bluuebunny/crossref_metadata_2025 huggingface dataset:
A highly invasive malaria parasite has expanded its range to non-migratory birds in North America
Authors: Theodosopoulos Angela N. , Grabenstein Kathryn C. , Bensch Staffan , Taylor Scott A.
Published: September 2021

Parasite range expansions are a direct consequence of globalization and are an increasing threat to biodiversity. Here, we report a recent range expansion of the SGS1 strain of a highly invasive parasite,
Plasmodium relictum
, to two non-migratory passerines in North America
. Plasmodium relictum
is considered one of the world's most invasive parasites and causes the disease avian malaria: this is the first reported case of SGS1 in wild non-migratory birds on the continent. Using a long-term database where researchers report avian malaria parasite infections, we summarized our current understanding of the geographical range of SGS1 and its known hosts. We also identified the most likely geographical region of this introduction event using the MSP1 allele. We hypothesize that this introduction resulted from movements of captive birds and subsequent spillover to native bird populations, via the presence of competent vectors and ecological fitting. Further work should be conducted to determine the extent to which SGS1 has spread following its introduction in North America.
Colourful traits in female birds relate to individual condition, reproductive performance and male-mate preferences: a meta-analytic approach
Authors: Hernández América , Martínez-Gómez Margarita , Beamonte-Barrientos René , Montoya Bibiana
Published: September 2021

Colourful traits in females are suggested to have evolved and be maintained by sexual selection. Although several studies have evaluated this idea, support is still equivocal. Evidence has been compiled in reviews, and a handful of quantitative syntheses has explored cumulative support for the link between condition and specific colour traits in males and females. However, understanding the potential function of females' colourful traits in sexual communication has not been the primary focus of any of those previous studies. Here, using a meta-analytic approach, we find that evidence from empirical studies in birds supports the idea that colourful female ornaments are positively associated with residual mass and immune response, clutch size and male-mate preferences. Hence, colourful traits in female birds likely evolved and are maintained by sexual selection as condition-dependent signals.
Migrating silver eels return from the sea to the river of origin after a false start
Authors: Tambets Meelis , Kärgenberg Einar , Järvalt Ain , Økland Finn , Kristensen Martin Lykke , Koed Anders , Bernotas Priit
Published: September 2021

The European eel's singular spawning migration from European waters towards the Sargasso Sea remains elusive, including the early phase of migration at sea. During spawning migration, the movement of freshwater resident eels from river to sea has been thought to be irreversible. We report the first recorded incidents of eels returning to the river of origin after spending up to a year in the marine environment. After migrating to the Baltic Sea, 21% of the silver eels, tagged with acoustic transmitters, returned to the Narva River. Half returned 11–12 months after moving to the sea, with 15 km being the longest upstream movement. The returned eels spent up to 33 days in the river and migrated to the sea again. The fastest specimen migrated to the outlet of the Baltic Sea in 68 days after the second start—roughly 1300 km. The surprising occurrence of returning migrants has implications for sustainable management and protection of this critically endangered species.
Predictive constitutive modelling of arteries by deep learning
Authors: Holzapfel Gerhard A. , Linka Kevin , Sherifova Selda , Cyron Christian J.
Published: September 2021

The constitutive modelling of soft biological tissues has rapidly gained attention over the last 20 years. Current constitutive models can describe the mechanical properties of arterial tissue. Predicting these properties from microstructural information, however, remains an elusive goal. To address this challenge, we are introducing a novel hybrid modelling framework that combines advanced theoretical concepts with deep learning. It uses data from mechanical tests, histological analysis and images from second-harmonic generation. In this first proof of concept study, our hybrid modelling framework is trained with data from 27 tissue samples only. Even such a small amount of data is sufficient to be able to predict the stress–stretch curves of tissue samples with a median coefficient of determination of
R
2
= 0.97 from microstructural information, as long as one limits the scope to tissue samples whose mechanical properties remain in the range commonly encountered. This finding suggests that deep learning could have a transformative impact on the way we model the constitutive properties of soft biological tissues.
Data-driven network models for genetic circuits from time-series data with incomplete measurements
Authors: Yeung Enoch , Kim Jongmin , Yuan Ye , Gonçalves Jorge , Murray Richard M.
Published: September 2021

Synthetic gene networks are frequently conceptualized and visualized as static graphs. This view of biological programming stands in stark contrast to the transient nature of biomolecular interaction, which is frequently enacted by labile molecules that are often unmeasured. Thus, the network topology and dynamics of synthetic gene networks can be difficult to verify
in vivo
or
in vitro
, due to the presence of unmeasured biological states. Here we introduce the dynamical structure function as a new mesoscopic, data-driven class of models to describe gene networks with incomplete measurements of state dynamics. We develop a network reconstruction algorithm and a code base for reconstructing the dynamical structure function from data, to enable discovery and visualization of graphical relationships in a genetic circuit diagram as
time-dependent functions
rather than static, unknown weights. We prove a theorem, showing that dynamical structure functions can provide a data-driven estimate of the size of crosstalk fluctuations from an idealized model. We illustrate this idea with numerical examples. Finally, we show how data-driven estimation of dynamical structure functions can explain failure modes in two experimentally implemented genetic circuits, a previously reported
in vitro
genetic circuit and a new
E. coli
-based transcriptional event detector.
Inferring simple but precise quantitative models of human oocyte and early embryo development
Authors: Leahy Brian D. , Racowsky Catherine , Needleman Daniel
Published: September 2021

