bluuebunny/crossref_metadata_2025 huggingface dataset:
Reasons for discontinuing urate-lowering treatment in community-dwelling adults with gout: results of a primary care-based cross-sectional study
Authors: Elmelegy Dalia , Abhishek Abhishek
Published: April 2021

Objectives

The aim was to examine the prevalence of urate-lowering treatment (ULT) in community-dwelling adults with gout and the reasons for drug discontinuation.

Methods

Adults with gout living in the East Midlands, UK, were mailed a postal questionnaire by their general practice surgery. It enquired about demographic details, co-morbidities, number of gout flares in the previous 12 months, current ULT and the reasons for discontinuing ULT if applicable. The number (percentage), median [interquartile range (IQR)] and mean (s.d.) were used for descriptive purposes. The Mann–Whitney U test and χ2 test were used for univariate analyses. STATA v.16 was used for data analysis. Statistical significance was set at P < 0.05.

Results

Data for 634 gout patients [89.3% men, mean (s.d.) age 64.77 (12.74) years)] were included. Of the respondents, 59.8% self-reported taking ULT currently, with the vast majority (95.6%) taking allopurinol. Participants self-reporting current ULT experienced fewer gout flares in the previous 12 months than those who did not self-report current ULT [median (IQR) 0 (0–2) and 1 (0–3), respectively, P < 0.05]. One hundred and seven participants (16.9%) self-reported ULT discontinuation previously. The most commonly cited reasons for this were side-effects (29.7%), being fed up with taking tablets (19.8%) and lack of benefit from treatment or ULT-induced gout flares (19.8%). Treatment being stopped by the general practitioner without a clear reason known to the participant (15.8%) was another common report.

Conclusion

This study identified patient-, physician- and treatment-related barriers to long-term ULT. These should be addressed when initiating ULT and during regular review. Further research is required to confirm these findings in other populations.
INCREASED EXPOSURE TO X-RAYS DURING CORONARY ANGIOGRAPHY AND PERCUTANEOUS CORONARY INTERVENTIONS ASSOCIATED WITH FRACTIONAL FLOW RESERVE MEASUREMENT AND ENDOCORONARY IMAGING TECHNIQUES
Authors: Bensaid Réda , Georges Jean-Louis , Angoulvant Denis , Chassaing Stephan , Deballon Ronan , Marcollet Pierre , Albert Franck , Fichaux Olivier , Bar Olivier , Rangé Grégoire
Published: April 2021

Growing use of fractional flow reserve (FFR) and intracoronary imaging techniques by optical coherence tomography or intravascular ultrasound has raised concerns about additional exposure during coronary angiography and percutaneous coronary interventions (PCIs). Using data from the prospective CRAC-France PCI Prospective Multicentre registry, we sought to evaluate the effect of these new techniques on the radiation dose to patients undergoing coronary procedures. Data on Kerma Area Product (PKA), total air kerma (KAr) and fluoroscopy time from 42 182 coronary procedures were retrospectively compared, using multivariable linear regression, according to whether they included FFR and intracoronary imaging. In coronary angiography, FFR was associated with longer fluoroscopy time and higher PKA (21.0 vs. 18.9 Gy.cm2) and KAr (372 vs. 299 mGy) (all p < 0.001). Intracoronary imaging was associated with longer fluoroscopy time, higher contrast volume (both p < 0.001), lower PKA (18.3 vs. 19.0 Gy.cm2, p = 0.02) and similar KAr. In PCI, FFR was associated with a moderate increase in KAr (682 vs. 626 mGy, p < 0.01) but not PKA (35.9 vs. 33.7 Gy.cm2, p = 0.34). For intracoronary imaging, there were no differences between groups, except for contrast volume. Increased patient exposure associated with FFR and intracoronary imaging is moderate in diagnostic coronary angiography and minimal or none in PCI, provided optimization techniques are used. It should not be a limitation on the use of these techniques given the important additional information they provide.
In defence of religious charitable trusts—when the ancient and the modern collide
Authors: Chevalier-Watts Juliet
Published: April 2021

Religious charitable trusts are no strangers to public and judicial criticism for a range of reasons, and this article considers their continued place within the charity narrative from the unusual perspective of the relationship between religious charitable trusts and commercialism, and whether such a position can be justified in contemporary society. This article does so by considering key cases from Australia and New Zealand, as well as Hong Kong. In doing so, this article demonstrates that religious trusts and commercialism make unusual but justifiable bed fellows, even in contemporary times, at least from a charitable perspective. As such, this article looks to quell some of the public disquiet concerning such trusts that continues unabated, and in doing so, this article may go some way in enhancing the quality of public conversations regarding religious charitable trusts.
Bead-assisted SARS-CoV-2 multi-antigen serological test allows effective identification of patients
Authors: Cáceres-Martell Yaiza , Fernández-Soto Daniel , Campos-Silva Carmen , García-Cuesta Eva M. , Casasnovas Jose M , Navas-Herrera David , Beneítez-Martínez Alexandra , Martínez-Fleta Pedro , Alfranca Arantzazu , Sánchez-Madrid Francisco , López Gabriela Escudero , Vilches Carlos , Jara-Acevedo Ricardo , Reyburn Hugh T. , Frade José M. Rodríguez , Valés-Gómez Mar
Published: April 2021

