SARS-CoV-2-specific antibodies in COVID-19 patients
Authors: Frasca Daniela , Reidy Lisa , Cray Carolyn , Diaz Alain , Romero Maria , Kahl Kristin , Blomberg Bonnie B. 
Published: December 2020

AbstractSARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2), cause of COVID-19 (Coronavirus Disease of 2019), represents a significant risk to people living with pre-existing conditions associated with exacerbated inflammatory responses and consequent dysfunctional immunity. In this paper, we have evaluated the effects of obesity, a condition associated with chronic systemic inflammation, on the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. Results have shown that SARS-CoV-2 IgG antibodies are negatively associated with Body Mass Index (BMI) in COVID-19 obese patients, as expected based on the known effects of obesity on humoral immunity. Antibodies in COVID-19 obese patients are also negatively associated with serum levels of pro-inflammatory and metabolic markers of inflammaging and pulmonary inflammation, such as SAA (serum amyloid A protein), CRP (C-reactive protein) and ferritin, but positively associated with NEFA (nonesterified fatty acids). These results altogether could help to identify an inflammatory signature with strong predictive value for immune dysfunction that could be targeted to improve humoral immunity in individuals with obesity as well as with other chronic inflammatory conditions.
De novo identification and visualization of important cell populations for classic Hodgkin lymphoma using flow cytometry and machine learning
Authors: Simonson Paul D. , Wu Yue , Wu David , Fromm Jonathan R. , Lee Aaron Y. 
Published: December 2020

AbstractObjectivesAutomated classification of flow cytometry data has the potential to reduce errors and accelerate flow cytometry interpretation. We desired a machine learning approach that is accurate, intuitively easy to understand, and highlights the cells that are most important in the algorithm’s prediction for a given case.MethodsWe developed an ensemble of convolutional neural networks (CNNs) for classification and visualization of impactful cell populations in detecting classic Hodgkin lymphoma, using two-dimensional (2D) histograms. Data from 977 and 245 clinical flow cytometry cases were used for training and testing, respectively. 78 non-gated 2D histograms were created per flow cytometry file. SHAP values were calculated to determine the most impactful 2D histograms and regions within the histograms. The SHAP values from all 78 histograms were then projected back to the original cells data for gating and visualization using standard flow cytometry software.ResultsThe algorithm achieved 67.7% recall (sensitivity), 82.4 % precision, and 0.92 AUROC. Visualization of the important cell populations in making individual predictions demonstrated correlations with known biology.ConclusionsThe method presented enables model explainability while highlighting important cell populations in individual flow cytometry specimens, with potential applications in both diagnosis and discovery of previously overlooked key cell populations.
Memory precision of object-location binding is unimpaired inAPOEε4-carriers with spatial navigation deficits
Authors: Gellersen Helena M. , Coughlan Gillian , Hornberger Michael , Simons Jon S. 
Published: December 2020