Macroscopic, phenomenological models are useful as concise framings of our understandings in fields from statistical physics to finance to biology. Constructing a phenomenological model for development would provide a framework for understanding the complicated, regulatory nature of oogenesis and embryogenesis. Here, we use a data-driven approach to infer quantitative, precise models of human oocyte maturation and pre-implantation embryo development, by analysing clinical
in-vitro
fertilization (IVF) data on 7399 IVF cycles resulting in 57 827 embryos. Surprisingly, we find that both oocyte maturation and early embryo development are quantitatively described by simple models with minimal interactions. This simplicity suggests that oogenesis and embryogenesis are composed of modular processes that are relatively siloed from one another. In particular, our analysis provides strong evidence that (i) pre-antral follicles produce anti-Müllerian hormone independently of effects from other follicles, (ii) oocytes mature to metaphase-II independently of the woman’s age, her BMI and other factors, (iii) early embryo development is memoryless for the variables assessed here, in that the probability of an embryo transitioning from its current developmental stage to the next is independent of its previous stage. Our results both provide insight into the fundamentals of oogenesis and embryogenesis and have implications for the clinical IVF.
Mechanical and hydrodynamic analyses of helical strake-like ridges in a glass sponge
Authors: Fernandes Matheus C. , Saadat Mehdi , Cauchy-Dubois Patrick , Inamura Chikara , Sirota Ted , Milliron Garrett , Haj-Hariri Hossein , Bertoldi Katia , Weaver James C.
Published: September 2021

From the discovery of functionally graded laminated composites, to near-structurally optimized diagonally reinforced square lattice structures, the skeletal system of the predominantly deep-sea sponge
Euplectella aspergillum
has continued to inspire biologists, materials scientists and mechanical engineers. Building on these previous efforts, in the present study, we develop an integrated finite element and fluid dynamics approach for investigating structure–function relationships in the complex maze-like organization of helical ridges that surround the main skeletal tube of this species. From these investigations, we discover that not only do these ridges provide additional mechanical reinforcement, but perhaps more significantly, provide a critical hydrodynamic benefit by effectively suppressing von Kármán vortex shedding and reducing lift forcing fluctuations over a wide range of biologically relevant flow regimes. By comparing the disordered sponge ridge geometry to other more symmetrical strake-based vortex suppression systems commonly employed in infrastructure applications ranging from antennas to underwater gas and oil pipelines, we find that the unique maze-like ridge organization of
E. aspergillum
can completely suppress vortex shedding rather than delaying their shedding to a more downstream location, thus highlighting their potential benefit in these engineering contexts.
Oscillations make a self-scaled model for honeybees’ visual odometer reliable regardless of flight trajectory
Authors: Bergantin Lucia , Harbaoui Nesrine , Raharijaona Thibaut , Ruffier Franck
Published: September 2021

Honeybees foraging and recruiting nest-mates by performing the waggle dance need to be able to gauge the flight distance to the food source regardless of the wind and terrain conditions. Previous authors have hypothesized that the foragers’ visual odometer mathematically integrates the angular velocity of the ground image sweeping backward across their ventral viewfield, known as translational optic flow. The question arises as to how mathematical integration of optic flow (usually expressed in radians/s) can reliably encode distances, regardless of the height and speed of flight. The vertical self-oscillatory movements observed in honeybees trigger expansions and contractions of the optic flow vector field, yielding an additional visual cue called optic flow divergence. We have developed a self-scaled model for the visual odometer in which the translational optic flow is scaled by the visually estimated current clearance from the ground. In simulation, this model, which we have called SOFIa, was found to be reliable in a large range of flight trajectories, terrains and wind conditions. It reduced the statistical dispersion of the estimated flight distances approximately 10-fold in comparison with the mathematically integrated raw optic flow model. The SOFIa model can be directly implemented in robotic applications based on minimalistic visual equipment.
Insights from those who live with impairments of facial mobility
Authors: Cole Jonathan
Published: September 2021

Havi Carel suggested that to ‘fully understand illness it also has to be studied as a lived experience … [in its] existential, ethical and social dimensions’. This paper focuses on empirical work with those with Möbius syndrome on face perception and its implications, on their resilience and on their first person experiences. Möbius is characterized by the congenital absence of movements of the facial muscles; people with the condition cannot shut their eyes or mouths, or make facial expressions. Some also have reduced emotional experience as children. Fortunately, most do develop embodied emotional expression (through gesture and prosody, etc.) and learn that, by sharing these with others, they can also develop emotional experience within themselves. The mutual exchanges of embodied expression may facilitate and reinforce emotional experience.
When numbers fail: do researchers agree on operationalization of published research?
Authors: Haucke Matthias , Hoekstra Rink , van Ravenzwaaij Don
Published: September 2021