Many new aspects of COVID-19 disease, including different clinical manifestations, have been identified during the pandemic. The wide array of symptoms and variation in disease severity after SARS-CoV-2 infection might be related to heterogeneity in the immune responses of different patients. Here we describe a new method for a simple multi-antigen serological test that generates a full picture of seroconversion in a single reaction. The assay is based on the detection by flow cytometry of multiple immunoglobulin classes (isotypes) specific for four SARS-CoV-2 antigens: the Spike glycoprotein (one of the highly immunogenic proteins), its RBD fragment (the major target for neutralising antibodies), the nucleocapsid protein and the main cysteine-like protease. Until now, most diagnostic serological tests measured antibodies to only one antigen and some patients seemed to not make any antibody response. Our data reveal that while most patients respond against all the viral antigens tested, others show a marked bias to make antibodies against either proteins exposed on the viral particle or those released after cellular infection. Combining all the four antigens and using machine learning techniques, it was possible to clearly discriminate between patients and healthy controls with 100% confidence. Further, combination of antigens and different immunoglobulin isotypes in this multi-antigen assay improved the classification of patients with mild and severe disease. Introduction of this method will facilitate massive screenings of patients to evaluate their immune response. It could also support vaccination campaigns both to select non-immune individuals and to distinguish infected patients from vaccine responders.
Real-world Effect of Monoclonal Antibody Treatment in COVID-19 Patients in a Diverse Population in the United States
Authors: Rainwater-Lovett Kaitlin , Redd John T. , Stewart Miles A. , Elías Calles Natalia , Cluff Tyler , Fang Mike , Panaggio Mark J. , Lambrou Anastasia S. , Thornhill Jonathan K. , Bradburne Christopher , Imbriale Samuel , Freeman Jeffrey D. , Anderson Michael , Kadlec Robert
Published: April 2021

Background

Monoclonal antibodies (mAbs) against SARS-CoV-2 are a promising treatment for limiting the progression of COVID-19 and decreasing strain on hospitals. Their use, however, remains limited, particularly in disadvantaged populations.

Methods

Electronic health records were reviewed from SARS-CoV-2 patients at a single medical center in the United States that initiated mAb infusions in January 2021 with the support of the U.S. Department of Health and Human Services’ National Disaster Medical System. Patients who received mAbs were compared to untreated patients from the time period before mAb availability who met eligibility criteria for mAb treatment. We used logistic regression to measure the effect of mAb treatment on the risk of hospitalization or emergency department (E.D.) visit within 30 days of laboratory-confirmed COVID-19.

Results

Of 598 COVID-19 patients, 270 (45%) received bamlanivimab and 328 (55%) were untreated. Two hundred and thirty-one patients (39%) were Hispanic. Among treated patients, 5/270 (1.9%) presented to the E.D. or required hospitalization within 30 days of a positive SARS-CoV-2 test, compared to 39/328 (12%) untreated patients (p<0.001). After adjusting for age, gender, and comorbidities, the risk of E.D. visit or hospitalization was 82% lower in mAb-treated patients compared to untreated patients (95% confidence interval [CI]: 66%-94%).

Conclusions

In this diverse, real-world COVID-19 patient population, mAb treatment significantly decreased the risk of subsequent E.D. visit or hospitalization. Broader treatment with mAbs, including in disadvantaged patient populations, can decrease the burden on hospitals and should be facilitated in all populations in the United States to ensure health equity.

In a diverse, real-world COVID-19 patient population, treatment with monoclonal antibodies significantly decreased the risk of subsequent emergency department visit or hospitalization within 30 days of a positive SARS-CoV-2 viral test.
Who funded the research behind the Oxford-AstraZeneca COVID-19 vaccine? Approximating the funding to the University of Oxford for the research and development of the ChAdOx vaccine technology
Authors: Cross Samuel , Rho Yeanuk , Reddy Henna , Pepperrell Toby , Rodgers Florence , Osborne Rhiannon , Eni-Olotu Ayolola , Banerjee Rishi , Wimmer Sabrina , Keestra Sarai
Published: April 2021

Objectives

The Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19 or Vaxzevira) builds on nearly two decades of research and development (R&D) into Chimpanzee adenovirus-vectored vaccine (ChAdOx) technology at the University of Oxford. This study aims to approximate the funding for the R&D of the ChAdOx technology and the Oxford-AstraZeneca vaccine, and assess the transparency of funding reporting mechanisms.

Design

We conducted a scoping review and publication history analysis of the principal investigators to reconstruct the funding for the R&D of the ChAdOx technology. We matched award numbers with publicly-accessible grant databases. We filed Freedom Of Information (FOI) requests to the University of Oxford for the disclosure of all grants for ChAdOx R&D.

Results

We identified 100 peer-reviewed articles relevant to ChAdOx technology published between 01/2002 and 10/2020, extracting 577 mentions of funding bodies from funding acknowledgement statements. Government funders from overseas were mentioned 158 (27.4%), the U.K. government 147 (25.5%) and charitable funders 138 (23.9%) times. Grant award numbers were identified for 215 (37.3%) mentions, amounts were available in the public realm for 121 (21.0%) mentions. Based on the FOIs, until 01/2020, the European Commision (34.0%), Wellcome Trust (20.4%) and CEPI (17.5%) were the biggest funders of ChAdOx R&D. From 01/2020, the U.K. Department of Health and Social Care was the single largest funder (89.3%). The identified R&D funding was £104,226,076 reported in the FOIs, and £228,466,771 reconstructed from the literature search.

