bluuebunny/crossref_metadata_2025 huggingface dataset:
Mammals with Small Populations Do Not Exhibit Larger Genomes
Authors: Roddy Adam B , Alvarez-Ponce David , Roy Scott W
Published: May 2021

Genome size in cellular organisms varies by six orders of magnitude, yet the cause of this large variation remains unexplained. The influential Drift-Barrier Hypothesis proposes that large genomes tend to evolve in small populations due to inefficient selection. However, to our knowledge no explicit tests of the Drift-Barrier Hypothesis have been reported. We performed the first explicit test, by comparing estimated census population size and genome size in mammals while incorporating potential covariates and the effect of shared evolutionary history. We found a lack of correlation between census population size and genome size among 199 species of mammals. These results suggest that population size is not the predominant factor influencing genome size and that the Drift-Barrier Hypothesis should be considered provisional.
Population Structure Limits Parallel Evolution in Sticklebacks
Authors: Fang Bohao , Kemppainen Petri , Momigliano Paolo , Merilä Juha
Published: May 2021

Population genetic theory predicts that small effective population sizes (Ne) and restricted gene flow limit the potential for local adaptation. In particular, the probability of evolving similar phenotypes based on shared genetic mechanisms (i.e., parallel evolution), is expected to be reduced. We tested these predictions in a comparative genomic study of two ecologically similar and geographically codistributed stickleback species (viz. Gasterosteus aculeatus and Pungitius pungitius). We found that P. pungitius harbors less genetic diversity and exhibits higher levels of genetic differentiation and isolation-by-distance than G. aculeatus. Conversely, G. aculeatus exhibits a stronger degree of genetic parallelism across freshwater populations than P. pungitius: 2,996 versus 379 single nucleotide polymorphisms located within 26 versus 9 genomic regions show evidence of selection in multiple freshwater populations of G. aculeatus and P. pungitius, respectively. Most regions involved in parallel evolution in G. aculeatus showed increased levels of divergence, suggestive of selection on ancient haplotypes. In contrast, haplotypes involved in freshwater adaptation in P. pungitius were younger. In accordance with theory, the results suggest that connectivity and genetic drift play crucial roles in determining the levels and geographic distribution of standing genetic variation, providing evidence that population subdivision limits local adaptation and therefore also the likelihood of parallel evolution.
Crystal structure and functional properties of the human CCR4-CAF1 deadenylase complex
Authors: Chen Ying , Khazina Elena , Izaurralde Elisa , Weichenrieder Oliver
Published: May 2021

The CCR4 and CAF1 deadenylases physically interact to form the CCR4-CAF1 complex and function as the catalytic core of the larger CCR4-NOT complex. Together, they are responsible for the eventual removal of the 3′-poly(A) tail from essentially all cellular mRNAs and consequently play a central role in the posttranscriptional regulation of gene expression. The individual properties of CCR4 and CAF1, however, and their respective contributions in different organisms and cellular environments are incompletely understood. Here, we determined the crystal structure of a human CCR4-CAF1 complex and characterized its enzymatic and substrate recognition properties. The structure reveals specific molecular details affecting RNA binding and hydrolysis, and confirms the CCR4 nuclease domain to be tethered flexibly with a considerable distance between both enzyme active sites. CCR4 and CAF1 sense nucleotide identity on both sides of the 3′-terminal phosphate, efficiently differentiating between single and consecutive non-A residues. In comparison to CCR4, CAF1 emerges as a surprisingly tunable enzyme, highly sensitive to pH, magnesium and zinc ions, and possibly allowing distinct reaction geometries. Our results support a picture of CAF1 as a primordial deadenylase, which gets assisted by CCR4 for better efficiency and by the assembled NOT proteins for selective mRNA targeting and regulation.
CPA: a web-based platform for consensus pathway analysis and interactive visualization
Authors: Nguyen Hung , Tran Duc , Galazka Jonathan M , Costes Sylvain V , Beheshti Afshin , Petereit Juli , Draghici Sorin , Nguyen Tin
Published: May 2021

In molecular biology and genetics, there is a large gap between the ease of data collection and our ability to extract knowledge from these data. Contributing to this gap is the fact that living organisms are complex systems whose emerging phenotypes are the results of multiple complex interactions taking place on various pathways. This demands powerful yet user-friendly pathway analysis tools to translate the now abundant high-throughput data into a better understanding of the underlying biological phenomena. Here we introduce Consensus Pathway Analysis (CPA), a web-based platform that allows researchers to (i) perform pathway analysis using eight established methods (GSEA, GSA, FGSEA, PADOG, Impact Analysis, ORA/Webgestalt, KS-test, Wilcox-test), (ii) perform meta-analysis of multiple datasets, (iii) combine methods and datasets to accurately identify the impacted pathways underlying the studied condition and (iv) interactively explore impacted pathways, and browse relationships between pathways and genes. The platform supports three types of input: (i) a list of differentially expressed genes, (ii) genes and fold changes and (iii) an expression matrix. It also allows users to import data from NCBI GEO. The CPA platform currently supports the analysis of multiple organisms using KEGG and Gene Ontology, and it is freely available at http://cpa.tinnguyen-lab.com.
b2bTools: online predictions for protein biophysical features and their conservation
Authors: Kagami Luciano Porto , Orlando Gabriele , Raimondi Daniele , Ancien Francois , Dixit Bhawna , Gavaldá-García Jose , Ramasamy Pathmanaban , Roca-Martínez Joel , Tzavella Konstantina , Vranken Wim
Published: May 2021