Current discussions on improving the reproducibility of science often revolve around statistical innovations. However, equally important for improving methodological rigour is a valid operationalization of phenomena. Operationalization is the process of translating theoretical constructs into measurable laboratory quantities. Thus, the validity of operationalization is central for the quality of empirical studies. But do differences in the validity of operationalization affect the way scientists evaluate scientific literature? To investigate this, we manipulated the strength of operationalization of three published studies and sent them to researchers via email. In the first task, researchers were presented with a summary of the Method and Result section from one of the studies and were asked to guess the hypothesis that was investigated via a multiple-choice questionnaire. In a second task, researchers were asked to rate the perceived quality of the study. Our results show that (1) researchers are better at inferring the underlying research question from empirical results if the operationalization is more valid, but (2) the different validity is only to some extent reflected in a judgement of the study's quality. These results combined give partial corroboration to the notion that researchers’ evaluations of research results are not affected by operationalization validity.
Frog nest foams exhibit pharmaceutical foam-like properties
Authors: Brozio Sarah , O'Shaughnessy Erin M. , Woods Stuart , Hall-Barrientos Ivan , Martin Patricia E. , Kennedy Malcolm W. , Lamprou Dimitrios A. , Hoskisson Paul A.
Published: September 2021

Foams have frequently been used as systems for the delivery of cosmetic and therapeutic molecules; however, there is high variability in the foamability and long-term stability of synthetic foams. The development of pharmaceutical foams that exhibit desirable foaming properties, delivering appropriate amounts of the active pharmaceutical ingredient (API) and that have excellent biocompatibility is of great interest. The production of stable foams is rare in the natural world; however, certain species of frogs have adopted foam production as a means of providing a protective environment for their eggs and larvae from predators and parasites, to prevent desiccation, to control gaseous exchange, to buffer temperature extremes, and to reduce UV damage. These foams show great stability (up to 10 days in tropical environments) and are highly biocompatible due to the sensitive nature of amphibian skin. This work demonstrates for the first time that nests of the túngara frog (
Engystomops pustulosus
) are stable
ex situ
with useful physiochemical and biocompatible properties and are capable of encapsulating a range of compounds, including antibiotics. These protein foam mixtures share some properties with pharmaceutical foams and may find utility in a range of pharmaceutical applications such as topical drug delivery systems.
Preparation of modified polysulfone material decorated by sulfonated citric chitosan for haemodialysis and its haemocompatibility
Authors: Lin Bingxian , Liu Kaiming , Qiu Yunren
Published: September 2021

Polysulfone (PSF) works potentially in haemodialysis due to its great mechanical and chemical stability, but performs poorly in haemocompatibility. For promoting the unpleasant haemocompatibility, sulfonated citric chitosan (SCACS) with the structure and groups similar to heparin was primarily synthesized by acylation and sulfonation. Furthermore, the chloroacylated PSF was pretreated by electrophilic chloroacetyl chloride to achieve more active sites for further reaction; the following membranes underwent the amination and were named amination polysulfone (AMPSF) membranes. Moreover, SCACS with abundant carboxyl and sulfonic groups was covalently grafted at the surface of pretreated PSF membranes, called PSF-SCACS membranes. The PSF-SCACS membranes were successfully synthesized and characterized by
1
H NMR, ATR-FTIR and XPS. In addition, the water contact angle of PSF-SCACS membranes decreased by 47° and the morphologies of the membranes changed little compared with the unmodified PSF membranes. The haemocompatible testing results, including protein adsorption, platelet adhesion, haemolysis rate, plasma recalcification time, activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT), demonstrated that the PSF-SCACS membranes possessed excellent haemocompatible performances, and SCACS played an important role in the modification.
A new carcharodontosaurian theropod dinosaur occupies apex predator niche in the early Late Cretaceous of Uzbekistan
Authors: Tanaka Kohei , Anvarov Otabek Ulugbek Ogli , Zelenitsky Darla K. , Ahmedshaev Akhmadjon Shayakubovich , Kobayashi Yoshitsugu
Published: September 2021

Carcharodontosauria is a group of medium to large-sized predatory theropods, distributed worldwide during the Cretaceous. These theropods were probably the apex predators of Asiamerica in the early Late Cretaceous prior to the ascent of tyrannosaurids, although few Laurasian species are known from this time due to a poor rock record. Here, we describe
Ulughbegsaurus uzbekistanensis
gen. et sp. nov. from the early Late Cretaceous (Turonian) of Central Asia, which represents the first record of a Late Cretaceous carcharodontosaurian from the region. This new taxon is represented by a large, isolated maxilla from the Bissekty Formation of the Kyzylkum Desert, the Republic of Uzbekistan, a formation yielding a rich and diverse assemblage of dinosaurs and other vertebrates from fragmentary remains. Comparison of the maxilla with that of other allosauroids indicates
Ulughbegsaurus
was 7.5–8 m in body length and greater than 1000 kg in body mass, suggesting it was the previously unrecognized apex predator of the Bissekty ecosystem while smaller known tryannosauroids and dromaeosaurids were probable mesopredators. The discovery of
Ulughbegsaurus
records the geologically latest stratigraphic co-occurrence of carcharodontosaurid and tyrannosauroid dinosaurs from Laurasia, and evidence indicates carcharodontosaurians remained the dominant predators relative to tyrannosauroids, at least in Asia, as late as the Turonian.
Three novel species of the Bacillus cereus group isolated from clinical samples in Japan
Authors: Tohya Mari , Hishinuma Tomomi , Watanabe Shin , Shimojima Masahito , Ogawa Miho , Tada Tatsuya , Kirikae Teruo
Published: September 2021