AbstractResearch suggests that tests of memory fidelity, feature binding and spatial navigation are promising for early detection of subtle behavioural changes related to Alzheimer’s disease (AD). In the absence of longitudinal data, one way of testing the early detection potential of cognitive tasks is through the comparison of individuals at different genetic risk for AD. Most studies have done so using samples aged 70 years or older. Here, we tested whether memory fidelity of long-term object-location binding may be a sensitive marker even among cognitively healthy individuals in their mid-60s by comparing participants at low and higher risk based on presence of the ε4-allele of the apolipoprotein gene (n=26 ε3ε3,n=20 ε3ε4 carriers). We used a continuous report paradigm in a visual memory task that required participants to recreate the spatial position of objects in a scene. We employed mixture modelling to estimate the two distinct memory processes that underpin the trial-by-trial variation in localisation errors: retrieval success which indexes the proportion of trials where participants recalled any information about an object’s position and the precision with which participants retrieved this information. Prior work has shown that these memory paradigms that separate retrieval success from precision are capable of detecting subtle differences in mnemonic fidelity even when retrieval success could not. Nonetheless, a Bayesian analysis found good evidence that ε3ε4 carriers did not remember fewer object locations (F(1, 42)=.450,p=.506, BF01=3.02), nor was their precision for the spatial position of objects reduced compared to ε3ε3 carriers (F(1, 42)=.12,p=.726, BF01=3.19). Because the participants in the sample presented here were a subset of a study onAPOEeffects on spatial navigation in the Sea Hero Quest game (Coughlan et al., 2019.PNAS, 116(9)), we obtained these data to contrastAPOEeffects on the two tasks within the same sample (n=33). Despite the smaller sample size, wayfinding deficits among ε3ε4 could be replicated (F(1, 33)=5.60,p=.024,BF10=3.44). Object-location memory metrics and spatial navigation scores were not correlated (allr<.25,p>.1, 0<BF10<3). These findings show spared object-location binding in the presence of a detrimentalAPOEε4 effect on spatial navigation. This suggests that the sensitivity of memory fidelity and binding tasks may not extend to individuals with one ε4-allele in their early to mid-60s. The results provide further support to prior proposals that spatial navigation may be a sensitive marker for the earliest AD-dependent cognitive changes, even before episodic memory.
Pollen sterols are associated with phylogenetics and environment but not with pollinators
Authors: Zu Pengjuan , Koch Hauke , Schwery Orlando , Pironon Samuel , Phillips Charlotte , Ondo Ian , Farrell Iain W. , Nes W. David , Moore Elynor , Wright Geraldine A. , Farman Dudley I. , Stevenson Philip C. 
Published: December 2020

SummaryPhytosterols are primary plant metabolites that have fundamental structural and regulatory functions. They are also essential nutrients for phytophagous insects, including pollinators, that cannot synthesize sterols. Despite the well-described composition and diversity in vegetative plant tissues, few studies have examined phytosterol diversity in pollen.We quantified 25 pollen phytosterols in 122 plant species (105 genera, 51 families) to determine their composition and diversity across plant taxa. We searched literature and databases for plant phylogeny, environmental conditions, and pollinator guilds of the species to examine the relationships with pollen sterols.24-methylenecholesterol, sitosterol and isofucosterol were the most common and abundant pollen sterols. We found phylogenetic clustering of twelve individual sterols, total sterol content and sterol diversity, and of sterol groupings that reflect their underlying biosynthesis pathway (24 carbon alkylation, ring B desaturation). Plants originating in tropical-like climates (higher mean annual temperature, lower temperature seasonality, higher precipitation in wettest quarter) were more likely to record higher pollen sterol content. However, pollen sterol composition and content showed no clear relationship with pollinator guilds.Our study is the first to show that pollen sterol diversity is phylogenetically clustered and that pollen sterol content may adapt to environmental conditions.
Development of an optimized and scalable method for isolation of umbilical cord blood-derived small extracellular vesicles for future clinical use
Authors: Cardoso R.M.S. , Rodrigues S.C. , Gomes C. F. , Duarte F.V. , Romao M. , Leal E.C. , Freire P.C. , Neves R. , Simões-Correia J. 
Published: December 2020

ABSTRACTExtracellular vesicles (EV) are a promising therapeutic tool in regenerative medicine. These particles were shown to accelerate wound healing, through delivery of regenerative mediators, such as microRNAs. Herein we describe an optimized and up-scalable process for the isolation of EV smaller than 200 nm (sEV), secreted by umbilical cord blood mononuclear cells (UCB-MNC) under ischemic conditions and propose quality control thresholds for the isolated vesicles, based on the thorough characterization of their protein, lipid and RNA content.Ultrafiltration and size exclusion chromatography (UF/SEC) optimized methodology proved superior to traditional ultracentrifugation (UC), regarding production time, standardization, scalability, and vesicle yield. Using UF/SEC, we were able to recover approximately 400 times more sEV per mL of media than with UC, and up-scaling this process further increases EV yield by about 3-fold. UF/SEC-isolated sEV display many of the sEV/exosomes classical markers and are enriched in molecules with anti-inflammatory and regenerative capacity, such as hemopexin and miR-150. Accordingly, treatment with sEV promotes angiogenesis and extracellular matrix remodeling,in vitro. In vivo, UCB-MNC-sEV significantly accelerate skin regeneration in a mouse model of delayed wound healing.The proposed isolation protocol constitutes a significant improvement compared to UC, the gold-standard in the field. Isolated sEV maintain their regenerative properties, whereas downstream contaminants are minimized. The use of UF/SEC allows for the standardization and up-scalability required for mass production of sEV to be used in a clinical setting.
Modeling population size independent tissue epigenomes by ChIL-seq with single-thin sections
Authors: Maehara Kazumitsu , Tomimatsu Kosuke , Harada Akihito , Tanaka Kaori , Sato Shoko , Okada Seiji , Handa Tetsuya , Kurumizaka Hitoshi , Kimura Hiroshi , Ohkawa Yasuyuki 
Published: December 2020