Conclusions

Our study identified that public funding accounted for 97.1-99.0% of the funding towards the R&D of ChAdOx and the Oxford-AstraZeneca vaccine. We furthermore encountered a severe lack of transparency in research funding reporting mechanisms.

Strengths and limitations of this study

This is the first study that analysed the R&D funding and funders contributing to the Oxford-AstraZeneca vaccine and the underlying ChAdOx technology.

We used multiple sources and methods to approximate the R&D funding of the Oxford-AstraZeneca Vaccine and ChAdOx technology.

We cross-matched award numbers with all publicly-accessible databases by major funders of R&D.

Freedom Of Information requests were a useful method to identify R&D funding, but face limitations in their scope of data collection.

Integration of the two data sets was not possible due to insufficient grant information and lack of award numbers in funding acknowledgement statements in peer-reviewed articles.
Carers using assistive technology in dementia care: an explanatory sequential mixed methods study
Authors: Sriram Vimal , Jenkinson Crispin , Peters Michele
Published: April 2021

INTRODUCTION

Informal carers support persons with dementia to live at home, even with deteriorating physical and cognitive issues. The purpose of this explanatory sequential mixed methods study is to examine the experiences and impact of Assistive Technology (AT) on carers, providing care for a person with dementia.

METHODS

The quantitative phase was a survey carried out with carers of persons with dementia in the UK, who used AT. The qualitative phase involved in-depth telephone interviews with a purposive sample of survey respondents. Data was analysed using hermeneutic phenomenology to develop, compare and explain the findings of the survey.

RESULTS

The survey included data from 201 carers. Smartphones and tablet computers were the most frequently used AT. Multiple AT were used in the care of persons with dementia predominantly for safety, communication, and reminders. The Short Form-12 questions in the survey showed that carers in the 46-65 age group and carers who were not extremely satisfied with AT had lower mental component scores and carers who lived with the person with dementia and older carers had lower physical component scores. Twenty-three carers participated in the interviews, and 5 themes with 14 sub-themes were identified. The interviews helped confirm data from the survey on the impact of AT on the physical, mental and social wellbeing of the carers. It helped describe reasons for satisfaction with AT; how AT was used in daily life and strengthened caring relationships; and how wider support systems enhanced the care of a person with dementia using AT.

CONCLUSIONS

This study describes the use of AT in the real-world context. AT supplements the care provided to a person with dementia in the community. Appropriate use, access to AT and abilities of the carer can enhance the support provided through AT to both carers and the person with dementia.
Prevention of COVID-19 by mRNA-based vaccines within the general population of California
Authors: Andrejko Kristin L. , Pry Jake , Myers Jennifer F. , Jewell Nicholas P. , Openshaw John , Watt James , Jain Seema , Lewnard Joseph A.
Published: April 2021

Background

Estimates of COVID-19 vaccine effectiveness under real-world conditions, and understanding of barriers to uptake, are necessary to inform vaccine rollout.

Methods

We enrolled cases (testing positive) and controls (testing negative) from among the population whose SARS-CoV-2 molecular diagnostic test results from 24 February-29 April 2021 were reported to the California Department of Public Health. Participants were matched on age, sex, and geographic region. We assessed participants’ self-reported history of COVID-19 vaccine receipt (BNT162b2 and mRNA-1273). Participants were considered fully vaccinated two weeks after second dose receipt. Among unvaccinated participants, we assessed willingness to receive vaccination, when eligible. We measured vaccine effectiveness (VE) via the matched odds ratio of prior vaccination, comparing cases with controls.

Results

We enrolled 1023 eligible participants aged ≥18 years. Among 525 cases, 71 (13.5%) received BNT162b2 or mRNA-1273; 20 (3.8%) were fully vaccinated with either product. Among 498 controls, 185 (37.1%) received BNT162b2 or mRNA-1273; 86 (16.3%) were fully vaccinated with either product. Two weeks after second dose receipt, VE was 86.8% (95% confidence interval: 68.6-94.7%) and 85.6% (69.1-93.9%) for BNT162b2 and mRNA-1273, respectively. Fully vaccinated participants receiving either product experienced 91.3% (79.7-96.3%) and 68.3% (28.5-86.0%) VE against symptomatic and asymptomatic infection, respectively. Among unvaccinated participants, 42.4% (159/375) residing in rural regions and 23.8% (67/281) residing in urban regions reported hesitancy to receive COVID-19 vaccination.

Conclusions

Authorized mRNA vaccines are effective at reducing documented SARS-CoV-2 infections within the general population of California. Vaccine hesitancy presents a barrier to reaching coverage levels needed for herd immunity.

Brief points

Vaccination is preventing documented SARS-CoV-2 infection in California, with 68% and 91% effectiveness against asymptomatic and symptomatic infection, respectively.

Vaccine effectiveness was equivalent for BNT126b2 and mRNA-1273.

Only 66% of unvaccinated participants were willing to receive the vaccine when eligible.
Spike protein antibodies mediate the apparent correlation between SARS-CoV-2 nucleocapsid antibodies and neutralization test results
Authors: Perkmann Thomas , Koller Thomas , Perkmann-Nagele Nicole , Klausberger Miriam , Duerkop Mark , Holzer Barbara , Hartmann Boris , Mucher Patrick , Radakovics Astrid , Ozsvar-Kozma Maria , Wagner Oswald F , Binder Christoph J , Haslacher Helmuth
Published: April 2021

Objectives

SARS-CoV-2 infection induces the formation of different antibodies. However, not all of which might prevent the virus from entering the cell, although their concentrations correlate with the titers of viral neutralization tests (NTs). Antibodies against the viral nucleocapsid (NC), e.g., can be classified as such. We aimed to prove the hypothesis that the apparent correlation between NC-antibody levels and NT-titers is mediated by simultaneously occurring antibodies against viral spike-protein components.