Three Gram-positive bacterial strains, BML-BC004, BML-BC017 and BML-BC059, isolated from blood samples from three inpatients in Japan, were identified as members of

Bacillus cereus

using matrix-assisted laser desorption ionization time-of-flight MS. The 16S rRNA gene sequences of these three strains were more than 97.1 % similar to 18 type strains belonging to the

B. cereus

group. Whole-genome comparisons, using average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH), confirmed that the three strains represented three individual distinct species belonging to the

B. cereus

group. A phylogenetic tree showed that BML-BC004, BML-BC017 and BML-BC059 were located close to

B. luti

,

B. mobilis

and

B. paramycoides

, respectively. Based on these phylogenetic and phenotypic data, including values below the threshold for ANI and dDDH, the three strains should be classified as representing three different novel species of the

B. cereus

group: Bacillus sanguinis sp. nov., with type strain BML-BC004T (=DSM 111102T=JCM 34122T), Bacillus paramobilis sp. nov., with type strain BML-BC017T (=DSM 111100T=JCM 34124T) and Bacillus hominis sp. nov., with type strain BML-BC059T (=DSM 111101T=JCM 34125T).
Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review
Authors: Wang Zijun , Zhao Siya , Tang Yuyi , Wang Zhili , Shi Qianling , Dang Xiangyang , Gan Lidan , Peng Shuai , Li Weiguo , Zhou Qi , Li Qinyuan , Mafiana Joy James , Cortés Rafael González , Luo Zhengxiu , Liu Enmei , Chen Yaolong
Published: September 2021

Introduction

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C.

Methods

We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C.

Results

A total of six cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that, after the treatment, 37.1% (95%CI, 0.0% to 74.5%) experienced adverse events, 5.9% (95%CI, 1.5% to 10.2%) died, 37.2% (95%CI, 0% to 76.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, the two included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.

Conclusions

Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.
Previous COVID-19 infection and antibody levels after vaccination
Authors: Ali Hamad , Alahmad Barrak , Al-Shammari Abdullah A. , Al-Terki Abdelmohsen , Hammad Maha , Cherian Preethi , Alkhairi Irina , Sindhu Sardar , Thanaraj Thangavel Alphonse , Mohammed Anwar , Alghanim Ghazi , Deverajan Sriraman , Ahmad Rasheed , El-Shazly Sherief , Dashti Ali A. , Shehab Mohammad , Al-Sabah Salman , Alkandari Abdullah , Abubaker Jehad , Abu-Farha Mohamed , Al-Mulla Fahd
Published: September 2021

Background

The emergence of new COVID-19 variants of concern coupled with a global inequity in vaccine access and distribution, prompted many public health authorities to circumvent the vaccine shortages by altering vaccination protocols and prioritizing high-risk individuals. Those with previous COVID-19 infection may have not been prioritized due to existing humoral immunity.

Objective

We aim to study the association between previous COVID-19 infection and antibody levels after COVID-19 vaccination.

Methods

A serological analysis to measure SARS-CoV-2 IgG, IgA and neutralizing antibodies was performed on individuals who received one or two doses of either BNT162b2 or ChAdOx1 vaccines in Kuwait. Generalized linear regression models adjusted for individual characteristics and comorbidities were fitted to study the average levels of IgG and neutralizing antibodies in vaccinated individuals based who had previous COVID-19 infection compared to those who had not.

Results

A total of 1025 individuals were recruited. The mean levels of IgG, IgA and neutralizing antibodies were higher in vaccinated subjects with previous COVID-19 infection when compared with those vaccinated without previous COVID-19 infection. Regression analysis showed a steeper slope of decline for IgG in vaccinated individuals without previous COVID-19 infection in comparison with vaccinated individuals with previous COVID-19 infection.

Conclusion

Previous COVID-19 infection appears to elicit robust and sustained levels of SARS-CoV-2 antibodies in vaccinated individuals. Given the inconsistent supply of COVID-19 vaccines in many countries due to the global inequity, our results point towards wider vaccination plans to especially cover individuals without previous COVID-19 infection.
Prevalence of Migraine and its associated factors among medical students of Bangladesh: A cross sectional study
Authors: Rafi Abdur , Shahriar Tasnim , Arafat Yeasin , Karmaker Abhishek , Chowdhury Showsan Kabir , Jahangir Benazir , Hossain Meherab , Sultana Mahamoda , Hossain Md. Golam
Published: September 2021

Introduction

Medical students are vulnerable group to migraine, one of the most common type of headache worldwide. The aim of the present study was to determine the prevalence of migraine and related disability among medical students of Bangladesh.