We provide integrated protein sequence-based predictions via https://bio2byte.be/b2btools/. The aim of our predictions is to identify the biophysical behaviour or features of proteins that are not readily captured by structural biology and/or molecular dynamics approaches. Upload of a FASTA file or text input of a sequence provides integrated predictions from DynaMine backbone and side-chain dynamics, conformational propensities, and derived EFoldMine early folding, DisoMine disorder, and Agmata β-sheet aggregation. These predictions, several of which were previously not available online, capture ‘emergent’ properties of proteins, i.e. the inherent biophysical propensities encoded in their sequence, rather than context-dependent behaviour (e.g. final folded state). In addition, upload of a multiple sequence alignment (MSA) in a variety of formats enables exploration of the biophysical variation observed in homologous proteins. The associated plots indicate the biophysical limits of functionally relevant protein behaviour, with unusual residues flagged by a Gaussian mixture model analysis. The prediction results are available as JSON or CSV files and directly accessible via an API. Online visualisation is available as interactive plots, with brief explanations and tutorial pages included. The server and API employ an email-free token-based system that can be used to anonymously access previously generated results.
Oocyte meiosis-coupled poly(A) polymerase α phosphorylation and activation trigger maternal mRNA translation in mice
Authors: Jiang Jun-Chao , Zhang Hua , Cao Lan-Rui , Dai Xing-Xing , Zhao Long-Wen , Liu Hong-Bin , Fan Heng-Yu
Published: May 2021

Mammalian oocyte maturation is driven by strictly regulated polyadenylation and translational activation of maternal mRNA stored in the cytoplasm. However, the poly(A) polymerase (PAP) that directly mediates cytoplasmic polyadenylation in mammalian oocytes has not been determined. In this study, we identified PAPα as the elusive enzyme that catalyzes cytoplasmic mRNA polyadenylation implicated in mouse oocyte maturation. PAPα was mainly localized in the germinal vesicle (GV) of fully grown oocytes but was distributed to the ooplasm after GV breakdown. Inhibition of PAPα activity impaired cytoplasmic polyadenylation and translation of maternal transcripts, thus blocking meiotic cell cycle progression. Once an oocyte resumes meiosis, activated CDK1 and ERK1/2 cooperatively mediate the phosphorylation of three serine residues of PAPα, 537, 545 and 558, thereby leading to increased activity. This mechanism is responsible for translational activation of transcripts lacking cytoplasmic polyadenylation elements in their 3′-untranslated region (3′-UTR). In turn, activated PAPα stimulated polyadenylation and translation of the mRNA encoding its own (Papola) through a positive feedback circuit. ERK1/2 promoted Papola mRNA translation in a 3′-UTR polyadenylation signal-dependent manner. Through these mechanisms, PAPα activity and levels were significantly amplified, improving the levels of global mRNA polyadenylation and translation, thus, benefiting meiotic cell cycle progression.
ncFANs v2.0: an integrative platform for functional annotation of non-coding RNAs
Authors: Zhang Yuwei , Bu Dechao , Huo Peipei , Wang Zhihao , Rong Hao , Li Yanguo , Liu Jingjia , Ye Meng , Wu Yang , Jiang Zheng , Liao Qi , Zhao Yi
Published: May 2021

Increasing evidence proves the essential regulatory roles of non-coding RNAs (ncRNAs) in biological processes. However, characterizing the specific functions of ncRNAs remains a challenging task, owing to the intensive consumption of the experimental approaches. Here, we present an online platform ncFANs v2.0 that is a significantly enhanced version of our previous ncFANs to provide multiple computational methods for ncRNA functional annotation. Specifically, ncFANs v2.0 was updated to embed three functional modules, including ncFANs-NET, ncFANs-eLnc and ncFANs-CHIP. ncFANs-NET is a new module designed for data-free functional annotation based on four kinds of pre-built networks, including the co-expression network, co-methylation network, long non-coding RNA (lncRNA)-centric regulatory network and random forest-based network. ncFANs-eLnc enables the one-stop identification of enhancer-derived lncRNAs from the de novo assembled transcriptome based on the user-defined or our pre-annotated enhancers. Moreover, ncFANs-CHIP inherits the original functions for microarray data-based functional annotation and supports more chip types. We believe that our ncFANs v2.0 carries sufficient convenience and practicability for biological researchers and facilitates unraveling the regulatory mechanisms of ncRNAs. The ncFANs v2.0 server is freely available at http://bioinfo.org/ncfans or http://ncfans.gene.ac.
Light signals generated by vegetation shade facilitate acclimation to low light in shade-avoider plants
Authors: Morelli Luca , Paulišić Sandi , Qin Wenting , Iglesias-Sanchez Ariadna , Roig-Villanova Irma , Florez-Sarasa Igor , Rodriguez-Concepcion Manuel , Martinez-Garcia Jaime F
Published: May 2021