Methods

We included 64 individuals with previous SARS-CoV-2 infection (>14d after symptom onset). SARS-CoV-2 antibodies against the NC (Roche total antibody ECLIA, Abbott IgG CMIA) and spike-protein (Technozym RBD ELISA, DiaSorin S1/S2 CLIA) were measured, and neutralization tests were performed. The effect of spike-protein antibodies on the correlation between NC-antibodies and NT-titers was evaluated by partial correlation and mediation analyses.

Results

Both tested assays assessing antibodies against the NC correlated significantly with NT titers: Abbott ρ=0.742, P<0.0001; Roche ρ=0.365, P<0.01. However, when controlling the rank correlations for the presence of RBD or S1/S2 antibodies, correlation coefficients dropped to ρ=0.318/ρ=0.329 (P<0.05/P<0.01), respectively for Abbott and vanished for Roche. As a result, only a maximum of 11% of NT titer variability could be explained by NC-antibody levels.

Conclusions

Our data suggest that the apparent correlation between NC antibodies and NT titers is strongly mediated by co-occurring RBD antibody concentrations. To avoid falsely implied causal relationships, all correlation analyses of non-spike-associated antibody assays and neutralization assays should include a partial correlation analysis to exclude a possible mediator effect of spike-associated antibodies.
COVID-19 outcomes among hospitalized men with or without exposure to alpha-1-adrenergic receptor blocking agents
Authors: Li Shilong , Jun Tomi , Wang Zichen , Kao Yu-Han , Schadt Emilio , Konig Maximilian F. , Bettegowda Chetan , Vogelstein Joshua T. , Papadopoulos Nickolas , Parsons Ramon E. , Chen Rong , Schadt Eric E. , Li Li , Oh William K.
Published: April 2021

Importance

Alpha-1-adrenergic receptor antagonists (α1-blockers) can abrogate pro-inflammatory cytokines and may improve outcomes among patients with respiratory infections. Repurposing readily available drugs such as α1-blockers could augment the medical response to the COVID-19 pandemic.

Objective

To evaluate the association between α1-blocker exposure and COVID-19 mortality

Design

Real-world evidence study

Setting

Patient level data with 32,355 records tested for SARS-CoV-2 at the Mount Sinai Health System including 8,442 laboratory-confirmed cases extracted from five member hospitals in the New York City metropolitan area.

Participants

2,627 men aged 45 or older admitted with COVID-19 between February 24 and May 31, 2020

Exposures

α1-blocker use as an outpatient or while admitted for COVID-19

Main Outcomes and Measures

In-hospital mortality

Results

Men exposed to α1-blockers (N=436) were older (median age 73 vs. 64 years, P<0.001) and more likely to have comorbidities than unexposed men (N=2,191). Overall, 758 (28.9%) patients died in hospital, 1,589 (60.5%) were discharged, and 280 (10.7%) were still hospitalized as of May 31, 2020. Outpatient exposure to α1-blockers was not associated with COVID-19 hospital outcomes, though there was a trend towards significance (OR 0.749, 95% CI 0.527-1.064; P=0.106). Conversely, inpatient use of α1-blockers was independently associated with improved in-hospital mortality in both multivariable logistic (OR 0.633, 95% CI 0.434-0.921; P=0.017) and Cox regression analyses (HR 0.721, 95% CI 0.572-0.908; P=0.006) adjusting for patient demographics, comorbidities, and baseline vitals and labs. Age-stratified analyses suggested greater benefit from inpatient α1-blocker use among younger age groups: Age 45-65 OR 0.384, 95% CI 0.164-0.896 (P=0.027); Age 55-75 OR 0.511, 95% CI 0.297-0.880 (P=0.015); Age 65-89 OR 0.810, 95% CI 0.509-1.289 (P=0.374).

Conclusions and Relevance

Inpatient α1-blocker use was independently associated with improved COVID-19 mortality among hospitalized men. Clinical trials to assess the therapeutic value of α1-blockers in COVID-19 are warranted.
Genomic sequence characteristics and the empiric accuracy of short-read sequencing
Authors: Marin Maximillian , Vargas Roger , Harris Michael , Jeffrey Brendan , Epperson L. Elaine , Durbin David , Strong Michael , Salfinger Max , Iqbal Zamin , Akhundova Irada , Vashakidze Sergo , Crudu Valeriu , Rosenthal Alex , Farhat Maha Reda
Published: April 2021

Background

Short-read whole genome sequencing (WGS) is a vital tool for clinical applications and basic research. Genetic divergence from the reference genome, repetitive sequences, and sequencing bias, reduce the performance of variant calling using short-read alignment, but the loss in recall and specificity has not been adequately characterized. For the clonal pathogen Mycobacterium tuberculosis (Mtb), researchers frequently exclude 10.7% of the genome believed to be repetitive and prone to erroneous variant calls. To benchmark short-read variant calling, we used 36 diverse clinical Mtb isolates dually sequenced with Illumina short-reads and PacBio long-reads. We systematically study the short-read variant calling accuracy and the influence of sequence uniqueness, reference bias, and GC content. å