Methods

This cross-sectional study was conducted among 1327 students from six medical colleges Bangladesh during March 2021 through a self-administered online survey. ID Migraine™ scale and MIDAS scale were used to screen migraine and migraine related disability respectively. Frequency distribution, and Chi-square test, t-test along with multiple logistic regressions model were used to determine the prevalence and associated factors of migraine respectively.

Results

The overall prevalence of migraine among the participants was 19%. The prevalence was higher among females (27%) than males (8%). Female sex (aOR 4.11, 95% CI 2.79-6.03) and poor sleep quality (aOR 2.07, 95% CI 1.48-2.91) were identified as independent risk factors of migraine. More than 90% migrainures reported to suffer from moderate to severe headache. Nausea was most commonly reported associated symptom (83.5%) followed by photophobia (72%) and vomiting (53%). Self-reported mental stress (55%), irregular sleep (49%), noise (30.5%), and usage of electronic device (30.5%) were most commonly reported triggering factor of migraine attack. More than half of the sufferers reported severe migraine related disability (MIDAS score ≥ 21).

Conclusions

The prevalence of migraine among medical students of Bangladesh is alarmingly high. Frequent migraine attacks and severe intensity of headache cause a substantial level of disability among the sufferers. Cautious avoidance of the triggering factors through appropriate interventions and prophylactic medication can mitigate the negative impact of migraine as well as improve the quality of life.
Informing behaviour change intervention design using systematic review with Bayesian meta-analysis: physical activity in heart failure
Authors: Amirova A. , Taylor L. , Volkmer B. , Ahmed N. , Chater A.M. , Fteropoulli T.
Published: September 2021

Embracing the Bayesian approach, we aimed to synthesise evidence regarding barriers and enablers to physical activity in heart failure (HF) in a way that can inform behaviour change intervention development. This approach helps in estimating and quantifying the uncertainty in the evidence and facilitates the synthesis of qualitative and quantitative studies. Qualitative and observational studies investigating barriers and enablers to physical activity in adults diagnosed with HF were included in this systematic review with a Bayesian meta-analysis. Qualitative evidence was annotated using the Theoretical Domains Framework and represented as a prior distribution using an expert elicitation task. The maximum a posteriori probability (MAP) was calculated as a summary statistic for the probability distribution for the log OR value estimating the relationship between physical activity and each determinant, according to qualitative evidence alone, quantitative evidence, and qualitative and quantitative evidence combined. The dispersion in the probability distribution for log OR associated with each barrier or enabler was used to evaluate the level of uncertainty in the evidence. Wide, medium, and narrow dispersion (SD) corresponded to high, moderate, and low uncertainty in the evidence, respectively. Evidence from three qualitative and 16 (N = 2739) quantitative studies was synthesised. High pro-b-type natriuretic peptide, pro-BNP (MAP value for log OR = -1.16; 95% CrI: [-1.21; -1.11]) and self-reported symptoms (MAP for log OR = 0.48; 95% CrI: [0.40; 0.55]) were suggested as barriers to physical activity with narrow distribution dispersion (SD = 0.18 and 0.19, respectively). Modifiable barriers were symptom distress (MAP for log OR = -0.46; 95% CrI: [-0.68; -0.24]), and negative attitude (MAP for log OR = -0.40; 95% CrI: [-0.49; -0.31]), SD = 0.36 and 0.26, respectively. Modifiable enablers were social support (MAP for log OR = 0.56; 95% CrI: [0.48; 0.63]), self-efficacy (MAP for log OR = 0.43; 95% CrI: [0.32; 0.54]), positive physical activity attitude (MAP for log OR = 0.92; 95% CrI: [0.77; 1.06]), SD = 0.26, 0.37, and 0.36, respectively. This work extends the limited research on the modifiable barriers and enablers for physical activity by individuals living with HF.
Combining antibody markers for serosurveillance of SARS-CoV-2 to estimate seroprevalence and time-since-infection
Authors: Bhuiyan Md S. , Brintz Ben J. , Whitcombe Alana L. , Markmann Alena J. , Bartelt Luther A. , Moreland Nicole J. , Azman Andrew S. , Leung Daniel T.
Published: September 2021

Serosurveillance is an important epidemiologic tool for SARS-CoV-2, used to estimate burden of disease and degree of population immunity. Which antibody biomarker, and the optimal number of biomarkers, has not been well-established, especially with the emerging rollout of vaccines globally. Here, we used random forest models to demonstrate that a single spike or receptor-binding domain (RBD) antibody was adequate for classifying prior infection, while a combination of two antibody biomarkers performed better than any single marker for estimating time-since-infection. Nucleocapsid antibodies performed worse than spike or RBD antibodies for classification, but is of utility for estimating time-since-infection, and in distinguishing infection-induced from vaccine-induced responses. Our analysis has the potential to inform the design of serosurveys for SARS-CoV-2, including decisions regarding number of antibody biomarkers measured.
Guidelines for reliable and reproducible functional enrichment analysis
Authors: Wijesooriya Kaumadi , Jadaan Sameer A , Perera Kaushalya L , Kaur Tanuveer , Ziemann Mark
Published: September 2021