When growing in search for light, plants can experience continuous or occasional shading by other plants. Plant proximity causes a decrease in the ratio of R to far-red light (low R:FR) due to the preferential absorbance of R light and reflection of FR light by photosynthetic tissues of neighboring plants. This signal is often perceived before actual shading causes a reduction in photosynthetically active radiation (low PAR). Here, we investigated how several Brassicaceae species from different habitats respond to low R:FR and low PAR in terms of elongation, photosynthesis, and photoacclimation. Shade-tolerant plants such as hairy bittercress (Cardamine hirsuta) displayed a good adaptation to low PAR but a poor or null response to low R:FR exposure. In contrast, shade-avoider species, such as Arabidopsis (Arabidopsis thaliana), showed a weak photosynthetic performance under low PAR but they strongly elongated when exposed to low R:FR. These responses could be genetically uncoupled. Most interestingly, exposure to low R:FR of shade-avoider (but not shade-tolerant) plants improved their photoacclimation to low PAR by triggering changes in photosynthesis-related gene expression, pigment accumulation, and chloroplast ultrastructure. These results indicate that low R:FR signaling unleashes molecular, metabolic, and developmental responses that allow shade-avoider plants (including most crops) to adjust their photosynthetic capacity in anticipation of eventual shading by nearby plants.
Skilled Labor Risk and Corporate Policies
Authors: Qiu Yue , Wang Tracy Yue
Published: May 2021

We measure U.S. listed companies’ skilled labor risk—that is, the potential failure in attracting and retaining skilled labor, by the intensity of discussions on this issue in 10-K filings. We show that this measure effectively captures firm risk due to the mobility of skilled labor. We find that an increase from the 25th to the 75th percentile in the skilled labor risk would increase the skilled labor wage by 22% (or $15,593) and also lead to higher equity-based incentive pay. The skilled labor risk also interacts with other corporate policies such as financial leverage, cash holdings, and M&As. (JEL G30, G32, G34, H20, J20, J24, J40, J41)

Received September 28, 2020; editorial decision March 12, 2021 by Editor Andrew Ellul.
Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus
Authors: Furie Richard A , Bruce Ian N , Dörner Thomas , Leon Manuel Gustavo , Leszczyński Piotr , Urowitz Murray , Haier Birgit , Jimenez Teri , Brittain Claire , Liu Jiajun , Barbey Catherine , Stach Christian
Published: May 2021

Objective

To evaluate the dose–response, efficacy and safety of dapirolizumab pegol (DZP) in patients with SLE.

Methods

Adults with moderately to severely active SLE (SLEDAI-2K score ≥6 and ≥1 BILAG A or ≥2 BILAG B domain scores), receiving stable CS (≤40 mg/day prednisone-equivalent), antimalarial or immunosuppressant drugs were included. Patients with stable LN (proteinuria ≤2 g/day) not receiving high-dose CS or CYC were permitted entry. Randomized patients received placebo or i.v. DZP (6/24/45 mg/kg) and standard-of-care (SOC) treatment every 4 weeks to week 24, after which patients received only SOC to week 48. The primary objective was to establish a dose–response relationship based on week 24 BILAG-Based Composite Lupus Assessment (BICLA) responder rates.

Results

All DZP groups exhibited improvements in clinical and immunological outcomes vs placebo at week 24; however, BICLA responder rates did not fit pre-specified dose–response models [best-fitting model (Emax): P = 0.07]. Incidences of serious treatment-emergent adverse events across DZP groups were low and similar to placebo. Following DZP withdrawal, SLEDAI-2K, physician’s global assessment (PGA), BILAG, and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores stabilized; BICLA and SLE Responder Index (SRI-4) responder rates declined (likely due to interventions with disallowed escape medications), BILAG flares increased, and immunologic parameters returned towards baseline.

Conclusions

Although the primary objective was not met, DZP appeared to be well tolerated, and patients exhibited improvements across multiple clinical and immunological measures of disease activity after 24 weeks relative to placebo. The potential clinical benefit of DZP warrants further investigation.
Effects of compassion training on brain responses to suffering others
Authors: Ashar Yoni K , Andrews-Hanna Jessica R , Halifax Joan , Dimidjian Sona , Wager Tor D
Published: May 2021

Compassion meditation (CM) is a promising intervention for enhancing compassion, although its active ingredients and neurobiological mechanisms are not well-understood. To investigate these, we conducted a three-armed placebo-controlled randomized trial (N = 57) with longitudinal functional magnetic resonance imaging (fMRI). We compared a 4-week CM program delivered by smartphone application with (i) a placebo condition, presented to participants as the compassion-enhancing hormone oxytocin, and (ii) a condition designed to control for increased familiarity with suffering others, an element of CM which may promote compassion. At pre- and post-intervention, participants listened to compassion-eliciting narratives describing suffering others during fMRI. CM increased brain responses to suffering others in the medial orbitofrontal cortex (mOFC) relative to the familiarity condition, p < 0.05 family-wise error rate corrected. Among CM participants, individual differences in increased mOFC responses positively correlated with increased compassion-related feelings and attributions, r = 0.50, p = 0.04. Relative to placebo, the CM group exhibited a similar increase in mOFC activity at an uncorrected threshold of P < 0.001 and 10 contiguous voxels. We conclude that the mOFC, a region closely related to affiliative affect and motivation, is an important brain mechanism of CM. Effects of CM on mOFC function are not explained by familiarity effects and are partly explained by placebo effects.
PULSATILE FILLING OF DILATED CHOROIDAL VESSELS IN MACULAR WATERSHED ZONES
Authors: Gemmy Cheung Chui Ming , Teo Kelvin Yi Chong , Spaide Richard F.
Published: May 2021

Purpose:

To describe pulsatile filling of dilated choroidal veins in the watershed zones and propose an alteration in choroidal perfusion pressure.