Results

Reference based Illumina variant calling had a recall ≥89.0% and precision ≥98.5% across parameters evaluated. The best balance between precision and recall was achieved by tuning the mapping quality (MQ) threshold, i.e. confidence of the read mapping (recall 85.8%, precision 99.1% at MQ ≥ 40). Masking repetitive sequence content is an alternative conservative approach to variant calling that maintains high precision (recall 70.2%, precision 99.6% at MQ≥40). Of the genomic positions typically excluded for Mtb, 68% are accurately called using Illumina WGS including 52 of the 168 PE/PPE genes (34.5%). We present a refined list of low confidence regions and examine the largest sources of variant calling error.

Conclusions

Our improved approach to variant calling has broad implications for the use of WGS in the study of Mtb biology, inference of transmission in public health surveillance systems, and more generally for WGS applications in other organisms.
Biotext: Exploiting Biological-Text Format for Text Mining
Authors: de Jesus Soares Machado Diogo , De Pierri Camilla Reginatto , Santos Letícia Graziela Costa , Scapin Leonardo , da Silva Filho Antonio Camilo , Perico Camila Pereira , de Oliveira Pedrosa Fabio , Raittz Roberto Tadeu
Published: April 2021

The large amount of existing textual data justifies the development of new text mining tools. Bioinformatics tools can be brought to Text Mining, increasing the arsenal of resources. Here, we present BIOTEXT, a package of strategies for converting natural language text into biological-like information data, providing a general protocol with standardized functions, allowing to share, encode and decode textual data for amino acid and DNA. The package was used to encode the arbitrary information present in the headings of the biological sequences found in a BLAST survey. The protocol implemented in this study consists of 12 steps, which can be easily executed and/ or changed by the user, depending on the study area. BIOTEXT empowers users to perform text mining using bioinformatics tools. BIOTEXT is freely available athttps://pypi.org/project/BIOTEXT/(Python package) andhttps://sourceforge.net/projects/BIOTEXTtools/files/AMINOcode_GUI/(Standalone tool).
Sensitive and specific spectral library searching with COSS and Percolator
Authors: Shiferaw Genet Abay , Gabriels Ralf , Bouwmeester Robbin , Van Den Bossche Tim , Vandermarliere Elien , Martens Lennart , Volders Pieter-Jan
Published: April 2021

Maintaining high sensitivity while limiting false positives is a key challenge in peptide identification from mass spectrometry data. Here, we therefore investigate the effects of integrating the machine learning-based post-processor Percolator into our spectral library searching tool COSS. To evaluate the effects of this post-processing, we have used forty data sets from two different projects and have searched these against the NIST and MassIVE spectral libraries. The searching is carried out using two spectral library search tools, COSS and MSPepSearch with and without Percolator post-processing, and using sequence database search engine MS-GF+ as a baseline comparator. The addition of the Percolator rescoring step to COSS is effective and results in a substantial improvement in sensitivity and specificity of the identifications. COSS is freely available as open source under the permissive Apache2 license, and binaries and source code are found athttps://github.com/compomics/COSS
MetaRNN: Differentiating Rare Pathogenic and Rare Benign Missense SNVs and InDels Using Deep Learning
Authors: Li Chang , Zhi Degui , Wang Kai , Liu Xiaoming
Published: April 2021

With advances in high-throughput DNA sequencing, numerous genetic variants have been discovered in the human genome. One challenge we face is interpreting these variants to help in disease screening, diagnosis, and treatment. While multiple computational approaches have been proposed to improve our understanding of genetic variants, their ability to identify rare pathogenic variants from rare benign ones is still lacking. Using context annotations and deep learning methods, we present pathogenicity prediction models, MetaRNN and MetaRNN-indel, to help identify and prioritize rare non-synonymous single nucleotide variants (nsSNVs) and non-frameshift insertion/deletions (nfINDELs). A recurrent neural network incorporating a +/- 1 codon window around the affected codon was combined with 28 high-level annotation scores and allele frequency features to develop the two proposed models. We use independent test datasets to demonstrate that these new models outperform state-of-the-art competitors and achieve a more interpretable score distribution. Importantly, prediction scores from the nsSNV-based and the nfINDEL-based models are comparable, enabling easy adoption of integrated genotype-phenotype association analysis methods. In addition, we provide pre-computed MetaRNN scores for all possible human nsSNVs and a Linux executable file for a fast one-stop annotation of nsSNVs and nfINDELs. All the resources are available athttp://www.liulab.science/MetaRNN.
Happy Cow or Thinking Pig? WUR Wolf – Facial Coding Platform for Measuring Emotions in Farm Animals
Authors: Neethirajan Suresh
Published: April 2021