Gene set enrichment tests (a.k.a. functional enrichment analysis) are among the most frequently used methods in computational biology. Despite this popularity, there are concerns that these methods are being applied incorrectly and the results of some peer-reviewed publications are unreliable. These problems include the use of inappropriate background gene lists, lack of false discovery rate correction and lack of methodological detail. An example analysis of public RNA-seq reveals that these methodological errors alter enrichment results dramatically. To ascertain the frequency of these errors in the literature, we performed a screen of 186 open access research articles describing functional enrichment results. We find that 95% of analyses using over-representation tests did not implement an appropriate background gene list or did not describe this in the methods. Failure to perform p-value correction for multiple tests was identified in 43% of analyses. Many studies lacked detail in the methods section about the tools and gene sets used. Only 15% of studies avoided major flaws, which highlights the poor state of functional enrichment rigour and reporting in the contemporary literature. We provide a set of minimum standards that should act as a checklist for researchers and peer-reviewers.
Social belonging: Brain structure and function is linked to membership in sports teams, religious groups and social clubs
Authors: Kieckhaefer Carolin , Schilbach Leonhard , Bzdok Danilo
Published: September 2021

Human behaviour across the life span is driven by the psychological need to belong, from kindergarten to bingo nights. Being part of social groups constitutes a backbone for communal life, and confers many benefits for physical and mental health. Capitalizing on neuroimaging and behavioural data from ~40.000 participants from the UK Biobank population cohort, we used structural and functional analyses to explore how social participation is reflected in the human brain. Across three different types of social groups, structural analyses point towards variance in ventromedial prefrontal cortex, fusiform gyrus and anterior cingulate cortex as structural substrates tightly linked to social participation. Functional connectivity analyses emphasized the importance of default mode and limbic network, but also showed differences for sports teams and religious groups as compared to social clubs.

Taken together, our findings establish the structural and functional integrity of the default mode network as a neural signature of social belonging.
Linear superposition of responses evoked by individual glottal pulses explain over 80% of the frequency following response to human speech in the macaque monkey
Authors: Teichert Tobias , Gnanateja G. Nike , Sadagopan Srivatsun , Chandrasekaran Bharath
Published: September 2021

The frequency-following response (FFR) is a scalp-recorded electrophysiological potential that closely follows the periodicity of complex sounds such as speech. It has been suggested that FFRs reflect the linear superposition of responses that are triggered by the glottal pulse in each cycle of the fundamental frequency (F0 responses) and sequentially propagate through auditory processing stages in brainstem, midbrain, and cortex. However, this conceptualization of the FFR is debated, and it remains unclear if and how well a simple linear superposition can capture the spectro-temporal complexity of FFRs that are generated within the highly recurrent and non-linear auditory system. To address this question, we used a deconvolution approach to compute the hypothetical F0 responses that best explain the FFRs in rhesus monkeys to human speech and click trains with time-varying pitch patterns. The linear superposition of F0 responses explained well over 90% of the variance of click train steady state FFRs and well over 80% of mandarin tone steady state FFRs. The F0 responses could be measured with high signal-to-noise ratio and featured several spectro-temporally and topographically distinct components that likely reflect the activation of brainstem (<5ms; 200-1000 Hz), midbrain (5-15 ms; 100-250 Hz) and cortex (15-35 ms; ~90 Hz). In summary, our results in the monkey support the notion that FFRs arise as the superposition of F0 responses by showing for the first time that they can capture the bulk of the variance and spectro-temporal complexity of FFRs to human speech with time-varying pitch. These findings identify F0 responses as a potential diagnostic tool that may be useful to reliably link altered FFRs in speech and language disorders to altered F0 responses and thus to specific latencies, frequency bands and ultimately processing stages.
STAAR Workflow: A cloud-based workflow for scalable and reproducible rare variant analysis
Authors: Gaynor Sheila M. , Westerman Kenneth E. , Ackovic Lea L. , Li Xihao , Li Zilin , Manning Alisa K. , Philippakis Anthony , Lin Xihong
Published: September 2021

We developed the STAAR WDL workflow to facilitate the analysis of rare variants in whole genome sequencing association studies. The open-access STAAR workflow written in the workflow description language (WDL) allows a user to perform rare variant testing for both gene-centric and genetic region approaches, enabling genome-wide, candidate, and conditional analyses. It incorporates functional annotations into the workflow as introduced in the STAAR method in order to boost the rare variant analysis power. This tool was specifically developed and optimized to be implemented on cloud-based platforms such as BioData Catalyst Powered by Terra. It provides easy-to-use functionality for rare variant analysis that can be incorporated into an exhaustive whole genome sequencing analysis pipeline.