Methods:

Retrospective review of original and digital subtraction indocyanine green angiography.

Results:

We observed pulsating blood flow within choroidal vein segments in the posterior pole in 14 eyes (diagnosis of polypoidal choroidal vasculopathy, central serous chorioretinopathy, or neovascular age-related macular degeneration). Pulsating dye front was observed in single or multiple large choroidal vein(s) in a location that is ordinarily a watershed zone between the segmental areas of venous drainage, and vessels proximal and distal were often dilated. The pulsatile venous segments filled more slowly than the neighboring veins. In digital subtraction indocyanine green angiography, the dye front advanced in an incremental fashion or oscillated in a back-and-forth manner during several cardiac cycles during the filling of these larger choroidal veins. With indocyanine green angiography, we observed dilated choroidal veins that violated the macula watershed zone, localized bulbous dilations, and arteriole-over-vein crossings with apparent compression.

Conclusion:

These novel observations suggest the pressure gradient for flow in the affected veins varied from low gradients when the filling was slow to high gradients when the filling was faster. The vessels violated the physiological watershed zone and seem to function as anastomoses between the ordinarily segmented venous drainage of the choroid. The dilated segments may result in pooling of venous blood as part of venous outflow abnormalities that may be operative in these diseases.
Phacofragmentation as an Effective Tool for Removal of Silicone Oil Adherent to Posterior Chamber Intraocular Lenses
Authors: Klisovic Nicholas D. , Suelves-Cogollos Ana
Published: May 2021

Background/Purpose:

To assess usefulness of phacofragmentation probe in the removal of silicone oil (SO) adherent to intraocular lenses (IOLs) during a SO removal procedure.

Methods:

A 20-gauge (G) phacofragmentation probe was used to emulsify and remove SO adherent to IOLs during 23-G vitrectomy for SO removal. The superotemporal 23-G cannula was removed, and 20-G sclerotomy was made by using a 20-G MVR blade.

Results:

In all cases used, SO adherent to the posterior surface of posterior capsule IOLs and anterior chamber IOLs was easily removed using a phacofragmentation probe. No intraoperative complications or IOL damage were noted.

Conclusion:

We describe a simple, quick and reliable method of SO removal from all types of IOLs by using a phacofragmentation probe during SO removal surgery. This simple method can prevent IOL removal and replacement due to adherent SO bubbles in pseudophakic eyes that were previously filled with SO.
Trauma Tertiary Survey: Trauma Service Medical Officers and Trauma Nurses Detect Similar Rates of Missed Injuries
Authors: Williamson Frances , Grant Kerena , Warren Jacelle , Handy Michael
Published: May 2021

Background:

Trauma tertiary surveys (TTSs) can improve patient outcomes by identifying missed injuries following initial trauma reception and resuscitation. Most TTSs are conducted by medical officers despite the multidisciplinary team approach of modern trauma care.

Objective:

The study aim was to assess the accuracy of detecting missed injuries when the TTS was performed by specialist trauma nursing staff, rather than trauma service medical officers (TSMOs).

Methods:

A prospective, convenience sample of adult trauma patients admitted to a tertiary trauma center and attended by the trauma service between October 2015 and August 2018 was obtained. For this sample, a TTS was completed by both the TSMO and the trauma nurse (TN). The number of radiological investigations ordered and missed injuries identified were compared between the two clinicians. Additional injuries were graded using the Clavien–Dindo system.

Results:

The study sample consisted of 165 patients with a dual TTS, for which at least one team member requested 35 additional radiological investigations. There was fair agreement (κ = 0.36) between the TN and the TSMO in requesting additional radiological investigations. Ten missed injuries were identified by TN-initiated review (n = 24), and 4 missed injuries were identified by TSMO-initiated review (n = 21). Injuries identified following TTSs ranged in severity grading from 0 to 3.

Conclusions:

Performance of the TN on the TTS in the identification of missed injuries is similar to that of the TSMO. Trauma nurses use an appropriate and rationalized approach to ordering additional radiological investigations and contribute a valuable addition to trauma patient care.
Food limitation and starvation independently affect predator macronutrient selection
Authors: Toft Søren , Lange Camilla Sandager , Kristensen Line
Published: May 2021

Predators are often food limited in their habitat, and some are limited by specific macronutrients (protein, lipid or carbohydrate). It is unresolved, however, to what extent and in what way food and macronutrient limitation are connected. Using a carabid beetle (
Nebria brevicollis
), we compared macronutrient self-selection of the animals three times: immediately after collection in the field, after being fed to satiation and nutritional balance and after a subsequent period of starvation. Both sexes were food and females lipid limited in the field; after 7–21 days of starvation both sexes increased proportional carbohydrate intake significantly. Thus, starvation created a nutrient deficit that was different from what the animals had experienced in the field. We conclude that while macronutrient limitation in nature may be influenced by hunger due to food limitation, this is not its main determinant. A nutritional imbalance of available food may override this effect.
‘Dunbar's number’ deconstructed
Authors: Lindenfors Patrik , Wartel Andreas , Lind Johan
Published: May 2021