Emotions play an indicative and informative role in the investigation of farm animal behaviors. Systems that respond and can measure emotions provide a natural user interface in enabling the digitalization of animal welfare platforms. The faces of farm animals can be one of the richest channels for expressing emotions. We present WUR Wolf (Wageningen University & Research: Wolf Mascot)—a real-time facial expression recognition platform that can automatically code the emotions of farm animals. Using Python-based algorithms, we detect and track the facial features of cows and pigs, analyze the appearance, ear postures, and eye white regions, and correlate with the mental/emotional states of the farm animals. The system is trained on dataset of facial features of images of the farm animals collected in over 6 farms and has been optimized to operate with an average accuracy of 85%. From these, we infer the emotional states of animals in real time. The software detects 13 facial actions and 9 emotional states, including whether the animal is aggressive, calm, or neutral. A real-time emotion recognition system based on YoloV3, and Faster YoloV4-based facial detection platform and an ensemble Convolutional Neural Networks (RCNN) is presented. Detecting expressions of farm animals simultaneously in real time makes many new interfaces for automated decision-making tools possible for livestock farmers. Emotions sensing offers a vast amount of potential for improving animal welfare and animal-human interactions.
Shorter effective lifespan in laboratory populations ofD. melanogastermight reduce sexual selection
Authors: Mital Avani , Sarangi Manaswini , Nandy Bodhisatta , Pandey Neha , Joshi Amitabh
Published: April 2021

The role of sexual selection in mediating levels of sexual conflict has been demonstrated in many experimental evolution studies onDrosophilaspp. where competition among males for mating was the target of selection. Sexual selection has also been shown to affect the evolution of life-histories. However, the influence of divergent life-histories on reproductive strategies and, therefore, sexual selection and possibly sexual conflict, has been less well studied. We examinedD. melanogasterpopulations selected for a short development time and early age at reproduction for changes in reproductive behaviour and traits that are proxies of sexual selection. We report a large reduction in reproductive competition experienced by the males of these populations, compared to ancestral populations that are not consciously selected for rapid development or early reproduction, potentially leading to reduced sexual selection. We show that rapidly developing and early reproducing populations have very low levels of mating in their lifetime (females are more or less monandrous), low courtship levels, shorter copulation duration, and longer time from eclosion to first mating, compared to the controls. These results are discussed in the context of the previously demonstrated reduction of inter-locus sexual conflict in these populations. We show that life-history strategies might have a large and significant impact on sexual selection, with each influencing the other and contributing to the complexities of adaptation.

Significance statement

Sexual conflict, often manifested as an arms-race between males and females trying to enhance their own reproductive success at some cost to the other, is of great evolutionary interest because it can maintain genetic variation in populations, prevent the independent optimization of male and female traits, and also promote speciation. Sexual selection, or variation in mating success, is well known to affect levels of sexual conflict. However, it is not so clear whether, and how, the regular evolution of life-histories also affects sexual selection. Here, we show that life-history evolution in fruit fly populations selected for traits not directly related to sexual conflict might, nevertheless, mediate the possible evolution of altered sexual conflict levels through effects on sexual selection. Populations that evolved to develop to adulthood fast, and reproduce relatively early in life, are shown to potentially experience less sexual selection, which can explain the low sexual conflict levels earlier observed in them.
Regulation of Plant Phototropic Growth by NPH3/RPT2-like Substrate Phosphorylation and 14-3-3 Binding
Authors: Sullivan Stuart , Waksman Thomas , Henderson Louise , Paliogianni Dimitra , Lütkemeyer Melanie , Suetsugu Noriyuki , Christie John M.
Published: April 2021

Polarity underlies all plant physiology and directional growth responses such as phototropism. Yet, our understanding of how plant tropic responses are established is far from complete. The plasma-membrane associated BTB-containing protein, NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) is a key determinant of phototropic growth which is regulated by AGC kinases known as the phototropins (phots). However, the mechanism by which phots initiate phototropic signalling via NPH3, and other NPH3/RPT2-like (NRL) members, has remained unresolved. Here we demonstrate that NPH3 is directly phosphorylated by phot1 bothin vitroandin vivo. Light-dependent phosphorylation within a conserved consensus sequence (RxS) located at the extreme C-terminus of NPH3 is necessary to promote its functionality for phototropism and petiole positioning inArabidopsis. Phosphorylation of this region by phot1 also triggers 14-3-3 binding combined with changes in NPH3 phosphorylation and localisation status. Seedlings expressing mutants of NPH3 that are unable to bind or constitutively bind 14-3-3s show compromised functionality that is consistent with a model where signalling outputs arising from a gradient in NPH3 RxS phosphorylation/localisation across the stem are a major contributor to phototropic responsiveness. Our current findings provide further evidence that 14-3-3 proteins are instrumental components regulating auxin-dependent growth and show for the first time that NRL proteins are direct phosphorylation targets for plant AGC kinases. Moreover, the C-terminal phosphorylation site/14-3-3-binding motif of NPH3 is conserved in several members of the NRL family, suggesting a common mechanism of regulation.
Integrative systems biology approach identified crucial genes and transcription factors associated with gallbladder cancer pathogenesis
Authors: Roy Nabanita , Kshattry Mrinmoy , Mandal Susmita , Jolly Mohit Kumar , Bhattacharyya Dhruba Kumar , Barah Pankaj
Published: April 2021