Availability and implementation

The workflow is freely available from https://dockstore.org/workflows/github.com/sheilagaynor/STAAR_workflow.
Dual transcriptional analysis of Peronospora belbahrii and Ocimum basilicum in susceptible interactions
Authors: Johnson Eric T. , Kim Hye-Seon , Tian Miaoying , Dudai Nativ , Tal Ofir , Gonda Itay
Published: September 2021

Basil downy mildew, caused by the pathogen Peronospora belbahrii, is a major problem for sweet basil growers worldwide. The genome sequences of both Ocimum basilicum and P. belbahrii were recently completed but extensive transcriptome analysis of this pathosystem has not been completed. RNA sequencing was performed using basil leaf samples collected three and six days after inoculation with sporangia from an Illinois isolate of P. belbahrii and differentially expressed genes were identified. Gene enrichment analysis identified 22 genes that were upregulated at day three, in comparison to mock inoculated leaf samples, that were classified as ‘defense response to oomycetes’; among this group were five orthologues of Arabidopsis thaliana DOWNY MILDEW RESISTANCE 6. During the same time interval, many genes contributing to photosynthesis in the infected leaves were downregulated in comparison to control leaf samples. Many more genes were differentially expressed in the inoculated basil leaves at day six, compared to mock inoculated leaves, as the pathogen began to produce sporangiophores. On days three and six, the pathogen produced high transcript levels of secreted glycoside hydrolases, which likely release sugars from the plant cell walls needed for the growth of the pathogen. These results contribute to a better understanding of the infection process of downy mildew and will aid the development of more effective measures for reducing the severity of the disease.
Targeting metabolic adaptations in the breast cancer–liver metastatic niche using dietary approaches to improve endocrine therapy efficacy
Authors: Zuo Qianying , Mogol Ayca Nazli , Liu Yu-Jeh , Casiano Ashlie Santaliz , Chien Christine , Drnevich Jenny , Imir Ozan Berk , Kulkoyluoglu-Cotul Eylem , Park Nicole Hwajin , Shapiro David J , Park Ben Ho , Ziegler Yvonne , Katzenellenbogen Benita S. , Aranda Evelyn , O’Neill John D. , Raghavendra Akshara Singareeka , Tripathy Debu , Erdogan Zeynep Madak
Published: September 2021

Estrogen receptor-positive (ER+) metastatic tumors contribute to nearly 70% of breast cancer-related deaths. Most patients with ER+metastatic breast cancer (MBC) undergo treatment with the estrogen receptor antagonist fulvestrant (Fulv) as standard-of-care. Yet, among such patients, metastasis in liver is associated with reduced overall survival compared to other metastasis sites. The factors underlying the reduced responsiveness of liver metastases to ER-targeting agents remain unknown, impeding the development of more effective treatment approaches to improve outcomes for patients with ER+liver metastases. We therefore evaluated site-specific changes in MBC cells and determined the mechanisms through which the liver metastatic niche specifically influences ER+tumor metabolism and drug resistance. We characterized ER activity of MBC cells both in vitro, using a novel system of tissue-specific extracellular matrix hydrogels representing the stroma of ER+tumor metastatic sites (liver, lung and bone), and in vivo, in liver and lung metastasis mouse models. ER+metastatic liver tumors and MBC cells grown in liver hydrogels displayed upregulated expression of glucose metabolism enzymes in response to Fulv. Furthermore, differential ERα activity, but not expression, was detected in liver hydrogels. In vivo, increased glucose metabolism led to increased glycogen deposition in liver metastatic tumors, while a fasting-mimicking diet increased efficacy of Fulv treatment to reduce the metastatic burden.

Implications

Our findings identify a novel mechanism of endocrine resistance driven by the liver tumor microenvironment. These results may guide the development of dietary strategies to circumvent drug resistance in liver metastasis, with potential applicability in other metastatic diseases.
Superinfection exclusion: a viral strategy with short-term benefits and long-term drawbacks
Authors: Hunter Michael , Fusco Diana
Published: September 2021

Viral superinfection occurs when multiple viral particles subsequently infect the same host. In nature, several viral species are found to have evolved diverse mechanisms to prevent superinfection (superinfection exclusion) but how this strategic choice impacts the fate of mutations in the viral population remains unclear. Using stochastic simulations, we find that genetic drift is suppressed when superinfection occurs, thus facilitating the fixation of beneficial mutations and the removal of deleterious ones. Interestingly, we also find that the competitive (dis)advantage associated with variations in life history parameters is not necessarily captured by the viral growth rate for either infection strategy. Putting these together, we then show that a mutant with superinfection exclusion will easily overtake a superinfecting population even if the latter has a much higher growth rate. Our findings suggest that while superinfection exclusion can negatively impact the long-term adaptation of a viral population, in the short-term it is ultimately a winning strategy.