A widespread and popular belief posits that humans possess a cognitive capacity that is limited to keeping track of and maintaining stable relationships with approximately 150 people. This influential number, ‘Dunbar's number’, originates from an extrapolation of a regression line describing the relationship between relative neocortex size and group size in primates. Here, we test if there is statistical support for this idea. Our analyses on complementary datasets using different methods yield wildly different numbers. Bayesian and generalized least-squares phylogenetic methods generate approximations of average group sizes between 69–109 and 16–42, respectively. However, enormous 95% confidence intervals (4–520 and 2–336, respectively) imply that specifying any one number is futile. A cognitive limit on human group size cannot be derived in this manner.
Effect of manual and digital contact tracing on COVID-19 outbreaks: a study on empirical contact data
Authors: Barrat A. , Cattuto C. , Kivelä M. , Lehmann S. , Saramäki J.
Published: May 2021

Non-pharmaceutical interventions are crucial to mitigate the COVID-19 pandemic and contain re-emergence phenomena. Targeted measures such as case isolation and contact tracing can alleviate the societal cost of lock-downs by containing the spread where and when it occurs. To assess the relative and combined impact of manual contact tracing (MCT) and digital (app-based) contact tracing, we feed a compartmental model for COVID-19 with high-resolution datasets describing contacts between individuals in several contexts. We show that the benefit (epidemic size reduction) is generically linear in the fraction of contacts recalled during MCT and quadratic in the app adoption, with no threshold effect. The cost (number of quarantines) versus benefit curve has a characteristic parabolic shape, independent of the type of tracing, with a potentially high benefit and low cost if app adoption and MCT efficiency are high enough. Benefits are higher and the cost lower if the epidemic reproductive number is lower, showing the importance of combining tracing with additional mitigation measures. The observed phenomenology is qualitatively robust across datasets and parameters. We moreover obtain analytically similar results on simplified models.
Optimizing the early detection of low pathogenic avian influenza H7N9 virus in live bird markets
Authors: Guinat Claire , Tago Damian , Corre Tifenn , Selinger Christian , Djidjou-Demasse Ramsès , Paul Mathilde , Raboisson Didier , Nguyen Thi Thanh Thuy , Inui Ken , Pham Thanh Long , Padungtod Pawin , Vergne Timothée
Published: May 2021

In Southeast Asia, surveillance at live bird markets (LBMs) has been identified as crucial for detecting avian influenza viruses (AIV) and reducing the risk of human infections. However, the design of effective surveillance systems in LBMs remains complex given the rapid turn-over of poultry. We developed a deterministic transmission model to provide guidance for optimizing AIV surveillance efforts. The model was calibrated to fit one of the largest LBMs in northern Vietnam at high risk of low pathogenic H7N9 virus introduction from China to identify the surveillance strategy that optimizes H7N9 detection. Results show that (i) using a portable diagnostic device would slightly reduce the number of infected birds leaving the LBM before the first detection, as compared to a laboratory-based diagnostic strategy, (ii) H7N9 detection could become more timely by sampling birds staying overnight, just before new susceptible birds are introduced at the beginning of a working day, and (iii) banning birds staying overnight would represent an effective intervention to reduce the risk of H7N9 spread but would decrease the likelihood of virus detection if introduced. These strategies should receive high priority in Vietnam and other Asian countries at risk of H7N9 introduction.
Population Vaccine Effectiveness and its Implication for Control of the Spread of COVID-19 in the US
Authors: Hu Zixin , Ge Qiyang , Luo Li , Xu Tao , Zhang Kai , Lu Henry H , Li Wei , Boerwinkle Eric , Jin Li , Xiong Momiao
Published: May 2021

Realized vaccine efficacy in population is highly different from the individual vaccine efficacy measured in clinical trial. The realized vaccine efficacy in population is substantially affected by the vaccine age-stratified prioritization strategy, population age-structure, non-pharmaceutical intervention (NPI). We proposed a population vaccine efficacy which integrated individual vaccine efficacy, vaccine prioritization strategy and NPI to measure and monitor the control of the spread of COVID-19. We found that 11 states in the US had low population vaccine efficacy and 20 states had high population efficacy. We demonstrated that although the proportion of the population who received at least one dose of COVID-19 vaccine across 11 low population vaccine efficacy states, in general, was greater than that in 20 high population vaccine efficacy states, the 11 low population vaccine efficacy states experienced the recent COVID-19 surge, while the number of new cases in the 20 high population vaccine efficacy states exponentially decreased. We demonstrated that the proportions of adults in the population across 50 states were significantly associated with the forecasted ending date of the COVID-19. We show that it was recent low proportion of adults vaccinated in Michigan that caused its COVID-19 surge. Using population vaccination efficacy, we forecasted that the earliest COVID-19 ending states were Hawaii, Arizona, Arkansas, and California (in the end of June, 2021) and the last COVID-19 ending states were Colorado, New York and Michigan (in the Spring, 2022).
Effect of commuting on the risk of COVID-19 and COVID-19-induced anxiety
Authors: Ando Hajime , Ikegami Kazunori , Nagata Tomohisa , Tateishi Seiichiro , Eguchi Hisashi , Tsuji Mayumi , Matsuda Shinya , Fujino Yoshihisa , Ogami Akira ,   CORoNaWork Project
Published: May 2021

Background

To prevent the spread of coronavirus disease (COVID-19), it is important to avoid 3Cs (closed spaces, crowded places, and close-contact settings). However, the risk of contact with an unspecified number of people is inevitable while commuting to and from work. In this study, we investigated the relationship between commuting, and the risk of COVID-19 and COVID-19-induced anxiety.