Gallbladder cancer (GBC) has a lower incidence rate among the population relative to other cancer types but majorly contributes to the total cancer cases of the biliary tract system. GBC is distinguished from other malignancies due to its high mortality, marked geographical variation and poor prognosis. To date no systemic targeted therapy is available for GBC. The main objective of this study is to determine the molecular signatures correlated with GBC development using integrative system level approaches. We performed analysis of publicly available transcriptomic data to identify differentially regulated genes and pathways. Co-expression network analysis and differential regulatory network analysis identified hub genes and hub transcription factors (TFs) associated with GBC pathogenesis and progression. We then assessed the epithelial-mesenchymal transition (EMT) status of the hub genes using a combination of three scoring methods. The hub genes such as; CDC6, MAPK15, CCNB2, BIRC7, L3MBTL1 identified are regulators of cell cycle components which suggests that cell cycle regulatory genes are significantly linked to GBC pathogenesis and progression.
Abundance-occupancy relationships along taxonomic ranks reveal a consistency of niche differentiation in marine bacterioplankton with distinct lifestyles
Authors: Izabel-Shen Dandan , Höger Anna-Lena , Jürgens Klaus
Published: April 2021

Abundance-occupancy relationships (AORs) are an important determinant of biotic community dynamics and habitat suitability. However, little is known about their role in complex bacterial communities, either within a phylogenetic framework or as a function of niche breadth. Based on data obtained in a field study in the St. Lawrence Estuary, we used 16S rRNA gene sequencing to examine the vertical patterns, strength, and character of AORs for particle-attached and free-living bacterial assemblages. Free-living communities were phylogenetically more diverse than particle-attached communities. The dominant taxa were consistent in terms of their presence/absence but population abundances differed in surface water vs. the cold intermediate layer. Significant, positive AORs characterized all of the surveyed communities across all taxonomic ranks of bacteria, thus demonstrating an ecologically conserved trend for both free-living and particle-attached bacteria. The strength of the AORs was low at the species level but higher at the genus and phylum levels. These results demonstrate that an assessment of the distributions and population densities of finely resolved taxa does not necessarily improve determinations of apparent niche differences in marine bacterioplankton communities at regional scales compared with the information inferred from a broad taxonomic classification.

Subject Category

microbial population and community ecology
The unresolved phylogenomic tree of butterflies and moths (Lepidoptera): assessing the potential causes and consequences
Authors: Rota Jadranka , Twort Victoria , Chiocchio Andrea , Peña Carlos , Wheat Christopher W. , Kaila Lauri , Wahlberg Niklas
Published: April 2021

The field of molecular phylogenetics is being revolutionised with next-generation sequencing technologies making it possible to sequence large numbers of genomes for non-model organisms ushering us into the era of phylogenomics. The current challenge is no longer how to get enough data, but rather how to analyse the data and how to assess the support for the inferred phylogeny. We focus on one of the largest animal groups on the planet – butterflies and moths (order Lepidoptera). We clearly demonstrate that there are unresolved issues in the inferred phylogenetic relationships of the major lineages, despite several recent phylogenomic studies of the group. We assess the potential causes and consequences of the conflicting phylogenetic hypotheses. With a dataset consisting of 331 protein-coding genes and the alignment length over 290 000 base pairs, including 200 taxa representing 81% of lepidopteran superfamilies, we compare phylogenetic hypotheses inferred from amino acid and nucleotide alignments. The resulting two phylogenies are discordant, especially with respect to the placement of the superfamily Gelechioidea, which is likely due to compositional bias of both the nucleotide and amino acid sequences. With a series of analyses, we dissect our dataset and demonstrate that there is sufficient phylogenetic signal to resolve much of the lepidopteran tree of life. Overall, the results from the nucleotide alignment are more robust to the various perturbations of the data that we carried out. However, the lack of support for much of the backbone within Ditrysia makes the current butterfly and moth tree of life still unresolved. We conclude that taxon sampling remains an issue even in phylogenomic analyses, and recommend that poorly sampled highly diverse groups, such as Gelechioidea in Lepidoptera, should receive extra attention in the future.
Improving estimation of species distribution from citizen-science records
using data-integration models
Authors: Zulian Viviane , Miller David A. W. , Ferraz Gonçalo
Published: April 2021

Mapping species distributions is a crucial but challenging requirement of
wildlife management. The frequent need to sample vast expanses of potential
habitat increases the cost of planned surveys and rewards accumulation of
opportunistic observations. In this paper, we integrate planned survey data from
roost counts with opportunistic samples from eBird, WikiAves and Xeno-canto
citizen-science platforms to map the geographic range of the endangered
Vinaceous-breasted Parrot. We demonstrate the estimation and mapping of species
occurrence based on data integration while accounting for specifics of each data
set, including observation technique and uncertainty about the observations. Our
analysis illustrates 1) the incorporation of sampling effort, spatial
autocorrelation, and site covariates in a joint-likelihood, hierarchical,
data-integration model; 2) the evaluation of the contribution of each data set,
as well as the contribution of effort covariates, spatial autocorrelation, and
site covariates to the predictive ability of fitted models using a
cross-validation approach; and 3) how spatial representation of the latent
occupancy state (i.e. realized occupancy) helps identify areas with high
uncertainty that should be prioritized in future field work. Our results reveal
a Vinaceous-breasted Parrot geographic range of 434,670
km2, which is three times larger than the ‘Extant’ area
previously reported in the IUCN Red List. The exclusion of one data set at a
time from the analyses always resulted in worse predictions by the models of
truncated data than by the full model, which included all data sets. Likewise,
exclusion of spatial autocorrelation, site covariates, or sampling effort
resulted in worse predictions. The integration of different data sets into one
joint-likelihood model produced a more reliable representation of the species
range than any individual data set taken on its own improving the use of citizen
science data in combination with planned survey results.
Direct and indirect cues can enable dual-adaptation, but through different learning processes
Authors: Forano Marion , Schween Raphael , Taylor Jordan A. , Hegele Mathias , Franklin David W.
Published: April 2021