Author summary

Viral social behaviour has recently been receiving increasing attention in the context of ecological and evolutionary dynamics of viral populations. One fascinating and still relatively poorly understood example is superinfection or co-infection, which occur when multiple viruses infect the same host. Among bacteriophages, a wide range of mechanisms have been discovered that enable phage to prevent superinfection (superinfection exclusion) even at the cost of using precious resources for this purpose. What is the evolutionary impact of this strategic choice and why do so many phages exhibit this behaviour? Here, we conduct an extensive simulation study of a phage population to address this question. In particular, we investigate the fate of viral mutations arising in an environment with a constant supply of bacterial hosts designed to mimic a “turbidostat,” as these are increasingly being used in laboratory evolution experiments. Our results show that allowing superinfection in the long-term yields a population which is more capable of adapting to changes in the environment. However, when in direct competition, mutants capable of preventing superinfection experience a very large advantage over their superinfecting counterparts, even if this ability comes at a significant cost to their growth rate. This indicates that while preventing superinfection can negatively impact the long-term prospects of a viral population, in the short-term it is ultimately a winning strategy.
Impact of pH and removed filtrate onE. coliregrowth and microbial community during storage of electro-dewatered biosolids
Authors: Navab-Daneshmand Tala , Guo Bing , Gehr Ronald , Frigon Dominic
Published: September 2021

Residual biosolids can be land applied if they meet microbiological requirements at the time of application. Electro-dewatering technology is shown to reduce biosolids bacterial counts to detection limits with little potential for bacterial regrowth during incubations. Here, we investigated the impacts onEscherichia coliregrowth and microbial communities of biosolids pH, removed nutrients via the filtrate, and inhibitory compounds produced in electro-dewatered biosolids. Findings suggest pH as the primary mechanism impactingE. coliregrowth in electro-dewatered biosolids. Propidium monoazide treatments were effective at removing DNA from dead cells, based on the removal of obligate anaerobes observed after anaerobic incubation. Analyses of high throughput sequenced data showed lower alpha-diversities associated with electro-dewatering treatment and incubation time. Moreover, biosolids pH and incubation period were the main factors contributing to the variations in microbial community compositions after incubation. Results highlight the role of electro-dewatered biosolids’ low pH on inhibiting the regrowth of culturable bacteria as well as reducing the microbial community variance.
Microbial habitability of early Mars lacustrine environments sustained by iron redox cycling
Authors: Moore Rachel A. , Carr Christopher E.
Published: September 2021

Several studies have reported new data on the estimated compositions of chemical components at Gale crater; however, there is still a lack of information regarding potential past support of biomass and detectable biomarkers of ancient life. In this study we evaluate microbial habitability of early Mars constrained by the recently reconstructed water chemistry at Gale. The modeled community is based on Fe-metabolizing bacteria with the ability to utilize solid-phase iron oxides (e.g., magnetite) as an electron source or sink. Our results illustrate the plausibility of a sustained community in Gale Lake and provides suggestions for future modelled and laboratory-based studies to further evaluate the past habitability of Mars, biosignatures and their preservation potential, and hidden metabolic potential.

One Sentence Summary

This work provides an existence proof of habitability on early Mars and demonstrates modeling processes by which the habitability of extraterrestrial environments can be explored quantitatively.
A high throughput bispecific antibody discovery pipeline
Authors: Segaliny Aude I. , Jayaraman Jayapriya , Chen Xiaoming , Chong Jonathan , Luxon Ryan , Fung Audrey , Fu Qiwei , Jiang Xianzhi , Rivera Rodrigo , Ma Xiaoya , Ren Ci , Zimak Jan , Hedde Per Niklas , Shang Yonglei , Wu George , Zhao Weian
Published: September 2021

Bispecific antibodies (BsAbs) represent an emerging class of immunotherapy but inefficiency in the current BsAb discovery paradigm has limited their broad clinical availability. Here we report a high throughput, agnostic, single-cell-based BsAb functional screening pipeline, comprising molecular and cell engineering for efficient generation of BsAb library cells, followed by functional interrogation at the single-cell level to identify and sort positive clones and downstream sequence identification with single-cell PCR and sequencing and functionality characterization. Using a CD19xCD3 bispecific T cell engager (BiTE) as a model system, we demonstrate that our single cell platform possesses a high throughput screening efficiency of up to one and half million variant library cells per run and can isolate rare functional clones at low abundance of 0.008%. Using a complex CD19xCD3 BiTE-expressing cell library with approximately 22,300 unique variants comprising combinatorially varied scFvs, connecting linkers and VL/VH orientations, we have identified 98 unique clones including extremely rare ones (∼ 0.001% abundance). We also discovered BiTEs that exhibit novel properties contradictory to conventional wisdom, including harboring rigid scFv connecting peptide linkers yet with in vitro cytotoxicity comparable to that of clinically approved Blinatumomab. Through sequencing analyses on sorted BiTE clones, we discovered multiple design variable preferences for functionality including the CD19VL-VH– CD3VH-VL and CD19VH-VL–CD3VH-VL arrangements being the most favored orientation. Sequence analysis further interrogated the sequence composition of the CDRH3 domain in scFvs and identified amino acid residues conserved for function. We expect our single cell platform to not only significantly increase the development speed of high quality of new BsAb therapeutics for cancer and other disorders, but also enable identifying generalizable design principles for new BsAbs and other immunotherapeutics based on an in-depth understanding of the inter-relationships between sequence, structure, and function.