Methods

An internet-based questionnaire survey was conducted to obtain a dataset from 27036 respondents. One-way commuting time was evaluated using a five-case method. The commuting distance was estimated using zip codes of the home and workplace. Logistic regression analysis was performed with the following outcomes: COVID-19 risk, close contact, infection anxiety, and infection anxiety due to commuting. Commuting distance and commuting time were analyzed separately in the model. We excluded participants with incalculable commuting distance, commuting distance exceeding 300 km, commuting distance of 0 km, or who telecommuted at least once a week.

Results

The total number of participants included in the analysis was 14038. The adjusted odds ratios (aORs) of using public transportation for severe acute respiratory syndrome coronavirus 2 infection were 4.17 (95% confidence interval [CI]: 2.51-6.93) (commuting time) and 5.18 (95% CI: 3.06-8.78) (commuting distance). The aOR of COVID-19 diagnosis decreased significantly with increasing commuting distance. The aORs of using public transportation to infection anxiety were 1.44 (95% CI: 1.31-1.59) (commuting time) and 1.45 (95% CI: 1.32-1.60) (commuting distance). The longer the commuting time, the more the aOR increased..

Conclusions

COVID-19 risk, close contact, and infection anxiety were all associated with the use of public transportation during commuting. Both commuting distance and time were associated with infection anxiety due to commuting, and the strength of the association increased with increase in commuting time distance. Since transportation by commuting is associated with COVID-19 risk and anxiety, we recommend the use of telecommuting and other means of work.
Methodological quality of recommendations on vitamin D and calcium – a systematic review of bone health guidelines
Authors: Dai Zhaoli , McKenzie Joanne E , McDonald Sally , Baram Liora , Page Matthew J , Allman-Farinelli Margaret , Raubenheimer David , Bero Lisa A.
Published: May 2021

There are numerous guidelines developed for bone health. Yet it is unclear the differences in guideline development methods explain the variability in recommendations for vitamin D and calcium intakes. The objective of this systematic review was to collate and compare recommendations for vitamin D and calcium across bone health guidelines, assess methods used to form the recommendations, and explore which methodological factors were associated with these guideline recommendations. We searched MEDLINE, EMBASE, CINAHL and other databases indexing guidelines to identify records in English between 2009 and 2019. Guidelines or policy statements on bone health or osteoporosis prevention for generally healthy adults aged ≥40 years were eligible for inclusion. Two reviewers independently extracted recommendations on daily vitamin D and calcium intake, supplement use, serum 25 hydroxy vitamin D [25(OH)D] level, and sunlight exposure; assessed guideline development methods against 25 recommended criteria in the World Health Organization (WHO) Handbook for Guideline Development; and, identified types of evidence underpinning the recommendations. We included 47 eligible guidelines from 733 records: 74% of the guidelines provided vitamin D (200∼600-4000 IU/day) and 70% provided calcium (600-1200 mg/day) recommendations; 96% and 88% recommended vitamin D and calcium supplements, respectively; and 70% recommended a specific 25(OH)D concentration. The mean of meeting 25 WHO methodological criteria per guideline was 10 (95% CI: 9-12; interquartile range: 6-15). There was uncertainty in the associations between the methodological criteria and the proportion of guidelines that provided recommendations on daily vitamin D or calcium. Various types of evidence, ranging from previous bone guidelines, nutrient reference reports, systematic reviews, observational studies, to perspectives/editorials were used to underpin the recommendations. In conclusion, there is considerable variability in vitamin D and calcium recommendation and in guideline development methods in bone health guidelines. Effort is required to strengthen methodological rigor of guideline development and utilize the best available evidence to underpin public health nutrition.

Highlights

This systematic review provides evidence on the variabilities in vitamin D and calcium recommendations as well as guideline development methods in 47 bone health guidelines globally.

Our findings point to continued effort to utilize the best available evidence to underpin nutrition recommendations and strengthen methodological rigor of guideline development in bone health guidelines.

Registration of protocol

PROSPERO: CRD42019126452
Tool to assess risk of bias due to missing evidence in network meta-analysis (ROB-MEN): elaboration and examples
Authors: Chiocchia Virginia , Nikolakopoulou Adriani , Higgins Julian PT , Page Matthew J , Papakonstantinou Theodoros , Cipriani Andrea , Furukawa Toshi A , Siontis George CM , Salanti Georgia
Published: May 2021

Selective outcome reporting and publication bias threaten the validity of systematic reviews and meta-analysis and ultimately can affect clinical decision-making. A rigorous methodology to evaluate the impact of this bias on the meta-analysis results of a network of interventions is still lacking. We present a tool to assess the Risk Of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) by expanding the methods previously developed for pairwise meta-analysis (ROB-ME, http://www.riskofbias.info).