Switching between motor tasks requires accurate adjustments for changes in dynamics (grasping a cup) or sensorimotor transformations (moving a computer mouse). Dual-adaptation studies have investigated how learning of context-dependent dynamics or transformations is enabled by sensory cues. However, certain cues, such as color, have shown mixed results. We propose that these mixed results may arise from two major classes of cues: “direct” cues, which are part of the dynamic state and “indirect” cues, which are not. We hypothesized that explicit strategies would primarily account for adaptation for an indirect color cue but would be limited to simple tasks while a direct visual separation cue would allow implicit adaptation regardless of task complexity. To test this idea, we investigated the relative contribution of implicit and explicit learning in relation to contextual cue type (colored or visually shifted workspace) and task complexity (one or eight targets) in a dual-adaptation task. We found that the visual workspace location cue enabled adaptation across conditions primarily through implicit adaptation. In contrast, we found that the color cue was largely ineffective for dual-adaptation, except in a small subset of participants who appeared to use explicit strategies. Our study suggests that the previously inconclusive role of color cues in dual-adaptation may be explained by differential contribution of explicit strategies across conditions.

New & Noteworthy

We present evidence that learning of context-dependent dynamics proceeds via different processes depending on the type of sensory cue used to signal the context. Visual workspace location enabled learning different dynamics implicitly, presumably because it directly enters the dynamic state estimate. In contrast, a color cue was only successful where learners were apparently able to leverage explicit strategies to account for changed dynamics. This suggests a unification for the previously inconclusive role of color cues.
The dual nature of metacommunity variability
Authors: Lamy Thomas , Wisnoski Nathan I. , Andrade Riley , Castorani Max C.N. , Compagnoni Aldo , Lany Nina , Marazzi Luca , Record Sydne , Swan Christopher M. , Tonkin Jonathan D. , Voelker Nicole , Wang Shaopeng , Zarnetske Phoebe L. , Sokol Eric R.
Published: April 2021

There is increasing interest in measuring ecological stability to understand how communities and ecosystems respond to broad-scale global changes. One of the most common approaches is to quantify the variation through time in community or ecosystem aggregate attributes (e.g., total biomass), referred to as aggregate variability. It is now widely recognized that aggregate variability represents only one aspect of communities and ecosystems, and compositional variability, the changes in the relative frequency of species in an assemblage, is equally important. Recent contributions have also begun to explore ecological stability at regional spatial scales, where interconnected local communities form metacommunities, a key concept in managing complex landscapes. However, the conceptual frameworks and measures of ecological stability in space have only focused on aggregate variability, leaving a conceptual gap. Here, we address this gap with a novel framework for quantifying the aggregate and compositional variability of communities and ecosystems through space and time. We demonstrate that the compositional variability of a metacommunity depends on the degree of spatial synchrony in compositional trajectories among local communities. We then provide a conceptual framework in which compositional variability of (i) the metacommunity through time and (ii) among local communities combine into four archetype scenarios:spatial stasis(low/low);spatial synchrony(high/low);spatial asynchrony(high/high) andspatial compensation(low/high). We illustrate this framework based on numerical examples and a case study of a macroalgal metacommunity in which low spatial synchrony reduced variability in aggregate biomass at the metacommunity scale, while masking high spatial synchrony in compositional trajectories among local communities. Finally, we discuss the role of dispersal, environmental heterogeneity, species interactions and suggest future avenues. We believe this framework will be helpful for considering both aspects of variability simultaneously which is important to better understand ecological stability in natural and complex landscapes in response to environmental changes.
The Hepcidin Regulator Erythroferrone is a New Member of the Erythropoiesis–Iron–Bone Circuitry
Authors: Castro-Mollo Melanie , Gera Sakshi , Martinez Marc Ruiz , Feola Maria , Gumerova Anisa , Planoutene Marina , Clementelli Cara , Sangkhae Veena , Casu Carla , Kim Se-Min , Ostland Vaughn , Han Huiling , Nemeth Elizabeta , Fleming Robert , Rivella Stefano , Lizneva Daria , Yuen Tony , Zaidi Mone , Ginzburg Yelena Z.
Published: April 2021

Erythroblast erythroferrone (ERFE) secretion inhibits hepcidin expression by sequestering several bone morphogenetic protein (BMP) family members to increase iron availability for erythropoiesis. We report that ERFE expression in osteoblasts is higher compared with erythroblasts, is independent of erythropoietin, and functional in suppressing hepatocyte hepcidin expression.Erfe-/-mice display low–bone–mass arising from increased bone resorption despite a concomitant increase in bone formation. Consistently,Erfe-/-osteoblasts exhibit enhanced mineralization,SostandRanklexpression, and BMP–mediated signalingex vivo. The ERFE effect on osteoclasts is mediated through increased osteoblastic RANKL and sclerostin expression, increasing osteoclastogenesis inErfe-/-mice. Importantly,Erfeloss in β–thalassemic (Hbbth3/+) mice, a disease model with increased ERFE expression, triggers profound osteoclastic bone resorption and bone loss. Together, ERFE exerts an osteoprotective effect by modulating BMP signaling in osteoblasts, decreasing RANKL production to limit osteoclastogenesis, and prevents excessive bone loss during expanded erythropoiesis in β–thalassemia.