AbstractRecent advances in omics studies have enabled analysis at the single-cell level; however, methods for analyzing the whole cell of large organs and tissues remain challenging. Here, we developed a method named tsChIL to understand the diverse cellular dynamics at the tissue level using high-depth epigenomic data. tsChIL allowed the analysis of a single tissue section and could reproducibly acquire epigenomic profiles from several types of tissues, based on the distribution of target epigenomic states, tissue morphology, and number of cells. The proposed method enabled the independent evaluation of changes in cell populations and gene activation of cells in regenerating skeletal muscle tissues, using a statistical model of RNA polymerase II distribution on gene loci. Thus, the integrative analysis by tsChIL can elucidatein vivocell-type dynamics of tissues.
Cell patterning by secretion-induced plasma membrane flows
Authors: Gerganova Veneta , Lamas Iker , Rutkowski David M. , Vještica Aleksandar , Castro Daniela Gallo , Vincenzetti Vincent , Vavylonis Dimitrios , Martin Sophie G 
Published: December 2020

AbstractCells self-organize using reaction-diffusion and fluid-flow principles. Whether bulk membrane flows contribute to cell patterning has not been established. Here, using mathematical modelling, optogenetics and synthetic probes, we show that polarized exocytosis causes lateral membrane flows away from regions of membrane insertion. Plasma membrane-associated proteins with sufficiently low diffusion and/or detachment rates couple to the flows and deplete from areas of exocytosis. In rod-shaped fission yeast cells, zones of Cdc42 GTPase activity driving polarized exocytosis are limited by GTPase activating proteins (GAPs). We show that membrane flows pattern the GAP Rga4 distribution and coupling of a synthetic GAP to membrane flows is sufficient to establish the rod shape. Thus, membrane flows induced by Cdc42-dependent exocytosis form a negative feedback restricting the zone of Cdc42 activity.One Sentence SummaryExocytosis causes bulk membrane flows that drag associated proteins and form a negative feedback restricting the exocytic site.
Effect of land use, habitat suitability, and hurricanes on the population connectivity of an endemic insular bat
Authors: Calderón-Acevedo Camilo A. , Rodríguez-Durán Armando , Soto-Centeno J. Angel 
Published: December 2020

AbstractHabitat loss and fragmentation are a leading cause of vertebrate population declines and extinction. Urbanization and natural disasters disrupt landscape connectivity, effectively isolating populations and increasing the risk of local extirpation particularly in island systems. Puerto Rico, one of the most isolated islands in the Caribbean, is home to 13 bat species that have been differentially affected by disturbance during the Anthropocene. We used circuit theory to model the landscape connectivity within Puerto Rico with the goal of understanding how fragmentation affects corridors among forested areas. Models combined species occurrences, land use, habitat suitability, and vegetation cover data to examine connectivity in the endemic bat Stenoderma rufum, and also at the bat community level across the island. Urbanization in Puerto Rico affected bat connectivity overall from east to west and underscored protected and rustic areas for the maintenance of forest corridors. Suitable habitat provided a reliable measure of connectivity among potential movement corridors that connected more isolated areas. We found that intense hurricanes can disrupt forest integrity and affect connectivity of suitable habitat. Some of the largest protected areas in the east of Puerto Rico are at an increasing risk of becoming disconnected from more continuous forest patches. The disruption of corridors that maintain connectivity on the island could explain previous findings of the slow post-hurricane population recovery of S. rufum. Given the increasing rate of urbanization, this pattern could also apply to other vertebrates not analyzed in this study. Our findings show the importance of maintaining forest integrity, emphasizing the considerable conservation value of rustic areas for the preservation of local biodiversity.