ROB-MEN first evaluates the risk of bias due to missing evidence for each pairwise comparison separately. This step considers possible bias due to the presence of studies with unavailable results (known unknowns) and the potential for unpublished studies (unknown unknowns). The second step combines the overall judgements about the risk of bias due to missing evidence in pairwise comparisons with the percentage contribution of direct comparisons on the NMA estimates, the presence or absence of small-study effects, as evaluated by network meta-regression, and any bias from unobserved comparisons. Then, a level of “low risk”, “some concerns” or “high risk” for the bias due to missing evidence is assigned to each NMA estimate, which is our tool’s final output.

We describe the methodology of ROB-MEN step-by-step using an illustrative example from a published NMA of non-diagnostic modalities for the detection of coronary artery disease in patients with low risk acute coronary syndrome. We also report a full application of the tool on a larger and more complex published network of 18 drugs from head-to-head studies for the acute treatment of adults with major depressive disorder. The ROB-MEN tool is the first tool for evaluating the risk of bias due to missing evidence in NMA and it is applicable to networks of all sizes and geometry.
Infants are more susceptible to COVID-19 than children
Authors: Leung Char
Published: May 2021

Angiotensin-converting enzyme 2 (ACE2) has been found to mediate the host cell entry of SARS-CoV-2 that causes COVID-19. However, the link between ACE2 and the observed susceptibility of SARS-CoV-2 infection remains elusive. In contrast, observational studies can help identify the susceptibility biomarker of SARS-CoV-2 infection, those associated with age for example. Data of all PCR tests performed in the state of São Paulo of Brazil were gathered from the government database and were analyzed using multivariate logistic regression. Adjusted odds ratios for positive test results were calculated with the adjustment of age, gender, and comorbidities. Over 1.7 million test results were included in the study of which 38% were positive. Elderly was most vulnerable to SARS-CoV-2 infection. While underages were less susceptible than adults aged below 60 years, susceptibility was not equal among different pediatric groups. It is found that age and susceptibility to SARS-CoV-2 infection are not inversely related, but U-shaped, with infants more susceptible than children. Biomarkers that are linearly associated with age cannot explain the reduced susceptibility in children. These include lymphocyte count and cross-reactive antibodies against other coronaviruses that offers cross-protection. The expression level of ACE2 may still be able to explain but further investigations are needed.
Lipid-Modulating Agents for Prevention or Treatment of COVID-19 in Randomized Trials
Authors: Talasaz Azita H. , Sadeghipour Parham , Aghakouchakzadeh Maryam , Dreyfus Isaac , Kakavand Hessam , Ariannejad Hamid , Gupta Aakriti , Madhavan Mahesh V. , Van Tassell Benjamin W. , Jimenez David , Monreal Manuel , Vaduganathan Muthiah , Fanikos John , Dixon Dave L , Piazza Gregory , Parikh Sahil A. , Bhatt Deepak L. , Lip Gregory YH , Stone Gregg W. , Krumholz Harlan M. , Libby Peter , Goldhaber Samuel Z. , Bikdeli Behnood
Published: May 2021

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multi-organ manifestations. Lipid modulating agents may be useful in treating patients with COVID-19. They may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglycerides portends worse outcome in patients with COVID-19. Upon a systematic search, 40 RCTs with lipid modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrates RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for management or prevention of COVID-19. This manuscript summarizes the ongoing or completed randomized controlled trials (RCTs) of lipid modulating agents in COVID-19 and the implications of these trials for patient management.
Protocol of the COVID-19 Health Adherence Research in Scotland Vaccination (CHARIS-V) study: Understanding the influence of vaccination decisions on adherence to transmission-reducing behaviours in a prospective longitudinal study of the Scottish Population
Authors: Maciver Marina , Den Daas Chantal , Johnston Marie , Dixon Diane , Hubbard Gill
Published: May 2021

Introduction

The global population has been asked to live under tight restrictions to slow the spread of SARS-CoV-2. Transmission-reducing behaviours (TRBs), (physical distancing, hand washing, wearing a face covering) were introduced by governments in 2020 prior to vaccine availability. People should maintain TRBs throughout the vaccination programme, because there is much uncertainty about the vaccine efficacy, immunity duration, whether there will be the requirement for booster vaccines, and whether vaccinated individuals can be carriers of the virus. This study will explore the effect of the vaccination programme in Scotland on adherence to TRBs.

Methods and analysis

Telephone interviews will be conducted with participants from the nationally representative CHARIS project that agreed to be contacted for further research. Approximately 200, ten-minute telephone interviews will be conducted. Data will be collected on vaccine uptake or intention and adherence to TRBs. Univariate and multivariate logistic regression analyses and moderation analyses will be used to analyse the data collected. Ethical approval was granted by the Life Sciences and Medicine School Ethics Review Board (SERB) at the University of Aberdeen.

Discussion

CHARIS-V will provide an understanding of the effect of the vaccination programme on adherence to TRBs in Scotland. Findings should be useful to governments and public health agencies for the current COVID-19 pandemic and vaccination programme and assist in the management of any future outbreaks.
COVID-19 infection and hospitalization according to the burden of chronic noncommunicable diseases in Brazil
Authors: Ferraz Fabiana R. , Conde Wolney L. , Venancio Isabela , Lopes Larrisa , Azeredo Catarina M.
Published: May 2021

Chronic diseases, worse socioeconomic conditions and old age can increase infection and hospitalization rate due to Coronavirus disease (COVID-19). We assessed the association between the burden of NCDs and the occurrence of infections and hospitalizations of COVID-19 in Brazil in a large COVID-19 national survey data. We analyzed only data collected between July and November 2020 (n= 1,071,782). The frequencies of positive COVID-19 diagnosis and NCD burden were estimated according to age, sex, socioeconomic strata and skin color categories. We estimated hazard ratios and 95% confidence intervals using Cox regression models. There is a non-linear dose-response inverse association betweenper capitaincome and the rates of infection and hospitalization due to COVID-19. The presence of NCDs was associated with a higher incidence of COVID-19 infection (HR1NCD= 1.34; 95% CI: 1.26; 1.43; HR2 or more NCD= 1.54 95% CI: 1.39; 1.71) and incidence of hospitalization (HR1NCD= 3.08 95% CI: 2.26; 4.19; HR2or more NCD= 6.81 95% CI: 4.88; 9.49).The difference between the risks of infection or hospitalization of COVID-19 attributable to the burden of NCDs is non-linearly associated with the income.
Impaired T-cell and antibody immunity after COVID-19 infection in chronically immunosuppressed transplant recipients
Authors: Ashokkumar Chethan , Rohan Vinayak , Kroemer Alexander H , Rao Sohail , Mazariegos George , Higgs Brandon W , Nadig Satish , Almeda Jose , Dhani Harmeet , Khan Khalid , Yazigi Nada , Ekong Udeme , Kaufman Stuart , Betancourt-Garcia Monica M , Mukund Kavitha , Sethi Pradeep , Mehrotra Shikhar , Soltys Kyle , Singh Manasi S , Bond Geoffrey , Khanna Ajai , Ningappa Mylarappa , Spishock Brianna , Sindhi Elizabeth , Atale Neha , Saunders Maggie , Baliga Prabhakar , Fishbein Thomas , Subramaniam Shankar , Sindhi Rakesh
Published: May 2021

Assessment of T-cell immunity to the COVID-19 coronavirus requires reliable assays and is of great interest, given the uncertain longevity of the antibody response. Some recent reports have used immunodominant spike (S) antigenic peptides and anti-CD28 co-stimulation in varying combinations to assess T-cell immunity to SARS-CoV-2. These assays may cause T-cell hyperstimulation and could overestimate antiviral immunity in chronically immunosuppressed transplant recipients, who are predisposed to infections and vaccination failures. Here, we evaluate CD154-expressing T-cells induced by unselected S antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. Subjects included 72 transplanted and 130 non-transplanted subjects. S-reactive CD154+T-cells co-express and can thus substitute for IFNγ (n=3). Assay reproducibility in a variety of conditions was acceptable with coefficient of variation of 2-10.6%. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed transplant recipients who were sampled pre-pandemic, compared with 59 healthy non-transplanted subjects (p=0.02), b) lower in Tr COVID-19 patients compared with healthy transplant patients (p<0.0001), c) lower in Tr patients with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr recipients. S-reactive T-cells were not significantly different between the various COVID-19 disease categories in NT recipients. Among transplant recipients with COVID-19, cytomegalovirus co-infection occurred in 34%; further, CMV-specific T-cells (p<0.001) and incidence of anti-receptor-binding-domain IgG (p=0.011) were lower compared with non-transplanted COVID-19 patients. Healthy unexposed transplant recipients exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 infection leads to impaired T-cell and antibody responses to SARS-CoV-2 and increased risk of CMV co-infection in transplant recipients.
Longitudinal Changes in COVID-19 Associated In-Hospital Mortality
Authors: Warner Frederick , Hitchings Matt D.T. , Cummings Derek A.T. , McPadden Jacob , Krumholz Harlan M. , Ko Albert I. , Schulz Wade L.
Published: May 2021

Objective

As the COVID-19 pandemic has evolved, a key question for health care systems is whether in-hospital mortality has changed over time and if so, what factors contributed to these changes. Our goal was to leverage real-world data spanning two COVID-19 surges over the first year of the pandemic to determine the temporal trend of in-hospital mortality.

Design

This was an observational, retrospective study based on real-world data for patients admitted with COVID-19. Generalized additive models (GAM) were used to evaluate the association of covariates with the composite outcome over time.

Setting and Population

We identified a retrospective cohort of all patients who were hospitalized within the Yale New Haven Health (YNHH) system with an admission diagnosis of COVID-19 between March 1, 2020 and February 28, 2021.

Main outcome

The primary outcome for the study was a composite endpoint of in-hospital mortality, defined as death during the index hospitalization or discharge to hospice.

Results

Among 6,477 discharges over the study period, the mean age was 66.2 years (SD=17.6), 52.5% (n=3,401) were male and the overall composite mortality was 14.2% (n=920). Composite in-hospital mortality was significantly associated with increased age, comorbidity index, respiratory rate, and heart rate; decreased systolic blood pressure; male sex; and admission from a long-term care facility (LTCF). The significant temporal decrease in mortality that was observed for patients admitted from a location other than a LTCF was not seen in those admitted from a LTCF.

Conclusions

We found that the adjusted in-hospital mortality rate declined over the first year of the pandemic, despite a second surge in COVID-19-related hospitalizations. Importantly, the decrease in mortality appeared to be driven by declines in risk in those not admitted from a LTCF. The observed decrease in mortality over time suggests that improved outcomes may be due to progressive, incremental learning and continuous evolution in hospital practice and policy over the course of the pandemic.